FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rong, PF Huang, P Liu, ZG Lin, J Jin, A Ma, Y Niu, G Yu, L Zeng, WB Wang, W Chen, XY AF Rong, Pengfei Huang, Peng Liu, Zhiguo Lin, Jing Jin, Albert Ma, Ying Niu, Gang Yu, Lun Zeng, Wenbin Wang, Wei Chen, Xiaoyuan TI Protein-based photothermal theranostics for imaging-guided cancer therapy SO NANOSCALE LA English DT Article ID MODIFIED GOLD NANORODS; ONE-POT SYNTHESIS; INDOCYANINE GREEN; NANOPARTICLE INTERACTIONS; IN-VIVO; ALBUMIN; CORONA; AGENT; BIOCOMPATIBILITY; NANOMATERIALS AB The development of imageable photothermal theranostics has attracted considerable attention for imaging guided photothermal therapy (PTT) with high tumor ablation accuracy. In this study, we strategically constructed a near-infrared (NIR) cyanine dye by introducing a rigid cyclohexenyl ring to the hepta-methine chain to obtain a heptamethine dye CySCOOH with high fluorescence intensity and good stability. By covalent conjugation of CySCOOH onto human serum albumin (HSA), the as-prepared HSA@CySCOOH nanoplatform is highly efficient for NIR fluorescence/photoacoustic/thermal multi-modality imaging and photothermal tumor ablation. The theranostic capability of HSA@CySCOOH was systematically evaluated both in vitro and in vivo. Most intriguingly, complete tumor elimination was achieved by intravenous injection of HSA@ CySCOOH (CySCOOH, 1 mg kg(-1); 808 nm, 1.0 W cm(-2) for 5 min) into 4T1 tumor-bearing mice, with no weight loss, noticeable toxicity, or tumor recurrence being observed. This as-prepared protein-based nanotheranostics exhibits high water dispersibility, no off target cytotoxicity, and good biodegradability and biocompatibility, thus facilitating its clinical translation to cancer photothermal theranostics. C1 [Rong, Pengfei; Wang, Wei] Cent S Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China. [Rong, Pengfei; Huang, Peng; Ma, Ying; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Huang, Peng] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Liu, Zhiguo; Yu, Lun; Zeng, Wenbin] Cent S Univ, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China. [Lin, Jing; Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Wang, W (reprint author), Cent S Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China. EM peng.huang@nih.gov; wbzeng@hotmail.com; cjr.wangwei@vip.163.com; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH); National Natural Science Foundation of China [51573096, 81401465, 81471715, 30900359, 30900377, 81271634]; Doctoral Station of Ministry of Education of China [20120162110070]; Hunan Provincial Natural Science Foundation of China [12JJ1012] FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), and grants from the National Natural Science Foundation of China (51573096, 81401465, 81471715, 30900359, 30900377 and 81271634), the Doctoral Station of Ministry of Education of China (no. 20120162110070), and Hunan Provincial Natural Science Foundation of China (12JJ1012). NR 36 TC 15 Z9 15 U1 15 U2 61 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2015 VL 7 IS 39 BP 16330 EP 16336 DI 10.1039/c5nr04428f PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CS8PQ UT WOS:000362350700024 PM 26382146 ER PT J AU Muller, YL Hanson, RL Wiessner, G Nieboer, L Kobes, S Piaggi, P Abdussamad, M Okani, C Knowler, WC Bogardus, C Baier, LJ AF Muller, Yunhua L. Hanson, Robert L. Wiessner, Gregory Nieboer, Lori Kobes, Sayuko Piaggi, Paolo Abdussamad, Mahdi Okani, Chidinma Knowler, William C. Bogardus, Clifton Baier, Leslie J. TI Assessing FOXO1A as a potential susceptibility locus for type 2 diabetes and obesity in American Indians SO OBESITY LA English DT Article ID GENOME-WIDE ASSOCIATION; RESPIRATORY CHAMBER; PIMA-INDIANS; FOOD-INTAKE; MELLITUS; DYSFUNCTION; INSIGHTS; RISK; GENE AB ObjectiveA prior genome-wide association study (GWAS) in Pima Indians identified variation within FOXO1A that modestly associated with early-onset (onset age <25years) type 2 diabetes (T2D). FOXO1A encodes the forkhead transcription factor involved in pancreatic -cell growth and hypothalamic energy balance; therefore, FOXO1A was analyzed as a candidate gene for T2D and obesity in a population-based sample of 7,710 American Indians. MethodsTag SNPs in/near FOXO1A (minor allele frequency0.05) were analyzed for association with T2D at early onset (n=1,060) and all ages (n=7,710) and with insulin secretion (n=298). SNPs were also analyzed for association with maximum body mass index (BMI) in adulthood (n=5,918), maximum BMI z-score in childhood (n=5,350), and % body fat (n=555). ResultsAn intronic SNP rs2297627 associated with early-onset T2D [OR=1.34 (1.13-1.58), P=8.7 x 10(-4)] and T2D onset at any age [OR=1.19 (1.09-1.30), P=1 x 10(-4)]. The T2D risk allele also associated with lower acute insulin secretion (=0.88, as a multiplier, P=0.02). Another intronic SNP (rs1334241, D=0.99, r(2)=0.49 with rs2297627) associated with maximum adulthood BMI (=1.02, as a multiplier, P=3 x 10(-5)), maximum childhood BMI z-score (=0.08, P=3 x 10(-4)), and % body fat (=0.83%, P=0.04). ConclusionsCommon variation in FOXO1A may modestly affect risk for T2D and obesity in American Indians. C1 [Muller, Yunhua L.; Hanson, Robert L.; Wiessner, Gregory; Nieboer, Lori; Kobes, Sayuko; Piaggi, Paolo; Abdussamad, Mahdi; Okani, Chidinma; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85001 USA. RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85001 USA. EM lbaier@phx.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. This study utilized the computational resources of the Biowulf system at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 18 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PY 2015 VL 23 IS 10 BP 1960 EP 1965 DI 10.1002/oby.21236 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CS6OX UT WOS:000362201100006 PM 26337673 ER PT J AU Dhawan, AP Heetderks, WJ Pavel, M Acharya, S Akay, M Mairal, A Wheeler, B Dacso, CC Sunder, T Lovell, N Gerber, M Shah, M Senthilvel, SG Wang, MD Bhargava, B AF Dhawan, Atam P. Heetderks, William J. Pavel, Misha Acharya, Soumyadipta Akay, Metin Mairal, Anurag Wheeler, Bruce Dacso, Clifford C. Sunder, T. Lovell, Nigel Gerber, Martin Shah, Milind Senthilvel, S. G. Wang, May D. Bhargava, Balram TI Current and Future Challenges in Point-of-Care Technologies: A Paradigm-Shift in Affordable Global Healthcare With Personalized and Preventive Medicine SO IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE-JTEHM LA English DT Article DE Global healthcare; healthcare challenges; healthcare innovations; point-of-care technologies ID DIAGNOSTICS AB This paper summarizes the panel discussion at the IEEE Engineering in Medicine and Biology Point-of-Care Healthcare Technology Conference (POCHT 2013) held in Bangalore India from Jan 16-18, 2013. Modern medicine has witnessed interdisciplinary technology innovations in healthcare with a continuous growth in life expectancy across the globe. However, there is also a growing global concern on the affordability of rapidly rising healthcare costs. To provide quality healthcare at reasonable costs, there has to be a convergence of preventive, personalized, and precision medicine with the help of technology innovations across the entire spectrum of point-of-care (POC) to critical care at hospitals. The first IEEE EMBS Special Topic POCHT conference held in Bangalore, India provided an international forum with clinicians, healthcare providers, industry experts, innovators, researchers, and students to define clinical needs and technology solutions toward commercialization and translation to clinical applications across different environments and infrastructures. This paper presents a summary of discussions that took place during the keynote presentations, panel discussions, and breakout sessions on needs, challenges, and technology innovations in POC technologies toward improving global healthcare. Also presented is an overview of challenges and trends in developing and developed economies with respect to priority clinical needs, technology innovations in medical devices, translational engineering, information and communication technologies, infrastructure support, and patient and clinician acceptance of POC healthcare technologies. C1 [Dhawan, Atam P.] New Jersey Inst Technol, Newark, NJ 07103 USA. [Heetderks, William J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20817 USA. [Pavel, Misha] Northeastern Univ, Boston, MA 02115 USA. [Acharya, Soumyadipta] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Akay, Metin] Univ Houston, Houston, TX 77004 USA. [Mairal, Anurag] Stanford Univ, Stanford, CA 94305 USA. [Mairal, Anurag] Orbees Infolabs India Pvt Ltd, Hyderabad 500081, Andhra Pradesh, India. [Wheeler, Bruce] Univ Florida, Gainesville, FL 32611 USA. [Dacso, Clifford C.] Baylor Coll Med, Houston, TX 77030 USA. [Sunder, T.] Apollo Hosp, Hyderabad 500072, Andhra Pradesh, India. [Lovell, Nigel] Univ New S Wales, Sydney, NSW 2052, Australia. [Gerber, Martin] Medtronic, Bombay 400093, Maharashtra, India. [Shah, Milind; Senthilvel, S. G.] Medtron India, Bombay 400093, Maharashtra, India. [Wang, May D.] Georgia Inst Technol, Atlanta, GA 30332 USA. [Bhargava, Balram] All India Inst Med Sci, Delhi 110029, India. RP Dhawan, AP (reprint author), New Jersey Inst Technol, Newark, NJ 07103 USA. EM dhawan@njit.edu NR 14 TC 3 Z9 3 U1 2 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2372 J9 IEEE J TRANSL ENG HE JI IEEE J. Transl. Eng. Health Med.-JTEHM PY 2015 VL 3 AR 2800110 DI 10.1109/JTEHM.2015.2400919 PG 10 WC Engineering, Biomedical SC Engineering GA CS8XA UT WOS:000362372000001 PM 27170902 ER PT S AU Bennett, BJ Hall, KD Hu, FB McCartney, AL Roberto, C AF Bennett, Brian J. Hall, Kevin D. Hu, Frank B. McCartney, Anne L. Roberto, Christina GP NY Acad Sci TI Nutrition and the science of disease prevention: a systems approach to support metabolic health SO ANNALS REPORTS, VOL 1352 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE gene-diet interactions; body weight; gut microbiome; systems science; diabetes; obesity ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TRIMETHYLAMINE-N-OXIDE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; MISSING HERITABILITY; BODY-WEIGHT; L-CARNITINE; OBESITY; MOUSE AB Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene-diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. C1 [Bennett, Brian J.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. [Bennett, Brian J.] Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC USA. [Hall, Kevin D.] Natl Inst Diabet & Digest & Kidney Dis, Integrat Physiol Sect, Bethesda, MD USA. [Hu, Frank B.; Roberto, Christina] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [McCartney, Anne L.] Univ Reading, Food & Nutr Sci, Reading, Berks, England. [Roberto, Christina] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Bennett, BJ (reprint author), Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. EM annals@nyas.org FU NHLBI NIH HHS [HL60712, R01 HL060712]; NIDDK NIH HHS [DK58845, P30 DK046200, R01 DK058845] NR 75 TC 3 Z9 3 U1 3 U2 8 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1352 BP 1 EP 12 DI 10.1111/nyas.12945 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BD6BU UT WOS:000362011100001 PM 26415028 ER PT S AU Zaslavsky, L Tatusova, T AF Zaslavsky, Leonid Tatusova, Tatiana BE Harrison, R Li, Y Mandoiu, I TI Clustering Analysis of Proteins from Microbial Genomes at Multiple Levels of Resolution SO BIOINFORMATICS RESEARCH AND APPLICATIONS (ISBRA 2015) SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 11th International Symposium on Bioinformatics Research and Applications (ISBRA) CY JUN 07-10, 2015 CL Norfolk, VA ID PAN-GENOME C1 [Zaslavsky, Leonid; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20854 USA. RP Zaslavsky, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20854 USA. EM zaslavsk@ncbi.nlm.nih.gov; tatiana@ncbi.nlm.nih.gov NR 7 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-19048-8; 978-3-319-19047-1 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2015 VL 9096 BP 438 EP 439 PG 2 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BD6CC UT WOS:000362026100046 ER PT J AU Basudhar, D Ridnour, LA Cheng, RY Wink, DA AF Basudhar, Debashree Ridnour, Lisa A. Cheng, Robert Y. Wink, David A. TI Role of NOS2 and COX2 as driver of poor prognosis in basal-like breast cancer SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Basudhar, Debashree; Ridnour, Lisa A.; Cheng, Robert Y.; Wink, David A.] NCI, Radiat Biol Branch, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2015 VL 36 SU 1 MA 431 BP S87 EP S87 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CS1XU UT WOS:000361863000332 ER PT S AU O'Reilly, M Jambou, R Rosenthal, E Montgomery, M Hassani, M Gargiulo, L Corrigan-Curay, J AF O'Reilly, Marina Jambou, Robert Rosenthal, Eugene Montgomery, Maureen Hassani, Morad Gargiulo, Linda Corrigan-Curay, Jacqueline BE Galli, MC Serabian, M TI The National Institutes of Health Oversight of Human Gene Transfer Research: Enhancing Science and Safety SO REGULATORY ASPECTS OF GENE THERAPY AND CELL THERAPY PRODUCTS: A GLOBAL PERSPECTIVE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Clinical trials; Adverse event database; Delivery system; GeMCRIS; Human gene transfer; Informed consent; Institute of Medicine; National Institutes of Health; NIH Guidelines; Office of Biotechnology Activities; Office of Science Policy; Recombinant DNA Advisory Committee; Safety data; Scientific review ID THERAPY AB The National Institutes of Health (NIH) oversight of human gene transfer research, which is defined as the deliberate transfer of recombinant and/or synthetic nucleic acid molecules to humans, originates with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). The NIH Guidelines, which were first published in the Federal Register almost 40 years ago, have been amended numerous times to remain responsive to scientific progress and to clearly define the responsibilities of NIH, the Recombinant DNA Advisory Committee (RAC), investigators, and institutions. Human gene transfer trials conducted at clinical sites in the United States (USA) are subject to the NIH Guidelines if they are conducted at, or sponsored by, an institution that receives any support for recombinant or synthetic nucleic acid research from the NIH. Human gene transfer trials conducted either in the USA or abroad are also subject to the NIH Guidelines if the investigational agent was developed with NIH funds and the institution that developed the investigational materials sponsors or participates in these projects. Trials are registered with the NIH Office Biotechnology Activities (OBA) and there are ongoing reporting requirements. Each new trial is reviewed by the RAC, and those that are novel or raise unique ethical or social issues are selected for review at quarterly public RAC meetings. The RAC also advises the NIH on policy and other matters relating to clinical gene transfer research and biosafety. C1 [O'Reilly, Marina] NIH, Program Biosecur & Biosafety Policy, Off Sci Policy, Bethesda, MD 20892 USA. [Jambou, Robert; Rosenthal, Eugene; Montgomery, Maureen; Hassani, Morad; Gargiulo, Linda; Corrigan-Curay, Jacqueline] NIH, Off Biotechnol Act, Off Sci Policy, Off Director, Bethesda, MD 20892 USA. RP Corrigan-Curay, J (reprint author), NIH, Off Biotechnol Act, Off Sci Policy, Off Director, Bldg 10, Bethesda, MD 20892 USA. EM corrigaja@nhlbi.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-18618-4; 978-3-319-18617-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 871 BP 31 EP 47 DI 10.1007/978-3-319-18618-4_2 D2 10.1007/978-3-319-18618-4 PG 17 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BD5TJ UT WOS:000361809700003 PM 26374211 ER PT S AU Jou, JD Jain, S Georgiev, I Donald, BR AF Jou, Jonathan D. Jain, Swati Georgiev, Ivelin Donald, Bruce R. BE Przytycka, TM TI BWM*: A Novel, Provable, Ensemble-Based Dynamic Programming Algorithm for Sparse Approximations of Computational Protein Design SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY (RECOMB 2015) SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 19th Annual International Conference on Research in Computational Molecular Biology (RECOMB) CY APR 12-15, 2015 CL Univ Warsaw, Warsaw, POLAND SP Int Soc Computat Biol, US Natl Sci Fdn, Polish Minist Sci & Educ, Warsaw Ctr Math & Comp Sci, Polish Bioinformat Soc, Univ Pittsburgh, Biogen Idec HO Univ Warsaw ID DEAD-END ELIMINATION; SIDE-CHAINS; GRAMICIDIN SYNTHETASE; PREDICTION; ENZYME; OPTIMIZATION; CONFORMATION; FLEXIBILITY; SPECIFICITY; REDESIGN AB Current dynamic programming protein design algorithms that exploit the optimal substructure induced by sparse energy functions compute only the Global Minimum Energy Conformation (GMEC). This disproportionately favors the sequence of a single, static conformation and overlooks better sequences with multiple low-energy conformations. We propose a novel, provable, dynamic programming algorithm called Branch-Width Minimization* (BWM*) to enumerate a gap-free ensemble of conformations in order of increasing energy. Given a branch-decomposition of branch-width w for an n-residue protein design with at most q discrete side-chain conformations per residue, BWM* returns the sparse GMEC in O(nw(2)q(3/2w)) time, and enumerates each additional conformation in O(n log q) time. BWM* outperforms the classical search algorithm A* in 49 of 67 protein design problems, computing the full ensemble or a close approximation up to two orders of magnitude faster. Performance of BWM* can be predicted cheaply beforehand, allowing selection of the most efficient algorithm for each design problem. C1 [Jou, Jonathan D.; Jain, Swati; Georgiev, Ivelin; Donald, Bruce R.] Duke Univ, Dept Comp Sci, Durham, NC 27706 USA. [Jain, Swati; Donald, Bruce R.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Jain, Swati] Duke Univ, Computat Biol & Bioinformat Program, Durham, NC USA. [Georgiev, Ivelin] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Donald, BR (reprint author), Duke Univ, Dept Comp Sci, Durham, NC 27706 USA. EM brd+recomb15@cs.duke.edu NR 44 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-16706-0; 978-3-319-16705-3 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2015 VL 9029 BP 154 EP 166 DI 10.1007/978-3-319-16706-0_16 PG 13 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BD6BD UT WOS:000361983900016 ER PT S AU Arunachalam, A Sornil, O AF Arunachalam, Ajay Sornil, Ohm BE Soni, AK Lobiyal, DK TI Issues of Implementing Random Walk and Gossip Based Resource Discovery Protocols in P2P MANETs & Suggestions for Improvement SO 3RD INTERNATIONAL CONFERENCE ON RECENT TRENDS IN COMPUTING 2015 (ICRTC-2015) SE Procedia Computer Science LA English DT Proceedings Paper CT 3rd International Conference on Recent Trends in Computing (ICRTC) CY MAR 12-13, 2015 CL Delhi, INDIA SP SRM Univ, NCR Campus, Dept Comp Sci & Engn DE flooding; random walk; gossip; MANET; Peer-to-Peer; resource discovery; MP2P AB Wireless multi-hop networks attracted much attention in recent years. Mobile Ad-hoc Network (MANET) being one of such networks has its own limitations in terms of resource discovery with unstable topology and paths through the networks. So eventually traditional searching techniques are still widely used. Peer-to-Peer (P2P) model is the major candidate for the internet traffic mainly due to its decentralized nature. This article evaluates classic flooding, random walk and gossip based resource discovery algorithms under mobile peer-to-peer (MP2P) networks and studied their performance. Further we suggest way to improve these algorithms to suit and work better under MANET. We compare the performance in terms of success rate, query response time, network overhead, battery power consumed, overall dropped packets, MAC load, network bandwidth, packet delivery ratio, network routing load and end to end delay. The experiments are validated through NS-2 simulations. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Arunachalam, Ajay; Sornil, Ohm] NIDA, Dept Comp Sci, Bangkok, Thailand. RP Arunachalam, A (reprint author), NIDA, Dept Comp Sci, Bangkok, Thailand. NR 14 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0509 J9 PROCEDIA COMPUT SCI PY 2015 VL 57 BP 509 EP 518 DI 10.1016/j.procs.2015.07.374 PG 10 WC Computer Science, Theory & Methods SC Computer Science GA BD5NJ UT WOS:000361632400060 ER PT S AU Armant, DR AF Armant, D. Randall BE Leese, HJ Brison, DR TI Intracellular Ca2+ Signaling and Preimplantation Development SO CELL SIGNALING DURING MAMMALIAN EARLY EMBRYO DEVELOPMENT SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Intracellular calcium signaling; Egg activation; Preimplantation development; Blastocyst; Phosphoinositide-specific phospholipase C; Trophoblast; Inositol-1,4,5-trisphosphate; Platelet-activating factor; Lysophosphatidic acid; Integrins ID PROTEIN-KINASE-C; CALCITONIN-GENE EXPRESSION; MAMMALIAN EGG ACTIVATION; MOUSE EMBRYO DEVELOPMENT; EPITHELIAL-CELL DEATH; GROWTH-FACTOR ALPHA; PHOSPHOLIPASE-C; IN-VITRO; TROPHOBLAST CELLS; POSTIMPLANTATION DEVELOPMENT AB The key, versatile role of intracellular Ca2+ signaling during egg activation after fertilization has been appreciated for several decades. More recently, evidence has accumulated supporting the concept that cytoplasmic Ca2+ is also a major signaling nexus during subsequent development of the fertilized ovum. This chapter will review the molecular reactions that regulate intracellular Ca2+ levels and cell function, the role of Ca2+ signaling during egg activation and specific examples of repetitive Ca2+ signaling found throughout pre- and peri-implantation development. Many of the upstream and downstream pathways utilized during egg activation are also critical for specific processes that take place during embryonic development. Much remains to be done to elucidate the full complexity of Ca2+ signaling mechanisms in preimplantation embryos to the level of detail accomplished for egg activation. However, an emerging concept is that because this second messenger can be modulated downstream of numerous receptors and is able to bind and activate multiple cytoplasmic signaling proteins, it can help the coordination of development through up-and downstream pathways that change with each embryonic stage. C1 [Armant, D. Randall] Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Armant, D. Randall] Wayne State Univ, Anat & Cell Biol, Detroit, MI 48201 USA. [Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD 20892 USA. RP Armant, DR (reprint author), Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, 275 E Hancock St, Detroit, MI 48201 USA. EM D.Armant@Wayne.edu OI Armant, D. Randall/0000-0001-5904-9325 FU Intramural NIH HHS; NICHD NIH HHS [HD067629, R21 HD071408] NR 112 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-2480-6; 978-1-4939-2479-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 843 BP 151 EP 171 DI 10.1007/978-1-4939-2480-6_6 D2 10.1007/978-1-4939-2480-6 PG 21 WC Biology; Cell Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Research & Experimental Medicine GA BD5TD UT WOS:000361797400007 PM 25956298 ER PT S AU Aravind, L Zhang, DP de Souza, RF Anand, S Iyer, LM AF Aravind, L. Zhang, Dapeng de Souza, Robson F. Anand, Swadha Iyer, Lakshminarayan M. BE KochNolte, F TI The Natural History of ADP-Ribosyltransferases and the ADP-Ribosylation System SO ENDOGENOUS ADP-RIBOSYLATION SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID COMPARATIVE GENOMICS; POLY(ADP-RIBOSE) GLYCOHYDROLASE; FUNCTIONAL-CHARACTERIZATION; CATALYTIC-PROPERTIES; TOXIN SYSTEMS; TRANSFER-RNA; SIR2 FAMILY; DNA-REPAIR; PROTEIN; MECHANISM AB Catalysis of NAD(+)-dependent ADP-ribosylation of proteins, nucleic acids, or small molecules has evolved in at least three structurally unrelated superfamilies of enzymes, namely ADP-ribosyltransferase (ART), the Sirtuins, and probably TM1506. Of these, the ART superfamily is the most diverse in terms of structure, active site residues, and targets that they modify. The primary diversification of the ART superfamily occurred in the context of diverse bacterial conflict systems, wherein ARTs play both offensive and defensive roles. These include toxin antitoxin systems, virus-host interactions, intraspecific antagonism (polymorphic toxins), symbiont/parasite effectors/toxins, resistance to antibiotics, and repair of RNAs cleaved in conflicts. ARTs evolving in these systems have been repeatedly acquired by lateral transfer throughout eukaryotic evolution, starting from the PARP family, which was acquired prior to the last eukaryotic common ancestor. They were incorporated into eukaryotic regulatory/epigenetic control systems (e.g., PARP family and NEURL4), and also used as defensive (e.g., pierisin and CARP-1 families) or immunity-related proteins (e.g., Gig2-like ARTs). The ADP-ribosylation system also includes other domains, such as the Macro, ADP-ribosyl glycohydrolase, NADAR, and ADP-ribosyl cyclase, which appear to have initially diversified in bacterial conflict-related systems. Unlike ARTs, sirtuins appear to have a much smaller presence in conflict-related systems. C1 [Aravind, L.; Zhang, Dapeng; Anand, Swadha; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [de Souza, Robson F.] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 90 TC 8 Z9 8 U1 1 U2 17 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-319-10771-4; 978-3-319-10770-7 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 384 BP 3 EP 32 DI 10.1007/82_2014_414 D2 10.1007/978-3-319-10771-4 PG 30 WC Immunology; Microbiology SC Immunology; Microbiology GA BD5JM UT WOS:000361510900002 PM 25027823 ER PT J AU Czako, R Subbarao, K AF Czako, Rita Subbarao, Kanta TI Refining the approach to vaccines against influenza A viruses with pandemic potential SO FUTURE VIROLOGY LA English DT Article DE antigenic mismatch; avian influenza; pandemic influenza; prepandemic vaccine; prime boost ID RANDOMIZED CONTROLLED-TRIAL; CROSS-REACTIVE IMMUNITY; A/DUCK/SINGAPORE/97 H5N3 VACCINE; MULTIBASIC CLEAVAGE SITE; RISK-ASSESSMENT TOOL; MEMORY B-CELLS; AVIAN-INFLUENZA; ANTIBODY-RESPONSE; SEASONAL INFLUENZA; HEALTHY-ADULTS AB Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration. C1 [Czako, Rita; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural Research Program of NIH and NIAID FX The authors are supported by funding from the Intramural Research Program of the NIH and NIAID. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 176 TC 1 Z9 2 U1 1 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PY 2015 VL 10 IS 9 BP 1033 EP 1047 DI 10.2217/FVL.15.69 PG 15 WC Virology SC Virology GA CS1IY UT WOS:000361818800003 PM 26587050 ER PT J AU Stephenson, D Hu, MT Romero, K Breen, K Burn, D Ben-Shlomo, Y Bhattaram, A Isaac, M Venuto, C Kubota, K Little, MA Friend, S Lovestone, S Morris, HR Grosset, D Sutherland, M Gallacher, J Williams-Gray, C Bain, LJ Aviles, E Marek, K Toga, AW Stark, Y Gordon, MF Ford, S AF Stephenson, Diane Hu, Michele T. Romero, Klaus Breen, Kieran Burn, David Ben-Shlomo, Yoav Bhattaram, Atul Isaac, Maria Venuto, Charles Kubota, Ken Little, Max A. Friend, Stephen Lovestone, Simon Morris, Huw R. Grosset, Donald Sutherland, Margaret Gallacher, John Williams-Gray, Caroline Bain, Lisa J. Aviles, Enrique Marek, Ken Toga, Arthur W. Stark, Yafit Gordon, Mark Forrest Ford, Steve TI Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Data standards; privacy; data integration; collaboration; quantitative disease progression; regulatory science ID MILD COGNITIVE IMPAIRMENT; POPULATION-BASED COHORT; NONMOTOR FEATURES; CRITICAL PATH; DISORDER; PD; RECOMMENDATIONS; PERSPECTIVE; SYMPTOMS; CAMPAIGN AB Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease. C1 [Stephenson, Diane; Romero, Klaus; Aviles, Enrique] CAMD, Crit Path Inst, Tucson, AZ USA. [Hu, Michele T.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Dept Neurol, Oxford OX3 9DU, England. [Lovestone, Simon] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Breen, Kieran] Sci Consultant, London, England. [Burn, David] Newcastle Univ, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Ben-Shlomo, Yoav] Univ Bristol, Bristol, Avon, England. [Bhattaram, Atul] US FDA, Silver Spring, MD USA. [Isaac, Maria] EMA, London, England. [Venuto, Charles] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Kubota, Ken] Michael J Fox Fdn Parkinsons Res, New York, NY USA. [Little, Max A.] Aston Univ, Cambridge, MA USA. [Little, Max A.] Aston Univ, MIT, Media Lab, Cambridge, MA USA. [Friend, Stephen] Sage Bionetworks, Seattle, WA USA. [Morris, Huw R.] UCL Inst Neurol, Dept Clin Neurosci, London, England. [Morris, Huw R.] Royal Free Hosp, Dept Neurol, London NW3 2QG, England. [Morris, Huw R.] Natl Hosp Neurol, Neurol, London, England. [Grosset, Donald] Univ Glasgow, Inst Neurosci & Psychol, Glasgow G12 8QQ, Lanark, Scotland. [Sutherland, Margaret] NINDS, Neurosci Ctr, Bethesda, MD 20892 USA. [Gallacher, John] Univ Oxford Hosp, Dept Psychiat, Oxford, England. [Williams-Gray, Caroline] Univ Cambridge, John Van Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge, England. [Bain, Lisa J.] Independent Sci & Med Writer, Elverson, PA USA. [Marek, Ken] Parkinsons Progress Markers Initiat, Inst Neurodegenerat Dis, New Haven, CT USA. [Toga, Arthur W.] Univ So Calif, Keck Sch Med, Lab Neuro Imaging, Los Angeles, CA 90089 USA. [Stark, Yafit] Teva Pharmaceut Ind Ltd, Petah Tiqwa, Israel. [Gordon, Mark Forrest] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Ford, Steve] Parkinsons UK, London, England. RP Stephenson, D (reprint author), Crit Path Inst, 1730 E River Rd, Tucson, AZ 85718 USA. EM dstephenson@c-path.org RI Morris, Huw/B-8527-2008; Breen, Kieran/N-4644-2014 OI Morris, Huw/0000-0002-5473-3774; Breen, Kieran/0000-0003-3974-4237 FU NIBIB NIH HHS [P41 EB015922]; NINDS NIH HHS [T32 NS007338]; Parkinson's UK [J-1301] NR 40 TC 2 Z9 2 U1 6 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2015 VL 5 IS 3 BP 581 EP 594 DI 10.3233/JPD-150570 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CR8LE UT WOS:000361602500018 PM 26406139 ER PT J AU Feng, J Fitz, Y Li, Y Fernandez, M Puch, IC Wang, D Pazniokas, S Bucher, B Cui, XZ Solomon, SB AF Feng, Jing Fitz, Yvonne Li, Yan Fernandez, Melinda Puch, Irene Cortes Wang, Dong Pazniokas, Stephanie Bucher, Brandon Cui, Xizhong Solomon, Steven B. TI Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 95; catheter; rat; carotid; artery; jugular; vein; vascular access; blood sampling; hemodynamic measures ID ESCHERICHIA-COLI; SEPSIS MODEL AB The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat C1 [Feng, Jing; Fitz, Yvonne; Li, Yan; Fernandez, Melinda; Puch, Irene Cortes; Wang, Dong; Cui, Xizhong; Solomon, Steven B.] NIH, Dept Crit Care Med, Ctr Clin, Washington, DC USA. RP Solomon, SB (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Washington, DC USA. EM ssolomon@cc.nih.gov FU Intramural NIH program; US government FX Intramural NIH program supported the development of this model. Publication support was provided by Harvard Apparatus Inc. and ADInstruments Inc. The work by the authors was done as part of US government-funded research; however, the opinions expressed are not necessarily those of the National Institutes of Health. NR 10 TC 3 Z9 3 U1 1 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2015 IS 95 AR e51881 DI 10.3791/51881 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MA UT WOS:000361532900011 ER PT J AU Garten, M Aimon, S Bassereau, P Toombes, GES AF Garten, Matthias Aimon, Sophie Bassereau, Patricia Toombes, Gilman E. S. TI Reconstitution of a Transmembrane Protein, the Voltage-gated Ion Channel, KvAP, into Giant Unilamellar Vesicles for Microscopy and Patch Clamp Studies SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Biochemistry; Issue 95; Biomimetic model system; Giant Unilamellar Vesicle; reconstitution; ion channel; transmembrane protein; KvAP; electroformation; gel assisted swelling; agarose; inside-out patch clamp; electrophysiology; fluorescence microscopy ID DEPENDENT K+ CHANNEL; PHOSPHOLIPID-VESICLES; MEMBRANE-PROTEINS; MOBILITY; BIOLOGY AB Giant Unilamellar Vesicles (GUVs) are a popular biomimetic system for studying membrane associated phenomena. However, commonly used protocols to grow GUVs must be modified in order to form GUVs containing functional transmembrane proteins. This article describes two dehydration-rehydration methods - electroformation and gel-assisted swelling - to form GUVs containing the voltage-gated potassium channel, KvAP. In both methods, a solution of protein-containing small unilamellar vesicles is partially dehydrated to form a stack of membranes, which is then allowed to swell in a rehydration buffer. For the electroformation method, the film is deposited on platinum electrodes so that an AC field can be applied during film rehydration. In contrast, the gel-assisted swelling method uses an agarose gel substrate to enhance film rehydration. Both methods can produce GUVs in low (e.g., 5 mM) and physiological (e.g., 100 mM) salt concentrations. The resulting GUVs are characterized via fluorescence microscopy, and the function of reconstituted channels measured using the inside-out patch-clamp configuration. While swelling in the presence of an alternating electric field (electroformation) gives a high yield of defect-free GUVs, the gel-assisted swelling method produces a more homogeneous protein distribution and requires no special equipment. C1 [Garten, Matthias; Bassereau, Patricia] Univ Paris 06, CNRS, Inst Curie, Ctr Rech,UMR 168,PhysicoChim Curie, F-75252 Paris 05, France. [Aimon, Sophie] Univ Calif San Diego, Kavli Inst Brain & Mind, San Diego, CA 92103 USA. [Toombes, Gilman E. S.] NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Bassereau, P (reprint author), Univ Paris 06, CNRS, Inst Curie, Ctr Rech,UMR 168,PhysicoChim Curie, F-75252 Paris 05, France. EM Patricia.Bassereau@curie.fr OI Toombes, Gilman/0000-0001-8346-1790; Bassereau, Patricia/0000-0002-8544-6778; Garten, Matthias/0000-0002-8660-1039 FU Agence Nationale de la Recherche [BLAN-0057-01]; European Commission (NoE SoftComp); Universite Pierre et Marie Curie [FED21]; Institut Curie International PhD Fellowship; Fondation pour la Recherche Medicale; Universite Pierre et Marie Curie; European Commission; Labex 'CelTisPhyBio' [ANR-11-LABX0038] FX We thank Susanne Fenz for discussing the possibility of reconstituting proteins by agarose swelling, Feng Ching Tsai for current measurements, and present and former members of the Bassereau group for support and assistance. The project was funded by the Agence Nationale de la Recherche (grant BLAN-0057-01), by the European Commission (NoE SoftComp), by the Universite Pierre et Marie Curie (grant from the FED21, Dynamique des Systemes Complexes). M.G. was supported by an Institut Curie International PhD Fellowship, S.A. by a fellowship from the Fondation pour la Recherche Medicale, G.E.S.T. by a Marie Curie Incoming International Fellowship from the European Commission and a grant from the Universite Pierre et Marie Curie. The publication fees were covered by the Labex 'CelTisPhyBio' (ANR-11-LABX0038). NR 38 TC 0 Z9 0 U1 6 U2 13 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2015 IS 95 AR e52281 DI 10.3791/52281 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MA UT WOS:000361532900043 ER PT J AU Haque, KD Pandey, AK Kelley, MW Puligilla, C AF Haque, Khujista D. Pandey, Atul K. Kelley, Matthew W. Puligilla, Chandrakala TI Culture of Embryonic Mouse Cochlear Explants and Gene Transfer by Electroporation SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 95; sensory epithelial cells; organ of Corti; cochlear explant cultures; electroporation; hearing; cell fate specification; differentiation ID HAIR CELL-DIFFERENTIATION; INNER-EAR; CORTI; ORGAN; MATH1 AB Auditory hair cells located within the mouse organ of Corti detect and transmit sound information to the central nervous system. The mechanosensory hair cells are aligned in one row of inner hair cells and three rows of outer hair cells that extend along the basal to apical axis of the cochlea. The explant culture technique described here provides an efficient method to isolate and maintain cochlear explants from the embryonic mouse inner ear. Also, the morphology and molecular characteristics of sensory hair cells and nonsensory supporting cells within the cochlear explant cultures resemble those observed in vivo and can be studied within its intrinsic cellular environment. The cochlear explants can serve as important experimental tools for the identification and characterization of molecular and genetic pathways that are involved in cellular specification and patterning. Although transgenic mouse models provide an effective approach for gene expression studies, a considerable number of mouse mutants die during embryonic development thereby hindering the analysis and interpretation of developmental phenotypes. The organ of Corti from mutant mice that die before birth can be cultured so that their in vitro development and responses to different factors can be analyzed. Additionally, we describe a technique for electroporating embryonic cochlear explants ex vivo which can be used to downregulate or overexpress specific gene(s) and analyze their potential endogenous function and test whether specific gene product is necessary or sufficient in a given context to influence mammalian cochlear development(1-8). C1 [Haque, Khujista D.; Pandey, Atul K.; Puligilla, Chandrakala] Med Univ S Carolina, Coll Med, Dept Pathol & Lab Med, Columbia, SC 29209 USA. [Kelley, Matthew W.] NIDCD, Lab Cochlear Dev, NIH, Bethesda, MD USA. RP Puligilla, C (reprint author), Med Univ S Carolina, Coll Med, Dept Pathol & Lab Med, Columbia, SC 29209 USA. EM puligill@musc.edu FU National Institutes of Health [5R00DC010220]; [C06RR014516] FX We would like to acknowledge Dr. Bradley Schulte for comments on this protocol. This work was supported by National Institutes of Health grant R00 (5R00DC010220). This project was performed in a renovated laboratory space supported by Grant C06RR014516. NR 16 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2015 IS 95 AR e52260 DI 10.3791/52260 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MA UT WOS:000361532900040 ER PT J AU Robin, JD Wright, WE Zou, YQ Cossette, SC Lawlor, MW Gussoni, E AF Robin, Jerome D. Wright, Woody E. Zou, Yaqun Cossette, Stacy C. Lawlor, Michael W. Gussoni, Emanuela TI Isolation and Immortalization of Patient-derived Cell Lines from Muscle Biopsy for Disease Modeling SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 95; Biopsy; skeletal muscle; skin; tissue dissociation; myoblast purification; myoblast immortalization; cell freezing ID SKELETAL-MUSCLE; MUSCULAR-DYSTROPHIES; DERMAL FIBROBLASTS; PREPLATE TECHNIQUE; HUMAN MYOBLASTS; STEM-CELLS; THERAPY AB The generation of patient-specific cell lines represents an invaluable tool for diagnostic or translational research, and these cells can be collected from skin or muscle biopsy tissue available during the patient's diagnostic workup. In this protocol, we describe a technique for live cell isolation from small amounts of muscle or skin tissue for primary cell culture. Additionally, we provide a technique for the immortalization of myogenic cell lines and fibroblast cell lines from primary cells. Once cell lines are immortalized, substantial expansion of patient-derived cells can be achieved. Immortalized cells are amenable to many downstream applications, including drug screening and in vitro correction of the genetic mutation. Altogether, these protocols provide a reliable tool to generate and preserve patient-derived cells for downstream applications. C1 [Robin, Jerome D.; Wright, Woody E.] UT Southwestern Med Ctr, Dept Cell Biol, Dallas, TX 75244 USA. [Zou, Yaqun] NINDS, NIH, Bethesda, MD 20892 USA. [Cossette, Stacy C.; Lawlor, Michael W.] Med Coll Wisconsin, Dept Pathol & Lab Med, Div Pediat Pathol, Milwaukee, WI 53226 USA. [Gussoni, Emanuela] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. RP Gussoni, E (reprint author), Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. EM gussoni@enders.tch.harvard.edu FU Cure CMD, an Association Contre Les Myopathies (AFM) [16297]; National Institutes of Health [K08 AR059750, L40 AR057721, 2R01NS047727] FX This publication is funded through Cure CMD, an Association Contre Les Myopathies (AFM) grant (project 16297), and by the National Institutes of Health (grant numbers K08 AR059750, L40 AR057721 and 2R01NS047727). NR 22 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2015 IS 95 AR e52307 DI 10.3791/52307 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MA UT WOS:000361532900049 ER PT J AU Wang, TG Choi, E Monaco, MCG Major, EO Medynets, M Nath, A AF Wang, Tongguang Choi, Elliot Monaco, Maria Chiara G. Major, Eugene O. Medynets, Marie Nath, Avindra TI Direct Induction of Human Neural Stem Cells from Peripheral Blood Hematopoietic Progenitor Cells SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 95; Hematopoietic progenitor cell; neural stem cell; blood; Sendai virus; neuron; differentiation ID DIRECT CONVERSION; HUMAN FIBROBLASTS; DEFINED FACTORS; NEURONS AB Human disease specific neuronal cultures are essential for generating in vitro models for human neurological diseases. However, the lack of access to primary human adult neural cultures raises unique challenges. Recent developments in induced pluripotent stem cells (iPSC) provides an alternative approach to derive neural cultures from skin fibroblasts through patient specific iPSC, but this process is labor intensive, requires special expertise and large amounts of resources, and can take several months. This prevents the wide application of this technology to the study of neurological diseases. To overcome some of these issues, we have developed a method to derive neural stem cells directly from human adult peripheral blood, bypassing the iPSC derivation process. Hematopoietic progenitor cells enriched from human adult peripheral blood were cultured in vitro and transfected with Sendai virus vectors containing transcriptional factors Sox2, Oct3/4, Klf4, and c-Myc. The transfection results in morphological changes in the cells which are further selected by using human neural progenitor medium containing basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The resulting cells are characterized by the expression for neural stem cell markers, such as nestin and SOX2. These neural stem cells could be further differentiated to neurons, astroglia and oligodendrocytes in specified differentiation media. Using easily accessible human peripheral blood samples, this method could be used to derive neural stem cells for further differentiation to neural cells for in vitro modeling of neurological disorders and may advance studies related to the pathogenesis and treatment of those diseases. C1 [Wang, Tongguang; Choi, Elliot; Medynets, Marie; Nath, Avindra] NINDS, Translat Neurosci Ctr, NIH, Bethesda, MD 20892 USA. [Monaco, Maria Chiara G.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Wang, TG (reprint author), NINDS, Translat Neurosci Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM david.wang@nih.gov NR 16 TC 0 Z9 0 U1 2 U2 4 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2015 IS 95 AR e52298 DI 10.3791/52298 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MA UT WOS:000361532900048 ER PT J AU Ueda, K Lee, L Hijioka, M Igarashi, H Ito, T Jensen, RT AF Ueda, K. Lee, L. Hijioka, M. Igarashi, H. Ito, T. Jensen, R. T. TI Usefulness of a Combination of a 48-Hour Fasting and a Glucagon Tolerance Test SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 11-13, 2015 CL Barcelona, SPAIN SP European Neuroendocrine Tumor Soc DE insulinoma; fasting test; glucagon tolerance test C1 [Ueda, K.; Lee, L.; Hijioka, M.; Igarashi, H.; Ito, T.] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. [Jensen, R. T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2015 VL 102 IS 1-2 MA R11 BP 162 EP 162 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CR9NM UT WOS:000361683500223 ER PT J AU Spassova, MA Miller, DJ Nikolov, AS AF Spassova, Maria A. Miller, David J. Nikolov, Alexander S. TI Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO3-Induced DNA Damage SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID CONTINUOUS END-POINTS; POTASSIUM BROMATE; OXIDATIVE STRESS; RISK-ASSESSMENT; CELL-PROLIFERATION; GENETIC TOXICOLOGY; IWGT REPORT; CARCINOGENICITY; MUTAGENICITY; KIDNEYS AB We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemical KBrO3 which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibits KBrO3-caused oxidative damage. Our modeling revealed that sustained exposure to KBrO3 can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical's toxicity dose dependence based on the dose-response of early genotoxic events. C1 [Spassova, Maria A.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. [Miller, David J.] NCI, Div Canc Biol, NIH, Rockville, MD 20892 USA. [Nikolov, Alexander S.] Langley High Sch, Mclean, VA 22101 USA. RP Spassova, MA (reprint author), US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. EM spassova.maria@epa.gov NR 36 TC 3 Z9 3 U1 0 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2015 AR 764375 DI 10.1155/2015/764375 PG 12 WC Cell Biology SC Cell Biology GA CR9HB UT WOS:000361664000001 ER PT B AU Regad, T Sayers, TJ Rees, RC AF Regad, Tarik Sayers, Thomas J. Rees, Robert C. BE Regad, T Sayers, TJ Rees, RC TI Principles of Stem Cell Biology and Cancer Preface SO PRINCIPLES OF STEM CELL BIOLOGY AND CANCER: FUTURE APPLICATIONS AND THERAPEUTICS LA English DT Editorial Material; Book Chapter C1 [Regad, Tarik; Rees, Robert C.] Nottingham Trent Univ, John van Geest Canc Res Ctr, Nottingham, England. [Sayers, Thomas J.] Leidos Biomed Res Inc, Frederick, MD USA. [Sayers, Thomas J.] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD USA. RP Regad, T (reprint author), Nottingham Trent Univ, John van Geest Canc Res Ctr, Nottingham, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-67061-3; 978-1-118-67062-0 PY 2015 BP XIII EP XIV D2 10.1002/9781118670613 PG 2 WC Cell & Tissue Engineering; Oncology SC Cell Biology; Oncology GA BD5RN UT WOS:000361754200001 ER PT J AU Thornton, IM Horowitz, TS AF Thornton, Ian M. Horowitz, Todd S. TI Does action disrupt Multiple Object Tracking (MOT)? SO PSIHOLOGIJA LA English DT Article DE Divided Attention; Action; Multiple Object Tracking; MOT; Tracking; Mobile Devices ID COMMON ATTENTIONAL MECHANISM; VISUAL-ATTENTION; MOVING-OBJECTS; WORKING-MEMORY; PERCEPTION; SELECTION; MOVEMENTS; INFORMATION; LOCATION; SACCADES AB While the relationship between action and focused attention has been well-studied, less is known about the ability to divide attention while acting. In the current paper we explore this issue using the multiple object tracking (MOT) paradigm (Pylyshyn & Storm, 1988). We asked whether planning and executing a display-relevant action during tracking would substantially affect the ability track and later identify targets. In all trials the primary task was to track 4 targets among a set of 8 identical objects. Several times during each trial, one object, selected at random, briefly changed colour. In the baseline MOT trials, these changes were ignored. During active trials, each changed object had to be quickly touched. On a given trial, changed objects were either from the tracking set or were selected at random from all 8 objects. Although there was a small dual-task cost, the need to act did not substantially impair tracking under either touch condition. C1 [Thornton, Ian M.] Univ Malta, Fac Media & Knowledge Sci, Dept Cognit Sci, Msida, Malta. [Horowitz, Todd S.] NCI, NIH, Bethesda, MD 20892 USA. RP Thornton, IM (reprint author), Univ Malta, Fac Media & Knowledge Sci, Dept Cognit Sci, Msida, Malta. EM ian.thornton@um.edu.m NR 36 TC 0 Z9 0 U1 4 U2 7 PU ASSOC SERBIAN PSYCHOLOGISTS PI BEOGRAD PA DUSINA 7-3, BEOGRAD, 11000, SERBIA SN 0048-5705 J9 PSIHOLOGIJA JI Psihologija PY 2015 VL 48 IS 3 BP 289 EP 301 DI 10.2298/PSI1503289T PG 13 WC Psychology, Multidisciplinary SC Psychology GA CS2JT UT WOS:000361897400007 ER PT J AU Sun, ZC Tong, G Kim, TH Ma, N Niu, G Cao, F Chen, XY AF Sun, Zhongchan Tong, Guang Kim, Tae Hyung Ma, Nan Niu, Gang Cao, Feng Chen, Xiaoyuan TI PEGylated Exendin-4, a Modified GLP-1 Analog Exhibits More Potent Cardioprotection than Its Unmodified Parent Molecule on a Dose to Dose Basis in a Murine Model of Myocardial Infarction SO THERANOSTICS LA English DT Article DE Exendin-4; PEGylation; cardioprotection; Angiogenesis; myocardial infarction ID GLUCAGON-LIKE PEPTIDE-1; SITE-SPECIFIC PEGYLATION; CARDIOVASCULAR-DISEASE; REPERFUSION INJURY; GLYCEMIC CONTROL; HEART-FAILURE; RECEPTOR; ADHERENCE; ISCHEMIA; IMPROVE AB A Site-specifically PEGylated exendin-4 (denoted as PEG-Ex4) is an exendin-4 (denoted as Ex4) analog we developed by site-specific PEGylation of exendin-4 with a high molecular weight trimeric poly(ethylene glycol) (tPEG). It has been shown to possess prolonged half-life in vivo with similar receptor binding affinity compared to unmodified exendin-4 by our previous work. This study is sought to test whether PEG-Ex4 is suitable for treating myocardial infarction (MI). In the MI model, PEG-Ex4 was administered every 3 days while equivalent amount of Ex4 was administered every 3 days or twice daily. Animal survival rate, heart function, remodeling and neoangiogenesis were evaluated and compared. Tube formation was examined in endothelial cells. In addition, Western blotting and histology were performed to determine the markers of cardiac hypertrophy and angiogenesis and to explore the possible molecular mechanism involved. PEG-Ex4 and Ex4 showed comparable binding affinity to GLP-1 receptor. In MI mice, PEG-Ex4 given at 3 days interval achieved similar extent of protection as Ex4 given twice daily, while Ex4 given at 3 days interval failed to produce protection. PEG-Ex4 elevated endothelial tube formation in vitro and capillary density in the border area of MI. PEG-Ex4 increased Akt activity and VEGF production in a GLP-1R dependent manner in endothelial cells and antagonism of GLP-1R, Akt or VEGF abolished the protection of PEG-Ex4 in the MI model. PEG-Ex4 is a potent long-acting GLP-1 receptor agonist for the treatment of chronic heart disease. Its protection might be attributed to enhanced angiogenesis mediated by the activation of Akt and VEGF. C1 [Sun, Zhongchan; Cao, Feng] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China. [Tong, Guang; Kim, Tae Hyung; Niu, Gang; Chen, Xiaoyuan] NIBIB, NIH, Lab Mol Imaging & Nanomed LOMIN, Bethesda, MD 20892 USA. [Tong, Guang] Gen Hosp Guangzhou Mil Command, Dept Cardiovasc Surg, Guangzhou 510010, Guangdong, Peoples R China. [Ma, Nan] Fourth Mil Med Univ, Tangdu Hosp, Dept Ophthalmol, Xian 710038, Peoples R China. [Cao, Feng] Chinese Peoples Liberat Army Gen Hosp, Dept Cardiol, Beijing 100853, Peoples R China. RP Cao, F (reprint author), Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China. EM gang.niu@nih.gov; wind8828@gmail.com; shawn.chen@nih.gov FU National Nature Science Foundation of China [81400366]; Xijing Research Boosting Program [XJZT13M11]; Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This study was supported by the National Nature Science Foundation of China (NO. 81400366), Xijing Research Boosting Program (NO. XJZT13M11), and the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 35 TC 5 Z9 5 U1 3 U2 13 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 3 BP 240 EP 250 DI 10.7150/thno.10226 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CS1PD UT WOS:000361838100001 PM 25553112 ER PT J AU Poliakov, E Cooper, DN Stepchenkova, EI Rogozin, IB AF Poliakov, Eugenia Cooper, David N. Stepchenkova, Elena I. Rogozin, Igor B. TI Genetics in Genomic Era SO GENETICS RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Poliakov, Eugenia] NEI, NIH, Bethesda, MD 20892 USA. [Cooper, David N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff, Wales. [Stepchenkova, Elena I.] Russian Acad Sci, St Petersburg Branch, N I Vavilov Inst Gen Genet, St Petersburg 196140, Russia. [Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Poliakov, E (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM poliakove@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-3154 EI 2090-3162 J9 GENET RES INT JI Genet. Res. Int. PY 2015 AR 364960 DI 10.1155/2015/364960 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CS0BM UT WOS:000361722000001 ER PT J AU Wang, Z Bhattacharyya, T AF Wang, Zhong Bhattacharyya, Timothy TI Trends of non-union and prescriptions for non-steroidal anti-inflammatory drugs in the United States, 1993-2012 SO ACTA ORTHOPAEDICA LA English DT Article ID TIBIAL NONUNION; RISK-FACTORS; FRACTURES AB Background and purpose - Surgical care and pain management for patients with fractures have evolved over the years. We wanted to ascertain if there were any changes in the incidence of non-unions and, if so, whether the use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective inhibitors, might have an effect. Patients and methods - We used the National Inpatient Sample (NIS) to estimate the annual number of patients hospitalized for surgical treatment of a non-union between 1993 and 2012, and calculated age-adjusted rates of non-union. We estimated the prevalence of prescriptions for NSAIDs from 1996 through 2012 using the Medical Expenditure Panel Survey (MEPS). The interrupted time-series analysis was used to relate quarterly rates of non-union to changes in prescriptions for NSAIDs between 1996 and 2009. Results - The annual estimate of non-unions in the USA declined 30% from 25,634 in 1993 to 17,815 in 2012 (p < 0.001). Specifically, the age-adjusted rate of non-unions decreased by 44% from 8.6 per 10(5) persons in 1996 to 4.8 per 10(5) persons in 2012 (p < 0.001). However, there was an 8% increase in the incidence rate of non-unions (p = 0.003) between 2000 and 2004, when certain COX-2 selective inhibitors were on the market and their prescriptions were prevalent at around 6% among those with fractures. A drop in non-union estimates from 22,321 in 2010 to 18,789 in 2011 (p = 0.04) also coincided with a marked decrease in prescriptions for NSAIDs in patients with fractures, from 22% to 14% (p = 0.02). Interpretation - Non-unions in the USA declined substantially between 1993 and 2012, but this was interrupted by changes in prescriptions for NSAIDs, with sustained increases between 2000 and 2004 followed by transient decreases in 2005 and 2011. C1 [Wang, Zhong; Bhattacharyya, Timothy] NIAMSD, Sect Clin & Invest Orthoped, Clin Trials & Outcomes Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Wang, Z (reprint author), NIAMSD, Sect Clin & Invest Orthoped, Clin Trials & Outcomes Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. EM john.wang@nih.gov FU Intramural Research Program at the National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health FX ZW has no competing interests. TB has had consultancies with Maximus, PDA, and Eli Lilly, Inc. The study was supported by the Intramural Research Program at the National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 20 TC 1 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PY 2015 VL 86 IS 5 BP 632 EP 637 DI 10.3109/17453674.2015.1028860 PG 6 WC Orthopedics SC Orthopedics GA CR4FF UT WOS:000361286600018 PM 25761793 ER PT S AU Fedota, JR Stein, EA AF Fedota, John R. Stein, Elliot A. BE Uhl, GR TI Resting-state functional connectivity and nicotine addiction: prospects for biomarker development SO ADDICTION REVIEWS 2015 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE addiction; nicotine; resting-state functional connectivity; biomarkers ID SCALE BRAIN NETWORKS; DEFAULT-MODE NETWORK; ANTERIOR CINGULATE CORTEX; TEST-RETEST RELIABILITY; SMOKING-CESSATION; REGIONAL HOMOGENEITY; CIGARETTE SMOKERS; WITHDRAWAL SYMPTOMS; INSULA CONNECTIVITY; ALZHEIMERS-DISEASE AB Given conceptual frameworks of addiction as a disease of intercommunicating brain networks, examinations of network interactions may provide a holistic characterization of addiction-related dysfunction. One such methodological approach is the examination of resting-state functional connectivity, which quantifies correlations in low-frequency fluctuations of the blood oxygen level-dependentmagnetic resonance imaging signal between disparate brain regions in the absence of task performance. Here, evidence of differentiated effects of chronic nicotine exposure, which reduces the efficiency of network communication across the brain, and acute nicotine exposure, which increases connectivity within specific limbic circuits, is discussed. Several large-scale resting networks, including the salience, default, and executive control networks, have also been implicated in nicotine addiction. The dynamics of connectivity changes among and between these large-scale networks during nicotine withdrawal and satiety provide a heuristic framework with which to characterize the neurobiological mechanism of addiction. The ability to simultaneously quantify effects of both chronic (trait) and acute (state) nicotine exposure provides a platform to develop a neuroimaging-based addiction biomarker. While such development remains in its early stages, evidence of coherent modulations in resting-state functional connectivity at various stages of nicotine addiction suggests potential network interactions on which to focus future addiction biomarker development. C1 [Fedota, John R.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Fedota, JR (reprint author), NIDA, Neuroimaging Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM john.fedota@nih.gov; estein@mail.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 148 TC 11 Z9 12 U1 3 U2 13 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1349 BP 64 EP 82 DI 10.1111/nyas.12882 PG 19 WC Substance Abuse; Neurosciences; Psychiatry; Psychology SC Substance Abuse; Neurosciences & Neurology; Psychiatry; Psychology GA BD5AK UT WOS:000361299500003 PM 26348486 ER PT S AU Zhong, XM Drgonova, J Li, CY Uhl, GR AF Zhong, Xiaoming Drgonova, Jana Li, Chuan-Yun Uhl, George R. BE Uhl, GR TI Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes SO ADDICTION REVIEWS 2015 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE cell adhesion molecules; addiction; dopamine; substance use disorders; lipid rafts; GWAS; connectome ID GENOME-WIDE ASSOCIATION; SMOKING-CESSATION SUCCESS; AUTISM SPECTRUM DISORDER; ALCOHOL DEPENDENCE; NICOTINE DEPENDENCE; SYNAPSE DEVELOPMENT; NUCLEUS-ACCUMBENS; CHRONIC COCAINE; G-PROTEINS; EXPRESSION AB Human cell adhesion molecules (CAMs) are essential for proper development, modulation, and maintenance of interactions between cells and cell-to-cell (and matrix-to-cell) communication about these interactions. Despite the differential functional significance of these roles, there have been surprisingly few systematic studies to enumerate the universe of CAMs and identify specific CAMs in distinct functions. In this paper, we update and review the set of human genes likely to encode CAMs with searches of databases, literature reviews, and annotations. We describe likely CAMs and functional subclasses, including CAMs that have a primary function in information exchange (iCAMs), CAMs involved in focal adhesions, CAM gene products that are preferentially involved with stereotyped and morphologically identifiable connections between cells (e.g., adherens junctions, gap junctions), and smaller numbers of CAM genes in other classes. We discuss a novel proposed mechanism involving selective anchoring of the constituents of iCAM-containing lipid rafts in zones of close neuronal apposition to membranes expressing iCAM binding partners. We also discuss data from genetic and genomic studies of addiction in humans and mouse models to highlight the ways in which CAM variation may contribute to a specific brain-based disorder such as addiction. Specific examples include changes in CAM mRNA splicing mediated by differences in the addiction-associated splicing regulator RBFOX1/A2BP1 and CAM expression in dopamine neurons. C1 [Zhong, Xiaoming; Li, Chuan-Yun] Peking Univ, Inst Mol Med, Lab Bioinformat & Genom Med, Beijing 100871, Peoples R China. [Drgonova, Jana; Uhl, George R.] NIDA, Mol Neurobiol, NIH, IRP, Baltimore, MD USA. [Uhl, George R.] New Mexico VA Hlth Care Syst, Res Off, Albuquerque, NM USA. RP Uhl, GR (reprint author), Mol Neurobiol, Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000165-12] NR 72 TC 5 Z9 6 U1 4 U2 11 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1349 BP 83 EP 95 DI 10.1111/nyas.12776 PG 13 WC Substance Abuse; Neurosciences; Psychiatry; Psychology SC Substance Abuse; Neurosciences & Neurology; Psychiatry; Psychology GA BD5AK UT WOS:000361299500004 PM 25988664 ER PT J AU Aagaard, K Harris, R Hao, K Chen, J Stodgell, C Dudley, J Schadt, E Miller, R AF Aagaard, Kjersti Harris, R. Hao, Ke Chen, Jia Stodgell, Chris Dudley, Joel Schadt, Eric Miller, RIchard CA Natl Children's Study Placenta Con TI Novel insights on molecular targets of environmental exposures during pregnancy using placental multiomics integration SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Aagaard, Kjersti; Harris, R.] Baylor Coll Med, Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA. [Hao, Ke; Chen, Jia; Dudley, Joel; Schadt, Eric] Mt Sinai Sch Med, Genet & Genom Sci, New York, NY USA. [Stodgell, Chris; Miller, RIchard] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Natl Children's Study Placenta Con] NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 345 BP S182 EP S182 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900344 ER PT J AU Ahmed, A Chaemsaithong, P Chaiworapongsa, T Zhong, D Shaman, M Lannaman, K Yeo, L Hassan, S Yoon, BH Romero, R AF Ahmed, Ahmed Chaemsaithong, Piya Chaiworapongsa, Tinnakorn Zhong, Dong Shaman, Majid Lannaman, Kia Yeo, Lami Hassan, Sonia Yoon, Bo Hyun Romero, Roberto TI A receptor for danger signals, advanced glycation end products (RAGE) in fetal systemic inflammation and clinical chorioamnionitis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Ahmed, Ahmed; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Zhong, Dong; Shaman, Majid; Lannaman, Kia; Yeo, Lami; Hassan, Sonia; Romero, Roberto] NICHD, NIH, DHHS, Detroit, MI USA. [Ahmed, Ahmed; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Zhong, Dong; Shaman, Majid; Lannaman, Kia; Yeo, Lami; Hassan, Sonia; Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 599 BP S298 EP S298 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900594 ER PT J AU Biggio, J AF Biggio, Joseph TI Effect of uterine contraction frequency on fetal oxygen saturation and neonatal outcome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Biggio, Joseph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 813 BP S391 EP S392 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900805 ER PT J AU Biggio, J Xiao, FF Baldwin, D Bukowski, R Parry, S Esplin, M Andrews, W Saade, G Varner, M Sadovsky, Y Reddy, U Ilekis, J Zhang, HP AF Biggio, Joseph Xiao, Feifei Baldwin, Don Bukowski, Radek Parry, Samuel Esplin, M. Andrews, William Saade, George Varner, Michael Sadovsky, Yoel Reddy, Uma Ilekis, John Zhang, Heping TI Neonatal, not maternal, copy number variants are associated with spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Biggio, Joseph; Xiao, Feifei; Baldwin, Don; Bukowski, Radek; Parry, Samuel; Esplin, M.; Andrews, William; Saade, George; Varner, Michael; Sadovsky, Yoel; Reddy, Uma; Ilekis, John; Zhang, Heping] Eunice Kennedy Shriver NICHD, Genom & Prote Network Preterm Birth Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 9 BP S8 EP S8 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900012 ER PT J AU Blackwell, S AF Blackwell, Sean TI Metabolic acidemia at birth and risk of adverse neonatal outcomes in term pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Blackwell, Sean] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 22 BP S16 EP S17 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900025 ER PT J AU Buhimschi, C Buhimschi, I AF Buhimschi, Catalin Buhimschi, Irina TI Cord blood (CB) haptoglobin (Hp) switch-on as a biomarker of exposure to intra-uterine inflammation and adverse neonatal and childhood outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Buhimschi, Catalin; Buhimschi, Irina] Eunice Kennedy Shriver Natl Inst Child Hlth, Bethesda, MD USA. [Buhimschi, Catalin; Buhimschi, Irina] Human Dev Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 139 BP S86 EP S86 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900141 ER PT J AU Casey, B AF Casey, Brian TI Effect of treatment of mild gestational diabetes on long-term maternal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Casey, Brian] Eunice Kennedy Shriver NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 3 BP S3 EP S3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900006 ER PT J AU Costantine, M AF Costantine, Maged TI Development and validation of a vaginal delivery calculator for low risk women at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Costantine, Maged] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 426 BP S221 EP S221 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900422 ER PT J AU Costantine, M AF Costantine, Maged TI Cervical length distribution for nulliparous women at 16 to 22 weeks SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Costantine, Maged] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 105 BP S70 EP S70 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900107 ER PT J AU Coviello, E Landy, H Kelly, T Huang, CC Grantz, KL AF Coviello, Elizabeth Landy, Helain Kelly, Tara Huang, Chun-Chih Grantz, Katherine Laughon TI Retained placenta: characterizing underlying factors SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Coviello, Elizabeth] MedStar Washington Hosp Ctr, Obstet & Gynecol, Washington, DC USA. [Landy, Helain; Kelly, Tara] MedStar Georgetown Univ Hosp, Obstet & Gynecol, Washington, DC USA. [Huang, Chun-Chih] MedStar Hlth Res Inst, Dept Biostat & Bioinformat, Hyattsville, MD USA. [Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 635 BP S313 EP S313 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900630 ER PT J AU Esplin, M Manuck, T Christensen, B Biggio, J Bukowski, R Parry, S Zhang, HP Varner, M Andrews, W Saade, G Sadovsky, Y Reddy, U Ilekis, J AF Esplin, M. Manuck, Tracy Christensen, Bryce Biggio, Joseph Bukowski, Radek Parry, Samuel Zhang, Heping Varner, Michael Andrews, William Saade, George Sadovsky, Yoel Reddy, Uma Ilekis, John TI Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations between preterm birth mechanisms SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Esplin, M.] Intermt Healthcare, MFM, Salt Lake City, UT USA. [Manuck, Tracy; Varner, Michael] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Christensen, Bryce] Golden Helix, Bozeman, MT USA. [Biggio, Joseph; Andrews, William] Univ Alabama Birmingham, Birmingham, AL USA. [Bukowski, Radek; Saade, George] Univ Texas Med Branch, Galveston, TX 77555 USA. [Parry, Samuel] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Zhang, Heping] Yale Univ, New Haven, CT USA. [Sadovsky, Yoel] Univ Pittsburgh, Magee Womens Res Inst, Sch Med, Pittsburgh, PA USA. [Reddy, Uma; Ilekis, John] NICHD, Pregnancy & Perinatol Branch, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 187 BP S107 EP S108 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900189 ER PT J AU Esplin, M Manuck, T Biggio, J Bukowski, R Parry, S Zhang, HP Varner, M Andrews, W Saade, G Sadovsky, Y Reddy, U Ilekis, J AF Esplin, M. Manuck, Tracy Biggio, Joseph Bukowski, Radek Parry, Samuel Zhang, Heping Varner, Michael Andrews, William Saade, George Sadovsky, Yoel Reddy, Uma Ilekis, John TI The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Esplin, M.; Manuck, Tracy; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Varner, Michael; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma; Ilekis, John] NICHD, Genom & Prote Network Preterm Birth Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 14 BP S11 EP S11 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900017 ER PT J AU Facco, F Reid, K Grobman, W Parker, C Silver, R Nhan-Chang, CL Parry, S Chung, J Louis, J Schubert, F Hunter, S Esplin, M Simhan, H Hoffman, M Elovitz, M Wing, D Latimer, C Haas, D Saade, G Zee, P AF Facco, Francesca Reid, Kathryn Grobman, William Parker, Corette Silver, Robert Nhan-Chang, Chia-Ling Parry, Samuel Chung, Judith Louis, Judette Schubert, Frank Hunter, Shannon Esplin, M. Simhan, Hyagriv Hoffman, Matthew Elovitz, Michal Wing, Deborah Latimer, Cheryl Haas, David Saade, George Zee, Phyllis CA Eunice Kennedy Shriver Natl Inst TI Short sleep duration is associated with the development of gestational diabetes mellitus SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Facco, Francesca; Simhan, Hyagriv] Univ Pittsburgh, Obstet & Gynecol, Pittsburgh, PA USA. [Reid, Kathryn; Zee, Phyllis] Northwestern Univ, Neurol, Chicago, IL 60611 USA. [Grobman, William] Northwestern Univ, Obstet & Gynecol, Chicago, IL 60611 USA. [Parker, Corette; Hunter, Shannon] RTI Int, Res Triangle Pk, NC USA. [Silver, Robert] Univ Utah, Obstet & Gynecol, Salt Lake City, UT USA. [Nhan-Chang, Chia-Ling] Columbia Univ, Med Ctr, Obstet & Gynecol, New York, NY USA. [Parry, Samuel; Elovitz, Michal] Univ Penn, Obstet & Gynecol, Philadelphia, PA 19104 USA. [Chung, Judith; Wing, Deborah] Univ Calif Irvine, Obstet & Gynecol, Irvine, CA USA. [Louis, Judette] CASE MetroHlth, Obstet & Gynecol, Cleveland, OH USA. [Schubert, Frank; Haas, David] Indiana Univ, Obstet & Gynecol, Indianapolis, IN 46204 USA. [Esplin, M.] Intermt Healthcare, Obstet & Gynecol, Salt Lake City, UT USA. [Hoffman, Matthew] Christiana Care Hlth Syst, Obstet & Gynecol, Newark, DE USA. [Latimer, Cheryl] Ohio State Univ, Obstet & Gynecol, Columbus, OH 43210 USA. [Saade, George] Univ Texas Med Branch, Obstet & Gynecol, Galveston, TX 77555 USA. [Eunice Kennedy Shriver Natl Inst] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 256 BP S141 EP S141 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900257 ER PT J AU Facco, FL AF Facco, Francesca L. TI Prospective study of the association between sleep disordered breathing and hypertensive disorders of pregnancy and gestational diabetes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Facco, Francesca L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NuMoM2b Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA LB2 BP S424 EP S425 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900878 ER PT J AU Factor-Litvak, P Susser, E Kezios, K Wapner, R Hoffman, M Bricca, C Aviv, A AF Factor-Litvak, Pam Susser, Ezra Kezios, Katrina Wapner, Ronald Hoffman, Matthew Bricca, Christina Aviv, Abraham CA NuMom2B Study Grp TI Determinants of leukocyte telomere length in the newborn SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Factor-Litvak, Pam; Susser, Ezra; Kezios, Katrina] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Wapner, Ronald] Columbia Univ, Sch Phys & Surg, Obstet & Gynecol, New York, NY USA. [Hoffman, Matthew] Christiana Care, Obstet & Gynecol, Newark, DE USA. [Bricca, Christina] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Aviv, Abraham] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA. [NuMom2B Study Grp] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 56 BP S39 EP S39 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900058 ER PT J AU Grantz, KL Sundaram, R Hinkle, S Berghella, V Hoffman, M Lu, ZH Reddy, U AF Grantz, Katherine Laughon Sundaram, Rajeshwari Hinkle, Stefanie Berghella, Vincenzo Hoffman, Matthew Lu, Zhaohui Reddy, Uma TI Reassessing duration of the second stage of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Grantz, Katherine Laughon; Hinkle, Stefanie] NICHD, NIH, Epidemiol Branch, Rockville, MD USA. [Sundaram, Rajeshwari] NICHD, NIH, Biostat & Bioinformat Branch, Rockville, MD USA. [Berghella, Vincenzo] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. [Hoffman, Matthew] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA. [Lu, Zhaohui] NICHD, NIH, Glotech Inc, Div Intramural Populat Hlth Res, Rockville, MD USA. [Reddy, Uma] NICHD, NIH, Pregnancy & Perinatol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 21 BP S16 EP S16 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900024 ER PT J AU Grobman, W AF Grobman, William TI Obstetric outcomes associated with the duration of pushing in nulliparas SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 564 BP S281 EP S281 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900559 ER PT J AU Grobman, W Parker, C Esplin, M Nhan-Chang, CL Simhan, H Parry, S Wing, D Mercer, B Haas, D Hunter, S Silver, R Hoffman, M Peaceman, A Caritis, S Ludmir, J Wadhwa, P Iams, J Perkins, E Saade, G Willinger, M Reddy, U AF Grobman, William Parker, Corette Esplin, M. Nhan-Chang, Chia-Ling Simhan, Hyagriv Parry, Samuel Wing, Deborah Mercer, Brian Haas, David Hunter, Shannon Silver, Robert Hoffman, Matthew Peaceman, Alan Caritis, Steve Ludmir, Jack Wadhwa, Pathik Iams, Jay Perkins, Emily Saade, George Willinger, Marian Reddy, Uma TI Racial/ethnic disparities in self-reported psychosocial measures during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Grobman, William; Parker, Corette; Esplin, M.; Nhan-Chang, Chia-Ling; Simhan, Hyagriv; Parry, Samuel; Wing, Deborah; Mercer, Brian; Haas, David; Hunter, Shannon; Silver, Robert; Hoffman, Matthew; Peaceman, Alan; Caritis, Steve; Ludmir, Jack; Wadhwa, Pathik; Iams, Jay; Perkins, Emily; Saade, George; Willinger, Marian; Reddy, Uma] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NuMoM2b Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 510 BP S256 EP S256 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900505 ER PT J AU Halscott, T Reddy, U Landy, H Ramsey, P Iqbal, S Huang, J Grantz, KL AF Halscott, Torre Reddy, Uma Landy, Helain Ramsey, Patrick Iqbal, Sara Huang, Jim Grantz, Katherine Laughon TI Maternal and neonatal outcomes by attempted mode of operative delivery during the second stage of labor in term singleton gestations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Halscott, Torre; Ramsey, Patrick; Iqbal, Sara] MedStar Georgetown Univ Hosp, Obstet & Gynecol, MedStar Washington Hosp Ctr, Washington, DC USA. [Reddy, Uma; Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Huang, Jim] MedStar Hlth Res Inst, Biostat & Epidemiol, Hyattsville, MD USA. [Landy, Helain] MedStar Georgetown Univ Hosp, Obstet & Gynecol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 722 BP S351 EP S352 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900716 ER PT J AU Hinkle, S Sjaarda, L Albert, P Mendola, P Grantz, KL AF Hinkle, Stefanie Sjaarda, Lindsey Albert, Paul Mendola, Pauline Grantz, Katherine Laughon TI Does high prepregnancy body mass index (BMI) mask increased risk for small-for-gestational-age (SGA) birthweight and associated perinatal mortality? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Hinkle, Stefanie; Sjaarda, Lindsey; Albert, Paul; Mendola, Pauline; Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 551 BP S275 EP S275 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900546 ER PT J AU Kawakita, T Reddy, U Iqbal, S Huang, J Landy, H Grantz, KL AF Kawakita, Tetsuya Reddy, Uma Iqbal, Sara Huang, Jim Landy, Helain Grantz, Katherine Laughon TI Complications associated with fetal scalp electrode SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Kawakita, Tetsuya; Iqbal, Sara] Medstar Washington Hosp Ctr, Obstet & Gynecol, Washington, DC USA. [Reddy, Uma; Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Huang, Jim] MedStar Hlth Res Inst, Dept Biostat & Epidemiol, Hyattsville, MD USA. [Landy, Helain] Medstar Georgetown Univ Hosp, Obstet & Gynecol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 273 BP S149 EP S149 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900274 ER PT J AU Landon, M AF Landon, Mark TI The effect of maternal glycemia on childhood obesity and metabolic dysfunction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Landon, Mark] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 30 BP S21 EP S21 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900032 ER PT J AU Lannaman, K Romero, R Chaemsaithong, P Ahmed, A Yeo, L Hassan, S Yoon, BH Chaiworapongsa, T AF Lannaman, Kia Romero, Roberto Chaemsaithong, Piya Ahmed, Ahmed Yeo, Lami Hassan, Sonia Yoon, Bo Hyun Chaiworapongsa, Tinnakorn TI Fetal death: an extreme form of maternal anti-fetal rejection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Lannaman, Kia; Romero, Roberto; Chaemsaithong, Piya; Ahmed, Ahmed; Yeo, Lami; Hassan, Sonia; Chaiworapongsa, Tinnakorn] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Lannaman, Kia; Romero, Roberto; Chaemsaithong, Piya; Ahmed, Ahmed; Yeo, Lami; Hassan, Sonia; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 497 BP S251 EP S251 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900492 ER PT J AU Louis, GB Grewal, J Albert, P Sciscione, A Nageotte, M Grobman, W Newman, R Wapner, R D'Alton, M Skupski, D Wing, D Ranzini, A Owen, J Chien, E Craigo, S Hediger, M Kim, S Zhang, CL Grantz, KL AF Louis, Germaine Buck Grewal, Jagteshwar Albert, Paul Sciscione, Anthony Nageotte, Michael Grobman, William Newman, Roger Wapner, Ronald D'Alton, Mary Skupski, Daniel Wing, Deborah Ranzini, Angela Owen, John Chien, Edward Craigo, Sabrina Hediger, Mary Kim, Sungduk Zhang, Cuilin Grantz, Katherine Laughon TI Racial/Ethnic differences in fetal growth, the NICHD fetal growth studies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Louis, Germaine Buck; Grewal, Jagteshwar; Albert, Paul; Hediger, Mary; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine Laughon] NICHD, Div Intramural Populat Hlth, Rockville, MD 60611 USA. [Sciscione, Anthony] Christiana Care Hlth Syst, Newark, DE 29425 USA. [Nageotte, Michael] Miller Childrens Hosp, Long Beach Mem Med Ctr, Long Beach, CA USA. [Grobman, William] Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. [Newman, Roger] Med Univ S Carolina, Charleston, SC USA. [Skupski, Daniel] New York Hosp Queens, New York, NY USA. [Wapner, Ronald; D'Alton, Mary] Columbia Univ, Med Ctr, New York, NY USA. [Wing, Deborah] Univ Calif Irvine, Irvine, CA 02908 USA. [Ranzini, Angela] St Peters Univ Hosp, New Brunswick, NJ USA. [Owen, John] Univ Alabama Birmingham, Birmingham, AL USA. [Chien, Edward] Women & Infants Hosp Rhode Isl, Providence, RI USA. [Craigo, Sabrina] Tufts Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 52 BP S36 EP S36 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900054 ER PT J AU Manuck, T AF Manuck, Tracy TI Maternal genotype and early preterm birth (PTB) among women with a short mid-trimester cervical length (CL) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Manuck, Tracy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 886 BP S421 EP S422 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900876 ER PT J AU Manuck, T Esplin, M Biggio, J Parry, S Zhang, HP Bukowski, R Saade, G Sadovsky, Y Baldwin, D Andrews, W Huang, H Reddy, U Ilekis, J Varner, M AF Manuck, Tracy Esplin, M. Biggio, Joseph Parry, Samuel Zhang, Heping Bukowski, Radek Saade, George Sadovsky, Yoel Baldwin, Don Andrews, William Huang, Hao Reddy, Uma Ilekis, John Varner, Michael TI Predictors of recurrent spontaneous preterm birth (R-SPTB): a longitudinal cohort SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Manuck, Tracy; Esplin, M.; Biggio, Joseph; Parry, Samuel; Zhang, Heping; Bukowski, Radek; Saade, George; Sadovsky, Yoel; Baldwin, Don; Andrews, William; Huang, Hao; Reddy, Uma; Ilekis, John; Varner, Michael] NICHD, Genom & Prote Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 879 BP S418 EP S419 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900869 ER PT J AU Manuck, T AF Manuck, Tracy TI Improving upon prediction based on gestational age alone: factors influencing likelihood of preterm neonatal morbidity and mortality SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Manuck, Tracy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 236 BP S131 EP S131 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900238 ER PT J AU Melamed, N Pittini, A Romero, R Nevo, O Ladhani, NN Cohen, H Hui, DN Berndl, A Asztalos, E Barrett, J AF Melamed, Nir Pittini, Alex Romero, Roberto Nevo, Ori Ladhani, Noor Niyar Cohen, Howard Hui, Dini Berndl, Anne Asztalos, Elizabeth Barrett, Jon TI Serial cervical length determination in twin pregnancies reveals four distinct patterns with prognostic significance for preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Melamed, Nir; Pittini, Alex; Nevo, Ori; Ladhani, Noor Niyar; Cohen, Howard; Hui, Dini; Berndl, Anne; Barrett, Jon] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Obstet & Gynecol, Div MFM, Toronto, ON, Canada. [Asztalos, Elizabeth] Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Dept Newborn & Dev Paediat, Toronto, ON, Canada. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 596 BP S297 EP S297 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900591 ER PT J AU Palatnik, A AF Palatnik, Anna TI The association of timing of treatment initiation for mild gestational diabetes with perinatal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Palatnik, Anna] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 608 BP S302 EP S302 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900603 ER PT J AU Peaceman, A AF Peaceman, Alan TI Should the presence of meconium stained amniotic fluid influence labor management in patients with recurrent late decelerations? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Peaceman, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 748 BP S364 EP S365 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900741 ER PT J AU Reddy, U AF Reddy, Uma TI Maternal metabolic syndrome 5-10 years after delivery in women with abnormal 1 hour glucose screening SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Reddy, Uma] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 563 BP S280 EP S281 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900558 ER PT J AU Reddy, U AF Reddy, Uma TI Postpartum complications in women with early preterm delivery (ePTD) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Reddy, Uma] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 400 BP S207 EP S208 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900396 ER PT J AU Reddy, U AF Reddy, Uma TI Neonatal morbidity and mortality by intended route of delivery in vertex early preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Reddy, Uma] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 238 BP S131 EP S132 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900239 ER PT J AU Rice, M AF Rice, Madeline TI Adverse pregnancy outcomes and subsequent metabolic syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Rice, Madeline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 33 BP S22 EP S23 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900035 ER PT J AU Rouse, D AF Rouse, Dwight TI The relationship of maternal age, BMI, and infant birth weight to uterine activity and labor progress SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Rouse, Dwight] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 95 BP S65 EP S65 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900097 ER PT J AU Saad, A AF Saad, Antonio TI Maternal and neonatal morbidities after operative vaginal delivery versus cesarean delivery: a propensity score analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Saad, Antonio] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 728 BP S356 EP S356 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900721 ER PT J AU Saade, G AF Saade, George TI Evaluation of the institute of medicine guidelines for gestational weight gain SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Saade, George] Eunice Kennedy Shriver Natl Inst Child Hlth, Bethesda, MD USA. [Saade, George] Human Dev Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 154 BP S93 EP S94 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900156 ER PT J AU Saade, G AF Saade, George TI Fetal ECG analysis of the ST segment as an adjunct to intrapartum fetal heart rate monitoring: a randomized clinical trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Saade, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 1 BP S2 EP S2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900004 ER PT J AU Tita, A AF Tita, Alan TI Natural history of pregnancy associated hypertension: outcomes by gestational age at diagnosis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Tita, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 279 BP S151 EP S152 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900280 ER PT J AU Tita, A AF Tita, Alan TI Neonatal outcomes of elective early term births after demonstrated fetal lung maturity compared with full term births SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med C1 [Tita, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2015 VL 212 IS 1 SU S MA 278 BP S151 EP S151 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CR2FG UT WOS:000361140900279 ER PT J AU Wu, SH Shu, XO Milne, G Xiang, YB Zhang, XL Cai, QY Fazio, S Linton, MF Chen, HL Purdue, M Rothman, N Gao, YT Zheng, W Yang, G AF Wu, Sheng Hui Shu, Xiao Ou Milne, Ginger Xiang, Yong-Bing Zhang, Xianglan Cai, Qiuyin Fazio, Sergio Linton, MacRae F. Chen, Honglei Purdue, Mark Rothman, Nathaniel Gao, Yu-Tang Zheng, Wei Yang, Gong TI Uric acid correlates to oxidation and inflammation in opposite directions in women SO BIOMARKERS LA English DT Article DE Biomarker; inflammation; oxidative stress; uric acid ID ACUTE ISCHEMIC-STROKE; C-REACTIVE PROTEIN; CHINESE WOMEN; HEART-FAILURE; IN-VIVO; STRESS; DISEASE; RISK; HYPERTENSION; ASSOCIATION AB Objective: To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation. Methods: Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women. Results: Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F-2-isoprostanes and positively correlated to levels of inflammatory markers, such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-a and interleukin-6) in blood as well as prostaglandin E-2 metabolites in urine. Conclusions: Plasma UA levels correlate to oxidation and inflammation biomarkers in opposite directions in women. C1 [Wu, Sheng Hui; Shu, Xiao Ou; Zhang, Xianglan; Cai, Qiuyin; Zheng, Wei; Yang, Gong] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN 37203 USA. [Wu, Sheng Hui] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Laredo, TX USA. [Milne, Ginger] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN 37203 USA. [Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Zhang, Xianglan] TN Dept Hlth, Div Policy Planning & Assessment, Nashville, TN USA. [Fazio, Sergio; Linton, MacRae F.] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiol, Nashville, TN 37203 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Purdue, Mark] Ontario Inst Canc Res, Toronto, ON, Canada. [Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Yang, G (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 2525 West End Ave,Suite 600 IMPH, Nashville, TN 37203 USA. EM wus@uthscsa.edu; Gong.Yang@Vanderbilt.edu RI Milne, Ginger/D-7648-2014; OI Milne, Ginger/0000-0003-3890-151X; Chen, Honglei/0000-0003-3446-7779 FU USPHS; National Institutes of Health [R01CA122364, R37CA070867, R01HL095931, N02 CP1101066]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This study was, in part, supported by USPHS grants and contracts from the National Institutes of Health, including R01CA122364 (to GY), R37CA070867 (to WZ), R01HL095931 (to XLZ), and N02 CP1101066 (to XOS). The plasma and urine sample preparation was performed at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 45 TC 1 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X EI 1366-5804 J9 BIOMARKERS JI Biomarkers PY 2015 VL 20 IS 4 BP 225 EP 231 DI 10.3109/1354750X.2015.1068852 PG 7 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA CR4LP UT WOS:000361304200002 PM 26301880 ER PT J AU Soto-Pantoja, DR Kaur, S Roberts, DD AF Soto-Pantoja, David R. Kaur, Sukhbir Roberts, David D. TI CD47 signaling pathways controlling cellular differentiation and responses to stress SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Autophagy; hydrogen sulfide; immune regulation; integrin signaling; Myc; nitric oxide; radioresistance; stem cells ID INTEGRIN-ASSOCIATED-PROTEIN; ISCHEMIA-REPERFUSION INJURY; C-TERMINAL DOMAIN; GROWTH-FACTOR-I; MEMBRANE-SPANNING DOMAINS; OVARIAN TUMOR-MARKER; SMOOTH-MUSCLE-CELLS; ALPHA SIRP-ALPHA; T-CELL; NITRIC-OXIDE AB CD47 is a widely expressed integral membrane protein that serves as the counter-receptor for the inhibitory phagocyte receptor signal-regulatory protein-alpha (SIRP alpha) and as a signaling receptor for the secreted matricellular protein thrombospondin-1. Recent studies employing mice and somatic cells lacking CD47 have revealed important pathophysiological functions of CD47 in cardiovascular homeostasis, immune regulation, resistance of cells and tissues to stress and chronic diseases of aging including cancer. With the emergence of experimental therapeutics targeting CD47, a more thorough understanding of CD47 signal transduction is essential. CD47 lacks a substantial cytoplasmic signaling domain, but several cytoplasmic binding partners have been identified, and lateral interactions of CD47 with other membrane receptors play important roles in mediating signaling resulting from the binding of thrombospondin-1. This review addresses recent advances in identifying the lateral binding partners, signal transduction pathways and downstream transcription networks regulated through CD47 in specific cell lineages. Major pathways regulated by CD47 signaling include calcium homeostasis, cyclic nucleotide signaling, nitric oxide and hydrogen sulfide biosynthesis and signaling and stem cell transcription factors. These pathways and other undefined proximal mediators of CD47 signaling regulate cell death and protective autophagy responses, mitochondrial biogenesis, cell adhesion and motility and stem cell self-renewal. Although thrombospondin-1 is the best characterized agonist of CD47, the potential roles of other members of the thrombospondin family, SIRP alpha and SIRP gamma binding and homotypic CD47 interactions as agonists or antagonists of signaling through CD47 should also be considered. C1 [Soto-Pantoja, David R.; Kaur, Sukhbir; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 163 TC 10 Z9 10 U1 1 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 2015 VL 50 IS 3 BP 212 EP 230 DI 10.3109/10409238.2015.1014024 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR4OZ UT WOS:000361316400004 PM 25708195 ER PT J AU Castaneto, MS Wohlfarth, A Desrosiers, NA Hartman, RL Gorelick, DA Huestis, MA AF Castaneto, Marisol S. Wohlfarth, Ariane Desrosiers, Nathalie A. Hartman, Rebecca L. Gorelick, David A. Huestis, Marilyn A. TI Synthetic cannabinoids pharmacokinetics and detection methods in biological matrices SO DRUG METABOLISM REVIEWS LA English DT Review DE Analysis; GC-MS; LC-MS/MS; metabolite profiling; methods; novel psychoactive substances; pharmacokinetics; review; synthetic cannabinoids ID TANDEM MASS-SPECTROMETRY; RECEPTOR AGONIST AM-2201; IN-VITRO METABOLITES; NEAT ORAL FLUID; LC-MS-MS; HUMAN URINE; QUANTITATIVE MEASUREMENT; HUMAN HEPATOCYTES; DESIGNER DRUGS; MS/MS METHOD AB Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. Of two main phases of SC research, the first investigated therapeutic applications, and the second abuse-related issues. Administration studies showed high lipophilicity and distribution into brain and fat tissue. Metabolite profiling studies, mostly with human liver microsomes and human hepatocytes, structurally elucidated metabolites and identified suitable SC markers. In general, SC underwent hydroxylation at various molecular sites, defluorination of fluorinated analogs and phase II metabolites were almost exclusively glucuronides. Analytical methods are critical for documenting intake, with different strategies applied to adequately address the continuous emergence of new compounds. Immunoassays have different cross-reactivities for different SC classes, but cannot keep pace with changing analyte targets. Gas chromatography and liquid chromatography mass spectrometry assays - first for a few, then numerous analytes - are available but constrained by reference standard availability, and must be continuously updated and revalidated. In blood and oral fluid, parent compounds are frequently present, albeit in low concentrations; for urinary detection, metabolites must be identified and interpretation is complex due to shared metabolic pathways. A new approach is non-targeted HRMS screening that is more flexible and permits retrospective data analysis. We suggest that streamlined assessment of new SC's pharmacokinetics and advanced HRMS screening provide a promising strategy to maintain relevant assays. C1 [Castaneto, Marisol S.; Wohlfarth, Ariane; Desrosiers, Nathalie A.; Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Dept Chem & Drug Metab, NIH, Baltimore, MD 21224 USA. [Castaneto, Marisol S.; Desrosiers, Nathalie A.; Hartman, Rebecca L.] Univ Maryland, Sch Med, Toxicol Program, Baltimore, MD 21201 USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, IRP, NIH,Biomed Res Ctr, 251 Bayview Blvd Suite 200 Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Chemistry and Drug Metabolism Section of the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health FX The authors report no declaration of interest. This research was funded by the Chemistry and Drug Metabolism Section of the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. NR 128 TC 19 Z9 19 U1 9 U2 38 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2015 VL 47 IS 2 BP 124 EP 174 DI 10.3109/03602532.2015.1029635 PG 51 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CR4UK UT WOS:000361334800003 PM 25853390 ER PT J AU Dluzen, DF Lazarus, P AF Dluzen, Douglas F. Lazarus, Philip TI MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors SO DRUG METABOLISM REVIEWS LA English DT Review DE miRNA; metabolizing enzymes; phase I metabolism; phase II metabolism; transcription factors; epigenetic regulation ID ESTROGEN-RECEPTOR-ALPHA; PREGNANE-X-RECEPTOR; VITAMIN-D-RECEPTOR; COLON-CANCER CELLS; MESSENGER-RNA DESTABILIZATION; HUMAN CYTOCHROME-P450 ENZYMES; NUCLEAR FACTOR 4-ALPHA; EMBRYONIC STEM-CELLS; HUMAN BREAST-CANCER; GENE-EXPRESSION AB Identifying novel mechanisms contributing to patient variability of drug response is a major goal of personalized medicine. Epigenetic regulation of gene expression by microRNA (miRNA) impacts a broad range of cellular processes, but knowledge of its regulation of drug-metabolizing enzymes (DMEs) is more limited. This review provides an introduction to miRNA and their functionality and summarizes known miRNA regulation of DME families, including the cytochrome P450s, UDP-glucuronoslytransferases, glutathione-S-transferases, sulfotransferases and aldo-keto reductases, and the transcription factors known to be involved in DME regulation. C1 [Dluzen, Douglas F.] NIH, Lab Epidemiol & Populat Sci, Baltimore, MD USA. [Lazarus, Philip] Washington State Univ, Dept Pharmaceut Sci, Spokane, WA 99210 USA. RP Lazarus, P (reprint author), Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA 99210 USA. EM phil.lazarus@wsu.edu OI Dluzen, Douglas/0000-0002-9426-5071 NR 202 TC 2 Z9 2 U1 2 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2015 VL 47 IS 3 BP 320 EP 334 DI 10.3109/03602532.2015.1076438 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CR4UQ UT WOS:000361335500003 PM 26300547 ER PT J AU Friend, K Pettibone, K Florin, P Vela, J Nargiso, J AF Friend, Karen Pettibone, Kristianna Florin, Paul Vela, Jamie Nargiso, Jessica TI Environmental change strategies targeting drug abuse prevention SO DRUGS-EDUCATION PREVENTION AND POLICY LA English DT Article DE Drug abuse; evaluation; environmental change strategies; policy; prevention ID COMMUNITY-LEVEL; TREATMENT SBIRT; ALCOHOL; INTERVENTION; TRIAL; CARE AB The purpose of this paper is to highlight the three articles included in a special focus of Drugs: Education, Prevention, and Policy that address environmental change strategies targeting drug abuse prevention. We define environmental change strategies and their effectiveness in public health domains such as alcohol abuse, smoking, and obesity. We then discuss the three articles, each of which addresses different aspects of how environmental change strategies might be best implemented and measured. The first paper by Agley et al. (2014) examines the challenges of implementing an evidence-based practice, specifically screening, brief intervention, and referral to treatment to address drug abuse in primary care settings. The second paper by Kreiner et al. looks at encouraging providers to implement safe prescribing practices for controlled substances and to translate work being done in the medical community to the prevention specialist domain. The third paper by Quinlan et al. conducts a review of the literature on environmental change strategies targeting nonmedical use of marijuana and provides results showing the most and least effective of these interventions. This special focus is intended to build the evidence base for effective environmental change strategies to prevent drug abuse, generate critical analyses, and spur future research that will help improve the implementation and evaluation of such interventions. C1 [Friend, Karen] Pacific Inst Res & Evaluat, Pawtucket, RI 02860 USA. [Pettibone, Kristianna] NIEHS, Program Anal Branch, Div Extramural Res & Training, NIH, Morrisville, NC USA. [Florin, Paul] Univ Rhode Isl, Dept Psychol, Providence, RI 02908 USA. [Vela, Jamie] Univ Rhode Isl, Dept Psychol, Kingston, NY USA. [Nargiso, Jessica] Harvard Univ, Sch Med, Dept Psychiat, Addict Recovery Management Serv,Massachusetts Gen, Boston, MA 02115 USA. RP Friend, K (reprint author), Pacific Inst Res & Evaluat, 1005 Main St, Pawtucket, RI 02860 USA. EM kfriend@pire.org OI Friend, Karen/0000-0002-7936-2930 NR 34 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0968-7637 EI 1465-3370 J9 DRUG-EDUC PREV POLIC JI Drug-Educ. Prev. Policy PY 2015 VL 22 IS 4 BP 311 EP 315 DI 10.3109/09687637.2014.977229 PG 5 WC Substance Abuse SC Substance Abuse GA CR4UZ UT WOS:000361336500001 ER PT J AU Baum, BJ Alevizos, I Chiorini, JA Cotrim, AP Zheng, CY AF Baum, Bruce J. Alevizos, Ilias Chiorini, John A. Cotrim, Ana P. Zheng, Changyu TI Advances in salivary gland gene therapy - oral and systemic implications SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE gene therapy; non-viral gene transfer; radiation damage; salivary glands; secretory proteins; Sjogren's syndrome; viral vectors ID ADENOVIRAL-MEDIATED TRANSFER; PIG PAROTID-GLANDS; TRANSGENIC SECRETORY PROTEINS; INCREASED FLUID SECRETION; RAT SUBMANDIBULAR-GLANDS; CELLS IN-VITRO; SJOGRENS-SYNDROME; GROWTH-HORMONE; EPITHELIAL-CELLS; ENDOCRINE SECRETION AB Introduction: Much research demonstrates the feasibility and efficacy of gene transfer to salivary glands. Recently, the first clinical trial targeting a salivary gland was completed, yielding positive safety and efficacy results. Areas covered: There are two major disorders affecting salivary glands: radiation damage following treatment for head and neck cancers and Sjogren's syndrome (SS). Salivary gland gene transfer has also been employed in preclinical studies using transgenic secretory proteins for exocrine (upper gastrointestinal tract) and endocrine (systemic) applications. Expert opinion: Salivary gland gene transfer is safe and can be beneficial in humans. Applications to treat and prevent radiation damage show considerable promise. A first-in-human clinical trial for the former was recently successfully completed. Studies on SS suffer from an inadequate understanding of its etiology. Proof of concept in animal models has been shown for exocrine and endocrine disorders. Currently, the most promising exocrine application is for the management of obesity. Endocrine applications are limited, as it is currently impossible to predict if systemically required transgenic proteins will be efficiently secreted into the bloodstream. This results from not understanding how secretory proteins are sorted. Future studies will likely employ ultrasound-assisted and pseudotyped adeno-associated viral vector-mediated gene transfer. C1 [Baum, Bruce J.; Alevizos, Ilias; Chiorini, John A.; Cotrim, Ana P.; Zheng, Changyu] Natl Inst Dent & Craniofacial Res, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. EM bbaum@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 87 TC 3 Z9 3 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PY 2015 VL 15 IS 10 BP 1443 EP 1454 DI 10.1517/14712598.2015.1064894 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CR4TR UT WOS:000361332700007 PM 26149284 ER PT J AU Wang, YY Geldres, C Ferrone, S Dotti, G AF Wang, Yangyang Geldres, Claudia Ferrone, Soldano Dotti, Gianpietro TI Chondroitin sulfate proteoglycan 4 as a target for chimeric antigen receptor-based T-cell immunotherapy of solid tumors SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE chimeric antigen receptor; CSPG4; solid tumors; T-cell therapies ID MELANOMA-ASSOCIATED ANTIGEN; ANTIBODY-BASED IMMUNOTHERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACRAL LENTIGINOUS MELANOMA; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; NG2 PROTEOGLYCAN; INITIATING CELLS; CANCER-IMMUNOTHERAPY; MALIGNANT-CELLS AB Introduction: Proteoglycans are critical molecules involved in multiple physiological cell functions, but also key players in cancer development and progression. In particular, chondroitin sulfate proteoglycan 4 (CSPG4) is recognized as an attractive target for antibody-based approaches because of its high expression on cancer cells in several types of human malignancies and its restricted distribution in normal tissues. Areas covered: Adoptive transfer of genetically modified T cells is emerging as a powerful therapeutic approach in cancer patients. In this regard, the selection of the appropriate antigen to be targeted in solid tumors becomes a critical aspect in promoting potent antitumor effects while preventing toxicities. This review summarizes the authors' current knowledge on the expression and function of CSPG4 in normal tissues and malignant tumors, with a particular focus on the potential use of CSPG4 as a target for antigen-specificity redirected T cells. Expert opinion: T cells expressing a CSPG4-specific chimeric antigen receptor (CAR) offer the possibility to target a broad spectrum of solid tumors for which no curative treatment is currently available. In addition, since CSPG4 is also selectively up-regulated on tumor-associated pericytes, targeting this antigen may also contribute to tumor regression via inhibition of neoangiogenesis. Preclinical experiments to date justify the clinical translation of CSPG4-specific CAR-T cells. C1 [Wang, Yangyang; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Geldres, Claudia] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Dotti, Gianpietro] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Dotti, Gianpietro] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. RP Dotti, G (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM Sferrone@MGH.Harvard.edu; gdotti@med.unc.edu NR 94 TC 0 Z9 0 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PY 2015 VL 19 IS 10 BP 1339 EP 1350 DI 10.1517/14728222.2015.1068759 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CR4RU UT WOS:000361326300006 PM 26190756 ER PT J AU Fisher, DE Li, CM Hoffman, HJ Chiu, MS Themann, CL Petersen, H Jonsson, PV Jonsson, H Jonasson, F Sverrisdottir, JE Launer, LJ Eiriksdottir, G Gudnason, V Cotch, MF AF Fisher, Diana E. Li, Chuan-Ming Hoffman, Howard J. Chiu, May S. Themann, Christa L. Petersen, Hannes Jonsson, Palmi V. Jonsson, Helgi Jonasson, Fridbert Sverrisdottir, Johanna Eyrun Launer, Lenore J. Eiriksdottir, Gudny Gudnason, Vilmundur Cotch, Mary Frances TI Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Age-related hearing loss; hearing impairment; hearing aids; older persons; sex differences ID NUTRITION EXAMINATION SURVEY; QUALITY-OF-LIFE; NATIONAL-HEALTH; HELP-SEEKING; ADULTS; IMPAIRMENT; PREVALENCE; POPULATION; REHABILITATION; MORTALITY AB Objective: We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Design : Population-based cohort study. Study sample: A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Results: Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz >= 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Conclusions: Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women. C1 [Fisher, Diana E.; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Li, Chuan-Ming; Hoffman, Howard J.; Chiu, May S.] NIDCD, Epidemiol & Stat Program, Div Sci Programs, NIH, Bethesda, MD USA. [Themann, Christa L.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Petersen, Hannes; Jonsson, Palmi V.; Jonsson, Helgi; Jonasson, Fridbert; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Petersen, Hannes] Landspitali Univ Hosp, Dept Otolaryngol Head & Neck Surg, Reykjavik, Iceland. [Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland. [Jonsson, Helgi] Landspitali Univ Hosp, Dept Rheumatol, Reykjavik, Iceland. [Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [Sverrisdottir, Johanna Eyrun; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Fisher, DE (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10 CRC,Room 3-2521, Bethesda, MD 20892 USA. EM diana.fisher@nih.gov RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural Research Programs of the National Institute of Aging [ZIAAG007380]; National Eye Institute [ZIAEY000401]; National Institute on Deafness and Other Communication Disorders [IAA Y2-DC-1004-02]; National Institutes of Health, Bethesda, Maryland, USA [N01-AG-12100]; Icelandic Heart Association, Kopavogur, Iceland; Icelandic Parliament, Reykjavik, Iceland; University of Iceland Research Fund, Reykjavik, Iceland; Helga Jonsdottir and Sigurlidi Kristjansson Research Fund, Reykjavik, Iceland FX The authors thank the AGES-RS participants; without whom the study would not be possible. Sources of funding: This work was supported by the Intramural Research Programs of the National Institute of Aging ZIAAG007380) and the National Eye Institute (ZIAEY000401), and the National Institute on Deafness and Other Communication Disorders (IAA Y2-DC-1004-02), National Institutes of Health (N01-AG-12100), Bethesda, Maryland, USA; the Icelandic Heart Association, Kopavogur, Iceland; the Icelandic Parliament, Reykjavik, Iceland; the University of Iceland Research Fund, Reykjavik, Iceland; and the Helga Jonsdottir and Sigurlidi Kristjansson Research Fund, Reykjavik, Iceland. The sponsors had no role in the design, methods, subject recruitment, data collection, data analysis, or preparation of the paper. NR 33 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1499-2027 EI 1708-8186 J9 INT J AUDIOL JI Int. J. Audiol. PY 2015 VL 54 IS 9 BP 634 EP 641 DI 10.3109/14992027.2015.1024889 PG 8 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA CR4UE UT WOS:000361334200009 PM 25816699 ER PT J AU Maples, D McLean, K Sahoo, K Newhardt, R Venkatesan, P Wood, B Ranjan, A AF Maples, Danny McLean, Kevin Sahoo, Kaustuv Newhardt, Ryan Venkatesan, Perumal Wood, Bradford Ranjan, Ashish TI Synthesis and characterisation of ultrasound imageable heat-sensitive liposomes for HIFU therapy SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE HIFU; Echogenic heat-sensitive liposome; Perfluoropentane; Image Guided Drug Delivery; Tumor; Spheroid ID INTENSITY FOCUSED ULTRASOUND; TUMOR XENOGRAFT MODEL; DRUG-DELIVERY; TRIGGERED DRUG; THERMOSENSITIVE LIPOSOMES; RELEASE; HYPERTHERMIA; DOXORUBICIN; MICROBUBBLES; NANOCARRIERS AB Background/Objective: Novel approaches allowing efficient, readily translatable image-guided drug delivery (IGDD) against solid tumours is needed. The objectives of this study were to: 1) develop echogenic low temperature sensitive liposomes (E-LTSLs) loaded with an ultrasound (US) contrast agent (perfluoropentane, PFP), 2) determine the in vitro and in vivo stability of contrast agent encapsulation, 3) co-encapsulate and characterise doxorubicin (Dox) E-LTSL, and cellular uptake and cytotoxicity in combination with high intensity focused ultrasound (HIFU). Method: E-LTSLs were loaded passively with PFP and actively with Dox. PFP encapsulation in E-LTSL was determined by transmission electron microscopy (TEM), and US imageability was determined in tissue-mimicking phantoms and mouse tumour model. Dox release from E-LTSL in physiological buffer was quantified by fluorescence spectroscopy. Cellular uptake and cytotoxicity of E-LTSL in the presence of HIFU-induced mild hyperthermia (similar to 40-42 degrees C) was determined in a 3D tumour spheroid model. Results: TEM and US confirmed that the PFP emulsion was contained within LTSLs. Phantom and animal studies showed that the E-LTSLs were echogenic. Temperature versus size increase and Dox release kinetics of E-LTSLs demonstrated no difference compared to LTSL alone. Dox release was 55% within 1 h at baseline (25 degrees C) and body (37 degrees C) temperatures, and was >99% under hyperthermia. E-LTSL plus HIFU achieved significantly greater Dox uptake in spheroids and cytotoxicity compared to body temperature. Conclusion: A stable US-imageable liposome co-loaded with Dox and PFP for in vivo IGDD was developed. Data suggest that HIFU can induce cellular uptake and toxicity with E-LTSLs. C1 [Maples, Danny; McLean, Kevin; Sahoo, Kaustuv; Newhardt, Ryan; Venkatesan, Perumal; Ranjan, Ashish] Oklahoma State Univ, Ctr Vet Hlth Sci, Stillwater, OK 74074 USA. [Wood, Bradford] Ctr Intervent Oncol, NIH, Bethesda, MD USA. RP Ranjan, A (reprint author), Oklahoma State Univ, Ctr Vet Hlth Sci, 169 McElroy Hall, Stillwater, OK 74074 USA. EM ashish.ranjan@okstate.edu FU Center for Veterinary Health Sciences; National Cancer Institute of the National Institutes of Health [R15CA179369]; Oklahoma Center for Advancement in Science and Technology (OCAST) FX Research reported in this publication was supported by the Center for Veterinary Health Sciences Seed Support, National Cancer Institute of the National Institutes of Health under Award Number R15CA179369, and the Oklahoma Center for Advancement in Science and Technology (OCAST). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or OCAST. We thank Dr. Jack Dillwith and Robin Madden for providing core-facility support and technical expertise. NR 36 TC 5 Z9 6 U1 0 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 EI 1464-5157 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2015 VL 31 IS 6 BP 674 EP 685 DI 10.3109/02656736.2015.1057622 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CR4VA UT WOS:000361336600012 PM 26185910 ER PT J AU Ren, LQ Chen, YC Li, P Mao, ZM Huang, PH Rufo, J Guo, F Wang, L McCoy, JP Levine, SJ Huang, TJ AF Ren, Liqiang Chen, Yuchao Li, Peng Mao, Zhangming Huang, Po-Hsun Rufo, Joseph Guo, Feng Wang, Lin McCoy, J. Philip Levine, Stewart J. Huang, Tony Jun TI A high-throughput acoustic cell sorter SO LAB ON A CHIP LA English DT Article ID MICROFLUIDIC CHANNEL; ON-CHIP; WAVES SSAW; INTERDIGITAL TRANSDUCERS; SEPARATION; MICROPARTICLES; ULTRASOUND; MANIPULATION; PARTICLES; DEVICE AB Acoustic-based fluorescence activated cell sorters (FACS) have drawn increased attention in recent years due to their versatility, high biocompatibility, high controllability, and simple design. However, the sorting throughput for existing acoustic cell sorters is far from optimum for practical applications. Here we report a high-throughput cell sorting method based on standing surface acoustic waves (SSAWs). We utilized a pair of focused interdigital transducers (FIDTs) to generate SSAW with high resolution and high energy efficiency. As a result, the sorting throughput is improved significantly from conventional acoustic-based cell sorting methods. We demonstrated the successful sorting of 10 mu m polystyrene particles with a minimum actuation time of 72 mu s, which translates to a potential sorting rate of more than 13800 events per second. Without using a cell-detection unit, we were able to demonstrate an actual sorting throughput of 3300 events per second. Our sorting method can be conveniently integrated with upstream detection units, and it represents an important development towards a functional acoustic-based FACS system. C1 [Ren, Liqiang; Chen, Yuchao; Li, Peng; Mao, Zhangming; Huang, Po-Hsun; Rufo, Joseph; Guo, Feng; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA. [Wang, Lin] Ascent Bionano Technol Inc, State Coll, State Coll, PA 16802 USA. [McCoy, J. Philip; Levine, Stewart J.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA. EM junhuang@psu.edu RI Huang, Po-Hsun/A-2713-2015; Li, Peng/B-3054-2013; Huang, Tony/A-1546-2009; Ren, Liqiang/E-8953-2015 OI Huang, Po-Hsun/0000-0001-9600-0141; Li, Peng/0000-0002-8332-7142; Ren, Liqiang/0000-0003-0863-4609 FU National Institutes of Health [1 R01 GM112048-01A1, 1R33EB019785-01]; National Science Foundation [IIP-1534645, IDBR-1455658]; Penn State Center for Nanoscale Science (MRSEC) [DMR-1420620]; NHLBI Division of Intramural Research; NSF FX We gratefully acknowledge financial support from National Institutes of Health (1 R01 GM112048-01A1 and 1R33EB019785-01), National Science Foundation (IIP-1534645 and IDBR-1455658), and the Penn State Center for Nanoscale Science (MRSEC) under grant DMR-1420620. J.P.M. and S.J.L. are supported by the NHLBI Division of Intramural Research. Components of this work were conducted at the Penn State node of the NSF-funded National Nanotechnology Infrastructure Network. We also acknowledge the Research Computing and Cyberinfrastructure Unit of Information Technology Services at The Pennsylvania State University for providing advanced computing resources and services that have contributed to the research results reported in this paper. NR 57 TC 13 Z9 13 U1 11 U2 45 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2015 VL 15 IS 19 BP 3870 EP 3879 DI 10.1039/c5lc00706b PG 10 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CR7QS UT WOS:000361546200006 PM 26289231 ER PT J AU Gupta, K Mattingly, SJ Knipp, RJ Afonin, KA Viard, M Bergman, JT Stepler, M Nantz, MH Puri, A Shapiro, BA AF Gupta, Kshitij Mattingly, Stephanie J. Knipp, Ralph J. Afonin, Kirill A. Viard, Mathias Bergman, Joseph T. Stepler, Marissa Nantz, Michael H. Puri, Anu Shapiro, Bruce A. TI Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts SO NANOMEDICINE LA English DT Article DE breast cancer cells; lipoplexes; nonsymmetric hydrophobic domain; oxime ether lipids; RNA interference; structure-activity relationship ID MOUSE VASCULAR ENDOTHELIUM; CATIONIC LIPIDS; GENE DELIVERY; IN-VIVO; RNA INTERFERENCE; TRANSFECTION LIPIDS; HYDROPHOBIC DOMAIN; CANCER-THERAPY; PLASMID DNA; NANOPARTICLES AB Aim: To evaluate the structure-activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231). Materials & methods: Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively. Results & conclusion: Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system. C1 [Gupta, Kshitij; Afonin, Kirill A.; Bergman, Joseph T.; Stepler, Marissa; Puri, Anu; Shapiro, Bruce A.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Mattingly, Stephanie J.; Knipp, Ralph J.; Nantz, Michael H.] Univ Louisville, Dept Chem, Louisville, KY 40292 USA. [Afonin, Kirill A.] Univ N Carolina, Dept Chem, Charlotte, NC 28223 USA. [Viard, Mathias] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Viard, Mathias] NCI, Basic Sci Program, Leidos Biomed Res Inc, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM puria@mail.nih.gov; shapirbr@mail.nih.gov FU Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]; NIH, Center for Cancer Research; University of Louisville School of Interdisciplinary and Graduate Studies FX This research has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of NIH, Center for Cancer Research. RJ Knipp thanks the University of Louisville School of Interdisciplinary and Graduate Studies for fellowship support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 48 TC 1 Z9 1 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 18 BP 2805 EP 2818 DI 10.2217/nnm.15.105 PG 14 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CR6RS UT WOS:000361475600003 PM 26107486 ER PT J AU Cashman, KD Dowling, KG Skrabakova, Z Kiely, M Lamberg-Allardt, C Durazo-Arvizu, RA Sempos, CT Koskinen, S Lundqvist, A Sundvall, J Linneberg, A Thuesen, B Husemoen, LLN Meyer, HE Holvik, K Gronborg, IM Tetens, I Andersen, R AF Cashman, Kevin D. Dowling, Kirsten G. Skrabakova, Zuzana Kiely, Mairead Lamberg-Allardt, Christel Durazo-Arvizu, Ramon A. Sempos, Christopher T. Koskinen, Seppo Lundqvist, Annamari Sundvall, Jouko Linneberg, Allan Thuesen, Betina Husemoen, Lise Lotte N. Meyer, Haakon E. Holvik, Kristin Gronborg, Ida M. Tetens, Inge Andersen, Rikke TI Standardizing serum 25-hydroxyvitamin D data from four Nordic population samples using the Vitamin D Standardization Program protocols: Shedding new light on vitamin D status in Nordic individuals SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE 25-hydroxyvitamin D; standardization; health surveys; Nordic countries ID D DEFICIENCY; D ASSAYS; ELDERLY-WOMEN; HEALTH; ADULTS; PREVENTION; NUTRITION; WINTER; LIMITATIONS; PAKISTANI AB Knowledge about the distributions of serum 25-hydroxyvitamin D (25(OH)D) concentrations in representative population samples is critical for the quantification of vitamin D deficiency as well as for setting dietary reference values and food-based strategies for its prevention. Such data for the European Union are of variable quality making it difficult to estimate the prevalence of vitamin D deficiency across member states. As a consequence of the widespread, method-related differences in measurements of serum 25(OH)D concentrations, the Vitamin D Standardization Program (VDSP) developed protocols for standardizing existing serum 25(OH)D data from national surveys around the world. The objective of the present work was to apply the VDSP protocols to existing serum 25(OH)D data from a Danish, a Norwegian, and a Finnish population-based health survey and from a Danish randomized controlled trial. A specifically-selected subset (n 100-150) of bio-banked serum samples from each of the studies were reanalyzed for 25(OH)D by LC-MS/MS and a calibration equation developed between old and new 25(OH)D data, and this equation was applied to the entire data-sets from each study. Compared to estimates based on the original serum 25(OH)D data, the percentage vitamin D deficiency (<30 nmol/L) decreased by 21.5% in the Danish health survey but by only 1.4% in the Norwegian health survey; but was relatively unchanged (0% and 0.2%) in the Finish survey or Danish RCT, respectively, following VDSP standardization. In conclusion, standardization of serum 25(OH)D concentrations is absolutely necessary in order to compare serum 25(OH) D concentrations across different study populations, which is needed to quantify and prevent vitamin D deficiency. C1 [Cashman, Kevin D.; Dowling, Kirsten G.; Skrabakova, Zuzana; Kiely, Mairead] Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Vitamin Res Grp D, Cork, Ireland. [Cashman, Kevin D.] Natl Univ Ireland Univ Coll Cork, Dept Med, Cork, Ireland. [Lamberg-Allardt, Christel] Univ Helsinki, Dept Food & Environm Sci, FIN-00014 Helsinki, Finland. [Durazo-Arvizu, Ramon A.] Loyola Univ, Stritch Sch Med, Dept Publ Hlth Sci, Chicago, IL 60611 USA. [Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Koskinen, Seppo; Lundqvist, Annamari] Natl Inst Hlth & Welf THL, Dept Hlth Funct Capac & Welf, Helsinki, Finland. [Sundvall, Jouko] THL, Dept Chron Dis Prevent, Helsinki, Finland. [Linneberg, Allan; Thuesen, Betina; Husemoen, Lise Lotte N.] Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark. [Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark. [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark. [Meyer, Haakon E.] Univ Oslo, Dept Community Med, N-0316 Oslo, Norway. [Meyer, Haakon E.; Holvik, Kristin] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Gronborg, Ida M.; Tetens, Inge; Andersen, Rikke] Tech Univ Denmark, Div Nutr, Natl Food Inst, DK-2860 Soborg, Denmark. RP Cashman, KD (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Cork, Ireland. EM k.cashman@ucc.ie OI Gronborg, Ida Marie/0000-0001-7316-1073; Linneberg, Allan/0000-0002-0994-0184 FU Nordic Council of Ministers (NORDEN); Vitamin D Research Group, School of Food and Nutritional Sciences, University College Cork; Higher Education Authority under its Programme for Research in Third Level Institutions (FoodIreland) [R14109] FX This research was funded in part by the Nordic Council of Ministers (NORDEN) and in part by internal strategic funding within the Vitamin D Research Group, School of Food and Nutritional Sciences, University College Cork. The authors wish to acknowledge support of the Higher Education Authority under its Programme for Research in Third Level Institutions (FoodIreland, R14109) for funding the LC-MS/MS used in this analysis. NR 30 TC 10 Z9 10 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0036-5513 EI 1502-7686 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PY 2015 VL 75 IS 7 BP 549 EP 561 DI 10.3109/00365513.2015.1057898 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CR4QN UT WOS:000361321700003 PM 26305421 ER PT S AU Diana, A Bennett, N AF Diana, Augusto Bennett, Nicole BE McCoy, KP Diana, A TI Federal Mechanisms to Support Intervention Dissemination SO SCIENCE, AND ART, OF PROGRAM DISSEMINATION: STRATEGIES, SUCCESSES, AND CHALLENGES SE New Directions for Child and Adolescent Development LA English DT Article; Book Chapter ID ABUSE PREVENTION PROGRAM; SUBSTANCE USE; BEHAVIOR AB This paper examines federal mechanisms that support program developers and researchers in disseminating effective interventions for public benefit. The purpose of this paper is not to discuss the dissemination of intervention research (i.e., how to inform stakeholders about research findings), nor is it intended to discuss the research of intervention dissemination (i.e., what is the best approach to disseminate an intervention). Rather, the paper discusses the challenges specific to finding pathways to disseminate an intervention and describes federal opportunities to support intervention dissemination. Three specific mechanisms are discussed: Federal Registries of Evidence-Based Programs, the Tiered Evidence Grant Programs, and the Small Business Innovative Research (SBIR) and the Small Technology Transfer Research (STTR) programs. The article presents some limitations associated with federal mechanisms for dissemination of effective interventions, but is intended to highlight current and future opportunities they may offer (C) 2015 Wiley Periodicals, Inc. C1 [Diana, Augusto] NINR, Bethesda, MD 20892 USA. [Bennett, Nicole] US Dept Hlth & Human Serv, Off Adolescent Hlth, Washington, DC USA. RP Diana, A (reprint author), NINR, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 3 U2 3 PU WILEY PERIODICALS PI SAN FRANCISCO PA 989 MARKET STREET, SAN FRANCISCO, CA 94103-1741 USA SN 1534-8687 J9 NEW DIR CHILD ADOLES PY 2015 VL 149 BP 69 EP 79 DI 10.1002/cad.20114 PG 11 WC Psychology, Developmental; Social Work SC Psychology; Social Work GA BD5DO UT WOS:000361332500006 ER PT J AU Rossouw, JE AF Rossouw, J. E. TI Serum cholesterol as a risk factor for coronary heart disease revisited SO SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID VASCULAR-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; RANDOMIZED-TRIALS; DIETARY-FAT; TRENDS; LIPOPROTEINS; METAANALYSIS; ASSOCIATION; CONSUMPTION; MUTATIONS AB The biology of lipoproteins and lipoprotein particles as mediators of atherosclerosis has been documented extensively. Numerous prospective epidemiological studies have shown a robust relationship between low-density lipoprotein (LDL) cholesterol, or particles bearing apolipoprotein B, and increased risk of coronary heart disease (CHD); and between high-density lipoprotein (HDL) cholesterol or particles bearing apolipoprotein A1, and decreased risk. These relationships are present across the age spectrum and in both sexes. The causality of LDL cholesterol for CHD has been established by the clinical trials on cholesterol lowering and the Mendelian randomisation studies. However, clinical trials that focus on raising HDL cholesterol, or lowering triglycerides, have yielded mixed results, and the Mendelian randomisation studies have generally not supported causality. Research on the effects of diet on serum cholesterol led to public health guidelines, whose implementation within the last five decades was accompanied by lower population cholesterol levels and CHD burden in all of the countries studied. Over the last three decades, the favourable trends in cholesterol levels and CHD have been supported by the increasing use of statin drugs and improved treatments for myocardial infarction. Peer reviewed. (P) (Submitted: 2014-08-04. Accepted: 2015-02-28.) (C) SAJCN C1 NHLBI, Womens Hlth Initiat Branch, Program Populat Sci & Prevent, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat Branch, Program Populat Sci & Prevent, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. EM jacqueserossouw@gmail.com NR 23 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1607-0658 EI 2221-1268 J9 S AFR J CLIN NUTR JI S. Afr. J. Clin. Nutr. PY 2015 VL 28 IS 1 BP 34 EP 37 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR8TL UT WOS:000361626800006 ER PT J AU Rossouw, JE AF JE, Rossouw TI The diet-heart hypothesis, obesity and diabetes SO SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID LIFE-STYLE INTERVENTION; CARDIOVASCULAR RISK-FACTORS; MODIFICATION TRIAL; MEDITERRANEAN DIET; RANDOMIZED-TRIAL; LOW-CARBOHYDRATE; SATURATED FAT; UNITED-STATES; WEIGHT-LOSS; DISEASE AB Human feeding studies show that dietary fat quality, but not total fat intake, influences levels of low-density lipoprotein (LDL) cholesterol. Meta-analyses indicate an association with reduced coronary heart disease (CHD) risk when saturated fatty acid is replaced with polyunsaturated fatty acid or with low-glycaemic index carbohydrates. A meta-analysis of eight small trials supports this benefit. Secular trends in populations that modified fat intake and quality show a consistent reduction in LDL cholesterol levels and CHD risk. The increase in obesity and diabetes in many developed countries does not track consistently with the implementation of dietary guidelines aimed at lowering fat intake. Obesity is more likely to be due to increases in total energy intake, coupled with an increasingly sedentary lifestyle. However, cohort studies indicate that poor dietary quality is associated with future weight gain. Both cohort studies and secular trends implicate the increased consumption of sugar-sweetened beverages as being associated with obesity, diabetes and cardiovascular disease. Weight reduction can be achieved with a range of energy-restricted diets, including low-fat, high-carbohydrate diets and low-carbohydrate, high-fat diets. Metabolic benefits are proportional to the degree of weight reduction, irrespective of the dietary approach used. The prevention of CHD requires an emphasis on fat quality, rather than fat quantity, while the prevention of obesity and diabetes requires a focus on energy balance and carbohydrate quality. (P) Peer reviewed. (Submitted: 2014-08-04. Accepted: 2015-02-28.) (C) SAJCN C1 NHLBI, Womens Hlth Initiat Branch, Program Populat Sci & Prevent, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat Branch, Program Populat Sci & Prevent, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. EM jacqueserossouw@gmail.com NR 39 TC 1 Z9 1 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1607-0658 EI 2221-1268 J9 S AFR J CLIN NUTR JI S. Afr. J. Clin. Nutr. PY 2015 VL 28 IS 1 BP 38 EP 43 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR8TL UT WOS:000361626800007 ER PT J AU Waidyanatha, S Mathews, JM Patel, PR Black, SR Snyder, RW Fennell, TR AF Waidyanatha, Suramya Mathews, James M. Patel, Purvi R. Black, Sherry R. Snyder, Rodney W. Fennell, Timothy R. TI Disposition of bisphenol AF, a bisphenol A analogue, in hepatocytes in vitro and in male and female Harlan Sprague-Dawley rats and B6C3F1/N mice following oral and intravenous administration SO XENOBIOTICA LA English DT Article DE Bisphenol AF; disposition; hepatocytes; metabolism; oral absorption ID UTEROTROPHIC ASSAY; DRUG-METABOLISM; TETRABROMOBISPHENOL; GLUCURONIDE; CHEMICALS; ROUTE; BILE AB 1. Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA). 2.In this study, comparative clearance and metabolism of BPAF and BPA in hepatocytes and the disposition and metabolism of BPAF in rodents following oral administration of 3.4, 34 or 340 mg/kg [C-14]BPAF were investigated. 3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat > mouse > human. 4. [C-14]BPAF was excreted primarily in feces by 72 h after oral administration to rats (65-80%) and mice (63-72%). Females excreted more in urine (rat, 15%; mouse, 24%) than males (rat, 1-4%; mouse, 10%). Residual tissue radioactivity was <2% of the dose at 72 h. Similar results were observed following intravenous administration. 5. In male rats, 52% of a 340 mg/kg oral dose was excreted in 24 h bile and was mostly comprised of BPAF glucuronide. However, >94% of fecal radioactivity was present as BPAF, suggesting extensive deconjugation in the intestine. 6. Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate. 7. In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF. C1 [Waidyanatha, Suramya] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Mathews, James M.; Patel, Purvi R.; Black, Sherry R.; Snyder, Rodney W.; Fennell, Timothy R.] RTI Int, Res Triangle Pk, NC USA. RP Waidyanatha, S (reprint author), NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM waidyanathas@niehs.nih.gov FU NIEHS NIH HHS [N01-ES-75563]; PHS HHS [HHSN29120077563] NR 24 TC 3 Z9 3 U1 3 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 EI 1366-5928 J9 XENOBIOTICA JI Xenobiotica PY 2015 VL 45 IS 9 BP 811 EP 819 DI 10.3109/00498254.2015.1021732 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CR4RN UT WOS:000361325400008 PM 25923777 ER PT J AU Beydoun, MA Beydoun, HA Gamaldo, AA Rostant, OS Dore, GA Zonderman, AB Eid, SM AF Beydoun, May A. Beydoun, Hind A. Gamaldo, Alyssa A. Rostant, Ola S. Dore, Greg A. Zonderman, Alan B. Eid, Shaker M. TI Nationwide Inpatient Prevalence, Predictors, and Outcomes of Alzheimer's Disease among Older Adults in the United States, 2002-2012 SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; co-morbidity; health care cost; inpatient sample; length of stay; mortality; older adults ID CARDIOVASCULAR RISK-FACTORS; BODY-MASS INDEX; COGNITIVE DECLINE; DEPRESSIVE SYMPTOMS; DIABETES-MELLITUS; INCIDENT DEMENTIA; BLOOD-PRESSURE; FUTURE RISK; WEIGHT-LOSS; ASSOCIATION AB In the inpatient setting, prevalence, predictors, and outcomes [ mortality risk (MR), length of stay (LOS), and total charges (TC)] of Alzheimer's disease (AD) are largely unknown. We used data on older adults (60+y) from the Nationwide Inpatient Sample (NIS) 2002-2012. AD prevalence was similar to 3.12% in 2012 (total weighted discharges with AD +/- standard error: 474, 410 +/- 6,276). Co-morbidities prevailing more in AD inpatient admissions included depression (OR = 1.67, 95% CI: 1.63-1.71, p < 0.001), fluid/electrolyte disorders (OR = 1.25, 95% CI: 1.22-1.27, p < 0.001), weight loss (OR = 1.26, 95% CI: 1.22-1.30, p < 0.001), and psychosis (OR = 2.59, 95% CI: 2.47-2.71, p < 0.001), with mean total co-morbidities increasing over time. AD was linked to higher MR and longer LOS, but lower TC. TC rose in AD, while MR and LOS dropped markedly over time. In AD, co-morbidities predicting simultaneously higher MR, TC, and LOS (2012) included congestive heart failure, chronic pulmonary disease, coagulopathy, fluid/electrolyte disorders, metastatic cancer, paralysis, pulmonary circulatory disorders, and weight loss. In sum, co-morbidities and TC increased over time in AD, while MR and LOS dropped. Few co-morbidities predicted occurrence of AD or adverse outcomes in AD. C1 [Beydoun, May A.; Gamaldo, Alyssa A.; Rostant, Ola S.; Dore, Greg A.; Zonderman, Alan B.] NIA, NIH, IRP, Baltimore, MD 21224 USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Noifolk, VA USA. [Eid, Shaker M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU NIA/NIH/IRP; Johns Hopkins University School of Medicine FX This study was supported in part by the NIA/NIH/IRP in collaboration with Johns Hopkins University School of Medicine. We would like to thank Ms. Danielle Shaked and Ms. Megan Williams for their internal review of the manuscript. NR 46 TC 1 Z9 1 U1 5 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 2 BP 361 EP 375 DI 10.3233/JAD-150228 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CR1EI UT WOS:000361066200005 PM 26402000 ER PT S AU Hinderlich, S Weidemann, W Yardeni, T Horstkorte, R Huizing, M AF Hinderlich, Stephan Weidemann, Wenke Yardeni, Tal Horstkorte, Ruediger Huizing, Marjan BE GerardySchahn, R Delannoy, P VonItzstein, M TI UDP-G1cNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis SO SIALOGLYCO CHEMISTRY AND BIOLOGY I: BIOSYNTHESIS, STRUCTURAL DIVERSITY AND SIALOGLYCOPATHOLOGIES SE Topics in Current Chemistry LA English DT Review; Book Chapter DE Bifunctional enzyme; GNE myopathy; GNE-opathy; N-Acetylneuraminic acid biosynthesis; Sialuria; Vertebrates ID INCLUSION-BODY MYOPATHY; ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; N-ACETYLNEURAMINIC ACID; UDP-GLCNAC 2-EPIMERASE; BIFUNCTIONAL KEY ENZYME; RIMMED VACUOLES DMRV; RESPONSE MEDIATOR PROTEIN-1; D-GLUCOSAMINE 2-EPIMERASE; CELL-SURFACE SIALYLATION; SINGLE PATIENT RESPONSE AB UDP-N-acetylglucos amine 2-epimerase/N-acetylmannos amine kinase is the key enzyme of sialic acid biosynthesis in vertebrates. It catalyzes the first two steps of the cytosolic formation of CMP-N-acetylneuraminic acid from UDP-N-acetylglucosamine. In this review we give an overview of structure, biochemistry, and genetics of the bifunctional enzyme and its complex regulation. Furthermore, we will focus on diseases related to UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. C1 [Hinderlich, Stephan] Univ Appl Sci, Beuth Hsch Tech Berlin, Dept Life Sci & Technol, Berlin, Germany. [Weidemann, Wenke; Horstkorte, Ruediger] Univ Halle Wittenberg, Inst Physiol Chem, D-06108 Halle, Germany. [Yardeni, Tal; Huizing, Marjan] NHGRI, NIH, Bethesda, MD 20892 USA. [Yardeni, Tal] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Hinderlich, S (reprint author), Univ Appl Sci, Beuth Hsch Tech Berlin, Dept Life Sci & Technol, Berlin, Germany. EM hinderlich@beuth-hochschule.de FU Intramural NIH HHS [ZIA HG200322-09]; NHGRI NIH HHS [ZIA HG200322-09] NR 176 TC 6 Z9 6 U1 1 U2 3 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0340-1022 BN 978-3-662-47940-7; 978-3-662-47939-1 J9 TOP CURR CHEM JI Top. Curr. Chem. PY 2015 VL 366 BP 97 EP 137 DI 10.1007/128_2013_464 D2 10.1007/978-3-662-47940-7 PG 41 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BD4TL UT WOS:000361070800005 PM 23842869 ER PT J AU Linder, C Andersson, M Wide, K Beck, O Pohanka, A AF Linder, Camilla Andersson, Maria Wide, Katarina Beck, Olof Pohanka, Anton TI A LC-MS/MS method for therapeutic drug monitoring of carbamazepine, lamotrigine and valproic acid in DBS SO BIOANALYSIS LA English DT Article ID DRIED BLOOD SPOTS; QUANTITATIVE BIOANALYSIS; ANTIEPILEPTIC DRUGS; SAMPLE COLLECTION; ASSAY BIAS; CHILDREN; SALIVA; QUANTIFICATION; CHROMATOGRAPHY; HEMATOCRIT AB Background: Therapeutic drug monitoring of antiepileptic drugs in children with epilepsy assists for personalized drug therapy but require numerous patient visits for venous blood sampling. DBS is an alternative matrix applicable to home sampling which can save time and reduce stress for this patient group. Results: A fast LC-MS/MS method for quantification of carbamazepine, lamotrigine and valproic acid based on DBS sampling was developed. The method showed linearity in therapeutically relevant concentration ranges and compatible with unknown volume sampling and expected hematocrit range of the patient group. Conclusion: A LC-MS/MS method for the three most commonly used antiepileptic drugs has been fully validated and clinically applied on DBSs from patients at the neuropediatric clinic at Karolinska University Hospital. C1 [Linder, Camilla; Beck, Olof; Pohanka, Anton] Karolinska Inst, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden. [Andersson, Maria] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD USA. [Wide, Katarina] Karolinska Univ Hosp, Dept Clin Sci, Technol & Intervent, Div Pediat, Stockholm, Sweden. [Wide, Katarina] Karolinska Inst, Stockholm, Sweden. RP Linder, C (reprint author), Karolinska Inst, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden. EM camilla.linder@karolinska.se OI Wide, Katarina/0000-0003-3024-0657 FU Margaretha Emmet Foundation; Federation of Epilepsy in Sweden; ALF [551398 ALF 2014]; Swedish Research Council [VR 2011-3440] FX Support for this study was made by Margaretha Emmet Foundation, the Federation of Epilepsy in Sweden, ALF-funded research by the county of Stockholm (project 551398 ALF 2014) and by Swedish Research Council (VR 2011-3440, awarded to LL Gustafsson). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 27 TC 5 Z9 5 U1 3 U2 15 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2015 VL 7 IS 16 BP 2031 EP 2039 DI 10.4155/bio.15.99 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CQ6KQ UT WOS:000360713600009 PM 26327183 ER PT J AU Ellefsen, KN da Costa, JL Concheiro, M Anizan, S Barnes, AJ Pirard, S Gorelick, DA Huestis, MA AF Ellefsen, Kayla N. da Costa, Jose Luiz Concheiro, Marta Anizan, Sebastien Barnes, Allan J. Pirard, Sandrine Gorelick, David A. Huestis, Marilyn A. TI Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration SO BIOANALYSIS LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; WHOLE-BLOOD; QUANTITATIVE-ANALYSIS; SPOT SAMPLES; QUANTIFICATION; PLASMA; DRUGS; ASSAY; BENZOYLECGONINE AB Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC-HRMS and 2D GC-MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 mu g/l were achieved, with acceptable bias and imprecision. Authentic matched specimens' (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4-105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. C1 [Ellefsen, Kayla N.; da Costa, Jose Luiz; Anizan, Sebastien; Barnes, Allan J.; Pirard, Sandrine; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ellefsen, Kayla N.] Univ Maryland, Program Toxicol, Baltimore, MD 21201 USA. [da Costa, Jose Luiz] Criminalist Inst Sao Paulo, Forens Toxicol & Chem Lab, Sao Paulo, Brazil. [Concheiro, Marta] CUNY, Dept Sci, John Jay Coll Criminal Justice, New York, NY 10019 USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov RI Costa, Jose/C-1741-2012 OI Costa, Jose/0000-0001-9954-0899 FU Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), NIH; Brazilian National Counsel of Technological and Scientific Development (CNPq) FX This work was supported by the Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), NIH. JL da Costa received a postdoctoral fellowship from Brazilian National Counsel of Technological and Scientific Development (CNPq) to conduct this research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 48 TC 3 Z9 3 U1 4 U2 12 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2015 VL 7 IS 16 BP 2041 EP 2056 DI 10.4155/bio.15.127 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CQ6KQ UT WOS:000360713600010 PM 26327184 ER PT J AU Dai, HJ Wei, CH Kao, HY Liu, RL Tsai, RTH Lu, ZY AF Dai, Hong-Jie Wei, Chih-Hsuan Kao, Hung-Yu Liu, Rey-Long Tsai, Richard Tzong-Han Lu, Zhiyong TI Text Mining for Translational Bioinformatics SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Dai, Hong-Jie] Natl Taitung Univ, Dept Comp Sci & Informat Engn, Taitung City 950, Taiwan. [Wei, Chih-Hsuan; Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Kao, Hung-Yu] Natl Cheng Kung Univ, Dept Comp Sci & Informat Engn, Tainan 701, Taiwan. [Liu, Rey-Long] Tzu Chi Univ, Dept Med Informat, Hualien 970, Taiwan. [Tsai, Richard Tzong-Han] Natl Cent Univ, Dept Comp Sci & Informat Engn, Taoyuan 320, Taiwan. RP Dai, HJ (reprint author), Natl Taitung Univ, Dept Comp Sci & Informat Engn, Taitung City 950, Taiwan. EM hjdai@nttu.edu.tw NR 0 TC 0 Z9 0 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 368264 DI 10.1155/2015/368264 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CQ6PE UT WOS:000360725600001 ER PT J AU Guadagnin, E Narola, J Bonnemann, CG Chen, YW AF Guadagnin, Eleonora Narola, Jigna Boennemann, Carsten G. Chen, Yi-Wen TI Tyrosine 705 Phosphorylation of STAT3 Is Associated with Phenotype Severity in TGF beta 1 Transgenic Mice SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID GROWTH-FACTOR-BETA; SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; EXPRESSION; ACTIVATION; CANCER; CELLS; CYTOKINE; RECEPTOR; IL-6 AB Transforming growth factor beta 1 (TGF beta 1) is a key player in skeletal muscle degenerative and regenerative processes. We previously showed that conditionally overexpressing TGF beta 1 in skeletal muscles caused myofiber atrophy and endomysial fibrosis in mice. However, the disease severity varied significantly among individual mice. While 40% of mice developed severe muscle pathology and lost body weight within 2 weeks of TGF beta 1 transgene induction in muscles, the rest showed milder or no phenotype. This study aims at determining whether signal transducer and activator of transcription 3 (STAT3) plays a role in the phenotypic difference and whether it can be activated by TGF beta 1 directly in muscle cells. Our results show that while total STAT3 was not differentially expressed between the two groups of mice, there was significantly higher pSTAT3 (Tyr705) in the muscles of the mice with severe phenotype. Immunohistochemistry showed that pSTAT3 (Tyr705) was localized in approximately 50% of the nuclei of the muscles. We further showed that TGF beta 1 induced Tyr705 phosphorylation of STAT3 in C2C12 cells within 30 minutes of treatment while total STAT3 was not affected. Our findings suggest that TGF beta 1 alone can induce Tyr705 phosphorylation of STAT3 in skeletal muscle cells and contribute to disease severity in transgenic TGF beta 1 mice. C1 [Guadagnin, Eleonora; Narola, Jigna; Chen, Yi-Wen] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. [Boennemann, Carsten G.] Natl Inst Neurol Disorders & Stroke, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Chen, Yi-Wen] George Washington Univ, Dept Integrat Syst Biol, Washington, DC 20052 USA. [Chen, Yi-Wen] George Washington Univ, Dept Pediat, Washington, DC 20052 USA. RP Chen, YW (reprint author), Childrens Natl Med Ctr, Res Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA. EM ychen@childrensnational.org FU Department of Defense [W81XWH-10-1-0659]; NIH/NICHD [1R24HD050846]; NIH/NIAMS [1R01AR052027]; intramural funds of NIH/NINDS FX Research reported in this paper was supported by the Department of Defense under Award no. W81XWH-10-1-0659 and the NIH/NICHD under Award no. 1R24HD050846. Yi-Wen. Chen was partially supported by NIH/NIAMS under Award no. 1R01AR052027. Carsten G. Bonnemann is supported by intramural funds of NIH/NINDS. NR 40 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 843743 DI 10.1155/2015/843743 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CQ6ZB UT WOS:000360751500001 ER PT J AU Towner, RA Smith, N Saunders, D Carrizales, J Lupu, F Silasi-Mansat, R Ehrenshaft, M Mason, RP AF Towner, R. A. Smith, N. Saunders, D. Carrizales, J. Lupu, F. Silasi-Mansat, R. Ehrenshaft, M. Mason, R. P. TI In vivo targeted molecular magnetic resonance imaging of free radicals in diabetic cardiomyopathy within mice SO FREE RADICAL RESEARCH LA English DT Article DE immuno-spin trapping; free radical targeted imaging; in vivo; streptozotocin; mice ID NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; MOUSE MODEL; MRI; MECHANISMS; GLIOMAS AB Free radicals contribute to the pathogenesis of diabetic cardiomyopathy. We present a method for in vivo observation of free radical events within murine diabetic cardiomyopathy. This study reports on in vivo imaging of protein/lipid radicals using molecular MRI (mMRI) and immuno-spin trapping (IST) in diabetic cardiac muscle. To detect free radicals in diabetic cardiomyopathy, streptozotocin (STZ)-exposed mice were given 5,5-dimethyl-pyrroline-N-oxide (DMPO) and administered an anti-DMPO probe (biotin-anti-DMPO antibody-albumin Gd-DTPA). For controls, non-diabetic mice were given DMPO (non-disease control), and administered an anti-DMPO probe; or diabetic mice were given DMPO but administered a non-specific IgG contrast agent instead of the anti-DMPO probe. DMPO administration started at 7 weeks following STZ treatment for 5 days, and the anti-DMPO probe was administered at 8 weeks for MRI detection. MRI was used to detect a significant increase (p < 0.001) in MRI signal intensity (SI) from anti-DMPO nitrone adducts in diabetic murine left-ventricular (LV) cardiac tissue, compared to controls. Regional increases in MR SI in the LV were found in the apical and upper-left areas (p < 0.01 for both), compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised cardiac tissues, which indicated elevated fluorescence only in cardiac muscle of mice administered the anti-DMPO probe. Oxidized lipids and proteins were also found to be significantly elevated (p < 0.05 for both) in diabetic cardiac muscle compared to controls. It can be concluded that diabetic mice have more heterogeneously distributed radicals in cardiac tissue than nondiabetic mice. C1 [Towner, R. A.; Smith, N.; Saunders, D.; Carrizales, J.] Oklahoma Med Res Fdn, Adv Magnet Resonance Ctr, Oklahoma City, OK 73104 USA. [Lupu, F.; Silasi-Mansat, R.] Oklahoma Med Res Fdn, Cardiovasc Biol, Oklahoma City, OK 73104 USA. [Ehrenshaft, M.; Mason, R. P.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Towner, RA (reprint author), Oklahoma Med Res Fdn, Adv Magnet Resonance Ctr, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Rheal-Towner@omrf.org OI Silasi, Robert/0000-0001-9590-6160 FU Oklahoma Medical Research Foundation (OMRF); National Institute of Environmental Health Sciences (NIEHS); NIH [5R25GM054938-10] FX This project was funded by the Oklahoma Medical Research Foundation (OMRF) (RAT), the National Institute of Environmental Health Sciences (NIEHS) (RPM), and supported by NIH grant number 5R25GM054938-10 (RAT). NR 23 TC 0 Z9 0 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 EI 1029-2470 J9 FREE RADICAL RES JI Free Radic. Res. PY 2015 VL 49 IS 9 BP 1140 EP 1146 DI 10.3109/10715762.2015.1050587 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ6KW UT WOS:000360714300009 PM 25968951 ER PT J AU Romero, R Miranda, J Chaemsaithong, P Chaiworapongsa, T Kusanovic, JP Dong, Z Ahmed, AI Shaman, M Lannaman, K Yoon, BH Hassan, SS Kim, CJ Korzeniewski, SJ Yeo, L Kim, YM AF Romero, Roberto Miranda, Jezid Chaemsaithong, Piya Chaiworapongsa, Tinnakorn Kusanovic, Juan P. Dong, Zhong Ahmed, Ahmed I. Shaman, Majid Lannaman, Kia Yoon, Bo Hyun Hassan, Sonia S. Kim, Chong Jai Korzeniewski, Steven Jai Yeo, Lami Kim, Yeon Mee TI Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Infection; polymerase chain reaction with electrospray ionization mass spectrometry; pregnancy; prematurity; preterm delivery; Sneathia sp. ID AMNIOTIC-FLUID INTERLEUKIN-6; IONIZATION MASS-SPECTROMETRY; FETAL BIOPHYSICAL PROFILE; TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; BLOOD-CELL COUNT; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; INTRAUTERINE CONTRACEPTIVE DEVICE; UMBILICAL-CORD INFLAMMATION; INDUCED PREMATURE RUPTURE AB Objective: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. Methods: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes. Results: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p = 0.001]. Conclusions: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation. C1 [Romero, Roberto; Miranda, Jezid; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Kusanovic, Juan P.; Dong, Zhong; Ahmed, Ahmed I.; Shaman, Majid; Lannaman, Kia; Hassan, Sonia S.; Kim, Chong Jai; Korzeniewski, Steven Jai; Yeo, Lami; Kim, Yeon Mee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Miranda, Jezid; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Ahmed, Ahmed I.; Shaman, Majid; Lannaman, Kia; Hassan, Sonia S.; Korzeniewski, Steven Jai; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kusanovic, Juan P.] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Santiago, Chile. [Kusanovic, Juan P.] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Kim, Chong Jai] Univ Ulsan, Coll Med, Med Ctr, Dept Pathol, Seoul, South Korea. [Kim, Yeon Mee] Inje Univ, Haeundae Paik Hosp, Coll Med, Dept Pathol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov; ykim.haeundae@gmail.com FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 277 TC 24 Z9 26 U1 2 U2 16 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 12 BP 1394 EP 1409 DI 10.3109/14767058.2014.958463 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NR UT WOS:000360438400005 PM 25190175 ER PT J AU Zhong, C Zhu, JF AF Zhong, Chao Zhu, Jinfang TI Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells SO MEDIATORS OF INFLAMMATION LA English DT Review ID ARYL-HYDROCARBON RECEPTOR; CD4(+) T-CELLS; TYPE-2 IMMUNITY; COMMENSAL BACTERIA; TISSUE HOMEOSTASIS; FACTOR GATA3; FACTOR TOX; DIFFERENTIATION; LINEAGE; INFLAMMATION AB Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the "innate" feature of conventional natural killer (cNK) cells and the "helper" feature of CD4(+) T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs. C1 [Zhong, Chao; Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhong, C (reprint author), NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhongc@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 FU Intramural Research Program of National Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), NIH, USA FX The authors thank Dr. Darah Christie for her comments and editing the paper. The work is supported by the Intramural Research Program of National Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), NIH, USA. NR 61 TC 0 Z9 0 U1 1 U2 4 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2015 AR 264502 DI 10.1155/2015/264502 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CQ6ZM UT WOS:000360752600001 ER PT J AU Bush, BG Shapiro, JM DelRio, FW Cook, RF Oyen, ML AF Bush, Brian G. Shapiro, Jenna M. DelRio, Frank W. Cook, Robert F. Oyen, Michelle L. TI Mechanical measurements of heterogeneity and length scale effects in PEG-based hydrogels SO SOFT MATTER LA English DT Article ID ATOMIC-FORCE MICROSCOPY; RUBBER-LIKE MATERIALS; SPHERICAL INDENTATION; SPATIAL INHOMOGENEITY; POLYACRYLAMIDE GELS; ELASTIC-MODULUS; LOAD; NANOINDENTATION; CARTILAGE; HARDNESS AB Colloidal-probe spherical indentation load-relaxation experiments with a probe radius of 3 mm are conducted on poly(ethylene glycol) (PEG) hydrogel materials to quantify their steady-state mechanical properties and time-dependent transport properties via a single experiment. PEG-based hydrogels are shown to be heterogeneous in both morphology and mechanical stiffness at this scale; a linear-harmonic interpolation of hyperelastic Mooney-Rivlin and Boussinesq flat-punch indentation models was used to describe the steady-state response of the hydrogels and determine upper and lower bounds for indentation moduli. Analysis of the transient load-relaxation response during displacement-controlled hold periods provides a means of extracting two time constants tau(1) and tau(2), where tau(1) and tau(2) are assigned to the viscoelastic and poroelastic properties, respectively. Large tau(2) values at small indentation depths provide evidence of a non-equilibrium state characterized by a phenomenon that restricts poroelastic fluid flow through the material; for larger indentations, the variability in tau(2) values decreases and pore sizes estimated from tau(2) via indentation approach those measured via macroscopic swelling experiments. The contact probe methodology developed here provides a means of assessing hydrogel heterogeneity, including time-dependent mechanical and transport properties, and has potential implications in hydrogel biomedical and engineering applications. C1 [Bush, Brian G.; DelRio, Frank W.; Cook, Robert F.] NIST, Nanomech Properties Grp, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Shapiro, Jenna M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Shapiro, Jenna M.; Oyen, Michelle L.] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England. RP Bush, BG (reprint author), NIST, Nanomech Properties Grp, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM brian.bush@nist.gov FU National Institutes of Health - University of Cambridge Scholars Program; laboratory of Dr Constantine Stratakis at the National Institute of Child Health and Human Development at NIH FX The authors would like to acknowledge funding from the National Institutes of Health - University of Cambridge Scholars Program and the laboratory of Dr Constantine Stratakis at the National Institute of Child Health and Human Development at NIH. In addition, the authors thank Dr Daniel Strange for help with Matlab analysis, and Dr Richard Gates for performing the laser Doppler vibrometry measurements. NR 49 TC 4 Z9 4 U1 6 U2 39 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X EI 1744-6848 J9 SOFT MATTER JI Soft Matter PY 2015 VL 11 IS 36 BP 7191 EP 7200 DI 10.1039/c5sm01210d PG 10 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA CQ5PF UT WOS:000360656900015 PM 26255839 ER PT B AU Stavreva, DA Varticovski, L Hager, GL AF Stavreva, Diana A. Varticovski, Lyuba Hager, Gordon L. BE Reisner, DE Pradeep, T TI Quantitative High Throughput Assay for Detection of Biologically Active Endocrine Disrupting Chemicals in Water SO AQUANANOTECHNOLOGY: GLOBAL PROSPECTS LA English DT Article; Book Chapter ID WASTE-WATER; ESTROGENIC ACTIVITY; IN-VITRO; GLUCOCORTICOID-RECEPTOR; TREATMENT-PLANT; REPRODUCTIVE HEALTH; LIVING CELLS; PESTICIDES; EXPRESSION; POTOMAC C1 [Stavreva, Diana A.; Varticovski, Lyuba; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Stavreva, DA (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 52 TC 0 Z9 0 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-1225-2; 978-1-4665-1224-5 PY 2015 BP 723 EP 735 PG 13 WC Water Resources SC Water Resources GA BC9AD UT WOS:000356246100037 ER PT J AU Laughlin, C Schleif, A Heilman, CA AF Laughlin, Catherine Schleif, Amanda Heilman, Carole A. TI Addressing viral resistance through vaccines SO FUTURE VIROLOGY LA English DT Review DE antimicrobial resistance; antiviral resistance; cytomegalovirus; hepatitis C; HIV; influenza; vaccines; vaccine design; vaccine evaluation; vaccine implementation ID RESPIRATORY SYNCYTIAL VIRUS; DRUG-RESISTANCE; SYSTEMS BIOLOGY; CYTOMEGALOVIRUS DISEASE; TRANSPLANT RECIPIENTS; COMPUTATIONAL DESIGN; EPITOPE-SCAFFOLDS; ANTIVIRAL DRUGS; UNITED-STATES; HIV-INFECTION AB Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider approaches to address this growing issue. While vaccination is a logical strategy, and has been shown to be successful many times over, next generation viral vaccines with a specific goal of curbing antiviral resistance will need to clear several hurdles including vaccine design, evaluation and implementation. This article suggests that a new model of vaccination may need to be considered: rather than focusing on public health, this model would primarily target sectors of the population who are at high risk for complications from certain infections. C1 [Laughlin, Catherine; Schleif, Amanda; Heilman, Carole A.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20852 USA. RP Schleif, A (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 5601 Fishers Lane, Bethesda, MD 20852 USA. EM schleifac@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 66 TC 0 Z9 0 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PY 2015 VL 10 IS 8 BP 1011 EP 1022 DI 10.2217/FVL.15.53 PG 12 WC Virology SC Virology GA CP9NT UT WOS:000360221900010 PM 26604979 ER PT J AU Xu, YL Jiang, L Fang, JC Fang, R Morse, HC Ouyang, GF Zhou, JX AF Xu, Yulian Jiang, Lei Fang, Jianchen Fang, Rong Morse, Herbert C., III Ouyang, Guifang Zhou, Jeff X. TI Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma SO JOURNAL OF CANCER LA English DT Article DE lymphoma; IRF8; DLBCL ID GENE-EXPRESSION; DIFFERENTIATION; PROLIFERATION; PATHOGENESIS; LYMPHOCYTES; METHYLATION; SUPPRESSOR; CARCINOMA; SURVIVAL; PROGRAM AB IRF8 is a transcription factor with a critical role in B lymphocyte development and functions. Its role in human diffuse large B-cell lymphoma (DLBCL), however, remained elusive. In this study, using shRNA-mediated knockdown of IRF8 expression, we found that the loss of IRF8 significantly reduced the proliferation of DLBCL cells (P<0.05). Mechanistically, decreasing the levels of IRF8 led to a suppression of the phosphorylation of p38 and ERK, molecules critical for B cell proliferation. Furthermore, using a xenograft lymphoma mouse model, we found that the loss of IRF8 significantly inhibited the growth of lymphomas in vivo (P<0.05). Immunohistochemical analysis of human DLBCL tissues revealed that the levels of IRF8 were significantly greater in non-germinal center B-cell-like (non-GCB) subtype than that in GCB subtype (P<0.05). Analysis of public available data also suggested that the expression levels of IRF8 mRNA in human DLBCL tissues were inversely correlated with patients' overall survival time. Taken together, this study suggested that IRF8 may play an oncogenic role in human DLBCL by promoting cell proliferation. C1 [Xu, Yulian; Jiang, Lei; Fang, Rong; Zhou, Jeff X.] Ningbo Univ, Sch Med, Dept Pathol, Ningbo 315211, Zhejiang, Peoples R China. [Fang, Jianchen] Pathol Serv Ctr, Ningbo, Zhejiang, Peoples R China. [Morse, Herbert C., III] NIAID, NIH, Rockville, MD USA. [Ouyang, Guifang] Ningbo Univ, Dept Hematol, Affiliated Hosp 1, Ningbo 315211, Zhejiang, Peoples R China. RP Zhou, JX (reprint author), Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China. EM ouyangguifang@medmail.com.cn; zhouxi-wu@nbu.edu.cn FU National Science Foundation of China (NSFC) [81172251, 81400098]; K.C. Wong Magna Fund at Ningbo University FX This work was supported by the National Science Foundation of China (NSFC) (grant # 81172251 to JXZ and # 81400098 to LJ) and by the K.C. Wong Magna Fund at Ningbo University. NR 34 TC 1 Z9 1 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2015 VL 6 IS 10 BP 953 EP 961 DI 10.7150/jca.12067 PG 9 WC Oncology SC Oncology GA CQ0PM UT WOS:000360298900004 PM 26316891 ER PT J AU Jimenez-Corona, A Avila-Hermosillo, A Nelson, RG Ramirez-Lopez, G AF Jimenez-Corona, Aida Avila-Hermosillo, Antonio Nelson, Robert G. Ramirez-Lopez, Guadalupe TI A Family History of Diabetes Modifies the Association between Elevated Urine Albumin Concentration and Hyperglycemia in Nondiabetic Mexican Adolescents SO JOURNAL OF DIABETES RESEARCH LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; CHRONIC KIDNEY-DISEASE; METABOLIC SYNDROME; US ADULTS; MICROALBUMINURIA; CHILDREN; PREVALENCE; EXCRETION; OBESITY; POPULATION AB We examined the frequency of elevated urine albumin concentration (UAC) and its association with metabolic syndrome (MetS) and metabolic markers in 515 nondiabetic Mexican adolescents stratified by family history of diabetes (FHD). UAC was measured in a first morning urine sample and considered elevated when excretion was >= 20mg/mL. MetS was defined using International Diabetes Federation criteria. Fasting insulin, insulin resistance, and lipids were evaluated. Multivariate logistic regression was performed. Elevated UAC was present in 12.4% and MetS was present in 8.9% of the adolescents. No association was found between elevated UAC and MetS. Among adolescents with FHD, 18.4% were overweight and 20.7% were obese, whereas, among those without a FHD, 15.9% were overweight and 7.5% were obese. Hyperglycemia was higher in those with elevated UAC than in those without (44.4% versus 5.1%, p = 0.003). Hyperglycemia (OR = 9.8, 95% CI 1.6-59.4) and number of MetS components (OR = 4.5, 95% CI 1.5-13.3) were independently associated with elevated UAC. Among female participants, abdominal obesity was associated with elevated UAC (OR = 4.5, 95% CI 1.2-16.9). Conclusion. Elevated UAC was associated neither with MetS nor with any metabolic markers in nondiabetic adolescents. However, FHD modified the association of elevated UAC with hyperglycemia and the number of MetS components. C1 [Jimenez-Corona, Aida] Hlth Secretariat, Gen Directorate Epidemiol, Mexico City 01480, DF, Mexico. [Jimenez-Corona, Aida] IAP, Inst Ophthalmol Fdn Conde Valenciana, Ocular Epidemiol Dept, Mexico City 06800, DF, Mexico. [Avila-Hermosillo, Antonio] Reg Gen Hosp 89, Mexican Inst Social Secur, Sect Juarez, Guadalajara 44150, Jal, Mexico. [Nelson, Robert G.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. [Ramirez-Lopez, Guadalupe] Mexican Inst Social Secur, Adolescent Epidemiol & Hlth Serv Res Unit, Guadalajara 45400, Jal, Mexico. RP Ramirez-Lopez, G (reprint author), Mexican Inst Social Secur, Adolescent Epidemiol & Hlth Serv Res Unit, Ave Tonala 121, Guadalajara 45400, Jal, Mexico. EM maria.ramirezlo@imss.gob.mx FU National Council of Science and Technology (CONACYT) [37951-M]; CONACYT Scholarship [159083] FX This research was supported by the National Council of Science and Technology (CONACYT), Grant 37951-M, and CONACYT Scholarship 159083. The authors thank the students, their parents, the school personnel, and those involved in the data collection. NR 45 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6745 EI 2314-6753 J9 J DIABETES RES JI J. Diabetes Res. PY 2015 AR 437079 DI 10.1155/2015/437079 PG 10 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CQ2XC UT WOS:000360464600001 ER PT J AU Sheikh, F Dickensheets, H Pedras-Vasconcelos, J Ramalingam, T Helming, L Gordon, S Donnelly, RP AF Sheikh, Faruk Dickensheets, Harold Pedras-Vasconcelos, Joao Ramalingam, Thirumalai Helming, Laura Gordon, Siamon Donnelly, Raymond P. TI The Interleukin-13 Receptor-alpha 1 Chain Is Essential for Induction of the Alternative Macrophage Activation Pathway by IL-13 but Not IL-4 SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Alternative macrophage activation; Arginase; Interleukin-4; Interleukin-13; Interleukin-13 receptor-alpha 1; STAT6 ID COMMON GAMMA-CHAIN; INTERFERON-GAMMA; GENE-EXPRESSION; IN-VITRO; DIFFERENTIAL EXPRESSION; CYTOKINE SIGNALING-1; HUMAN MONOCYTES; MICE LACKING; STAT6; CELLS AB Macrophages coexpress both the interleukin (IL)-2R gamma chain (gamma(c)) and IL-13R alpha 1. These receptor chains can heterodimerize with IL-4R alpha to form type I or type II IL-4 receptor complexes, respectively. We used macrophages derived from Il2rg and Il13ra1 knockout (KO) mice to evaluate the requirements for these receptor chains for induction of the alternative macrophage activation (AMA) pathway by IL-4 and IL-13. Absence of gamma(c) significantly decreased activation of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was markedly reduced in gamma(c) KO macrophages, it was not abolished, indicating that IL-4 can still signal through type II IL-4 receptors via the IL-13R alpha 1 chain. IL-13 failed to activate STAT6 in macrophages derived from Il13ra1 KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in Il13ra1(-/-) macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as Arg1, Retnla and Ccl11 that are characteristically expressed by alternatively activated macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and giant cell formation by Il13ra1 KO macrophages. These findings demonstrate that the IL-13R alpha 1 chain is essential for induction of the AMA pathway by IL-13 but not IL-4. (C) 2015 S. Karger AG, Basel C1 [Sheikh, Faruk; Dickensheets, Harold; Pedras-Vasconcelos, Joao; Donnelly, Raymond P.] US FDA, Div Therapeut Proteins, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Ramalingam, Thirumalai] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Helming, Laura] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-80290 Munich, Germany. [Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Donnelly, RP (reprint author), Div Biotechnol Res & Review, FFDA CDER WO Bldg 52,Room 2106, Silver Spring, MD 20993 USA. EM raymond.donnelly@fda.hhs.gov FU Intramural NIH HHS [Z99 OD999999] NR 46 TC 5 Z9 5 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2015 VL 7 IS 5 BP 494 EP 505 DI 10.1159/000376579 PG 12 WC Immunology SC Immunology GA CQ2YU UT WOS:000360469300007 PM 25766112 ER PT J AU Lepiller, Q Soulier, E Li, QS Lambotin, M Barths, J Fuchs, D Stoll-Keller, F Liang, TJ Barth, H AF Lepiller, Quentin Soulier, Eric Li, Qisheng Lambotin, Melanie Barths, Jochen Fuchs, Dietmar Stoll-Keller, Francoise Liang, T. Jake Barth, Heidi TI Antiviral and Immunoregulatory Effects of Indoleamine-2,3-Dioxygenase in Hepatitis C Virus Infection SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Indoleamine-2,3-dioxygenase; Hepatocyte; Hepatitis C virus; Antiviral immune response ID INTERFERON REGULATORY FACTOR-1; PLASMACYTOID DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; T-CELLS; TRYPTOPHAN 2,3-DIOXYGENASE; GAMMA-INTERFERON; IDO ACTIVITY; REPLICATION; GENE; PATHOGENESIS AB In patients with hepatitis C virus (HCV) infection, enhanced activity of indoleamine-2,3-dioxygenase 1 (IDO) has been reported. IDO - a tryptophan-catabolizing enzyme - has been considered as both an innate defence mechanism and an important regulator of the immune response. The molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we show that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of types I and III interferons (IFNs) and IFN-stimulated genes in HCV-infected hepatocytes. Overexpression of hepatic IDO prior to HCV infection markedly impaired HCV replication in hepatocytes, suggesting that IDO limits the spread of HCV within the liver. siRNA-mediated IDO knock-down revealed that IDO functions as an IFN-mediated anti-HCV effector. Hepatic IDO was most potently induced by IFN-gamma, and ongoing HCV replication could significantly upregulate IDO expression. IRF1 (IFN-regulatory factor 1) and STAT1 (signal transducer and activator of transcription 1) regulated hepatic IDO expression. Hepatic IDO expression also had a significant inhibitory effect on CD4+ T-cell proliferation. Our data suggest that hepatic IDO plays a dual role during HCV infection by slowing down viral replication and also regulating host immune responses. (C) 2015 S. Karger AG, Basel C1 [Lepiller, Quentin; Stoll-Keller, Francoise; Barth, Heidi] Hop Univ Strasbourg, Virol Lab, FR-67000 Strasbourg, France. [Lepiller, Quentin; Soulier, Eric; Stoll-Keller, Francoise; Barth, Heidi] Univ Strasbourg, INSERM U1109, Strasbourg, France. [Lambotin, Melanie; Barths, Jochen] Univ Strasbourg, INSERM U1110, Strasbourg, France. [Lepiller, Quentin; Soulier, Eric; Stoll-Keller, Francoise; Barth, Heidi] Univ Strasbourg, Fed Med Translationnelle Strasbourg, Strasbourg, France. [Fuchs, Dietmar] Med Univ Innsbruck, Bioctr, Div Biol Chem, A-6020 Innsbruck, Austria. [Li, Qisheng; Liang, T. Jake] NIDDKD, NIH, Liver Dis Branch, Bethesda, MD USA. RP Liang, TJ (reprint author), Hop Univ Strasbourg, Virol Lab, 3 Rue Koeberl, FR-67000 Strasbourg, France. EM JakeL@bdg10.niddk.nih.gov; barth@unistra.fr FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH; Agence Nationale de la Recherche sur le Sida [2010-242] FX We would like to thank T. Baumert, INSERM U1110, for supporting the study and providing access to the L3 laboratory facility. We also wish to thank S. Strom and his colleagues at the University of Pittsburgh for providing the PHH through the Liver Tissue Procurement and Distribution System (N01-DK-7-0004/HHSN26700700004C) and the team of P. Bachellier, Pole des Pathologies Digestives, Hepatiques et Transplantation, Hopitaux Universitaires de Strasbourg, France for providing liver resections for PHH isolation. We are grateful to S. Durand, INSERM U1110, Strasbourg for excellent technical assistance in the isolation of PHH and to S. Raghuraman, Inflammation and Infection Research Centre, University of New South Wales, Sydney, Australia for helpful discussion. Finally, we thank C. Sodroski, Liver Diseases Branch, NIDDK, NIH for proofreading the manuscript. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH and the Agence Nationale de la Recherche sur le Sida (2010-242 to H.B.). NR 47 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2015 VL 7 IS 5 BP 530 EP 544 DI 10.1159/000375161 PG 15 WC Immunology SC Immunology GA CQ2YU UT WOS:000360469300010 PM 25792183 ER PT J AU Chaemsaithong, P Romero, R Tarca, AL Korzeniewski, SJ Schwartz, AG Miranda, J Ahmed, AI Dong, Z Hassan, SS Yeo, L Tinnakorn, T AF Chaemsaithong, Piya Romero, Roberto Tarca, Adi L. Korzeniewski, Steven J. Schwartz, Alyse G. Miranda, Jezid Ahmed, Ahmed I. Dong, Zhong Hassan, Sonia S. Yeo, Lami Tinnakorn, Tinnakorn TI Maternal plasma fetuin-A concentration is lower in patients who subsequently developed preterm preeclampsia than in uncomplicated pregnancy: a longitudinal study SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 11th World Congress of Perinatal Medicine CY JUN 19-22, 2013 CL Moscow, RUSSIA SP World Assoc Perinatal Med DE alpha(2)-Heremans-Schmid glycoprotein; hypertensive disorders in pregnancy; insulin resistance; intravascular inflammation; negative acute phase protein reactant ID TUMOR-NECROSIS-FACTOR; FOR-GESTATIONAL-AGE; LATE-ONSET PREECLAMPSIA; PRO-INFLAMMATORY CYTOKINES; GROWTH-FACTOR RECEPTOR-1; ANTI-ANGIOGENIC FACTORS; ENDOTHELIAL-CELL DYSFUNCTION; INSULIN-RESISTANCE SYNDROME; ELEVATED LIVER-ENZYMES; C-REACTIVE PROTEIN AB Objective: Fetuin-A is a negative acute phase protein reactant that acts as a mediator for lipotoxicity, leading to insulin resistance. Intravascular inflammation and insulin resistance have been implicated in the mechanisms of disease responsible for preeclampsia (PE). Maternal plasma concentrations of fetuin-A at the time of diagnosis of preterm PE are lower than in control patients with a normal pregnancy outcome. However, it is unknown if the changes in maternal plasma fetuin-A concentrations precede the clinical diagnosis of the disease. We conducted a longitudinal study to determine whether patients who subsequently developed PE had a different profile of maternal plasma concentrations of fetuin-A as a function of gestational age (GA) than those with uncomplicated pregnancies. Methods: A longitudinal case-control study was performed and included 200 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n = 160); and (2) patients who subsequently developed PE (n = 40). Longitudinal samples were collected at each prenatal visit and scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma fetuin-A concentrations were determined by ELISA. Analysis was performed using mixed-effects models. Results: The profiles of maternal plasma concentrations of fetuin-A differ between PE and uncomplicated pregnancies. Forward analysis indicated that the rate of increase of plasma fetuin-A concentration in patients who subsequently developed PE was lower at the beginning of pregnancy (p =0.001), yet increased faster mid-pregnancy (p = 0.0017) and reached the same concentration level as controls by 26 weeks. The rate of decrease was higher towards the end of pregnancy in patients with PE than in uncomplicated pregnancies (p = 0.002). The mean maternal plasma fetuin-A concentration was significantly lower in patients with preterm PE at the time of clinical diagnosis than in women with uncomplicated pregnancies (p<0.05). In contrast, there were no significant differences in maternal plasma fetuin-A concentration in patients who developed PE at term. Conclusions: (1) The profile of maternal plasma concentrations of fetuin-A over time (GA) in patients who develop PE is different from that of normal pregnant women; (2) the rate of change of maternal plasma concentrations of fetuin-A is positive (increases over time) in the midtrimester of normal pregnancy, and negative (decreases over time) in patients who subsequently develop PE; (3) at the time of diagnosis, the maternal plasma fetuin-A concentration is lower in patients with preterm PE than in those with a normal pregnancy outcome; however, such differences were not demonstrable in patients with term PE. C1 [Chaemsaithong, Piya; Romero, Roberto; Tarca, Adi L.; Korzeniewski, Steven J.; Schwartz, Alyse G.; Miranda, Jezid; Ahmed, Ahmed I.; Dong, Zhong; Hassan, Sonia S.; Yeo, Lami; Tinnakorn, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Chaemsaithong, Piya; Romero, Roberto; Tarca, Adi L.; Korzeniewski, Steven J.; Schwartz, Alyse G.; Miranda, Jezid; Ahmed, Ahmed I.; Dong, Zhong; Hassan, Sonia S.; Yeo, Lami; Tinnakorn, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Chaemsaithong, Piya; Tarca, Adi L.; Korzeniewski, Steven J.; Schwartz, Alyse G.; Miranda, Jezid; Ahmed, Ahmed I.; Hassan, Sonia S.; Yeo, Lami; Tinnakorn, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov NR 202 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 11 BP 1260 EP 1269 DI 10.3109/14767058.2014.954242 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NA UT WOS:000360436500004 ER PT J AU Romero, R Miranda, J Chaiworapongsa, T Chaemsaithong, P Gotsch, F Dong, Z Ahmed, AI Yoon, BH Hassan, SS Kim, CJ Korzeniewski, SJ Yeo, L Kim, YM AF Romero, Roberto Miranda, Jezid Chaiworapongsa, Tinnakorn Chaemsaithong, Piya Gotsch, Francesca Dong, Zhong Ahmed, Ahmed I. Yoon, Bo Hyun Hassan, Sonia S. Kim, Chong J. Korzeniewski, Steven J. Yeo, Lami Kim, Yeon Mee TI Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry; cervical length; infection; pregnancy; prematurity; premature birth; preterm delivery; ureaplasma urealyticim ID PRETERM PREMATURE RUPTURE; POLYMERASE-CHAIN-REACTION; IONIZATION MASS-SPECTROMETRY; AMNIOTIC-FLUID INTERLEUKIN-6; TUMOR-NECROSIS-FACTOR; ANTENATAL MAGNESIUM-SULFATE; BLOOD-CELL COUNT; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; MONOCYTE CHEMOTACTIC PROTEIN-1; RANDOMIZED CONTROLLED-TRIAL AB Objective: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. Methods: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) <= 25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration >= 2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-elivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations. Results: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p<0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD534 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p<.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47-98) days, (p<.0001)]. Conclusion: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (534 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD. C1 [Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong J.; Korzeniewski, Steven J.; Yeo, Lami; Kim, Yeon Mee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res, Bethesda, MD USA. [Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong J.; Korzeniewski, Steven J.; Yeo, Lami; Kim, Yeon Mee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Korzeniewski, Steven J.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Gotsch, Francesca] Azienda Osped Univ, Integrata Verona, Ostetricia Ginecol, Verona, Italy. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Kim, Chong J.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. [Kim, Yeon Mee] Inje Univ, Haeundae Paik Hosp, Dept Pathol, Coll Med, Busan, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov; ykim.haeundae@gmail.com FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C] FX The authors report no conflicts of interest. This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 294 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 11 BP 1343 EP 1359 DI 10.3109/14767058.2014.954243 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NA UT WOS:000360436500017 ER PT J AU Kim, SM Romero, R Park, JW Oh, KJ Jun, JK Yoon, BH AF Kim, Sun Min Romero, Roberto Park, Jeong Woo Oh, Kyung Joon Jun, Jong Kwan Yoon, Bo Hyun TI The relationship between the intensity of intra-amniotic inflammation and the presence and severity of acute histologic chorioamnionitis in preterm gestation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniotic fluid; matrix metalloproteinase-8; preterm birth; prematurity ID AMNIOTIC-FLUID INTERLEUKIN-6; BLOOD-CELL COUNT; POLYMERASE-CHAIN-REACTION; UMBILICAL-CORD PLASMA; NECROSIS-FACTOR-ALPHA; BIRTH-WEIGHT INFANTS; C-REACTIVE PROTEIN; MONOCYTE CHEMOTACTIC PROTEIN-1; RAPID DIAGNOSTIC-TESTS; WHITE-MATTER LESIONS AB Objective: Acute histologic chorioamnionitis (HCA) is associated with an increased risk of perinatal mortality and morbidity. The purpose of this study was to determine the relationship between the intensity of intra-amniotic inflammation (IAI) and the severity of acute HCA in preterm gestation. Methods: The relationship between the intensity of IAI and the presence and severity of acute HCA was examined in 412 patients with singleton gestations who delivered within 120 h of transabdominal amniocentesis. The concentration of amniotic fluid (AF) matrix metalloproteinase (MMP)-8 was assayed to determine the presence and intensity of IAI. Acute HCA was defined as the presence of inflammatory change in any tissue samples according to the criteria previously reported. The total grade of acute HCA was used to determine the severity of HCA. Results: (1) Patients with IAI had a significantly higher rate of acute HCA than those without IAI [76.9% (133/173)] versus 20.9% (50/239), p<0.001]. The AF MMP-8 concentration was significantly higher in patients with acute HCA than in those without acute HCA (median [range]; 188.3 ng/ml [0.3-6142.6] versus 1.8 ng/ml [0.3-2845.5], p<0.001); (2) Of 183 patients with acute HCA, the AF MMP-8 concentration was positively correlated with the severity of acute HCA (p<0.001). Conclusions: AF MMP-8 concentration was not only a predictor of the presence of acute HCA, but its concentration also correlated with the severity of acute HCA. The higher the intensity of IAI, the worse the degree of acute HCA in preterm gestation. C1 [Kim, Sun Min; Park, Jeong Woo; Oh, Kyung Joon; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr OI Park, Jeong Woo/0000-0001-6499-0814 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS; Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI12C0768]; SNUH Research Fund [03-2009-0250] FX This study was supported, in part, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS, by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0768) and by grant #03-2009-0250 from the SNUH Research Fund. The authors report no conflicts of interest. NR 226 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 13 BP 1500 EP 1509 DI 10.3109/14767058.2014.961009 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NV UT WOS:000360438900002 PM 25184305 ER PT J AU Chaemsaithong, P Romero, R Korzeniewski, SJ Dong, Z Yeo, L Hassan, SS Kim, YM Yoon, BH Chaiworapongsa, T AF Chaemsaithong, Piya Romero, Roberto Korzeniewski, Steven J. Dong, Zhong Yeo, Lami Hassan, Sonia S. Kim, Yeon Mee Yoon, Bo Hyun Chaiworapongsa, Tinnakorn TI A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10 SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniocentesis; chronic chorioamnionitis; interferon-gamma - inducible protein 10 (IP-10); intra-amniotic inflammation/infection; lateral flow-based immunoassay; MIAC; prematurity; sterile inflammation ID PRETERM PREMATURE RUPTURE; BLOOD-CELL COUNT; TUMOR-NECROSIS-FACTOR; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; SYSTEMIC INFLAMMATORY RESPONSE; MATERNAL ANTIFETAL REJECTION; POLYMERASE-CHAIN-REACTION; RAPID DIAGNOSTIC-TESTS; INTRAAMNIOTIC INFECTION; MICROBIAL INVASION AB Objective: Intra-amniotic inflammation is a mechanism of disease implicated in preterm labor, preterm prelabor rupture of membrane, cervical insufficiency, a short cervix, and idiopathic vaginal bleeding. Determination of interleukin (IL)-6 with immunoassays has been proven for more than two decades to be an excellent method for the detection of intra-amniotic inflammation. However, assessment of IL-6 for this indication has been based on immunoassays which are not clinically available, and this has been an obstacle for the implementation of this test in clinical practice. It is now possible to obtain results within 20 min with a point of care (POC) test which requires minimal laboratory support. This test is based on lateral flow-based immunoassay. The objective of this study was to compare amniotic fluid (AF) IL-6 and interferon- gamma - inducible protein 10 (IP-10 or CXCL-10) concentrations determined using lateral flow-based immunoassay or POC test and standard enzyme-linked immunosorbent assay (ELISA) techniques. Material and methods: AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n = 20). AF IL-6 and IP-10 concentrations were determined by lateral flow-based immunoassay and ELISA. Intra-amniotic inflammation was defined as AF IL-6 >= 2.6 ng/ml. AF IL-6 and IP-10 concentrations between two assays were compared. Results: (1) Lateral flow-based immunoassay POC AF IL-6 and IP-10 test results were strongly correlated with concentrations of this cytokine/chemokine determined by ELISA (Spearman's rho = 0.92 and 0.83, respectively, both p<0.0001); (2) AF IL-6 concentrations determined by the lateral flow-based immunoassay test were, on average, 30% lower than those determined by ELISA, and the median difference was statistically significant (p<0.0001); and (3) in contrast, AF IP-10 concentrations determined by the lateral flow-based immunoassay test were, on average, only 7% lower than those determined by ELISA, and the median difference was not statistically significant (p = 0.81). Conclusion: AF IL-6 and IP-10 concentrations determined using a lateral flow-based immunoassay POC are strongly correlated with concentrations determined by conventional ELISA. This justifies further studies about the diagnostic indices and predictive values of this POC test. C1 [Chaemsaithong, Piya; Romero, Roberto; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Kim, Yeon Mee; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Program Perinatal Res & Obstet,Perintol Res Branc, Bethesda, MD 20892 USA. [Chaemsaithong, Piya; Romero, Roberto; Korzeniewski, Steven J.; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Kim, Yeon Mee] Inje Univ, Coll Med, Haeundae Paik Hosp, Dept Pathol, Seoul, South Korea. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet,Div Intramural Res, DHHS,Perinatol Res Branch,Hutzel Womens Hosp,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. Authors declare no conflict of interest. NR 177 TC 8 Z9 8 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 13 BP 1510 EP 1519 DI 10.3109/14767058.2014.961417 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NV UT WOS:000360438900003 PM 25182862 ER PT J AU Kim, YM Chaemsaithong, P Romero, R Shaman, M Kim, CJ Kim, JS Qureshi, F Jacques, SM Ahmed, AI Chaiworapongsa, T Hassan, SS Yeo, L Korzeniewski, SJ AF Kim, Yeon Mee Chaemsaithong, Piya Romero, Roberto Shaman, Majid Kim, Chong Jai Kim, Jung-Sun Qureshi, Faisal Jacques, Suzanne M. Ahmed, Ahmed I. Chaiworapongsa, Tinnakorn Hassan, Sonia S. Yeo, Lami Korzeniewski, Steven J. TI Placental lesions associated with acute atherosis SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniotic fluid infection; chronic chorioamnionitis; chronic villitis; fetal vascular thrombo-occlusive disease; ischemic placental disease; maternal anti-fetal rejection; maternal underperfusion; pregnancy ID MATERNAL FLOOR INFARCTION; FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH-RETARDATION; PERIVILLOUS FIBRIN DEPOSITION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SPONTANEOUS PRETERM LABOR; LATE-ONSET PREECLAMPSIA; FETAL THROMBOTIC VASCULOPATHY; MOLECULAR-WEIGHT HEPARIN; FACTOR PATHWAY INHIBITOR AB Objective: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion (MVU), amniotic fluid infection (AFI), fetal vascular thrombo-occlusive disease (FVTOD) or chronic inflammation. Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted examine 16 457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis. Results: Among 16 457 women who were enrolled, 10.2% (1671/16 457) were excluded, leaving 14 786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14 786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio - aOR: 6.7; 95% CI 5.2-8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with FVTOD (aOR 1.7; 95% CI 1.2-2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3-3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with AFI, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3-0.5). Conclusions: Acute atherosis is associated with increased risks of having placental lesions consistent with MVU, and to a lesser extent, chronic chorioamnionitis and those consistent with FVTOD. C1 [Kim, Yeon Mee] Inje Univ, Coll Med, Haeundae Paik Hosp, Dept Pathol, Busan, South Korea. [Chaemsaithong, Piya; Romero, Roberto; Shaman, Majid; Kim, Chong Jai; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M.; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet, Div Intramural Res,Perinatol Res Branch, Bethesda, MD 20892 USA. [Chaemsaithong, Piya; Romero, Roberto; Shaman, Majid; Kim, Chong Jai; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M.; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet, Div Intramural Res,Perinatol Res Branch, Detroit, MI USA. [Chaemsaithong, Piya; Shaman, Majid; Ahmed, Ahmed I.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Korzeniewski, Steven J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Kim, Chong Jai] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea. [Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Qureshi, Faisal; Jacques, Suzanne M.] Harper Univ Hosp, Dept Pathol, Detroit, MI USA. [Qureshi, Faisal; Jacques, Suzanne M.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM ykim.haeundae@gmail.com; romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. The authors declare no declaration of interest. NR 183 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 13 BP 1554 EP 1562 DI 10.3109/14767058.2014.960835 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2NV UT WOS:000360438900010 PM 25183023 ER PT J AU Adekola, H Romero, R Chaemsaithong, P Korzeniewski, SJ Dong, Z Yeo, L Hassan, SS Chaiworapongsa, T AF Adekola, Henry Romero, Roberto Chaemsaithong, Piya Korzeniewski, Steven J. Dong, Zhong Yeo, Lami Hassan, Sonia S. Chaiworapongsa, Tinnakorn TI Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Endothelial cell activation; endothelial dysfunction; fetal death; preterm labor; small-for-gestational age; soluble endoglin; soluble vascular endothelial growth factor receptor-1 ID NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; INTERCELLULAR-ADHESION MOLECULE-1; INTRAUTERINE GROWTH-RETARDATION; NECROSIS-FACTOR-ALPHA; VON-WILLEBRAND-FACTOR; SYSTEMIC INFLAMMATORY RESPONSE; PREGNANCY-INDUCED HYPERTENSION; INCREASED MATERNAL SERUM; ANTI-ANGIOGENIC FACTORS AB Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0.1), abnormal uterine artery Doppler velocimetry (p = 0.7) or whether diagnosis was made before or after 34 weeks gestational age (p = 0.3); (3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [sVEGFR-1: Spearman rho 0.34, p = 0.001 and sEng: Spearman rho 0.30, p = 0.003]; (4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p = 0.004), as well as uncomplicated pregnancies (p = 0.001); and (5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the "great obstetrical syndromes"; each p > 0.05). Conclusion: Median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction. C1 [Adekola, Henry; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Adekola, Henry; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Adekola, Henry; Chaemsaithong, Piya; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C] FX The authors declare no conflicts of interest. This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 251 TC 2 Z9 2 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2015 VL 28 IS 14 BP 1621 EP 1632 DI 10.3109/14767058.2014.964676 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ2OA UT WOS:000360439400001 PM 25211383 ER PT J AU Benninger, DH Hallett, M AF Benninger, David H. Hallett, Mark TI Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015 SO NEUROREHABILITATION LA English DT Review DE Non-invasive brain stimulation; therapeutic study; Parkinson's disease; repetitive transcranial magnetic stimulation (rTMS); transcranial Direct Current Stimulation (tDCS); plasticity; neurophysiology ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; LEVODOPA-INDUCED DYSKINESIAS; THETA-BURST STIMULATION; CEREBRAL-BLOOD-FLOW; SUBTHALAMIC NUCLEUS STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; HIGH-FREQUENCY STIMULATION; THALAMIC-STIMULATION; CORTICAL STIMULATION AB BACKGROUND AND PURPOSE: In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. CONCLUSION: Most trials of non-invasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. Published studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS, including increasing stimulation intensity and novel stimulation parameters, derive their rationale from studies of brain physiology. These novel parameters simulate normal firing patterns or act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control. There may also be diagnostic potential of TMS in characterizing individual traits for personalized medicine. C1 [Benninger, David H.] CHU Vaudois, Serv Neurol, Dept Neurosci Clin, CH-1011 Lausanne, Switzerland. [Hallett, Mark] NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Benninger, DH (reprint author), CHU Vaudois, Serv Neurol, Dept Neurosci Clin, Rue Bugnon 46, CH-1011 Lausanne, Switzerland. EM David.Benninger@chuv.ch RI Benninger, David/A-8157-2015 OI Benninger, David/0000-0002-1049-9533 FU Swiss Parkinson Association; Baasch-Medicus Award; NINDS Intramural Program FX Dr. Benninger is supported by funding from the Swiss Parkinson Association and the Baasch-Medicus Award. Dr. Hallett is supported by the NINDS Intramural Program. This paper is similar to, and updated from, a recent book chapter (Benninger, 2013). NR 133 TC 4 Z9 4 U1 5 U2 19 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2015 VL 37 IS 1 BP 11 EP 24 DI 10.3233/NRE-151237 PG 14 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CQ2ET UT WOS:000360412900003 PM 26409690 ER PT J AU Haymaker, CL Wu, RC Ritthipichai, K Bernatchez, C Forget, MA Chen, JQ Liu, H Wang, E Marincola, F Hwu, P Radvanyi, LG AF Haymaker, Cara L. Wu, Richard C. Ritthipichai, Krit Bernatchez, Chantale Forget, Marie-Andree Chen, Jie Qing Liu, Hui Wang, Ena Marincola, Francesco Hwu, Patrick Radvanyi, Laszlo G. TI BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties SO ONCOIMMUNOLOGY LA English DT Article DE B- and T-lymphocyte attenuator; CD8(+) effector-memory; melanoma; T cell survival/persistence; tumor-infiltrating lymphocytes ID CD8(+) T-CELLS; CHRONIC VIRAL-INFECTION; METASTATIC MELANOMA; INHIBITORY RECEPTORS; MOLECULAR SIGNATURE; CENTRAL MEMORY; NK CELLS; ACTIVATION; THERAPY; EXHAUSTION AB In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8(+) T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8(+)BTLA(+) TIL subset and their CD8(+)BTLA(-) counterparts. We found that the CD8(+) BTLA(+) TILs had an increased response to IL-2, were less-differentiated effector-memory (T-EM) cells, and persisted longer in vivo after infusion. In contrast, CD8(+)BTLA(-) TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8(+)BTLA(+) TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8(+) T cells. These attributes may explain our previous observation that BTLA expression on CD8(+) TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma. C1 [Haymaker, Cara L.; Wu, Richard C.; Ritthipichai, Krit; Bernatchez, Chantale; Forget, Marie-Andree; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo G.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Wu, Richard C.] Univ Texas Med Sch Houston, MD PhD Program, Houston, TX USA. [Wu, Richard C.; Ritthipichai, Krit] Univ Texas Grad Sch Biomed Sci, Grad Program Immunol, Houston, TX USA. [Wu, Richard C.; Bernatchez, Chantale] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo G.] Lion Biotechnol, Tampa, FL USA. [Liu, Hui; Wang, Ena] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Liu, Hui; Wang, Ena] NIH, TransNIH Ctr Human Immunol, Bethesda, MD 20892 USA. [Wang, Ena] Sidra Med Res Hosp, Doha, Qatar. [Marincola, Francesco] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Marincola, Francesco; Radvanyi, Laszlo G.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Immunol, Tampa, FL 33682 USA. RP Radvanyi, LG (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. EM laszlo.radvanyi@lionbio.com FU National Cancer Institute (NCI) [R01-CA111999, 1R21CA178580-01]; University of Texas M.D. Anderson Cancer Center Support Grant [P30-CA16672]; National Center for Research Resources [TL1RR024147]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Mulva Foundation; National Institutes of Health [5T32CA009598-22]; Melanoma SPORE Development Grant [P50-CA093459-05-DRP21]; Melanoma Research Alliance (MRA) FX This work was supported by the National Cancer Institute (NCI) grants R01-CA111999 to PH and LR and 1R21CA178580-01 to LR; by the University of Texas M.D. Anderson Cancer Center Support Grant (P30-CA16672) to the Flow Cytometry Core Facility; Award No. TL1RR024147 from the National Center for Research Resources to RCW; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF), and the Mulva Foundation. CLH was supported by the National Institutes of Health training grant 5T32CA009598-22. This work was also supported by a Melanoma SPORE Development Grant (P50-CA093459-05-DRP21) and a Team Science Award from the Melanoma Research Alliance (MRA) to LR. NR 47 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 8 AR e1014246 DI 10.1080/2162402X.2015.1014246 PG 15 WC Oncology; Immunology SC Oncology; Immunology GA CP9UD UT WOS:000360239300004 PM 26405566 ER PT J AU Ji, Y Gattinoni, L AF Ji, Yun Gattinoni, Luca TI miR-155 releases the brakes on antitumor T cells SO ONCOIMMUNOLOGY LA English DT Editorial Material DE adoptive immunotherapy; homeostatic gamma(C) cytokines; lymphodepletion; miR-155; Ptpn2; SHIP-1; SOCS-1 ID ADOPTIVE IMMUNOTHERAPY; LYMPHODEPLETION; CANCER; HOSTS AB Homeostatic gamma(C) cytokines are essential to support the expansion and function of tumor-specific T cells, but their effects are constrained by suppressor of cytokine signaling (SOCS) proteins as well as phosphoinositide and tyrosine-specific phosphatases. The microRNA miR-155 counteracts these inhibitory hurdles to potentiate intracellular cytokine signaling and T cell antitumor immunity. C1 [Ji, Yun; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ji, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jiyun@mail.nih.gov; gattinol@mail.nih.gov RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009 OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009 NR 10 TC 0 Z9 0 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 8 AR e1026533 DI 10.1080/2162402X.2015.1026533 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA CP9UD UT WOS:000360239300024 ER PT J AU Lake, JE Vo, QT Jacobson, LP Sacktor, N Miller, EN Post, WS Becker, JT Palella, FJ Ragin, A Martin, E Munro, CA Brown, TT AF Lake, Jordan E. Vo, Quynh T. Jacobson, Lisa P. Sacktor, Ned Miller, Eric N. Post, Wendy S. Becker, James T. Palella, Frank J., Jr. Ragin, Ann Martin, Eileen Munro, Cynthia A. Brown, Todd T. TI Adiponectin and interleukin-6, but not adipose tissue, are associated with worse neurocognitive function in HIV-infected men SO ANTIVIRAL THERAPY LA English DT Article ID MULTICENTER AIDS COHORT; MOLECULAR-WEIGHT ADIPONECTIN; VASCULAR ENDOTHELIAL-CELLS; KAPPA-B ACTIVATION; CARDIOVASCULAR-DISEASE; ANTIRETROVIRAL THERAPY; COGNITIVE DECLINE; INSULIN-RESISTANCE; LIPOPROTEIN LEVELS; RISK-FACTORS AB Background: Generalized obesity has been associated with cognitive decline, a process potentially mediated by adipocytokines. The effects of regional adipose tissue (AT) on cognition, however, are not well understood. We explored cross-sectional relationships between regional AT, adipocytokines, inflammatory markers and neuropsychological (NP) test scores among HIV+ and HIV-men enrolled in the Multicenter AIDS Cohort Study. Methods: Visceral, subcutaneous abdominal and subcutaneous thigh AT areas were quantified by computed tomography (CT). NP tests (Trail Making Test parts A and B, and Symbol-Digit Modalities) obtained within 2 years of CT screened for psychomotor speed and executive function. Adiponectin, leptin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were measured. Results: Of 509 HIV+ and 271 HIV-participants, HIV+ men (98% on antiretroviral therapy, 81% HIV-1 RNA< 50 copies/ml) had lower median subcutaneous AT and adiponectin levels and higher hs-CRP levels, but visceral AT, body mass index, IL-6 and NP scores did not vary by HIV serostatus. In multivariable analysis, older age, <= high school education and African American race, but not AT area or site, were associated with worse NP test scores among all participants. In HIV+ only, higher adiponectin and IL-6 were associated with worse cognitive function independent of AT area. No HIV-specific factors were associated with NP test scores. Conclusions: Demographic factors were associated with NP test performance, but regional adiposity was not. In HIV+ only, higher adiponectin and IL-6 were associated with worse NP test scores, supporting a role for chronic inflammation and adipocytokine imbalance in neurocognitive decline in HIV+ persons. C1 [Lake, Jordan E.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Vo, Quynh T.] NIAID, Epidemiol Branch, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20892 USA. [Jacobson, Lisa P.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Sacktor, Ned] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Miller, Eric N.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Post, Wendy S.; Brown, Todd T.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Becker, James T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Becker, James T.] Univ Pittsburgh, Dept Neurol & Psychol, Pittsburgh, PA USA. [Palella, Frank J., Jr.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Ragin, Ann] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Martin, Eileen] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Munro, Cynthia A.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Munro, Cynthia A.] Johns Hopkins Univ, Dept Behav Sci & Neurol, Baltimore, MD USA. RP Lake, JE (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. EM jlake@mednet.ucla.edu OI Miller, Eric/0000-0002-0650-714X FU National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); National Institute on Deafness and Communication Disorders (NIDCD); JHU CTSA [UL1-TR000424]; National Institutes of Health [U01 Al035040, R01 HL095129, UL1TR000124, P30 AG028748, K23 AI110532-01A1]; US Department of Health and Human Services [HHSN272200800014C] FX Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centres at Baltimore (U01-AI35042): The Johns Hopkins University Bloomberg School of Public Health: Joseph B Margolick (PI), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Cynthia Munro, Michael W Plankey, Ned Sacktor, James Shepard, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M Wolinsky (PI), John P Phair, Sheila Badri, Maurice O'Gorman, David Ostrow, Frank Palella, Ann Ragin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels PI), Otoniel Martinez-Maza (Co-P I), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, Beth Jamieson, Eric N Miller, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R Rinaldo (PI), Lawrence A Kingsley (Co-PI), James T Becker, Ross D Cranston, Jeremy J Martinson, John W Mellors, Anthony J Silvestre, Ronald D Stall; and the Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P Jacobson (PI), Alvaro Munoz (Co-PI), Alison Abraham, Keri Althoff, Christopher Cox, Jennifer Deal, Gypsyamber D'Souza, Priya Duggal, Janet Schollenberger, Eric C Seaberg, Sol Su, Pamela Surkan. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR000424 (JHU CTSA). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).; The authors would also like to acknowledge the study participants for their generous participation, the staff at the University of Vermont Laboratory for Clinical Biochemistry Research for their assistance with biomarker measurement, and Matthew Budoff at LA BioMed (Harbor-University of California, Los Angeles, Torrance, CA, USA) for CT scan interpretation. Additional research support was provided by the National Institutes of Health grants U01 Al035040, R01 HL095129, UL1TR000124, P30 AG028748 and K23 AI110532-01A1 and the US Department of Health and Human Services contract number HHSN272200800014C. NR 46 TC 3 Z9 3 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2015 VL 20 IS 2 BP 235 EP 244 DI 10.3851/IMP2952 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CP5GL UT WOS:000359909200015 PM 25810377 ER PT J AU Horai, R Chong, WP Zhou, R Chen, J Silver, PB Agarwal, RK Caspi, RR AF Horai, R. Chong, W. P. Zhou, R. Chen, J. Silver, P. B. Agarwal, R. K. Caspi, R. R. TI Spontaneous Ocular Autoimmunity in Mice Expressing a Transgenic T Cell Receptor Specific to Retina: A Tool to Dissect Mechanisms of Uveitis SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Autoimmunity; uveitis; EAU; animal model; Th1; Th17 ID IMMUNE PRIVILEGE; DISEASE; AUTOANTIGEN; TH17; EYE AB The "classical" EAU model induced by immunization of mice with the retinal protein IRBP or its peptides has been very useful to study basic mechanisms of ocular inflammation, but is inadequate for some types of studies due to the need for active immunization in the context of strong bacterial adjuvants. We generated transgenic (Tg) mice on the B10. RIII background that express a T cell receptor (TCR) specific for IRBP161-180. Three strains of TCR Tg mice were established. Spontaneous uveitis developed in two of the three strains by 2-3 months of age. Susceptibility correlated with a higher copy number of the transgenic TCR and a higher proportion of TCR Tg T cells in the peripheral repertoire. Even in mice with uveitis, peripheral IRBP-specific CD4(+) T cells displayed mostly a naive phenotype. In contrast, T cells infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T regulatory cells. These mice thus provide a new and distinct model of uveitis from the "classical" EAU, and may represent some types of uveitis more faithfully. Importantly, this new transgenic model of uveitis can serve as a template for therapeutic manipulations, and as a source of naive retina-specific T cells for a variety of basic and pre-clinical studies. Several examples of such studies will be discussed. C1 [Horai, R.; Chong, W. P.; Zhou, R.; Chen, J.; Silver, P. B.; Agarwal, R. K.; Caspi, R. R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU NIH/NEI [EY000184] FX The authors thank the NEI Genetic Engineering Core for assistance in generating the R161 TCR mouse strains. This study was supported by NIH/NEI Intramural funding, Project # EY000184. NR 15 TC 1 Z9 1 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 6 BP 511 EP 516 DI 10.2174/1566524015666150731095201 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CP6HM UT WOS:000359986900003 PM 26238373 ER PT J AU Egwuagu, CE Sun, L Kim, SH Dambuza, IM AF Egwuagu, C. E. Sun, L. Kim, S. -H. Dambuza, I. M. TI Ocular Inflammatory Diseases: Molecular Pathogenesis and Immunotherapy SO CURRENT MOLECULAR MEDICINE LA English DT Article DE B cell therapy; IL-12 cytokines; IL-35-expressing Breg cell (i35-Breg); interleukin 35 (IL-35); regulatory B cells (Breg); therapeutic cytokines; uveitis ID RETINOID-BINDING PROTEIN; EXPERIMENTAL AUTOIMMUNE UVEITIS; ENDOTOXIN-INDUCED UVEITIS; S-ANTIGEN; T-CELLS; THYMIC EXPRESSION; COSTIMULATORY MOLECULES; PREVENTS DEVELOPMENT; NEGATIVE REGULATION; CENTRAL TOLERANCE AB Uveitis is a diverse group of potentially sight-threatening intraocular inflammatory diseases of infectious or autoimmune etiology and accounts for more than 10% of severe visual handicaps in the United States. Pathology derives from the presence of inflammatory cells in the optical axis and sustained production of cytotoxic cytokines and other immune-regulatory proteins in the eye. The main therapeutic goals are to down-regulate the immune response, preserve the integrity of the ocular architecture and eventually eliminate the inciting uveitogenic stimuli. Current therapy is based on topical or systemic corticosteroid with or without second line agents and serious adverse effects of these drugs are the impetus for development of less toxic and more specific therapies for uveitis. This review summarizes the pathophysiology of uveitis, molecular mechanisms that regulate the initiation and progression of uveitis and concludes with emerging strategies for the treatment of this group of potentially blinding diseases. C1 [Egwuagu, C. E.; Sun, L.; Kim, S. -H.; Dambuza, I. M.] NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, NIH, Bldg 10,Room 10N109A,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov RI Sun, Lin/I-3146-2016 NR 69 TC 2 Z9 2 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 6 BP 517 EP 528 DI 10.2174/1566524015666150731095426 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CP6HM UT WOS:000359986900004 PM 26238372 ER PT J AU Chen, J Qian, H Horai, R Chan, CC Caspi, RR AF Chen, J. Qian, H. Horai, R. Chan, C. -C. Caspi, R. R. TI Mouse Models of Experimental Autoimmune Uveitis: Comparative Analysis of Adjuvant-Induced vs Spontaneous Models of Uveitis SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Electroretinography; experimental autoimmune uveitis; histology; mice; optical coherence tomography; uveitis ID UVEORETINITIS; MICE AB Mouse models of experimental autoimmune uveitis (EAU) mimic unique features of human uveitis, and serve as a template for preclinical study. The "classical" EAU model is induced by active immunization of mice with the retinal protein IRBP in adjuvant, and has proved to be a useful tool to study basic mechanisms and novel therapy in human uveitis. Several spontaneous models of uveitis induced by autoreactive T cells targeting on IRBP have been recently developed in IRBP specific TCR transgenic mice (R161H) and in AIRE(-/-) mice. The "classical" immunization-induced EAU exhibits acute ocular inflammation with two distinct patterns: (i) severe monophasic form with extensive destruction of the retina and rapid loss of visual function, and (ii) lower grade form with an acute onset followed by a prolonged chronic phase of disease. The spontaneous models of uveitis in R161H and AIRE(-/-) mice have a gradual onset and develop chronic ocular inflammation that ultimately leads to retinal degeneration, along with a progressive decline of visual signal. The adjuvant-dependent model and adjuvant-free spontaneous models represent distinct aspects and/or various forms of human uveitis. This review will discuss and compare clinical manifestations, pathology as well as visual function of the retina in the different models of uveitis, as measured by fundus imaging and histology, optical coherence tomography (OCT) and electroretinography (ERG). C1 [Chen, J.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. [Chen, J.; Horai, R.; Chan, C. -C.; Caspi, R. R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Qian, H.] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. RP Chen, J (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. EM chenjun35@mail.sysu.edu.cn OI Caspi, Rachel/0000-0002-7140-7671 FU NIH/NEI [EY000184] FX The authors thank the NEI Histology Core Facility for assistance in preparing the histology slides, and the NEI Vision Function Core Facility and the Biological Imaging Care Facility for assistance in providing excellent technical support. The study was supported by NIH/NEI Intramural funding, project # EY000184. NR 16 TC 3 Z9 3 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 6 BP 550 EP 557 DI 10.2174/1566524015666150731100318 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CP6HM UT WOS:000359986900007 PM 26238369 ER PT J AU Schmid, M Smith, J Burt, DW Aken, BL Antin, PB Archibald, AL Ashwell, C Blackshear, PJ Boschiero, C Brown, CT Burgess, SC Cheng, HH Chow, W Coble, DJ Cooksey, A Crooijmans, RPMA Damas, J Davis, RVN de Koning, DJ Delany, ME Derrien, T Desta, TT Dunn, IC Dunn, M Ellegren, H Eory, L Erb, I Farre, M Fasold, M Fleming, D Flicek, P Fowler, KE Fresard, L Froman, DP Garceau, V Gardner, PP Gheyas, AA Griffin, DK Groenen, MAM Haaf, T Hanotte, O Hart, A Hasler, J Hedges, SB Hertel, J Howe, K Hubbard, A Hume, DA Kaiser, P Kedra, D Kemp, SJ Klopp, C Kniel, KE Kuo, R Lagarrigue, S Lamont, SJ Larkin, DM Lawal, RA Markland, SM McCarthy, F McCormack, HA McPherson, MC Motegi, A Muljo, SA Munsterberg, A Nag, R Nanda, I Neuberger, M Nitsche, A Notredame, C Noyes, H O'Connor, R O'Hare, EA Oler, AJ Ommeh, SC Pais, H Persia, M Pitel, F Preeyanon, L Barja, PP Pritchett, EM Rhoads, DD Robinson, CM Romanov, MN Rothschild, M Roux, PF Schmidt, CJ Schneider, AS Schwartz, MG Searle, SM Skinner, MA Smith, CA Stadler, PF Steeves, TE Steinlein, C Sun, L Takata, M Ulitsky, I Wang, Q Wang, Y Warren, WC Wood, JMD Wragg, D Zhou, HJ AF Schmid, Michael Smith, Jacqueline Burt, David W. Aken, Bronwen L. Antin, Parker B. Archibald, Alan L. Ashwell, Chris Blackshear, Perry J. Boschiero, Clarissa Brown, C. Titus Burgess, Shane C. Cheng, Hans H. Chow, William Coble, Derrick J. Cooksey, Amanda Crooijmans, Richard P. M. A. Damas, Joana Davis, Richard V. N. de Koning, Dirk-Jan Delany, Mary E. Derrien, Thomas Desta, Takele T. Dunn, Ian C. Dunn, Matthew Ellegren, Hans Eoery, Lel Erb, Ionas Farre, Marta Fasold, Mario Fleming, Damarius Flicek, Paul Fowler, Katie E. Fresard, Laure Froman, David P. Garceau, Valerie Gardner, Paul P. Gheyas, Almas A. Griffin, Darren K. Groenen, Martien A. M. Haaf, Thomas Hanotte, Olivier Hart, Alan Haesler, Julien Hedges, S. Blair Hertel, Jana Howe, Kerstin Hubbard, Allen Hume, David A. Kaiser, Pete Kedra, Darek Kemp, Stephen J. Klopp, Christophe Kniel, Kalmia E. Kuo, Richard Lagarrigue, Sandrine Lamont, Susan J. Larkin, Denis M. Lawal, Raman A. Markland, Sarah M. McCarthy, Fiona McCormack, Heather A. McPherson, Marla C. Motegi, Akira Muljo, Stefan A. Muensterberg, Andrea Nag, Rishi Nanda, Indrajit Neuberger, Michael Nitsche, Anne Notredame, Cedric Noyes, Harry O'Connor, Rebecca O'Hare, Elizabeth A. Oler, Andrew J. Ommeh, Sheila C. Pais, Helio Persia, Michael Pitel, Frederique Preeyanon, Likit Barja, Pablo Prieto Pritchett, Elizabeth M. Rhoads, Douglas D. Robinson, Charmaine M. Romanov, Michael N. Rothschild, Max Roux, Pierre-Francois Schmidt, Carl J. Schneider, Alisa-Sophia Schwartz, Matthew G. Searle, Steve M. Skinner, Michael A. Smith, Craig A. Stadler, Peter F. Steeves, Tammy E. Steinlein, Claus Sun, Liang Takata, Minoru Ulitsky, Igor Wang, Qing Wang, Ying Warren, Wesley C. Wood, Jonathan M. D. Wragg, David Zhou, Huaijun TI Third Report on Chicken Genes and Chromosomes 2015 SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID MAREKS-DISEASE VIRUS; GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; BACTERIAL ARTIFICIAL CHROMOSOME; INDUCED CYTIDINE DEAMINASE; AVIAN SEX-CHROMOSOMES; STRAND BREAK REPAIR; SINGLE-NUCLEOTIDE POLYMORPHISMS; MITOCHONDRIAL RIBOSOMAL GENES; HUMAN METAPHASE CHROMOSOMES C1 [Schmid, Michael; Haaf, Thomas; Hart, Alan; Nanda, Indrajit; Schneider, Alisa-Sophia; Steinlein, Claus] Univ Wurzburg, Dept Human Genet, DE-97074 Wurzburg, Germany. [Fasold, Mario; Hertel, Jana; Nitsche, Anne; Stadler, Peter F.] Univ Leipzig, Bioinformat Grp, Dept Comp Sci, D-04109 Leipzig, Germany. [Fasold, Mario; Hertel, Jana; Nitsche, Anne; Stadler, Peter F.] Univ Leipzig, Interdisciplinary Ctr Bioinformat, D-04109 Leipzig, Germany. [Smith, Jacqueline; Burt, David W.; Archibald, Alan L.; Dunn, Ian C.; Eoery, Lel; Garceau, Valerie; Gheyas, Almas A.; Hart, Alan; Hume, David A.; Kuo, Richard; McCormack, Heather A.] Univ Edinburgh, Roslin Inst, Div Genet & Gen, Edinburgh EH25 9RG, Midlothian, Scotland. [Smith, Jacqueline; Burt, David W.; Archibald, Alan L.; Dunn, Ian C.; Eoery, Lel; Garceau, Valerie; Gheyas, Almas A.; Hart, Alan; Hume, David A.; Kuo, Richard; McCormack, Heather A.] Univ Edinburgh, Roslin Inst, RDSVS, Edinburgh EH25 9RG, Midlothian, Scotland. [Kaiser, Pete] Univ Edinburgh, Roslin Inst, Div Infect & Immun, Edinburgh EH25 9RG, Midlothian, Scotland. [Aken, Bronwen L.; Flicek, Paul; Nag, Rishi] EMBL, European Bioinformat Inst, Hinxton, England. [Chow, William; Dunn, Matthew; Howe, Kerstin; Searle, Steve M.; Wood, Jonathan M. D.] Wellcome Trust Sanger Inst, Hinxton, England. [Haesler, Julien; Neuberger, Michael] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. [Damas, Joana; Farre, Marta; Larkin, Denis M.] Univ London, Royal Vet Coll, Dept Comparat Biomed Sci, London, England. [Skinner, Michael A.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Virol Sect, London, England. [Desta, Takele T.; Hanotte, Olivier; Lawal, Raman A.] Univ Nottingham, Sch Life Sci, Nottingham NG7 2RD, England. [Fowler, Katie E.] Canterbury Christ Church Univ, Sch Human & Life Sci, Canterbury, Kent, England. [Griffin, Darren K.; O'Connor, Rebecca; Romanov, Michael N.] Univ Kent, Sch Biosci, Canterbury, Kent, England. [Hart, Alan] Univ Sheffield, Royal Hallamshire Hosp, Biol Serv, Sheffield S10 2JF, S Yorkshire, England. [Kemp, Stephen J.; Noyes, Harry] Univ Liverpool, Inst Integrat Biol, Liverpool L69 3BX, Merseyside, England. [Muensterberg, Andrea] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. [Pais, Helio] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. [Crooijmans, Richard P. M. A.; Groenen, Martien A. M.] Wageningen Univ, Anim Breeding & Genom Ctr, NL-6700 AP Wageningen, Netherlands. [de Koning, Dirk-Jan] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden. [Ellegren, Hans] Uppsala Univ, Evolutionary Biol Ctr, Dept Evolutionary Biol, Uppsala, Sweden. [Derrien, Thomas] Univ Rennes 1, Inst Genet & Dev Rennes, Rennes, France. [Lagarrigue, Sandrine; Roux, Pierre-Francois] INRA, PEGASE, Equipe Genet & Genom, F-35042 Rennes, France. [Fresard, Laure; Pitel, Frederique; Wragg, David] INRA, GenPhySE, F-31326 Castanet Tolosan, France. [Klopp, Christophe] INRA, Biometrie & Intelligence Artificielle, Plateforme Bioinformat Toulouse Midi Pyrenees, F-31326 Castanet Tolosan, France. [Erb, Ionas; Kedra, Darek; Notredame, Cedric; Barja, Pablo Prieto] Ctr Genom Regulat, Comparat Bioinformat Grp, Bioinformat & Genom Programme, Barcelona, Spain. [Ulitsky, Igor] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. [Antin, Parker B.] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA. [Burgess, Shane C.; Warren, Wesley C.] Univ Arizona, Coll Agr & Life Sci, Tucson, AZ USA. [Cooksey, Amanda; McCarthy, Fiona] Univ Arizona, Dept Vet Sci & Microbiol, Tucson, AZ USA. [Ashwell, Chris] N Carolina State Univ, Dept Poultry Sci, Raleigh, NC 27695 USA. [Blackshear, Perry J.] Duke Univ, Dept Biochem, Sch Med, NIEHS, Durham, NC USA. [Brown, C. Titus; Preeyanon, Likit] Michigan State Univ, Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Brown, C. Titus] Michigan State Univ, Comp Sci & Engn, E Lansing, MI 48824 USA. [Cheng, Hans H.] ARS, Avian Dis & Oncol Lab, USDA, E Lansing, MI USA. [Davis, Richard V. N.] Univ Delaware, Dept Biol, Newark, DE USA. [Hubbard, Allen; Kniel, Kalmia E.; Markland, Sarah M.; Pritchett, Elizabeth M.; Schmidt, Carl J.; Sun, Liang; Wang, Qing] Univ Delaware, Dept Anim & Food Sci, Newark, DE USA. [Delany, Mary E.; McPherson, Marla C.; Wang, Ying; Zhou, Huaijun] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. [Robinson, Charmaine M.] Calif State Univ Monterey Bay, Div Sci & Environm Policy, Seaside, CA USA. [Froman, David P.] Oregon State Univ, Dept Anim & Rangeland Sci, Corvallis, OR 97331 USA. [Hedges, S. Blair] Temple Univ, Ctr Biodivers, Philadelphia, PA 19122 USA. [Coble, Derrick J.; Fleming, Damarius; Lamont, Susan J.; Rothschild, Max] Iowa State Univ, Dept Anim Sci, Ames, IA USA. [Muljo, Stefan A.] NIAID, NIH, Bethesda, MD 20892 USA. [Oler, Andrew J.] Med Sci & Comp Inc, Computat Biol Sect, Bethesda, MD USA. [O'Hare, Elizabeth A.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Persia, Michael] Virginia Tech Univ, Dept Anim & Poultry Sci, Blacksburg, VA USA. [Rhoads, Douglas D.] Univ Arkansas, Dept Biol Sci, Sci & Engn, Fayetteville, AR 72701 USA. [Schwartz, Matthew G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Washington Univ, Sch Med, Genome Inst, St Louis, MO USA. [Boschiero, Clarissa] Univ Sao Paulo, Dept Zootecnia, Piracicaba, Brazil. [Ommeh, Sheila C.] Jomo Kenyatta Univ Agr & Technol, Biotechnol Res Inst, Anim Biotechnol Grp, Nairobi, Kenya. [Smith, Craig A.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia. [Gardner, Paul P.; Steeves, Tammy E.] Univ Canterbury, Sch Biol Sci, Christchurch 1, New Zealand. [Gardner, Paul P.] Univ Canterbury, Biomol Interact Ctr, Christchurch 1, New Zealand. [Motegi, Akira] Kyoto Univ Yoshida Konoe, Grad Sch Med, Dept Radiat Genet, Kyoto, Japan. [Takata, Minoru] Kyoto Univ Yoshida Konoe, Dept Late Effects Studies, Ctr Radiat Biol, Kyoto, Japan. RP Schmid, M (reprint author), Univ Wurzburg, Dept Human Genet, Biozentrum, DE-97074 Wurzburg, Germany. EM m.schmid@biozentrum.uni-wuerzburg.de; jacqueline.smith@roslin.ed.ac.uk; dave.burt@roslin.ed.ac.uk RI de Koning, Dirk Jan /F-3399-2013; Romanov, Michael/O-9419-2014; Stadler, Peter F./L-7857-2015; Groenen, Martien/D-8408-2012; Pitel, Frederique/C-2847-2009; O'Connor, Rebecca/R-6475-2016; Munsterberg, Andrea/E-2205-2011; Crooijmans, Richard/E-2492-2012; Prieto Barja, Pablo/H-2035-2015; OI Dunn, Ian/0000-0003-3630-0120; Fresard, Laure/0000-0001-8154-6328; Christophe, KLOPP/0000-0001-7126-5477; Fowler, Katie/0000-0003-0359-2390; kemp, stephen/0000-0003-4041-1720; Damas, Joana/0000-0003-4857-2510; Skinner, Michael/0000-0002-0050-4167; Nag, Rishi/0000-0001-6399-3773; Flicek, Paul/0000-0002-3897-7955; Archibald, Alan/0000-0001-9213-1830; de Koning, Dirk Jan /0000-0001-6343-8155; Romanov, Michael/0000-0003-3584-4644; Stadler, Peter F./0000-0002-5016-5191; Schmidt, Carl/0000-0002-8386-4781; Groenen, Martien/0000-0003-0484-4545; Pitel, Frederique/0000-0002-1477-7633; O'Connor, Rebecca/0000-0002-4270-970X; Munsterberg, Andrea/0000-0002-4577-4240; Prieto Barja, Pablo/0000-0002-1615-3998; Chow, William/0000-0002-9056-201X; Ulitsky, Igor/0000-0003-0555-6561 FU Biotechnology and Biological Sciences Research Council (BBSRC); USDA Agriculture and Food Research Initiative Competitive Grant; NIH Intramural Research Program of the National Institute of Allergy and Infectious Diseases; European Union; Deutsche Forschungsgemeinschaft (DFG); Swiss National Science Foundation; Lady Tata Memorial Trust; French 'Agence Nationale de la Recherche' EpiBird; Intramural Research Program of the NIEHS, NIH; Department for International Development (DFID) FX Supported by Biotechnology and Biological Sciences Research Council (BBSRC); USDA Agriculture and Food Research Initiative Competitive Grant; NIH Intramural Research Program of the National Institute of Allergy and Infectious Diseases; European Union FP-7 project QUANTOMICS; Deutsche Forschungsgemeinschaft (DFG); Swiss National Science Foundation; Lady Tata Memorial Trust; French 'Agence Nationale de la Recherche' EpiBird; Intramural Research Program of the NIEHS, NIH; Department for International Development (DFID). NR 674 TC 16 Z9 17 U1 6 U2 41 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2015 VL 145 IS 2 BP 78 EP 179 DI 10.1159/000430927 PG 102 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA CP6HS UT WOS:000359987500001 PM 26282327 ER PT J AU Wen, YK Feng, DC Wu, HL Liu, WJ Li, HJ Wang, F Xia, Q Gao, WQ Kong, XN AF Wen, Yankai Feng, Dechun Wu, Hailong Liu, Wenjun Li, Hongjie Wang, Fang Xia, Qiang Gao, Wei-Qiang Kong, Xiaoni TI Defective Initiation of Liver Regeneration in Osteopontin-Deficient Mice after Partial Hepatectomy due to Insufficient Activation of IL-6/Stat3 Pathway SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Osteopontin; partial hepatectomy; liver regeneration; Kupffer cell; IL-6; Stat3 ID ACETAMINOPHEN HEPATOTOXICITY; MACROPHAGE-MIGRATION; EXPRESSION; HEPATOCYTES; SEVERITY; CYTOKINE; DISEASES; CANCER; ALPHA; RAT AB The initial process in liver regeneration after partial hepatectomy involves the recruitment of immune cells and the release of cytokines. Osteopontin (OPN), a pro-inflammatory protein, plays critical roles in immune cell activation and migration. Although OPN has been implicated in the pathogenesis of many liver diseases, the role of OPN in liver regeneration remains obscure. In the present study, we found that serum and hepatic OPN protein levels were significantly elevated in wild-type (WT) mice after partial hepatectomy (PHx) and that bile ductal epithelia were the major cell source of hepatic OPN. Compared to WT mice, OPN knockout (KO) mice exhibited delayed liver regeneration after PHx. This delay in OPN-/- mice was attributed to impaired hepatic infiltration of macrophages and neutrophils, decreased serum and hepatic IL-6 levels, and blunted activation of macrophages after PHx. Furthermore, we demonstrate that the attenuated activation of macrophages is at least partially due to decreased hepatic and portal vein LPS levels in OPN-/- mice. In response to decreased IL-6 levels, the activation of signal transducer and transcription (Stat) 3 was reduced in hepatocytes of OPN-/- mice compared to WT mice after PHx. Consequently, hepatic activation of the downstream direct targets of IL6/Stat3, such as c-fos, c-jun, and c-myc, was also suppressed post-PHx in OPN-/- mice compared to WT mice. Collectively, these results support a unique role for OPN during the priming phase of liver regeneration, in which OPN enhances the recruitment of macrophages and neutrophils, and triggers hepatocyte proliferation through Kupffer cell-derived IL-6 release and the downstream activation of Stat3. C1 [Wen, Yankai; Wu, Hailong; Liu, Wenjun; Li, Hongjie; Wang, Fang; Xia, Qiang; Gao, Wei-Qiang; Kong, Xiaoni] Shanghai Jiao Tong Univ, Sch Biomed Engn, State Key Lab Oncogenes & Related Genes,Ren Ji Ho, Renji Med X Clin Stem Cell Res Ctr,Dept Liver Sur, Shanghai 200127, Peoples R China. [Gao, Wei-Qiang] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. RP Kong, XN (reprint author), Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Liver Surg, Shanghai 200127, Peoples R China. EM gao.weiqiang@sjtu.edu.cn; xiaonikong@sjtu.edu.cn RI Wen, Yankai/J-2205-2016; Feng, Dechun/Q-5962-2016 OI Wen, Yankai/0000-0002-8144-1515; FU National Natural Science Foundation of China [31300742, 81372233, 8147224, 81130038, 81372189]; Shanghai Education Committee (Eastern Scholar Program); Chinese Ministry of Science and Technology [2012CB966800]; Shanghai Health Bureau Key Joint Efforts Foundation [2013ZYJB001]; Shanghai Health Bureau Key Discipline and Specialty Foundation; KC Wong Foundation FX We thank Dr. Bin Gao from National Institutes of Health, Bethesda, MD for editing the manuscript. This work was supported by the National Natural Science Foundation of China (31300742 to X Kong, 81372233 to H. Wu, 8147224 to Q Xia, 81130038 and 81372189 to WQ Gao), and the Shanghai Education Committee (Eastern Scholar Program) to X Kong, the Chinese Ministry of Science and Technology (2012CB966800 to WQ Gao), the Shanghai Health Bureau Key Joint Efforts Foundation (2013ZYJB001) to Q Xia, the Shanghai Health Bureau Key Discipline and Specialty Foundation and the KC Wong Foundation to WQ Gao. NR 35 TC 6 Z9 8 U1 0 U2 5 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2015 VL 11 IS 10 BP 1236 EP 1247 DI 10.7150/ijbs.12118 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CP7SE UT WOS:000360087500011 PM 26327817 ER PT J AU Dai, XM Hummel, SL Salazar, JB Taffet, GE Zieman, S Schwartz, JB AF Dai, Xuming Hummel, Scott L. Salazar, Jorge B. Taffet, George E. Zieman, Susan Schwartz, Janice B. TI Cardiovascular physiology in the older adults SO JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Editorial Material DE Aging; Cardiovascular disease; Left ventricular ID ARTERIAL STIFFNESS; PHYSICAL-ACTIVITY; HEALTHY-MEN; AGE; PATHOPHYSIOLOGY; DISEASE; WOMEN C1 [Dai, Xuming] Univ N Carolina, Div Cardiol, Chapel Hill, NC USA. [Hummel, Scott L.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Hummel, Scott L.] Ann Arbor Vet Affairs Hlth Syst, Ann Arbor, MI USA. [Salazar, Jorge B.] Mayo Clin, Div Cardiol, Rochester, MN USA. [Taffet, George E.] Baylor Coll Med, Houston Methodist Hosp, Div Geriatr Geriatr & Cardiovasc Sci, Houston, TX 77030 USA. [Zieman, Susan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Schwartz, Janice B.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Schwartz, Janice B.] Univ Calif San Francisco, Dept Med, Div Clin Pharmacol, San Francisco, CA USA. RP Schwartz, JB (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM janice.schwartz@ucsf.edu NR 12 TC 6 Z9 6 U1 1 U2 1 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1671-5411 J9 J GERIATR CARDIOL JI J. Geriatr. Cardiol. PY 2015 VL 12 IS 3 BP 196 EP 201 PG 6 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA CP6SE UT WOS:000360017600003 PM 26089840 ER PT S AU Tanawongsuwan, P AF Tanawongsuwan, P. BE Chan, K Yeh, J TI Relation between a Book Review Content and Its Rating SO PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON COMPUTER INFORMATION SYSTEMS AND INDUSTRIAL APPLICATIONS (CISIA 2015) SE ACSR-Advances in Comptuer Science Research LA English DT Proceedings Paper CT International Conference on Computer Information Systems and Industrial Applications (CISIA) CY JUN 28-29, 2015 CL Bangkok, THAILAND DE text analysis; text mining; opinion mining; book review; product review AB While millions of products and services are consumed everyday, consumers may share their experiences by posting a review on the Web. A review usually consists of paragraphs of text. Readers wishing to learn details may choose to read the textual description. In many reviews, a product rating is also provided. Such rating might appear simply as a number of stars, a list of adjectives (excellent, good, poor, etc) to choose from. Readers may quickly look at those ratings, just to get a rough idea about the tone of the reviews. This research aims to discover the relation between a product review content and its rating. Specifically, different parts of speech in the review text are analyzed and used to predict the rating. Some classification algorithms are employed as discovery tools. Data used for this study in particular is a number of book reviews from amazon. com's Books department. C1 NIDA, Ctr Informat Technol, Grad Sch Appl Stat, Bangkok, Thailand. RP Tanawongsuwan, P (reprint author), NIDA, Ctr Informat Technol, Grad Sch Appl Stat, Bangkok, Thailand. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ATLANTIS PRESS PI PARIS PA 29 AVENUE LAVMIERE, PARIS, 75019, FRANCE SN 2352-538X BN 978-94-62520-72-1 J9 ACSR ADV COMPUT PY 2015 VL 18 BP 853 EP 856 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Theory & Methods SC Computer Science GA BD3LO UT WOS:000359866200229 ER PT J AU Patel, V Beckjord, E Moser, RP Hughes, P Hesse, BW AF Patel, Vaishali Beckjord, Ellen Moser, Richard P. Hughes, Penelope Hesse, Bradford W. TI The Role of Health Care Experience and Consumer Information Efficacy in Shaping Privacy and Security Perceptions of Medical Records: National Consumer Survey Results SO JMIR MEDICAL INFORMATICS LA English DT Article DE electronic health records; privacy confidentiality; health information exchange; health surveys; health knowledge; attitudes; practice ID TRENDS SURVEY; EXCHANGE; TECHNOLOGY; ATTITUDES AB Background: Providers' adoption of electronic health records (EHRs) is increasing and consumers have expressed concerns about the potential effects of EHRs on privacy and security. Yet, we lack a comprehensive understanding regarding factors that affect individuals' perceptions regarding the privacy and security of their medical information. Objective: The aim of this study was to describe national perceptions regarding the privacy and security of medical records and identify a comprehensive set of factors associated with these perceptions. Methods: Using a nationally representative 2011-2012 survey, we reported on adults' perceptions regarding privacy and security of medical records and sharing of health information between providers, and whether adults withheld information from a health care provider due to privacy or security concerns. We used multivariable models to examine the association between these outcomes and sociodemographic characteristics, health and health care experience, information efficacy, and technology-related variables. Results: Approximately one-quarter of American adults (weighted n=235,217,323; unweighted n=3959) indicated they were very confident (n=989) and approximately half indicated they were somewhat confident (n=1597) in the privacy of their medical records; we found similar results regarding adults' confidence in the security of medical records (very confident: n=828; somewhat confident: n=1742). In all, 12.33% (520/3904) withheld information from a health care provider and 59.06% (2100/3459) expressed concerns about the security of both faxed and electronic health information. Adjusting for other characteristics, adults who reported higher quality of care had significantly greater confidence in the privacy and security of their medical records and were less likely to withhold information from their health care provider due to privacy or security concerns. Adults with higher information efficacy had significantly greater confidence in the privacy and security of medical records and less concern about sharing of health information by both fax and electronic means. Individuals' perceptions of whether their providers use an EHR was not associated with any privacy or security outcomes. Conclusions: Although most adults are confident in the privacy and security of their medical records, many express concerns regarding sharing of information between providers; a minority report withholding information from their providers due to privacy and security concerns. Whether individuals thought their provider was using an EHR was not associated with negative privacy/security perceptions or withholding, suggesting the transition to EHRs is not associated with negative perceptions regarding the privacy and security of medical information. However, monitoring to see how this evolves will be important. Given that positive health care experiences and higher information efficacy were associated with more favorable perceptions of privacy and security, efforts should continue to encourage providers to secure medical records, provide patients with a "meaningful choice" in how their data are shared, and enable individuals to access information they need to manage their care. C1 [Patel, Vaishali; Hughes, Penelope] US Dept HHS, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. [Beckjord, Ellen] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Moser, Richard P.] NCI, NIH, Sci Res & Technol Branch, Bethesda, MD 20892 USA. [Hesse, Bradford W.] NCI, NIH, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Patel, V (reprint author), US Dept HHS, Off Natl Coordinator Hlth Informat Technol, 200 Independence Ave SW, Washington, DC 20201 USA. EM vaishali.patel@hhs.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 31 TC 2 Z9 2 U1 4 U2 9 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-9694 J9 JMIR MED INF JI JMIR Med. Inf. PD JAN-MAR PY 2015 VL 3 IS 1 AR e14 DI 10.2196/medinform.3238 PG 15 WC Medical Informatics SC Medical Informatics GA CP3ON UT WOS:000359789800006 PM 25843686 ER PT J AU Pittman, CA Fitzhugh, CD AF Pittman, Corinne A. Fitzhugh, Courtney D. TI Do the Eyes Reveal More Than Scleral Icterus in Sickle Cell Disease? SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Editorial Material C1 [Pittman, Corinne A.; Fitzhugh, Courtney D.] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA. RP Fitzhugh, CD (reprint author), NHLBI, Sickle Cell Branch, NIH, 10 Ctr Dr,Room 6-3142, Bethesda, MD 20892 USA. EM fitzhughc@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 7 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 41 IS 6 BP 485 EP 486 DI 10.1159/000438679 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CO8UR UT WOS:000359448100008 PM 26277980 ER PT J AU Joo, J Park, JH Lee, B Park, B Kim, S Yoon, KA Lee, JS Geller, NL AF Joo, Jungnam Park, Ju-Hyun Lee, Bora Park, Boram Kim, Sohee Yoon, Kyong-Ah Lee, Jin Soo Geller, Nancy L. TI Robust Association Tests for the Replication of Genome-Wide Association Studies SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID TREND TESTS; SAMPLE-SIZE; POWER; GENE AB In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson's Chi-square testwith 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies. C1 [Joo, Jungnam; Lee, Bora; Park, Boram; Kim, Sohee] Natl Canc Ctr, Res Inst & Hosp, Biometr Res Branch, Gyeonggi Do 410769, Goyang Si, South Korea. [Park, Ju-Hyun] Dongguk Univ, Dept Stat, Seoul 100715, South Korea. [Yoon, Kyong-Ah; Lee, Jin Soo] Natl Canc Ctr, Res Inst & Hosp, Lung Canc Branch, Gyeonggi Do 410769, Goyang Si, South Korea. [Geller, Nancy L.] Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. RP Joo, J (reprint author), Natl Canc Ctr, Res Inst & Hosp, Biometr Res Branch, Gyeonggi Do 410769, Goyang Si, South Korea. EM jooj@ncc.re.kr OI Kim, Sohee/0000-0003-4660-6043 FU National Cancer Center [NCC-1210060] FX The authors are indebted to late Dr. Gang Zheng for his inspiration and support on their work. This work was supported by grant of the National Cancer Center (no. NCC-1210060). NR 27 TC 0 Z9 0 U1 2 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 461593 DI 10.1155/2015/461593 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CP0FV UT WOS:000359552100001 ER PT J AU He, QJ Guo, SR Qian, ZY Chen, XY AF He, Qianjun Guo, Shengrong Qian, Zhiyong Chen, Xiaoyuan TI Development of individualized anti-metastasis strategies by engineering nanomedicines SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID CIRCULATING TUMOR-CELLS; MESOPOROUS SILICA NANOPARTICLES; IRON-OXIDE NANOPARTICLES; BREAST-CANCER METASTASIS; MESENCHYMAL STEM-CELLS; NEAR-INFRARED LIGHT; ENDOTHELIAL GROWTH-FACTOR; ANTICANCER DRUG-DELIVERY; GUIDED PHOTOTHERMAL THERAPY; SUPPORTED LIPID-BILAYERS AB Metastasis is deadly and also tough to treat as it is much more complicated than the primary tumour. Anti-metastasis approaches available so far are far from being optimal. A variety of nanomedicine formulae provide a plethora of opportunities for developing new strategies and means for tackling metastasis. It should be noted that individualized anti-metastatic nanomedicines are different from common anti-cancer nanomedicines as they specifically target different populations of malignant cells. This review briefly introduces the features of the metastatic cascade, and proposes a series of nanomedicine-based anti-metastasis strategies aiming to block each metastatic step. Moreover, we also concisely introduce the advantages of several promising nanoparticle platforms and their potential for constructing state-of-the-art individualized anti-metastatic nanomedicines. C1 [He, Qianjun; Qian, Zhiyong] Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China. [He, Qianjun; Qian, Zhiyong] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China. [He, Qianjun; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Guo, Shengrong] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China. RP He, QJ (reprint author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China. EM nanoflower@126.com; anderson-qian@163.com; shawn.chen@nih.gov RI HE, QIANJUN/M-2642-2013 OI HE, QIANJUN/0000-0003-0689-8838 FU National Nature Science Foundation of China [51102259, 31271021, 31222023]; Distinguished Young Scholars of Sichuan University [2011SCU04B18]; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We thank the financial support from the National Nature Science Foundation of China (Grant No. 51102259, 31271021 and 31222023), Distinguished Young Scholars of Sichuan University (Grant No. 2011SCU04B18) and the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 298 TC 20 Z9 21 U1 19 U2 113 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2015 VL 44 IS 17 BP 6258 EP 6286 DI 10.1039/c4cs00511b PG 29 WC Chemistry, Multidisciplinary SC Chemistry GA CP0FM UT WOS:000359551200016 PM 26056688 ER PT J AU Cutler, RG Camandola, S Malott, KF Edelhauser, MA Mattson, MP AF Cutler, Roy G. Camandola, Simonetta Malott, Kelli F. Edelhauser, Maria A. Mattson, Mark P. TI The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-Related Neurodegenerative Disorders SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Aging; Antioxidant; Caffeine; Neurodegeneration; Theobromine; Urate Oxidase; Uric acid ID EXTRACELLULAR-SUPEROXIDE DISMUTASE; MILD COGNITIVE IMPAIRMENT; ISCHEMIC BRAIN-INJURY; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; URATE OXIDASE; SERUM URATE; PLASMA ANTIOXIDANTS; HOMINOID EVOLUTION AB High uric acid (UA) levels have been correlated with a reduced risk of many neurodegenerative diseases through mechanisms involving chelating Fenton reaction transitional metals, antioxidant quenching of superoxide and hydroxyl free radicals, and as an electron donor that increases antioxidant enzyme activity (e.g. SOD). However, the clinical usefulness of UA is limited by its' low water solubility and propensity to form inflammatory crystals at hyperuricemic levels. This review focuses on the role of UA in neuroprotection, as well as potential strategies aimed at increasing UA levels in the soluble range, and the potential therapeutic use of more water-soluble methyl-UA derivatives from the natural catabolic end-products of dietary caffeine, theophylline, and theobromine. C1 [Cutler, Roy G.; Camandola, Simonetta; Malott, Kelli F.; Edelhauser, Maria A.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Cutler, RG (reprint author), Neurosci Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rcutler@nih.gov FU National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 82 TC 2 Z9 2 U1 2 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2015 VL 15 IS 21 BP 2233 EP 2238 DI 10.2174/1568026615666150610143234 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CO7ZS UT WOS:000359384100009 PM 26059354 ER PT J AU Ebbesson, SOE Voruganti, VS Higgins, PB Fabsitz, RR Ebbesson, LO Laston, S Harris, WS Kennish, J Umans, BD Wang, H Devereux, RB Okin, PM Weissman, NJ MacCluer, JW Umans, JG Howard, BV AF Ebbesson, Sven O. E. Voruganti, Venkata S. Higgins, Paul B. Fabsitz, Richard R. Ebbesson, Lars O. Laston, Sandra Harris, William S. Kennish, John Umans, Benjamin D. Wang, Hong Devereux, Richard B. Okin, Peter M. Weissman, Neil J. MacCluer, Jean W. Umans, Jason G. Howard, Barbara V. TI Fatty acids linked to cardiovascular mortality are associated with risk factors SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article DE Alaska Natives; cardiovascular risk factors; dietary fat consumption; fatty acids; fish oil consumption; Inuit; saturated fatty acids ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; TRAIT LINKAGE ANALYSIS; SERUM-LIPIDS PREDICTS; LOW-CARBOHYDRATE-DIET; INSULIN-RESISTANCE; METABOLIC SYNDROME; MYOCARDIAL-INFARCTION; FOLLOW-UP; RANDOMIZED-TRIAL AB Background. Although saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors. Objective. We tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated with individual CVD risk factors. Methods. In this community-based, cross-sectional study, relative proportions of FAs in plasma and red blood cell membranes were compared with CVD risk factors in a sample of 758 men and women aged] 35 years. Linear regression analyses were used to analyze relations between specific FAs and CVD risk factors (LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, systolic blood pressure, diastolic blood pressure, heart rate, body mass index, fasting glucose and fasting insulin, 2-hour glucose and 2-hour insulin). Results. The specific saturated FAs previously identified as related to CVD mortality, the palmitic and myristic acids, were adversely associated with most CVD risk factors, whereas unsaturated linoleic acid (18:2n-6) and the marine n-3 FAs were not associated or were beneficially associated with CVD risk factors. Conclusions. The results suggest that CVD risk factors are more extensively affected by individual FAs than hitherto recognized, and that risk for CVD, MI and stroke can be reduced by reducing the intake of palmitate, myristic acid and simple carbohydrates and improved by greater intake of linoleic acid and marine n-3 FAs. C1 [Ebbesson, Sven O. E.] Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, Nome, AK USA. [Voruganti, Venkata S.] Univ North Carolina Chapel Hill, Dept Nutr, Kannapolis, NC USA. [Voruganti, Venkata S.] Univ North Carolina Chapel Hill, UNC Nutr Res Inst, Kannapolis, NC USA. [Higgins, Paul B.] Kunming Biomed Int, Kunming, Yunnan, Peoples R China. [Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA. [Ebbesson, Lars O.] Uni Targeting Res AS, Bergen, Norway. [Laston, Sandra; MacCluer, Jean W.] Texas Biomed Res Inst, San Antonio, TX USA. [Harris, William S.] Univ S Dakota, Sanford Sch Med, Dept Med, Sioux Falls, SD USA. [Harris, William S.] Hlth Diagnost Lab Inc, Richmond, VA USA. [Kennish, John] Univ Alaska Anchorage, Dept Chem, Anchorage, AK USA. [Umans, Benjamin D.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Wang, Hong; Weissman, Neil J.; Umans, Jason G.; Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Devereux, Richard B.; Okin, Peter M.] Weill Cornell Med Coll, New York, NY USA. [Howard, Barbara V.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC USA. RP Ebbesson, SOE (reprint author), 3165 Anella Ave, Fairbanks, AK 99709 USA. EM soebbesson@alaska.edu FU National Heart, Lung, and Blood Institute [R01-HL64244, U01 HL082458, U01 HL082490]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD [2U54-NS041069] FX The study was funded by grants R01-HL64244, U01 HL082458 and U01 HL082490 from the National Heart, Lung, and Blood Institute, and by 2U54-NS041069 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD. WSH is on the scientific advisory board of Aker Biomarine (maker of krill oil) and is the President of OmegaQuant Analytics, LLC, a lab that offers RBC omega-3 testing. None of the other authors have any potential conflicts to report. NR 70 TC 5 Z9 5 U1 4 U2 8 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1239-9736 EI 2242-3982 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PY 2015 VL 74 AR 28055 DI 10.3402/ijch.v74.28055 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CO8RS UT WOS:000359439000001 PM 26274054 ER PT S AU Candemir, S Antani, S Jaeger, S Browning, R Thoma, G AF Candemir, Sema Antani, Sameer Jaeger, Stefan Browning, Renee Thoma, George BE Cook, TS Zhang, J TI Lung Boundary Detection in Pediatric Chest X-rays SO MEDICAL IMAGING 2015: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 22-23, 2015 CL Orlando, FL SP SPIE, Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind DE Pediatric chest X-rays; Lung boundary detection; Model-based segmentation; Tuberculosis ID RADIOGRAPHS AB Tuberculosis (TB) is a major public health problem worldwide, and highly prevalent in developing countries. According to the World Health Organization (WHO), over 95% of TB deaths occur in low-and middle-income countries that often have under-resourced health care systems. In an effort to aid population screening in such resource challenged settings, the U.S. National Library of Medicine has developed a chest X-ray (CXR) screening system that provides a pre-decision on pulmonary abnormalities. When the system is presented with a digital CXR image from the Picture Archive and Communication Systems (PACS) or an imaging source, it automatically identifies the lung regions in the image, extracts image features, and classifies the image as normal or abnormal using trained machine-learning algorithms. The system has been trained on adult CXR images, and this article presents enhancements toward including pediatric CXR images. Our adult lung boundary detection algorithm is model-based. We note the lung shape differences during pediatric developmental stages, and adulthood, and propose building new lung models suitable for pediatric developmental stages. In this study, we quantify changes in lung shape from infancy to adulthood toward enhancing our lung segmentation algorithm. Our initial findings suggest pediatric age groupings of 0 - 23 months, 2 - 10 years, and 11 - 18 years. We present justification for our groupings. We report on the quality of boundary detection algorithm with the pediatric lung models. C1 [Candemir, Sema; Antani, Sameer; Jaeger, Stefan; Thoma, George] NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bethesda, MD 20894 USA. [Browning, Renee] NIAID, NIH, Bethesda, MD 20894 USA. RP Candemir, S (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bethesda, MD 20894 USA. EM sema.candemir@nih.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-508-7 J9 PROC SPIE PY 2015 VL 9418 AR 94180Q DI 10.1117/12.2081060 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD3CH UT WOS:000359469100023 ER PT S AU Rahman, MM Antani, SK Demner-Fushman, D Thoma, GR AF Rahman, Md Mahmudur Antani, Sameer K. Demner-Fushman, Dina Thoma, George R. BE Cook, TS Zhang, J TI A Concept-Based Interactive Biomedical Image Retrieval Approach using Visualness and Spatial Information SO MEDICAL IMAGING 2015: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 22-23, 2015 CL Orlando, FL SP SPIE, Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind DE Medical Image Retrieval; Feature Extraction; Concept Feature; Entropy; Region-Of-Interest ID MEDICAL APPLICATIONS AB This paper presents a novel approach to biomedical image retrieval by mapping image regions to local concepts and represent images in a weighted entropy-based concept feature space. The term concept refers to perceptually distinguishable visual patches that are identified locally in image regions and can be mapped to a glossary of imaging terms. Further, the visual significance (e.g., visualness) of concepts is measured as Shannon entropy of pixel values in image patches and is used to refine the feature vector. Moreover, the system can assist user in interactively select a Region-Of-Interest (ROI) and search for similar image ROIs. Further, a spatial verification step is used as a post-processing step to improve retrieval results based on location information. The hypothesis that such approaches would improve biomedical image retrieval, is validated through experiments on a data set of 450 lung CT images extracted from journal articles from four different collections. C1 [Rahman, Md Mahmudur] Morgan State Univ, Baltimore, MD 21239 USA. [Antani, Sameer K.; Demner-Fushman, Dina; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Rahman, MM (reprint author), Morgan State Univ, Baltimore, MD 21239 USA. EM md.rahman@morgan.edu NR 24 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-508-7 J9 PROC SPIE PY 2015 VL 9418 AR 94180U DI 10.1117/12.2081456 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD3CH UT WOS:000359469100027 ER PT S AU Wang, XM Edwardson, M Dromerick, A Winstein, CL Wang, J Liu, B AF Wang, Ximing Edwardson, Matthew Dromerick, Alexander Winstein, Caro Lee Wang, Jing Liu, Brent BE Cook, TS Zhang, J TI Characterizing stroke lesions using digital templates and lesion quantification tools in a web-based imaging informatics system for a large-scale stroke rehabilitation clinical trial SO MEDICAL IMAGING 2015: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 22-23, 2015 CL Orlando, FL SP SPIE, Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind DE electronic Patient Record (ePR); Clinical Service; Digital brain templates AB Previously, we presented an Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) imaging informatics system that supports a large-scale phase III stroke rehabilitation trial. The ePR system is capable of displaying anonymized patient imaging studies and reports, and the system is accessible to multiple clinical trial sites and users across the United States via the web. However, the prior multicenter stroke rehabilitation trials lack any significant neuroimaging analysis infrastructure. In stroke related clinical trials, identification of the stroke lesion characteristics can be meaningful as recent research shows that lesion characteristics are related to stroke scale and functional recovery after stroke. To facilitate the stroke clinical trials, we hope to gain insight into specific lesion characteristics, such as vascular territory, for patients enrolled into large stroke rehabilitation trials. To enhance the system's capability for data analysis and data reporting, we have integrated new features with the system: a digital brain template display, a lesion quantification tool and a digital case report form. The digital brain templates are compiled from published vascular territory templates at each of 5 angles of incidence. These templates were updated to include territories in the brainstem using a vascular territory atlas and the Medical Image Processing, Analysis and Visualization (MIPAV) tool. The digital templates are displayed for side-by-side comparisons and transparent template overlay onto patients' images in the image viewer. The lesion quantification tool quantifies planimetric lesion area from user-defined contour. The digital case report form stores user input into a database, then displays contents in the interface to allow for reviewing, editing, and new inputs. In sum, the newly integrated system features provide the user with readily-accessible web-based tools to identify the vascular territory involved, estimate lesion area, and store these results in a web-based digital format. C1 [Wang, Ximing; Wang, Jing; Liu, Brent] Univ So Calif, Image Proc & Informat Lab, Los Angeles, CA 90089 USA. [Winstein, Caro Lee] Univ So Calif, Motor Behav & Neurorehabil Lab, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA. [Edwardson, Matthew] NINDS, NIH, Bethesda, MD 20892 USA. [Dromerick, Alexander] Georgetown Univ Hosp, Pasquerilla Healthcare Ctr, Dept Neurol, Washington, DC 20007 USA. [Dromerick, Alexander] Georgetown Univ Hosp, Pasquerilla Healthcare Ctr, Dept Rehabil Med, Washington, DC 20007 USA. RP Wang, XM (reprint author), Univ So Calif, Image Proc & Informat Lab, Los Angeles, CA 90089 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-508-7 J9 PROC SPIE PY 2015 VL 9418 AR 94180E DI 10.1117/12.2082735 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD3CH UT WOS:000359469100011 ER PT S AU Weisenthal, S Folio, L Derderian, V Summers, RM Yao, JH AF Weisenthal, Samuel Folio, Les Derderian, Vana Summers, Ronald M. Yao, Jianhua BE Cook, TS Zhang, J TI Open-source Radiation Exposure Extraction Engine (RE3) for Dose Monitoring SO MEDICAL IMAGING 2015: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 22-23, 2015 CL Orlando, FL SP SPIE, Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind DE Radiation Dose; Radiation Dose Monitoring; Picture Archiving and Communication System (PACS) and Imaging Informatics; Safety and Quality Assurance; Digital Imaging and Communications in Medicine (DICOM); Computed Tomography (CT); Radiology; Dose Length Product (DLP) ID CT AB Our goal was to investigate the feasibility of an open-source, PACS-integrated, DICOM header-based tool that automatically provides granular data for monitoring of CT radiation exposure. To do so, we constructed a radiation exposure extraction engine (RE3) that is seamlessly connected to the PACS using the digital imaging and communications in medicine (DICOM) toolkit (DCMTK) and runs on the fly within the workflow. We evaluated RE3's ability to determine the number of acquisitions and calculate the exposure metric dose length product (DLP) by comparing its output to the vendor dose pages. RE3 output closely correlated to the dose pages for both contiguously acquired exams (R-2=0.9987) and non-contiguously acquired exams (R-2= 0.9994). RE3 is an open-source, automated radiation monitoring program to provide study-, series-, and slice-level radiation data. C1 [Weisenthal, Samuel; Folio, Les; Derderian, Vana; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Weisenthal, S (reprint author), NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-508-7 J9 PROC SPIE PY 2015 VL 9418 AR 941813 DI 10.1117/12.2082197 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD3CH UT WOS:000359469100034 ER PT S AU Xue, ZY You, D Chachra, S Antani, S Long, LR Demner-Fushman, D Thoma, GR AF Xue, Zhiyun You, Daekeun Chachra, Suchet Antani, Sameer Long, L. Rodney Demner-Fushman, Dina Thoma, George R. BE Cook, TS Zhang, J TI Extraction of Endoscopic Images for Biomedical Figure Classification SO MEDICAL IMAGING 2015: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 22-23, 2015 CL Orlando, FL SP SPIE, Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind DE image modality classification; content-based image retrieval; endoscopic image figure extraction; ophthalmic image figure extraction AB Modality filtering is an important feature in biomedical image searching systems and may significantly improve the retrieval performance of the system. This paper presents a new method for extracting endoscopic image figures from photograph images in biomedical literature, which are found to have highly diverse content and large variability in appearance. Our proposed method consists of three main stages: tissue image extraction, endoscopic image candidate extraction, and ophthalmic image filtering. For tissue image extraction we use image patch level clustering and MRF relabeling to detect images containing skin/tissue regions. Next, we find candidate endoscopic images by exploiting the round shape characteristics that commonly appear in these images. However, this step needs to compensate for images where endoscopic regions are not entirely round. In the third step we filter out the ophthalmic images which have shape characteristics very similar to the endoscopic images. We do this by using text information, specifically, anatomy terms, extracted from the figure caption. We tested and evaluated our method on a dataset of 115,370 photograph figures, and achieved promising precision and recall rates of 87% and 84%, respectively. C1 [Xue, Zhiyun; You, Daekeun; Chachra, Suchet; Antani, Sameer; Long, L. Rodney; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-508-7 J9 PROC SPIE PY 2015 VL 9418 AR 94180P DI 10.1117/12.2081033 PG 13 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD3CH UT WOS:000359469100022 ER PT B AU Berninger, V McCardle, P AF Berninger, Virginia McCardle, Peggy BE McCardle, P Berninger, V TI The Importance of Combining Culturally Sensitive and Evidence-Based Literacy Instruction SO NARROWING THE ACHIEVEMENT GAP FOR NATIVE AMERICAN STUDENTS: PAYING THE EDUCATIONAL DEBT SE Routledge Research in Education Policy and Politics LA English DT Article; Book Chapter C1 [Berninger, Virginia] Univ Washington, Educ Psychol Fac, Seattle, WA 98195 USA. [McCardle, Peggy] NIH, Bethesda, MD USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85561-5; 978-0-415-72716-7 J9 ROUT RES EDUC POL PY 2015 BP 1 EP 5 PG 5 WC Education & Educational Research; Ethnic Studies SC Education & Educational Research; Ethnic Studies GA BD0MQ UT WOS:000357400100002 ER PT B AU Hurtado, DS McCardle, P Berninger, V AF Hurtado, Denny Sparr McCardle, Peggy Berninger, Virginia BE McCardle, P Berninger, V TI A Model for 21st-Century Indian Education A Story of State, School, and Community Collaboration SO NARROWING THE ACHIEVEMENT GAP FOR NATIVE AMERICAN STUDENTS: PAYING THE EDUCATIONAL DEBT SE Routledge Research in Education Policy and Politics LA English DT Article; Book Chapter C1 [Hurtado, Denny Sparr] Superintendent Publ Instruct, Washington State Off, Indian Educ, Washington, DC USA. [McCardle, Peggy] NIH, Bethesda, MD USA. [Berninger, Virginia] Univ Washington, Educ Psychol Fac, Seattle, WA 98195 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85561-5; 978-0-415-72716-7 J9 ROUT RES EDUC POL PY 2015 BP 65 EP 78 PG 14 WC Education & Educational Research; Ethnic Studies SC Education & Educational Research; Ethnic Studies GA BD0MQ UT WOS:000357400100007 ER PT B AU McCardle, P Berninger, V AF McCardle, Peggy Berninger, Virginia BE McCardle, P Berninger, V TI Visions for the Future of Indian Education Thoughts to Guide Ongoing Work at the Intersection of Evidence-Based Practice and Culturally Sensitive Education SO NARROWING THE ACHIEVEMENT GAP FOR NATIVE AMERICAN STUDENTS: PAYING THE EDUCATIONAL DEBT SE Routledge Research in Education Policy and Politics LA English DT Article; Book Chapter C1 [McCardle, Peggy] NIH, Bethesda, MD USA. [Berninger, Virginia] Harvard & Tufts New England Med Sch, Boston, MA USA. [Berninger, Virginia] Univ Washington, Educ Psychol Fac, Seattle, WA 98195 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85561-5; 978-0-415-72716-7 J9 ROUT RES EDUC POL PY 2015 BP 196 EP 206 PG 11 WC Education & Educational Research; Ethnic Studies SC Education & Educational Research; Ethnic Studies GA BD0MQ UT WOS:000357400100018 ER PT S AU Coates, PM Thomas, PR AF Coates, Paul M. Thomas, Paul R. BE Bier, DM Mann, J Alpers, DH Vorster, HHE Gibney, MJ TI Dietary Supplements SO NUTRITION FOR THE PRIMARY CARE PROVIDER SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter DE Dietary supplements; Multivitamin-multimineral supplements; Efficacy; Safety; Food and Drug Administration C1 [Coates, Paul M.; Thomas, Paul R.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-318-02667-2; 978-3-318-02666-5 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2015 VL 111 BP 58 EP 63 DI 10.1159/000362298 D2 10.1159/isbn.978-3-318-02667-2 PG 6 WC Primary Health Care; Nutrition & Dietetics SC General & Internal Medicine; Nutrition & Dietetics GA BD3CM UT WOS:000359472600011 PM 25418390 ER PT S AU Phoochinda, W AF Phoochinda, Wisakha BE Elatter, EE Tsai, SB TI The Appropriate Mode in the Application of the Philosophy of Sufficiency Economy in the Environmental Management of the Industrial Sector SO PROCEEDINGS OF THE 2015 AASRI INTERNATIONAL CONFERENCE ON CIRCUITS AND SYSTEMS (CAS 2015) SE ACSR-Advances in Comptuer Science Research LA English DT Proceedings Paper CT AASRI International Conference on Circuits and Systems (CAS) CY AUG 09-10, 2015 CL Paris, FRANCE SP AASRI DE philosophy of sufficiency economy; environmental management; business and industrial sectors AB This study aims to investigate success in the application of sufficiency economy philosophy of industries, to investigate factors affecting the application in environmental management and to suggest appropriate mode. Data are collected using in-depth interviews with nine businesses successfully applied the philosophy; a questionnaire surveying on samples of 400 factories; and in-depth interviews with three businesses surveyed, interested in applying the philosophy. According to in-depth interviews of the nine businesses, success in the application depends on e.g. social awareness, management's vision and policy, faith in the philosophy, knowledge and understanding of the philosophy. Factors contributing to the application in environmental management from the questionnaire are the size of the industry, policy on environmental management, access to information, opinion on the application and participation in activities involving the application. Appropriate mode in the application involves management, staff involvement, the faith in the philosophy as well as knowledge and understanding of the philosophy. C1 NIDA, Grad Sch Social & Environm Dev, Bangkok 10240, Thailand. RP Phoochinda, W (reprint author), NIDA, Grad Sch Social & Environm Dev, Bangkok 10240, Thailand. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ATLANTIS PRESS PI PARIS PA 29 AVENUE LAVMIERE, PARIS, 75019, FRANCE SN 2352-538X BN 978-94-62520-74-5 J9 ACSR ADV COMPUT PY 2015 VL 9 BP 9 EP 12 PG 4 WC Automation & Control Systems; Environmental Sciences SC Automation & Control Systems; Environmental Sciences & Ecology GA BD3HN UT WOS:000359721400003 ER PT J AU Buell, TJ Ksendzovsky, A Shah, BB Kesser, BW Elias, WJ AF Buell, Thomas J. Ksendzovsky, Alexander Shah, Binit B. Kesser, Bradley W. Elias, W. Jeffrey TI Deep Brain Stimulation in the Setting of Cochlear Implants: Case Report and Literature Review SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Review DE Deep brain stimulation; Parkinson's disease; Cochlear implant ID CARDIAC-PACEMAKERS AB Background/Aims: As technology continues to advance for our aging population, an increasing number of deep brain stimulation (DBS) candidates will have preexisting implanted electrical devices. In this article, we discuss safe and successful DBS in a patient with Parkinson's disease (PD) and bilateral cochlear implants. Methods: A 70-year-old male with PD and bilateral cochlear implants underwent successful microelectrode-guided DBS implantation into bilateral subthalamic nuclei (STN). The patient's cochlear implant magnets were removed and replaced in the outpatient clinic for preoperative MRI and stereotactic targeting. The cochlear implants were turned off intraoperatively for STN microelectrode recordings. Results: Precise, MRI-guided stereotactic DBS implantation was possible. Intraoperative high-fidelity microelectrode recordings confirmed STN neurons with the cochlear implants turned off. These recordings were not possible with active cochlear implant devices. Our literature review describes the other approaches/techniques that have been used to manage DBS surgery in the setting of cochlear implants. Conclusions: Despite the risk of electrical interference between implanted medical devices, DBS and cochlear implants may be safe and compatible in the same patient if necessary precautions are taken. (C) 2015 S. Karger AG, Basel C1 [Buell, Thomas J.; Ksendzovsky, Alexander; Elias, W. Jeffrey] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Shah, Binit B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Kesser, Bradley W.] Univ Virginia, Dept Otolaryngol, Charlottesville, VA USA. [Ksendzovsky, Alexander] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Buell, TJ (reprint author), Univ Virginia Hlth Syst, Dept Neurosurg, POB 800212, Charlottesville, VA 22908 USA. EM tjb4p@hscmail.mcc.virginia.edu FU Intramural NIH HHS [Z99 NS999999] NR 11 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 EI 1423-0372 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2015 VL 93 IS 4 BP 245 EP 249 DI 10.1159/000380824 PG 5 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CO8CL UT WOS:000359392500004 PM 25998722 ER PT J AU Mi, BM Yu, CJ Pan, DH Yang, M Wan, WX Niu, G Chen, XY AF Mi, Baoming Yu, Chunjing Pan, Donghui Yang, Min Wan, Weixing Niu, Gang Chen, Xiaoyuan TI Pilot Prospective Evaluation of F-18-Alfatide II for Detection of Skeletal Metastases SO THERANOSTICS LA English DT Article DE RGD peptide; Alfatide II; FDG; PET/CT; bone metastasis ID INTEGRIN ALPHA(V)BETA(3) EXPRESSION; POSITRON-EMISSION-TOMOGRAPHY; GLY-ASP PEPTIDE; BONE METASTASES; BREAST-CANCER; RGD PEPTIDE; LUNG-CANCER; PET; MARROW; ANGIOGENESIS AB This pilot prospective evaluation study is to verify the efficiency of F-18-Alfatide II, a specific PET imaging agent for integrin alpha v beta 3, in detecting bone metastasis in human, with comparison to F-18-FDG PET. Thirty recruited patients underwent F-18-FDG and F-18-alfatide II PET/CT successively within days. The final diagnosis of bone lesions was established based on the comprehensive assessment of all available data and clinical follow-up, which fall into four groups: osteolytic, osteoblastic, mixed and bone marrow. Visual analysis and quantification of SUVmax were performed to compare the detection sensitivity of F-18-Alfatide II and F-18-FDG PET. Eleven patients were found to have a total of 126 bone metastasis lesions. F-18-Alfatide II PET can detect the bone metastatic lesions with good contrast and higher sensitivity (positive rate of 92%) than F-18-FDG PET (77%). Especially, F-18-Alfatide II PET showed superiority to F-18-FDG PET in detecting osteoblastic (70% vs. 53%) and bone marrow metastatic lesions (98% vs. 77%). In conclusion, F-18-Alfatide II PET/CT can be used to detect skeletal and bone marrow metastases, with nearly 100% sensitivity in osteolytic, mixed and bone marrow lesions. The sensitivity of F-18-Alfatide II PET/CT in osteoblastic metastases is relatively low but still significantly higher than that of F-18-FDG PET/CT. This pilot clinical study warrants the further application of F-18-Alfatide II PET/CT in metastatic lesion detection, patient management and drug therapy response monitoring. C1 [Mi, Baoming; Yu, Chunjing; Wan, Weixing] Jiangnan Univ, Wuxi Peoples Hosp 4, Affiliated Hosp, Dept Nucl Med, Wuxi, Peoples R China. [Pan, Donghui; Yang, Min] Jiangsu Inst Nucl Med, Minist Hlth, Jiangsu Key Lab Mol Nucl Med, Key Lab Nucl Med, Wuxi, Peoples R China. [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Wan, WX (reprint author), Jiangnan Univ, Wuxi Peoples Hosp 4, Affiliated Hosp, Dept Nucl Med, Wuxi, Peoples R China. EM ymzfk@yahoo.com.hk; wwxjs@126.com; niug@mail.nih.gov; shawn.chen@nih.gov FU National Basic Research Program of China (973 program) [2013CB733802, 2014CB744503]; National Natural Science Foundation [81028009, 81171399, 51473071, 81472749, 81401450, 81471691]; National Significant New Drugs Creation Program [2012ZX09505-001-001]; Jiangsu Province Foundation [BE2012622, BL2012031, BM2012066, BE2014609]; Outstanding Professional Fund of Health Ministry in Jiangsu Province [RC2011095, Q201406]; Wuxi Hospital Management Center Project [YGZXM14026, YGZXL1316]; Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported in part, by the National Basic Research Program of China (973 program, 2013CB733802, 2014CB744503), National Natural Science Foundation (81028009, 81171399, 51473071, 81472749, 81401450, 81471691), National Significant New Drugs Creation Program (2012ZX09505-001-001), Jiangsu Province Foundation (BE2012622, BL2012031, BM2012066, BE2014609), Outstanding Professional Fund of Health Ministry in Jiangsu Province (RC2011095, Q201406), Wuxi Hospital Management Center Project (YGZXM14026, YGZXL1316), and Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 39 TC 7 Z9 7 U1 2 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 10 BP 1115 EP 1121 DI 10.7150/thno.12938 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CO9DK UT WOS:000359472700006 PM 26199649 ER PT S AU Kuczmarski, MF Mason, MA Allegro, D Zonderman, AB Evans, MK AF Kuczmarski, M. Fanelli Mason, M. A. Allegro, D. Zonderman, A. B. Evans, M. K. BE Mitchell, DC Braithwaite, E TI The Impact of Conventional Dietary Intake Data Coding Methods on Snacks Typically Consumed by Socioeconomically Diverse African American and White Urban Population: A Comparison of Coding Methods SO 38TH NATIONAL NUTRIENT DATABANK CONFERENCE SE Procedia Food Science LA English DT Proceedings Paper CT 38th National Nutrient Databank Conference (NNDC) CY MAY, 2014 CL Oregon Hlth Sci Univ, Portland, OR HO Oregon Hlth Sci Univ DE Snacks; African Americans; Whites; Diet ID UNITED-STATES; RISK-FACTORS; PATTERNS; ADULTS; QUALITY; CONSUMPTION; WOMEN AB This study assessed the significance of implementing combination codes generated by USDA's Automated Multiple Pass Method and the impact on the assessment of snacking using the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. African American and White participants (n=2177) completed two 24-hour dietary recalls. All self-reported snacks were assigned a food group code, while snacks eaten in combination (e.g. cereal with milk) were additionally assigned a combination code and associated with a food group based on primary component (e.g. cereal). Combination codes produced significant variation in snack lists by race, providing a better depiction of snacking patterns. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommonsmrgilicenses/hy-nc-nd/4.0/). Peer-review under responsibility of the National Nutrient Databank Steering Committee C1 [Kuczmarski, M. Fanelli; Allegro, D.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE 19716 USA. [Mason, M. A.; Zonderman, A. B.; Evans, M. K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. RP Kuczmarski, MF (reprint author), Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE 19716 USA. EM mfk@udel.edu NR 27 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-601X J9 PROC FOOD SCI PY 2015 VL 4 BP 94 EP 103 DI 10.1016/j.profoo.2015.06.014 PG 10 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BD2HB UT WOS:000358738000013 ER PT S AU Kuczmarski, MF Mason, MA Allegro, D Beydoun, MA Zonderman, AB Evans, MK AF Kuczmarski, M. Fanelli Mason, M. A. Allegro, D. Beydoun, M. A. Zonderman, A. B. Evans, M. K. BE Mitchell, DC Braithwaite, E TI Dietary Quality and Nutritional Biomarkers associated with Dietary Patterns of Socioeconomically Diverse Urban African American and White Population SO 38TH NATIONAL NUTRIENT DATABANK CONFERENCE SE Procedia Food Science LA English DT Proceedings Paper CT 38th National Nutrient Databank Conference (NNDC) CY MAY, 2014 CL Oregon Hlth Sci Univ, Portland, OR HO Oregon Hlth Sci Univ DE Diet quality; DASH; nutritional status; cluster patterns; African Americans ID FASTING PLASMA-GLUCOSE; US ADULTS; HEALTH; INCOME; MARKERS; RACE/ETHNICITY; PREVENTION; SUBGROUPS; STATEMENT; DIAGNOSIS AB The objective of this cross-sectional study was to determine the dietary and health-related quality of cluster patterns of African Americans and Whites, 30 to 64 years of age, examined in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. All ten clusters reflected a Western diet with low adherence to the Dietary Approaches to Stop Hypertension (DASH) eating pattern, ranging from 0.9 to 15.3%. Micronutrient adequacy scores ranged from 68.6 to 81.6 out of 100. Clinical and blood biomarkers provided evidence of the health risks for metabolic syndrome, inflammation, hypertension and prediabetes, suggesting the need for dietary improvement. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under he CC BY-NC-ND license (http://creativecommons.orgdlicenses/by-nc-nd/4.0/). Peer-review under responsibility of the National Nutrient Databank Steering Committee C1 [Kuczmarski, M. Fanelli; Allegro, D.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE 19716 USA. [Mason, M. A.; Beydoun, M. A.; Zonderman, A. B.; Evans, M. K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. RP Kuczmarski, MF (reprint author), Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE 19716 USA. EM mfk@udel.edu NR 38 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-601X J9 PROC FOOD SCI PY 2015 VL 4 BP 104 EP 113 DI 10.1016/j.profoo.2015.06.015 PG 10 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BD2HB UT WOS:000358738000014 ER PT S AU Zimmerman, TP Potischman, N Douglass, D Dixit-Joshi, S Kirkpatrick, SI Subar, AF McNutt, S Coleman, LA Alexander, GL Kushi, LH Thompson, FE AF Zimmerman, Thea Palmer Potischman, Nancy Douglass, Deirdre Dixit-Joshi, Sujata Kirkpatrick, Sharon I. Subar, Amy F. McNutt, Suzanne Coleman, Laura A. Alexander, Gwen L. Kushi, Lawrence H. Thompson, Frances E. BE Mitchell, DC Braithwaite, E TI The Effect of Editing Open-Ended Text Responses on Nutrient and Food Group Estimates from the Automated Self-Administered 24-Hour Dietary Recall (A5A24) SO 38TH NATIONAL NUTRIENT DATABANK CONFERENCE SE Procedia Food Science LA English DT Proceedings Paper CT 38th National Nutrient Databank Conference (NNDC) CY MAY, 2014 CL Oregon Hlth Sci Univ, Portland, OR HO Oregon Hlth Sci Univ DE ASA24; 24-hour dietary recall AB The National Cancer Institute (NCI) Food Reporting and Comparison Study (FORCS) compares nutrient and food group estimates obtained from recalls collected through the web-based Automated Self-Administered 24-hour Recall (A5A24) to those from standard interviewer-administered telephone recalls among 1054 adults. Within the A5A24 software, respondents may choose to enter open-ended text to report "unfound food" and "other, specify." Respondents use the "unfound food" field to report a food or drink they cannot find; the A5A24 system then asks a series of general questions to better identify the food. Respondents use the "other, specify" field to provide food details, such as brand name or cooking method, that differ from the responses offered by A5A24. When respondents use these two open-ended text fields, the system assigns default food codes. Nutritionists reviewed these codes and assigned new codes when appropriate. Nutrient and My Pyramid Equivalent (MPE) values from default food codes (unedited) and the researcher assigned food codes (edited) were compared. Of the 716 food codes evaluated, changes were made to 248 foods (1.5% of total foods reported) which affected 194 (19.1%) of all recalls and required over 60 hours of specialized staff time. Although 43% of the 1013 completed recalls included at least one of the two text field responses, the A5A24 system assigned acceptable default food codes 68% of the time. Editing did not significantly affect the means and ranking for most nutrients and food group MPE values; correlation coefficients for energy and macronutrient values before and after editing were 0.95 or higher, suggesting that this editing may not be necessary for most large studies using ASA24. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (lttp://creativecommonsAwglicensesThy-nc-nd/40/). Peer-review under responsibility of the National Nutrie Jatabank Steering Committee C1 [Zimmerman, Thea Palmer; Douglass, Deirdre; Dixit-Joshi, Sujata; McNutt, Suzanne] WESTAT Corp, Rockville, MD 20850 USA. [Potischman, Nancy; Subar, Amy F.; Thompson, Frances E.] US Naval Hosp, NCI, NIH, Bethesda, MD 20814 USA. [Kirkpatrick, Sharon I.] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada. [Coleman, Laura A.] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Alexander, Gwen L.] Henry Ford Hlth Syst, Detroit, MI 48202 USA. [Kushi, Lawrence H.] Kaiser Permanente No Calif, Oakland, CA 94612 USA. RP Zimmerman, TP (reprint author), WESTAT Corp, 1650 Res Blvd, Rockville, MD 20850 USA. EM TheaZimmerman@westat.com NR 7 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-601X J9 PROC FOOD SCI PY 2015 VL 4 BP 160 EP 172 DI 10.1016/j.profoo.2015.06.021 PG 13 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BD2HB UT WOS:000358738000020 ER PT S AU Giedd, JN Denker, AH AF Giedd, Jay N. Denker, Alexander H. BE Bourguignon, JP Carel, JC Christen, Y TI The Adolescent Brain: Insights from Neuroimaging SO BRAIN CROSSTALK IN PUBERTY AND ADOLESCENCE SE Research and Perspectives in Endocrine Interactions LA English DT Article; Book Chapter ID WHITE-MATTER; NEURITE OUTGROWTH; CEREBRAL-CORTEX; PSYCHIATRIC-DISORDERS; SEXUAL-DIMORPHISM; GRAY-MATTER; MATURATION; NEUROANATOMY; CHILDHOOD; INHIBITOR AB Adolescence is a time of dramatic changes in body, behavior, and brain. Although the adolescent brain has different features than those of a child or mature adult, it is not broken or defective. The changes in the teen brain have been exquisitely forged by evolution to facilitate the survival of our species. During the second decade of life the brain does not mature by becoming larger; it matures by becoming more specialized and its subcomponents becoming more "inter-connected." Recent advances in neuroimaging and the application of graph theoretical methods of analysis are enabling scientists to characterize these changes in connectivity and how they vary by age, sex, health/illness, and other cognitive or behavioral measures. C1 [Giedd, Jay N.; Denker, Alexander H.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 NR 46 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1861-2253 BN 978-3-319-09168-6; 978-3-319-09167-9 J9 RES PERSPECT END INT JI Res. Perspect. End. Int. PY 2015 VL 13 BP 85 EP 96 DI 10.1007/978-3-319-09168-6_7 D2 10.1007/978-3-319-09168-6 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA BD0NM UT WOS:000357416300008 ER PT J AU Liu, G Allen, B Lopez, O Aizenstein, H Boudreau, R Newman, A Yaffe, K Kritchevsky, S Launer, L Satterfield, S Simonsick, E Rosano, C AF Liu, Ge Allen, Ben Lopez, Oscar Aizenstein, Howard Boudreau, Robert Newman, Anne Yaffe, Kristine Kritchevsky, Stephen Launer, Lenore Satterfield, Suzanne Simonsick, Eleanor Rosano, Caterina TI Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Brain MRI; cognitive aging; DTI; racial differences ID SYMBOL SUBSTITUTION TEST; OLDER-ADULTS; ANATOMIC CHARACTERISTICS; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; NORTHERN MANHATTAN; ALZHEIMERS-DISEASE; AFRICAN-AMERICANS; BLOOD-PRESSURE; MR-IMAGES AB Objective: To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Methods: Cross-sectional study of 283 adults 79-89 years old (59.4% white; 42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (s beta) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Results: Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (s beta=-.209, p=0.037and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (s beta =-.277, p=.002 and -.250, p=0.029, respectively). Conclusions: In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions. C1 [Liu, Ge; Boudreau, Robert; Newman, Anne; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Allen, Ben] Univ Pittsburgh, Cardiovasc Behav Med Res Program, Dept Psychiat, Pittsburgh, PA 15213 USA. [Lopez, Oscar] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Aizenstein, Howard] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA. [Aizenstein, Howard] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA 15213 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Launer, Lenore] Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. [Simonsick, Eleanor] NIH, Bethesda, MD 20892 USA. RP Rosano, C (reprint author), Ctr Aging & Populat Hlth, 130 N Bellefield Ave, Pittsburgh, PA 15213 USA. EM RosanoC@edc.pitt.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01-NR012459]; Intramural Research Program of the NIH, National Institute on Aging FX The authors report no conflicts of interest. This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 37 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2015 VL 12 IS 7 BP 648 EP 654 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN9RB UT WOS:000358785400007 PM 25387332 ER PT J AU Azoury, SC Straughan, DM Shukla, V AF Azoury, Said C. Straughan, David M. Shukla, Vivek TI Immune Checkpoint Inhibitors for Cancer Therapy: Clinical Efficacy and Safety SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Cancer; CTLA-4; inhibitors; immune checkpoint; PD-1; PDL-1 ID T-CELL COSTIMULATION; METASTATIC MELANOMA; PHASE-II; OPEN-LABEL; ANTITUMOR IMMUNITY; PANCREATIC-CANCER; BRAIN METASTASES; CTLA-4 BLOCKADE; PD-1 BLOCKADE; RECOMBINANT INTERLEUKIN-2 AB A major breakthrough in cancer immunotherapy was the discovery of immune checkpoint proteins, which function to effectively inhibit the immune system through various mechanisms. The first of such molecules shown to inhibit both T-cell proliferation and IL-2 production was cytotoxic T-lymphocyte associated protein 4 (CTLA-4). With this discovery, efforts turned to blocking this inhibitory pathway in an attempt to activate dormant T-cells directed at cancer cells. The first antibody directed against CTLA-4, ipilimumab, was quickly ushered into clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011. Following the success of ipilimumab, other immune checkpoints were studied as possible targets for inhibition. One such interaction was that of the programmed cell death-1 (PD-1) T-cell receptor and its ligand found on many cancer cells, programmed death-ligand 1 (PD-L1). Unfortunately, the untoward effects of blocking the immune system's natural inhibitory mechanisms have manifested clinically as diarrhea, rash, and hepatitis. Nevertheless, the exciting field of immune checkpoint inhibitors offers a potential curative option for many cancer patients who previously had a more dismal prognosis. The authors aim to provide a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of cancer and other molecules still in the early development phase. C1 [Azoury, Said C.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Straughan, David M.] Univ S Florida, Dept Surg, Morsani Coll Med, Tampa, FL 33620 USA. [Shukla, Vivek] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Shukla, V (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, NIH, 10 Ctr Dr,Room 3W5848, Bethesda, MD 20892 USA. EM vivek.shukla@nih.gov NR 111 TC 10 Z9 10 U1 2 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2015 VL 15 IS 6 BP 452 EP 462 PG 11 WC Oncology SC Oncology GA CO6FL UT WOS:000359252500002 PM 26282545 ER PT J AU Fujii, Y Narita, T Tice, RR Takeda, S Yamada, R AF Fujii, Yosuke Narita, Takeo Tice, Raymond Richard Takeda, Shunich Yamada, Ryo TI ISOTONIC REGRESSION BASED-METHOD IN QUANTITATIVE HIGH-THROUGHPUT SCREENINGS FOR GENOTOXICITY SO DOSE-RESPONSE LA English DT Article DE Isotonic regression; Hill equation; quantitative high-throughput screening; genotoxicity ID DNA-DAMAGE; CELLS; TOLERANCE AB Quantitative high-throughput screenings (qHTSs) for genotoxicity are conducted as part of comprehensive toxicology screening projects. The most widely used method is to compare the dose-response data of a wild-type and DNA repair gene knockout mutants, using model-fitting to the Hill equation (HE). However, this method performs poorly when the observed viability does not fit the equation well, as frequently happens in qHTS. More capable methods must be developed for qHTS where large data variations are unavoidable. In this study, we applied an isotonic regression (IR) method and compared its performance with HE under multiple data conditions. When dose-response data were suitable to draw HE curves with upper and lower asymptotes and experimental random errors were small, HE was better than IR, but when random errors were big, there was no difference between HE and IR. However, when the drawn curves did not have two asymptotes, IR showed better performance (p < 0.05, exact paired Wilcoxon test) with higher specificity (65% in HE vs. 96% in IR). In summary, IR performed similarly to HE when dose-response data were optimal, whereas IR clearly performed better in suboptimal conditions. These findings indicate that IR would be useful in qHTS for comparing dose-response data. C1 [Fujii, Yosuke; Yamada, Ryo] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto 6068507, Japan. [Narita, Takeo; Takeda, Shunich] Kyoto Univ, Dept Radiat Genet, Grad Sch Med, Kyoto 6068507, Japan. [Tice, Raymond Richard] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC USA. RP Yamada, R (reprint author), Kyoto Univ, Ctr Genom Med, Grad Sch Med, South Res Bldg 1,Room 515,Syogoinkawaharamachi, Kyoto 6068507, Japan. EM ryamada@genome.med.kyoto-u.ac.jp FU Japanese Society for the Promotion of Science (JSPS) KAKENHI [23221005] FX This work was supported in part by the Japanese Society for the Promotion of Science (JSPS) KAKENHI [the Grant-in-Aid for Scientific Research (S) No. 23221005]. NR 29 TC 1 Z9 1 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PD JAN-MAR PY 2015 VL 13 IS 1 DI 10.2203/dose-response.13-045.Fujii PG 20 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA CO4RF UT WOS:000359147600007 ER PT J AU Li, HH Wang, YW Chen, RX Zhou, B Ashwell, JD Fornace, AJ AF Li, Heng-Hong Wang, Yi-wen Chen, Renxiang Zhou, Bin Ashwell, Jonathan D. Fornace, Albert J., Jr. TI Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE metabolic reprogramming; metabolomics; mass spectrometry; UPLC-QTOF; ionizing radiation; TCR activation ID ATOMIC-BOMB SURVIVORS; INFLAMMATORY RESPONSE; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION; ANTIGEN; DIFFERENTIATION; EXPOSURE; RECEPTOR; STIMULATION; LYMPHOCYTES AB Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures. C1 [Li, Heng-Hong; Wang, Yi-wen; Chen, Renxiang; Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. [Li, Heng-Hong; Chen, Renxiang] Chinese Acad Med Sci, Inst Radiat Med, Tianjin 300192, Peoples R China. [Li, Heng-Hong; Chen, Renxiang] Peking Union Med Coll, Tianjin 300192, Peoples R China. [Zhou, Bin; Fornace, Albert J., Jr.] Georgetown Univ, Dept Oncol, Med Ctr, Washington, DC 20057 USA. [Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fornace, Albert J., Jr.] King Abdulaziz Univ, CEGMR, Jeddah 22254, Saudi Arabia. RP Li, HH (reprint author), Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. EM hl234@georgetown.edu OI Fornace, Albert/0000-0001-9695-085X FU Department of Energy [DE-SC0002345]; National Natural Science Foundation of China [81372927] FX We thank the Proteomic and Metabolomics Shared Resources at Georgetown University, NIH P30CA51008, for providing UPLC-MSTOF service. This work was supported by a research grant from Department of Energy (DE-SC0002345), and a research grant from National Natural Science Foundation of China (81372927). NR 37 TC 6 Z9 6 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2015 VL 11 IS 7 BP 726 EP 736 DI 10.7150/ijbs.12009 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CO2SU UT WOS:000359007700001 PM 26078715 ER PT J AU Bai, HH Liu, HP Suyalatu, S Guo, XS Chu, SD Chen, Y Lan, TM Borjigin, B Orlov, YL Posukh, OL Yang, XQ Guilan, GL Osipova, LP Wu, QZ Narisu, N AF Bai, Haihua Liu, Haiping Suyalatu, Suyalatu Guo, Xiaosen Chu, Shandan Chen, Ying Lan, Tianming Borjigin, Burenbatu Orlov, Yuriy L. Posukh, Olga L. Yang, Xiuqin Guilan, Guilan Osipova, Ludmila P. Wu, Qizhu Narisu, Narisu TI Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China SO JOURNAL OF DIABETES RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; METAANALYSIS AB The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations. C1 [Bai, Haihua; Liu, Haiping; Suyalatu, Suyalatu; Chu, Shandan; Borjigin, Burenbatu; Guilan, Guilan; Wu, Qizhu] Inner Mongolia Univ Nationalities, Tongliao 028000, Inner Mongolia, Peoples R China. [Guo, Xiaosen; Chen, Ying; Lan, Tianming] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Guo, Xiaosen] Univ Copenhagen, Dept Biol, DK-2100 Copenhagen, Denmark. [Orlov, Yuriy L.; Posukh, Olga L.; Osipova, Ludmila P.] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia. [Orlov, Yuriy L.; Posukh, Olga L.] Novosibirsk State Univ, Novosibirsk 630090, Russia. [Yang, Xiuqin] Northeast Agr Univ, Coll Anim Sci & Technol, Harbin 150030, Peoples R China. [Narisu, Narisu] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. RP Wu, QZ (reprint author), Inner Mongolia Univ Nationalities, Tongliao 028000, Inner Mongolia, Peoples R China. EM qizhu_wu2014@163.com; narisu@mail.nih.gov RI Posukh, Olga/Q-6065-2016; Orlov, Yuriy/F-1520-2013 OI Posukh, Olga/0000-0003-1352-3591; Orlov, Yuriy/0000-0003-0587-1609 FU National Natural Science Foundation of China [81160101, 81060098]; NSFC-RFBR Cooperation and Exchange Projects [81511130050]; National Human Genome Research Institute, National Institutes of Health; RFBR [15-54-53091] FX The authors thank their study individuals for their generous participation in this study. This study was supported by the National Natural Science Foundation of China (81160101 and 81060098) and NSFC-RFBR Cooperation and Exchange Projects (81511130050). Narisu Narisu was supported by the intramural program of the National Human Genome Research Institute, National Institutes of Health. Yuriy L. Orlov, Olga L. Posukh, and Ludmila P. Osipova were supported by RFBR (15-54-53091). The authors thank Anne Jackson and Clement Ma for advice in statistical analysis and comments in writing. They also thank Francis S. Collins for critical comments. NR 31 TC 0 Z9 0 U1 2 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6745 EI 2314-6753 J9 J DIABETES RES JI J. Diabetes Res. PY 2015 AR 613236 DI 10.1155/2015/613236 PG 7 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CO5XH UT WOS:000359231300001 ER PT J AU Narendran, G Andrade, BB Vijay, K Susaimuthu, S Chandrasekar, C Sathiyavelu, S Swaminathan, S AF Narendran, Gopalan Andrade, Bruno Bezerril Vijay, Krishnamoorthy Susaimuthu, Stella Chandrasekar, Chockalingam Sathiyavelu, Sekhar Swaminathan, Soumya TI Hiccups as an unusual manifestation of tuberculosis-associated immune reconstitution inflammatory syndrome SO NATIONAL MEDICAL JOURNAL OF INDIA LA English DT Letter C1 [Narendran, Gopalan; Vijay, Krishnamoorthy; Susaimuthu, Stella; Swaminathan, Soumya] Natl Inst Res TB, Madras, Tamil Nadu, India. [Andrade, Bruno Bezerril] NIAID, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Chockalingam] Govt Hosp Thorac Med, Madras, Tamil Nadu, India. [Sathiyavelu, Sekhar] Rajiv Gandhi Govt Gen Hosp, Madras, Tamil Nadu, India. RP Narendran, G (reprint author), Natl Inst Res TB, 1 Mayor Sathyamoorthy Rd, Madras, Tamil Nadu, India. EM gopalannaren@yahoo.co.in; brunobezerril@gmail.com; calldrvijay@gmail.com; soosaistella78@gmail.com; drcc.ghtm@gmail.com; drsekarsmo@gmail.com; doctorsoumya@yahoo.com FU Intramural NIH HHS NR 7 TC 0 Z9 0 U1 0 U2 0 PU ALL INDIA INST MEDICAL SCIENCES PI NEW DELHI PA ANSARI NAGAR, NEW DELHI 110 029, INDIA SN 0970-258X J9 NATL MED J INDIA JI Natl. Med. J. India PD JAN-FEB PY 2015 VL 28 IS 1 BP 49 EP 50 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CO0AW UT WOS:000358813500017 PM 26219328 ER PT J AU Breslau, ES Weiss, ES Williams, A Burness, A Kepka, D AF Breslau, Erica S. Weiss, Elisa S. Williams, Abigail Burness, Allison Kepka, Deanna TI The Implementation Road: Engaging Community Partnerships in Evidence-Based Cancer Control Interventions SO HEALTH PROMOTION PRACTICE LA English DT Article DE cancer prevention and control; health disparities; health education; health promotion; partnerships/coalitions; program planning and evaluation; women's health ID PARTICIPATORY RESEARCH; HEALTH; PREVENTION; POPULATIONS; SETTINGS; SYNERGY; WOMEN AB Southern rural and underserved counties have high proportions of individuals with increased mortality for cervical and breast cancers. To improve the integration of behavioral research into practice, the dissemination and implementation of efficacious interventions to encourage the use of screening have increased in recent years. This study addressed gaps in the dissemination and implementation of evidence-based interventions with a pilot called Team Up. Qualitative interviews with 24 key individuals in six state-level partnerships explored partnership characteristics that influenced selection and use of evidence-based interventions among low-income, rarely or never screened women. Guided by diffusion of innovations theory and the Lasker and Weiss partnership functioning model, interviews about the intervention centered on (a) knowledge surrounding evidence base; (b) identification, selection, and adoption; (c) planning and adaptation; (d) implementation; and (e) partnership reflections and impact. Using grounded theory and content analysis, data revealed that lack of communication and high partner turnover hindered adoption and adaptation, whereas failure of partnership leaders to engage local stakeholders and lack of sufficient funds hampered implementation. Delivery of evidence-based interventions was more effective when partnerships included local partners in early decision making and when coaches were introduced to facilitate strategic thinking about translating evidence-based interventions into practice. A challenge for public health partnerships was the translation of interventions into successful programs, such that underserved communities benefited from early detection intervention research. C1 [Breslau, Erica S.; Burness, Allison; Kepka, Deanna] NCI, Rockville, MD 20852 USA. [Weiss, Elisa S.] Leukemia & Lymphoma Soc, White Plains, NY USA. [Williams, Abigail] CUNY, Mayors Off Combat Domest Violence, New York, NY 10021 USA. [Burness, Allison] MedStar Washington Hosp Ctr, Washington, DC USA. [Kepka, Deanna] Univ Utah, Salt Lake City, UT USA. RP Breslau, ES (reprint author), NCI, Proc Care Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,3E520,MSC 9761, Rockville, MD 20852 USA. EM breslaue@mail.nih.gov NR 28 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1524-8399 EI 1552-6372 J9 HEALTH PROMOT PRACT JI Health Promot. Pract. PD JAN PY 2015 VL 16 IS 1 BP 46 EP 54 DI 10.1177/1524839914528705 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL9KZ UT WOS:000357298500008 PM 24700166 ER PT J AU Braue, J Murugesan, V Holland, S Patel, N Naik, E Leiding, J Yacoub, AT Prieto-Granada, CN Greene, JN AF Braue, Jonathan Murugesan, Vagishwari Holland, Steven Patel, Nishit Naik, Eknath Leiding, Jennifer Yacoub, Abraham Tareq Prieto-Granada, Carlos N. Greene, John Norman TI NF-kappa B Essential Modulator Deficiency Leading to Disseminated Cutaneous Atypical Mycobacteria SO MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES LA English DT Article ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; X-LINKED DISORDER; INCONTINENTIA PIGMENTI; IMMUNE-DEFICIENCY; INFECTION; NEMO; MUTATIONS; DISEASE; AUTOANTIBODIES; SUSCEPTIBILITY AB NF-kappa B essential modulator (NEMO) is a kinase integral to the macrophage TNF-alpha pathway, which leads to the intracellular destruction of Mycobacteria species. Defects in the NEMO pathway result in spectrum of diseases, including but not limited to ectodermal dysplasia, Mendelian susceptibility to mycobacterial diseases, and incontinentia pigmenti. In addition, paucity of NEMO can lead to the inability to mount a proper immune response against opportunistic pyogenic and mycobacterial infections, leading to dissemination to various organ systems. This manuscript will discuss the numerous clinical manifestations of NEMO deficiency, the differential diagnosis of atypical mycobacterial infections in immunocompetent adults, and feature a case report of rare isolated susceptibility to disseminated atypical mycobacteria due to a mutation in the first exon of the NEMO gene. C1 [Braue, Jonathan] Univ S Florida, Morsani Coll Med, Tampa, FL USA. [Murugesan, Vagishwari; Yacoub, Abraham Tareq; Greene, John Norman] H Lee Moffitt Canc Ctr & Res Inst, Div Infect Dis, Tampa, FL 33612 USA. [Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Patel, Nishit] Univ S Florida, Morsani Coll Med, Dept Dermatol & Cutaneous Surg, Tampa, FL USA. [Naik, Eknath] Univ S Florida, Morsani Coll Med, Div Infect Dis & Int Med, Tampa, FL USA. [Leiding, Jennifer] Univ S Florida, Morsani Coll Med, Dept Pediat, Div Allergy Immunol & Rheumatol, Tampa, FL USA. [Prieto-Granada, Carlos N.] Univ S Florida, Morsani Coll Med, Dept Dermatol, Tampa, FL USA. RP Greene, JN (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Div Infect Dis, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM John.greene@moffitt.org NR 27 TC 2 Z9 2 U1 0 U2 2 PU PAGEPRESS PUBL PI PAVIA PA MEDITGROUP, VIA G BELLI, 4, PAVIA, 27100, ITALY SN 2035-3006 J9 MEDITERR J HEMATOL I JI Med. J. Hematol. Infect. Dis. PD JAN 1 PY 2015 VL 7 AR e2015010 DI 10.4084/MJHID.2015.010 PG 6 WC Hematology SC Hematology GA CM0UR UT WOS:000357394800010 PM 25574369 ER PT J AU Foster, MC Hwang, SJ Massaro, JM Jacques, PF Fox, CS Chu, AY AF Foster, Meredith C. Hwang, Shih-Jen Massaro, Joseph M. Jacques, Paul F. Fox, Caroline S. Chu, Audrey Y. TI Lifestyle Factors and Indices of Kidney Function in the Framingham Heart Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Lifestyle factors; Dietary quality; Physical activity; Smoking; Alcohol intake; Chronic kidney disease; Epidemiology ID BODY-MASS INDEX; GLOMERULAR-FILTRATION-RATE; COMMUNITY-BASED POPULATION; 2005 DIETARY GUIDELINES; APPARENTLY HEALTHY-MEN; STAGE RENAL-DISEASE; ALCOHOL-CONSUMPTION; FUNCTION DECLINE; PHYSICAL-ACTIVITY; CENTRAL OBESITY AB Background and Objectives: Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) and rapid eGFR decline in older adults in the United States. Methods: Prospective cohort study of Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m(2) (n = 1,802) who attended the seventh (1998-2001; baseline) and eighth (2005-2008; follow-up) examinations (mean age = 59 years, 54.8% women). Predictors included measures of diet quality, physical activity, alcohol intake, and current smoking status assessed during baseline. Outcomes were based on creatinine-based eGFR at baseline and follow-up and included incident eGFR <60 ml/min/1.73 m(2) (at followup) and rapid eGFR decline (annual eGFR decrease >= 3 ml/min/1.73 m(2)). Results: Over an average follow-up of 6.6 years, 9.5% (n = 171) of participants developed incident eGFR <60. A trend was observed across quartiles of diet quality, with higher levels of diet quality associated with a decreased odds ratio (OR) of incident eGFR <60 (p trend = 0.045). Higher diet quality was associated with decreased odds of rapid eGFR decline (p trend = 0.03) and was attenuated with additional adjustment (p trend = 0.07). In sensitivity analysis for rapid eGFR decline using a secondary definition (annual eGFR decrease >= 3 and incident eGFR <60), diet associations remained significant with additional adjustment (p trend = 0.04). No associations were observed with physical activity, smoking status, or alcohol intake with incident eGFR <60 or rapid eGFR decline (all p > 0.19). Conclusions: Higher diet quality may be associated with a decreased risk of incident eGFR <60 ml/min/1.73 m(2), and rapid eGFR decline. Whether adherence to a healthy diet can prevent reduction in kidney function warrants further study. (C) 2015 National Institutes of Health (NIH) Published by S. Karger AG, Basel C1 [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.; Chu, Audrey Y.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Foster, Meredith C.; Hwang, Shih-Jen; Chu, Audrey Y.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Foster, Meredith C.] Tufts Med Ctr, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Jacques, Paul F.] Tufts Univ, US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Div Endocrinol & Metab, Brigham & Womens Hosp, Boston, MA 02115 USA. [Chu, Audrey Y.] Harvard Univ, Sch Med, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chu, AY (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM audrey.chu@nih.gov FU National Heart, Lung, and Blood Institute [N01-HC-25195] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). The study sponsor did not have a role in study design, the collection, analysis, and interpretation of data, writing the report, and the decision to submit the report for publication. NR 47 TC 3 Z9 3 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 41 IS 4-5 BP 267 EP 274 DI 10.1159/000430868 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CN6AF UT WOS:000358515000001 PM 25998023 ER PT J AU Seliger, SL Wendell, CR Waldstein, SR Ferrucci, L Zonderman, AB AF Seliger, Stephen L. Wendell, Carrington R. Waldstein, Shari R. Ferrucci, Luigi Zonderman, Alan B. TI Renal Function and Long-Term Decline in Cognitive Function: The Baltimore Longitudinal Study of Aging SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney function; Creatinine; Estimated glomerular filtration rate; Cognitive function; Neuropsychology; Longitudinal trajectories ID CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; CYSTATIN-C; IMPAIRMENT; ADULTS; HEALTH; PREVALENCE; DEMENTIA; AGE AB Background: Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Methods: Stroke-and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Results: Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m(2) and 18.5% had at least one comorbidity. With increasing age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual Retention Test, a test of visual memory (p < 0.01). Associations were similar for changes in eGFR MDRD, which was also associated with the rate of decline in verbal memory. Conclusion: In a community-based adult population, declines in renal function independently associated with greater long-term declines in visual memory and verbal memory and learning. (C) 2015 National Institutes of Health (NIH) Published by S. Karger AG, Basel C1 [Seliger, Stephen L.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA. [Waldstein, Shari R.] Univ Maryland, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA. [Wendell, Carrington R.; Waldstein, Shari R.] Univ Maryland, Dept Psychol, Baltimore, MD 21201 USA. [Wendell, Carrington R.; Ferrucci, Luigi; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Waldstein, Shari R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. RP Seliger, SL (reprint author), Univ Maryland, Sch Med, Dept Med, Div Nephrol, 22 S Greene St N3W143, Baltimore, MD 21201 USA. EM sseliger@medicine.umaryland.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging Intramural Research Program of the National Institutes of Health FX The National Institute on Aging Intramural Research Program of the National Institutes of Health supported this research. NR 24 TC 6 Z9 6 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 41 IS 4-5 BP 305 EP 312 DI 10.1159/000430922 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CN6AF UT WOS:000358515000008 PM 26201453 ER PT J AU Michener, KH Mitchell, GF Noubary, F Huang, N Harris, T Andresdottir, MB Palsson, R Gudnason, V Levey, AS AF Michener, Katherine H. Mitchell, Gary F. Noubary, Farzad Huang, Naya Harris, Tamara Andresdottir, Margret B. Palsson, Runolfur Gudnason, Vilmundur Levey, Andrew S. TI Aortic Stiffness and Kidney Disease in an Elderly Population SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Albuminuria; Aortic stiffness; Chronic kidney disease; Elderly; Glomerular filtration rate ID PULSE-WAVE VELOCITY; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; TYPE-2 DIABETIC-PATIENTS; ARTERIAL STIFFNESS; CYSTATIN C; FUNCTION DECLINE; ESSENTIAL-HYPERTENSION; CARDIOVASCULAR EVENTS; SERUM CREATININE AB Background/Aims: The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in the transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations. Methods: We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. The relationship of carotid pulse pressure (CPP) and carotid-femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and urine albumin-creatinine ratio (ACR) was assessed using linear regression, adjusting for demographics and CVD risk factors. Results: 940 participants (mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73 m(2), and median (IQR) ACR 3 (2-6) mg/g) were included in this study. At CPP greater than 85 mm Hg, a higher CPP was associated with a lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with a higher ACR in fully adjusted models (beta (95% CI) = 0.14 (0.03, 0.24) ln mg/g per SD). Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment. Conclusion: Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association between aortic stiffness and lower eGFR may be confounded by age and CVD risk factors. (C) 2015 National Institutes of Health (NIH) Published by S. Karger AG, Basel C1 [Michener, Katherine H.; Huang, Naya; Levey, Andrew S.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Harris, Tamara] NIA, Bethesda, MD 20892 USA. [Andresdottir, Margret B.; Palsson, Runolfur] Natl Univ Hosp Iceland, Div Nephrol, Landspitali, Reykjavik, Iceland. [Palsson, Runolfur; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. RP Levey, AS (reprint author), Tufts Med Ctr, Dept Med, Div Nephrol, 800 Washington St, Boston, MA 02111 USA. EM alevey@tuftsmedicalcenter.org RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institutes of Health [R01 DK082447]; National Institute on Aging [N01-AG-1-2100]; Hjartavernd (the Icelandic Heart Association); Icelandic Parliament (Althingi) FX This study was supported by a grant from National Institutes of Health (R01 DK082447), contract from the National Institute on Aging (N01-AG-1-2100), Hjartavernd (the Icelandic Heart Association) and the Icelandic Parliament (Althingi). The funding sources were not required to approve publication of the finished manuscript. Dr. Aghogho Okparavero assisted with manuscript preparation. NR 60 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 41 IS 4-5 BP 320 EP 328 DI 10.1159/000431332 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CN6AF UT WOS:000358515000010 PM 26067356 ER PT J AU Prager, KC Alt, DP Buhnerkempe, MG Greig, DJ Galloway, RL Wu, QZ Gulland, FMD Lloyd-Smith, JO AF Prager, K. C. Alt, David P. Buhnerkempe, Michael G. Greig, Denise J. Galloway, Renee L. Wu, Qingzhong Gulland, Frances M. D. Lloyd-Smith, James O. TI Antibiotic Efficacy in Eliminating Leptospiruria in California Sea Lions (Zalophus californianus) Stranding with Leptospirosis SO AQUATIC MAMMALS LA English DT Article DE antibiotic; California sea lion; Zalophus californianus; Leptospira interrogans; leptospiruria; renal disease; chronic shedding ID INTERROGANS SEROVAR POMONA; ANTIMICROBIAL AGENTS; DIAGNOSIS; SUSCEPTIBILITIES; COAST; PCR; SEROPREVALENCE; DOXYCYCLINE; PINNIPEDS; THERAPY AB Stranded California sea lions (Zalophus californianus) along the California coast have been diagnosed with leptospirosis every year since at least the 1980s. Between September 2010 and November 2011, we followed 14 stranded California sea lions that survived to release and evaluated antibiotic efficacy in eliminating leptospiruria (urinary shedding of leptospires). Leptospiruria was assessed by real-time PCR of urine and urine culture, with persistence assessed using longitudinally collected samples. Serum chemistry was used to assess recovery of normal renal function. Microscopic agglutination testing (MAT) was performed to assess serum anti-Leptospira antibody titers, and the MAT reactivity patterns were consistent with L. interrogans serovar Pomona infection frequently observed in this population. Animals were initially treated for 6 to 16 d (median = 10.5; mean = 10.8) with antibiotics from the penicillin family, with some receiving additional antibiotics to treat other medical conditions. All urine cultures were negative; therefore, the presence of leptospiruria was assessed using PCR. Leptospiruria continued beyond the initial course of penicillin family antibiotics in 13 of the 14 sea lions, beyond the last antibiotic dose in 11 of the 14 sea lions, beyond recovery of renal function in 13 of the 14 sea lions, and persisted for at least 8 to 86 d (median = 45; mean = 46.8). Five animals were released with no negative urine PCR results detected; thus, their total shedding duration may have been longer. Cessation of leptospiruria was more likely in animals that received antibiotics for a greater duration, especially if coverage was uninterrupted. Real-time PCR results indicate that an antibiotic protocol commonly used to treat leptospirosis in rehabilitating California sea lions does not eliminate leptospiruria. It is possible that antibiotic protocols given for a longer duration and/or including other antibiotics may be effective in eliminating leptospiruria. These results may have important human and animal health implications, especially in rehabilitation facilities, as Leptospira transmission may occur through contact with animals with persistent leptospiruria. C1 [Prager, K. C.; Buhnerkempe, Michael G.; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Prager, K. C.; Buhnerkempe, Michael G.; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Alt, David P.] Natl Anim Dis Ctr, Infect Bacterial Dis Res Unit, Ames, IA 50010 USA. [Greig, Denise J.; Gulland, Frances M. D.] Marine Mammal Ctr, Sausalito, CA 94965 USA. [Galloway, Renee L.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Wu, Qingzhong] Natl Ocean Serv, Hollings Marine Lab, Charleston, SC 29412 USA. RP Prager, KC (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. EM kcprager@ucla.edu RI Lloyd-Smith, James/K-4080-2012 OI Lloyd-Smith, James/0000-0001-7941-502X FU John H. Prescott Marine Mammal Rescue Assistance Grant Program; National Science Foundation [OCE-1335657]; De Logi Chair in Biological Sciences; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This work was supported by the John H. Prescott Marine Mammal Rescue Assistance Grant Program; the National Science Foundation (OCE-1335657); the De Logi Chair in Biological Sciences; and the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health. The authors thank the staff and volunteers at The Marine Mammal Center in Sausalito, California, as they were integral to sample collection, sample management, and treatment choice, particularly Jen Soper, Carlos Rios, and William Van Bonn. NR 36 TC 0 Z9 0 U1 3 U2 8 PU EUROPEAN ASSOC AQUATIC MAMMALS PI MOLINE PA C/O DR JEANETTE THOMAS, BIOLOGICAL SCIENCES, WESTERN ILLIONIS UNIV-QUAD CITIES, 3561 60TH STREET, MOLINE, IL 61265 USA SN 0167-5427 J9 AQUAT MAMM JI Aquat. Mamm. PY 2015 VL 41 IS 2 BP 203 EP 212 DI 10.1578/AM.41.2.2015.203 PG 10 WC Marine & Freshwater Biology; Zoology SC Marine & Freshwater Biology; Zoology GA CN3AZ UT WOS:000358296900008 ER PT J AU Riley, AM Wang, HC Shears, SB Potter, BVL AF Riley, Andrew M. Wang, Huanchen Shears, Stephen B. Potter, Barry V. L. TI Synthetic tools for studying the chemical biology of InsP(8) SO CHEMICAL COMMUNICATIONS LA English DT Article ID INOSITOL PYROPHOSPHATES MEDIATE; DIPHOSPHOINOSITOL POLYPHOSPHATES; ANALOGS; TETRAKISPHOSPHATE; METABOLISM; KINASE; PHOSPHATES; STRESS AB To synthesise stabilised mimics of InsP(8), the most phosphorylated inositol phosphate signalling molecule in Nature, we replaced its two diphosphate (PP) groups with either phosphonoacetate (PA) or methylenebisphosphonate (PCP) groups. Utility of the PA and PCP analogues was verified by structural and biochemical analyses of their interactions with enzymes of InsP(8) metabolism. C1 [Riley, Andrew M.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England. [Wang, Huanchen; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Potter, Barry V. L.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. RP Potter, BVL (reprint author), Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England. EM barry.potter@pharm.ox.ac.uk FU Wellcome Trust [101010]; NIH/National Institute of Environmental Health Sciences FX B.V.L.P. is a Wellcome Trust Senior Investigator (Grant 101010). This research was also supported by the Intramural Research Program of the NIH/National Institute of Environmental Health Sciences. NR 29 TC 4 Z9 4 U1 1 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2015 VL 51 IS 63 BP 12605 EP 12608 DI 10.1039/c5cc05017k PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA CN6CC UT WOS:000358520200023 PM 26153667 ER PT J AU Keenan, CM Baker, JF Bradley, AE Goodman, DG Harada, T Herbert, R Kaufmann, W Kellner, R Mahler, B Meseck, E Nolte, T Rittinghausen, S Vahle, J Yoshizawa, K AF Keenan, Charlotte M. Baker, Julia F. Bradley, Alys E. Goodman, Dawn G. Harada, Takanori Herbert, Ronald Kaufmann, Wolfgang Kellner, Rupert Mahler, Beth Meseck, Emily Nolte, Thomas Rittinghausen, Susanne Vahle, John Yoshizawa, Katsuhiko TI International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) progress to date and future plans SO JOURNAL OF TOXICOLOGIC PATHOLOGY LA English DT Article DE rodent; terminology; regulatory science; toxicologic pathology AB The INHAND Proposal (International harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) has been operational since 2005. A Global Editorial Steering Committee (GESC) manages the overall objectives of the project and the development of harmonized terminology for each organ system is the responsibility of the Organ Working Groups (OWG), drawing upon experts from North America, Europe and Japan Great progress has been made with 9 systems published to date Respiratory, Hepatobiliary, Urinary, Central/Peripheral Nervous Systems, Male Reproductive and Mammary, Zymbals, Clitoral and Preputial Glands in Toxicologic Pathology and the Integument and Soft Tissue and Female Reproductive System in the Journal of Toxicologic Pathology as supplements and on a web site - www.goreni.org. INHAND nomenclature guides offer diagnostic criteria and guidelines for recording lesions observed in rodent toxicity and carcinogenicity studies. The guides provide representative photo-micrographs of morphologic changes, information regarding pathogenesis, and key references. During 2012, INHAND GESC representatives attended meetings with representatives of the FDA Center for Drug Evaluation and Research (CDER). Clinical Data Interchange Standards Consortium (CDISC), and the National Cancer Institute (NCI) Enterprise Vocabulary Services (EVS) to begin incorporation of INHAND terminology as preferred terminology for SEND (Standard for Exchange of Nonclinical Data) submissions lathe FDA. The interest in utilizing the INHAND nomenclature, based on input from industry and government toxicologists as well as information technology specialists, suggests that there will be wide acceptance of this nomenclature. The purpose of this publication is to provide an update on the progress of INHAND. C1 [Keenan, Charlotte M.] CM Keenan ToxPath Consulting, Doylestown, PA USA. [Baker, Julia F.] Charles River, Frederick, MD USA. [Bradley, Alys E.] Charles River, Tranent, Scotland. [Harada, Takanori] Inst Environm Toxicol, Ibaraki, Japan. [Herbert, Ronald; Mahler, Beth] NIEHS, Res Triangle Pk, NC 27709 USA. [Kaufmann, Wolfgang] Merck KGaA, Darmstadt, Germany. [Kellner, Rupert; Rittinghausen, Susanne] Fraunhofer ITEM, Hannover, Germany. [Meseck, Emily] Novartis Inst Biomed Res, E Hanover, NJ USA. [Nolte, Thomas] Boeringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Vahle, John] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Yoshizawa, Katsuhiko] Kansai Med Univ, Dept Pathol 2, Hirakata, Osaka, Japan. RP Keenan, CM (reprint author), CM Keenan ToxPath Consulting, Doylestown, PA USA. EM charlotte.keenan@msn.com NR 2 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE SOC TOXICOLOGIC PATHOLOGY PI TOKYO PA DEPT ACAD SOC, MEDICAL TRIBUNE INC, ITALIAN CULTURAL INST BLDG 8F 2-1-30, KUDAN MINAMI, CHIYODA, TOKYO, 102-0074, JAPAN SN 0914-9198 EI 1881-915X J9 J TOXICOL PATHOL JI J. Toxicol. Pathol. PD JAN PY 2015 VL 28 IS 1 BP 48 EP 53 DI 10.1293/tox.28.2014-0049 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA CN8PV UT WOS:000358704000008 ER PT J AU Ghieh, F Jurjus, R Ibrahim, A Geagea, AG Daouk, H El Baba, B Chams, S Matar, M Zein, W Jurjus, A AF Ghieh, Fadi Jurjus, Rosalyn Ibrahim, Amir Geagea, Alice Gerges Daouk, Hisham El Baba, Bassel Chams, Sana Matar, Michel Zein, Wadih Jurjus, Abdo TI The Use of Stem Cells in Burn Wound Healing: A Review SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID LIMBAL EPITHELIAL TRANSPLANTATION; OCULAR SURFACE BURNS; ENDOTHELIAL PROGENITOR CELLS; CUTANEOUS RADIATION SYNDROME; CLINICAL-OUTCOMES; CORNEAL SURFACE; CHEMICAL BURNS; SKIN INJURY; RAT MODEL; FACTOR-I AB Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stemcells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they have decreased the inflammation levels with less scar progression and fibrosis. This review aims to highlight the beneficial therapeutic effect of stem cells in burn wound healing and to discuss the involved pathways and signaling molecules. The review covers various types of burn wound healing like skin and corneal burns, along with the alternative recent therapies being studied in the field of burn wound healing. The current reflection of the attitudes of people regarding the use of stem cells in burn wound healing is also stated. C1 [Ghieh, Fadi] Amer Univ Beirut, Fac Med, Beirut, Lebanon. [Jurjus, Rosalyn] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA. [Ibrahim, Amir] Amer Univ Beirut, Dept Surg, Beirut, Lebanon. [Geagea, Alice Gerges; Matar, Michel] Lebanese Hlth Soc, Beirut, Lebanon. [Daouk, Hisham; El Baba, Bassel; Chams, Sana; Jurjus, Abdo] Amer Univ Beirut, Fac Med, Dept Anat Cell Biol & Physiol, Beirut, Lebanon. [Zein, Wadih] NIH, Inst Eye, Bethesda, MD 20892 USA. RP Jurjus, A (reprint author), Amer Univ Beirut, Fac Med, Dept Anat Cell Biol & Physiol, Beirut, Lebanon. EM aj00@aub.edu.lb OI Daouk, Hisham/0000-0002-8682-2843; Jurjus, Abdo/0000-0002-5955-656X NR 86 TC 4 Z9 4 U1 3 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 684084 DI 10.1155/2015/684084 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CN2QB UT WOS:000358265700001 ER PT J AU Galis, ZS AF Galis, Z. S. TI THE SECRET SUPREMACY OF SMALL BLOOD VESSELS, AN ENDURING PUZZLE OF THE CARDIOVASCULAR SYSTEM: RESEARCH GAPS AND OPPORTUNITIES SO CARDIOLOGY LA English DT Meeting Abstract C1 [Galis, Z. S.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2015 VL 131 SU 2 MA 004 BP 16 EP 16 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN6BK UT WOS:000358518200005 ER PT J AU Leng, YK Sun, K Chen, XY Li, WW AF Leng, Yuankui Sun, Kang Chen, Xiaoyuan Li, Wanwan TI Suspension arrays based on nanoparticle-encoded microspheres for high-throughput multiplexed detection SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID ENHANCED RAMAN-SCATTERING; QUANTUM-DOT BARCODES; CATALYZED REPORTER DEPOSITION; CONVERSION FLUORESCENT NANOPARTICLES; SCANNING AUTOMATED MICROSCOPY; ROLLING CIRCLE AMPLIFICATION; HYBRIDIZATION CHAIN-REACTION; SOLUBLE CONJUGATED POLYMERS; PARTICLE-BASED IMMUNOASSAYS; CORE-SHELL NANOPARTICLES AB Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple analytes within a small, single sample volume. Thanks to the rapid development of nanotechnology, tremendous progress has been made in the multiplexed detecting capability, sensitivity, and photostability of suspension arrays. In this review, we first focus on the current stock of nanoparticle-based barcodes as well as the manufacturing technologies required for their production. We then move on to discuss all existing barcode-based bioanalysis patterns, including the various labels used in suspension arrays, label-free platforms, signal amplification methods, and fluorescence resonance energy transfer (FRET)-based platforms. We then introduce automatic platforms for suspension arrays that use superparamagnetic nanoparticle-based microspheres. Finally, we summarize the current challenges and their proposed solutions, which are centered on improving encoding capacities, alternative probe possibilities, nonspecificity suppression, directional immobilization, and "point of care" platforms. Throughout this review, we aim to provide a comprehensive guide for the design of suspension arrays, with the goal of improving their performance in areas such as multiplexing capacity, throughput, sensitivity, and cost effectiveness. We hope that our summary on the state-of-the-art development of these arrays, our commentary on future challenges, and some proposed avenues for further advances will help drive the development of suspension array technology and its related fields. C1 [Leng, Yuankui; Sun, Kang; Li, Wanwan] Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, Shanghai 200240, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Sun, K (reprint author), Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, Shanghai 200240, Peoples R China. EM ksun@sjtu.edu.cn; shawn.chen@nih.gov; wwli@sjtu.edu.cn FU National Basic Research Program of China (973 program) [2010CB933901, 2013CB733802, 2014CB744503]; National Natural Science Foundation of China [50902093, 81371596, 81371645]; Medicine & Engineering Cross Research Foundation of Shanghai Jiao Tong University [YG2012MS61, YG2014MS33]; Intramural Research Program of National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported in part by the National Basic Research Program of China (973 program, 2010CB933901, 2013CB733802, 2014CB744503), the National Natural Science Foundation of China (Project No. 50902093, 81371596 and 81371645), Medicine & Engineering Cross Research Foundation of Shanghai Jiao Tong University (Project No. YG2012MS61, YG2014MS33), and the Intramural Research Program of National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 365 TC 18 Z9 18 U1 44 U2 157 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2015 VL 44 IS 15 BP 5552 EP 5595 DI 10.1039/c4cs00382a PG 44 WC Chemistry, Multidisciplinary SC Chemistry GA CN1ZI UT WOS:000358219300022 PM 26021602 ER PT J AU Gorka, AP Nani, RR Schnermann, MJ AF Gorka, Alexander P. Nani, Roger R. Schnermann, Martin J. TI Cyanine polyene reactivity: scope and biomedical applications SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Review ID INFRARED FLUORESCENT-PROBES; BIOMATERIAL-ASSOCIATED INFLAMMATION; DYE LABELING REAGENTS; IN-VIVO; LIVING CELLS; HYDROGEN-SULFIDE; ORGANIC FLUOROPHORES; PHOTOACTIVATABLE FLUOROPHORES; IMPROVED PHOTOSTABILITY; NIR FLUORESCENCE AB Cyanines are indispensable fluorophores that form the chemical basis of many fluorescence-based applications. A feature that distinguishes cyanines from other common fluorophores is an exposed polyene linker that is both crucial to absorption and emission and subject to covalent reactions that dramatically alter these optical properties. Over the past decade, reactions involving the cyanine polyene have been used as foundational elements for a range of biomedical techniques. These include the optical sensing of biological analytes, super-resolution imaging, and near-IR light-initiated uncaging. This review surveys the chemical reactivity of the cyanine polyene and the biomedical methods enabled by these reactions. The overarching goal is to highlight the multifaceted nature of cyanine chemistry and biology, as well as to point out the key role of reactivity-based insights in this promising area. C1 [Gorka, Alexander P.; Nani, Roger R.; Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM martin.schnermann@nih.gov FU Intramural Research Program of the National Institutes of Health; Center for Cancer Research; National Cancer Institute, National Institutes of Health FX We thank Rolf Swenson (NIH, NHLBI) and members of the Chemical Biology Laboratory for helpful suggestions. This work was supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, and the National Cancer Institute, National Institutes of Health. NR 141 TC 14 Z9 14 U1 13 U2 54 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2015 VL 13 IS 28 BP 7584 EP 7598 DI 10.1039/c5ob00788g PG 15 WC Chemistry, Organic SC Chemistry GA CN2IC UT WOS:000358243200001 PM 26052876 ER PT S AU Cogswell, ME Maalouf, J Elliott, P Loria, CM Patel, S Bowman, BA AF Cogswell, Mary E. Maalouf, Joyce Elliott, Paul Loria, Catherine M. Patel, Sheena Bowman, Barbara A. BE Bowman, BA Stover, PJ TI Use of Urine Biomarkers to Assess Sodium Intake: Challenges and Opportunities SO ANNUAL REVIEW OF NUTRITION, VOL 35 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE 24 h; spot; overnight; balance; metabolism; sweat ID NIGHTTIME BLOOD-PRESSURE; CHRONIC KIDNEY-DISEASE; POPULATION SALT INTAKE; EXCESS DIETARY-SODIUM; POTASSIUM EXCRETION; CARDIOVASCULAR EVENTS; SOCCER PLAYERS; SWEAT RATE; REPRESENTATIVE SAMPLE; ELECTROLYTE EXCRETION AB This article summarizes current data and approaches to assess sodium intake in individuals and populations. A review of the literature on sodium excretion and intake estimation supports the continued use of 24-h urine collections for assessing population and individual sodium intake. Since 2000, 29 studies used urine biomarkers to estimate population sodium intake, primarily among adults. More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h specimen. Associations between individual sodium intake and health outcomes were investigated in 13 prospective cohort studies published since 2000. Only three included an indicator of long-term individual sodium intake, i.e., multiple 24-h urine specimens collected several days apart. Although not insurmountable, logistic challenges of 24-h urine collection remain a barrier for research on the relationship of sodium intake and chronic disease. Newer approaches, including modeling based on shorter collections, offer promise for estimating population sodium intake in some groups. C1 [Cogswell, Mary E.; Maalouf, Joyce; Patel, Sheena; Bowman, Barbara A.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA 30341 USA. [Maalouf, Joyce] IHRC Inc, Atlanta, GA 30346 USA. [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W21 PG, England. [Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Cogswell, ME (reprint author), Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA 30341 USA. EM mcogswell@cdc.gov; jmaalouf@cdc.gov; p.elliott@imperial.ac.uk; loriac@nhlbi.nih.gov; spatel@cdc.gov; bbowman@cdc.gov FU USDHHS; NIHR Biomedical Research Center at Imperial College Healthcare NHS Trust and Imperial College; NIHR Health Protection Research Unit on Health Impact of Environmental Hazards; MRC-PHE Center for Environment and Health FX The authors thank Katherine John, Joanna Taliano, and Lauren Clark for their help with the literature search and references, and Christine Pfeiffer, PhD for the helpful review and comments on the section on data collection and laboratory analysis. This work was supported by the USDHHS. Dr. Elliott acknowledges support from the NIHR Biomedical Research Center at Imperial College Healthcare NHS Trust and Imperial College, the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards, and the MRC-PHE Center for Environment and Health. He is an NIHR Senior Investigator. NR 151 TC 6 Z9 6 U1 6 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2835-1 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2015 VL 35 BP 349 EP + DI 10.1146/annurev-nutr-071714-034322 PG 41 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BD1QC UT WOS:000358259600012 PM 25974702 ER PT J AU Bogoslovsky, T Maric, D Gong, YH Qu, BX Yang, K Spatz, M Hallenbeck, J Diaz-Arrastia, R AF Bogoslovsky, Tanya Maric, Dragan Gong, Yunhua Qu, Baoxi Yang, Kelly Spatz, Maria Hallenbeck, John Diaz-Arrastia, Ramon TI Preservation and enumeration of endothelial progenitor and endothelial cells from peripheral blood for clinical trials SO BIOMARKERS IN MEDICINE LA English DT Article DE angiogenesis; cryopreservation; endothelial cells; endothelial progenitor cells; flow cytometry ID FLOW-CYTOMETRY; IMMUNOMAGNETIC ISOLATION; CARDIOVASCULAR RISK; SYSTEMIC-SCLEROSIS; ISCHEMIC-STROKE; STEM-CELLS; DISEASE; PROTOCOL; QUANTIFICATION; EXPRESSION AB Aims: Endothelial progenitor cells (EPCs) are markers of vascular repair. Increased numbers of circulating endothelial cells (ECs) are associated with endothelial damage. Materials & Methods: We enumerated EPC-EC by using Enrichment kit with addition of anti-human CD146-PE/Cy7 from peripheral blood mononuclear cell (PBMC) isolated either by red blood cell (RBC) lysing solution or by Ficoll centrifugation, and from fresh and preserved samples. PBMCs were quantified by flow cytometry. Results: RBC lysis yielded higher percentage of PBMC (p = 0.0242) and higher numbers of PBMC/ml (p = 0.0039) than Ficoll. Absolute numbers of CD34+CD133+VEGFR2+ and CD146+CD34+VEGFR2+ were higher (p = 0.0117 for both), when isolated by RBC lysis than by Ficoll, when no difference in other subsets was found. Cryopreservation at -160 degrees C and -80 degrees C and short-term preservation at room temperature decreased EPCEC. Conclusions: Our data support use of fresh samples and isolation of PBMC from human blood by RBC lysis for enumeration of EPC and EC. C1 [Bogoslovsky, Tanya; Gong, Yunhua; Qu, Baoxi; Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Rockville, MD 20852 USA. [Bogoslovsky, Tanya; Spatz, Maria; Hallenbeck, John] NINDS, Stroke Branch, Bethesda, MD 20814 USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, Bethesda, MD 20814 USA. [Yang, Kelly] NINDS, Bethesda, MD 20814 USA. RP Bogoslovsky, T (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM tanya.bogoslovsky.ctr@usuhs.edu FU Department of Defense in the Center for Neuroscience and Regenerative Medicine; Intramural Research Program of NIH, NINDS FX Support for this work included funding from Department of Defense in the Center for Neuroscience and Regenerative Medicine and from the Intramural Research Program of NIH, NINDS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 68 TC 5 Z9 5 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PY 2015 VL 9 IS 7 BP 625 EP 637 DI 10.2217/BMM.15.34 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CM8KR UT WOS:000357950100003 PM 26174838 ER PT J AU Walitt, B Urrutia, G Nishishinya, MB Cantrell, SE Hauser, W AF Walitt, Brian Urrutia, Gerard Betina Nishishinya, Maria Cantrell, Sarah E. Haeuser, Winfried TI Selective serotonin reuptake inhibitors for fibromyalgia syndrome SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID BIOGENIC-AMINE METABOLITES; DOUBLE-BLIND; GENERAL-POPULATION; LONGITUDINAL DATA; CONTROLLED TRIAL; ANTIDEPRESSANTS; METAANALYSIS; PAROXETINE; PREVALENCE; FLUOXETINE AB Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17. SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement. SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05. Authors' conclusions There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate. C1 [Walitt, Brian] NIH, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA. [Urrutia, Gerard] CIBER Epidemiol & Salud Publ, Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Barcelona, Spain. [Betina Nishishinya, Maria] Inst Biomed Res IIB St Pau, Iberoamer Cochrane Ctr, Barcelona, Spain. [Cantrell, Sarah E.] Walter Reed Natl Mil Med Ctr, Darnall Med Lib, Bethesda, MD USA. [Haeuser, Winfried] Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, D-80290 Munich, Germany. RP Walitt, B (reprint author), NIH, Natl Ctr Complementary & Integrat Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM brian.walitt@nih.gov RI Cantrell, Sarah/A-1966-2016; OI Cantrell, Sarah/0000-0003-2694-7836; Urrutia, Gerard/0000-0002-8850-0960 FU Iberoamerican Cochrane Centre, Spain; Agencia d'Avaluacio de Tecnologia i Recerca Mediques, Spain [146/24/2004] FX Internal sources; Iberoamerican Cochrane Centre, Spain.; External sources; Agencia d'Avaluacio de Tecnologia i Recerca Mediques (146/24/2004), Spain. NR 74 TC 3 Z9 3 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2015 IS 6 AR CD011735 DI 10.1002/14651858.CD011735 PG 66 WC Medicine, General & Internal SC General & Internal Medicine GA CM3TE UT WOS:000357606400079 PM 26046493 ER PT J AU Patwardhan, M Hernandez-Andrade, E Ahn, H Korzeniewski, SJ Schwartz, A Hassan, SS Romero, R AF Patwardhan, Manasi Hernandez-Andrade, Edgar Ahn, Hyunyoung Korzeniewski, Steven J. Schwartz, Alyse Hassan, Sonia S. Romero, Roberto TI Dynamic Changes in the Myometrium during the Third Stage of Labor, Evaluated Using Two-Dimensional Ultrasound, in Women with Normal and Abnormal Third Stage of Labor and in Women with Obstetric Complications SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Pregnancy; Labor; Myometrial thickness; Uterine contractions; Postpartum hemorrhage; Clinical chorioamnionitis; Preterm delivery; Prolonged third stage of labor ID FETAL HEAD POSITION; INTRAPARTUM TRANSLABIAL ULTRASOUND; OCCIPUT POSTERIOR POSITION; TRANSVAGINAL DIGITAL EXAMINATION; INTRAUTERINE PRESSURE CATHETER; COLOR DOPPLER SONOGRAPHY; SEGMENT HUMAN MYOMETRIUM; RAPID SPERM TRANSPORT; PROLONGED 1ST STAGE; UTERINE PERISTALSIS AB Objective: To investigate dynamic changes in myometrial thickness during the third stage of labor. Methods: Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the midregion of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. Results:There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. Conclusion: A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage. (C) 2015 S. Karger AG, Basel C1 [Patwardhan, Manasi; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Korzeniewski, Steven J.; Hassan, Sonia S.] Wayne State Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Korzeniewski, Steven J.; Schwartz, Alyse; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, DHHS, NIH, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD, NIH [HHSN 275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN 275201300006C. NR 124 TC 0 Z9 0 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 EI 1423-002X J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2015 VL 80 IS 1 BP 26 EP + DI 10.1159/000370001 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CN0MY UT WOS:000358109000006 PM 25634647 ER PT J AU Van der Heiden, E Delmarcelle, M Simon, P Counson, M Galleni, M Freedberg, DI Thompson, J Joris, B Battistel, MD AF Van der Heiden, Edwige Delmarcelle, Michael Simon, Patricia Counson, Melody Galleni, Moreno Freedberg, Daron I. Thompson, John Joris, Bernard Battistel, Marcos D. TI Synthesis and Physicochemical Characterization of D-Tagatose-1-Phosphate: The Substrate of the Tagatose-1-Phosphate Kinase in the Phosphotransferase System-Mediated D-Tagatose Catabolic Pathway of Bacillus licheniformis SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Tagatose; Phosphoenolpyruvate:sugar phosphotransferase system; Tagatose-1-phosphate kinase; Bacillus licheniformis; Klebsiella pneumoniae; P-31 and H-1 nuclear magnetic resonance; Nuclear magnetic resonance characterization of tagatose phosphate ID D-GALACTOSE METABOLISM; PHOSPHORYL TRANSFER COMPLEX; GLUCOSYL-D-FRUCTOSES; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; STREPTOCOCCUS-MUTANS; 6-PHOSPHATE PATHWAY; LACTOSE METABOLISM; BACTERIAL PHOSPHOENOLPYRUVATE; KLEBSIELLA-PNEUMONIAE AB We report the first enzymatic synthesis of D-tagatose-1-phosphate (Tag-1P) by the multicomponent phosphoenolpyruvate: sugar phosphotransferase system (PEP-PTS) present in tagatose-grown cells of Klebsiella pneumoniae. Physicochemical characterization by P-31 and H-1 nuclear magnetic resonance spectroscopy reveals that, in solution, this derivative is primarily in the pyranose form. Tag-1P was used to characterize the putative tagatose-1-phosphate kinase (TagK) of the Bacillus licheniformis PTS-mediated D-tagatose catabolic pathway (Bli -TagP). For this purpose, a soluble protein fusion was obtained with the 6 His-tagged trigger factor (TFHis6) of Escherichia coli. The active fusion enzyme was named TagK-TFHis6. Tag-1P and D-fructose-1-phosphate are substrates for the TagK-TFHis6 enzyme, whereas the isomeric derivatives D-tagatose-6-phosphate and D-fructose-6-phosphate are inhibitors. Studies of catalytic efficiency (k(cat)/K-m) reveal that the enzyme specificity is markedly in favor of Tag-1P as the substrate. Importantly, we show in vivo that the transfer of the phosphate moiety from PEP to the B. licheniformis tagatose-specific Enzyme II in E. coli is inefficient. The capability of the PTS general cytoplasmic components of B. subtilis, HPr and Enzyme I to restore the phosphate transfer is demonstrated. (C) 2015 S. Karger AG, Basel C1 [Van der Heiden, Edwige; Delmarcelle, Michael; Simon, Patricia; Galleni, Moreno; Joris, Bernard] Univ Liege, Inst Chim, Ctr Prot Engn, Sart Tilman Par Liege, Belgium. [Counson, Melody] NUTRILAB NV, Heusden Zolder, Belgium. [Freedberg, Daron I.; Battistel, Marcos D.] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Thompson, John] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Delmarcelle, M (reprint author), Univ Liege, Inst Chim B6a, CIP, BE-4000 Sart Tilman Par Liege, Belgium. EM michael.delmarcelle@ulg.ac.be FU Intramural Research Program of the NIDCR, National Institutes of Health, Bethesda, Md., USA; FRIA (Fonds de la Recherche pour l'Industrie et l'Agriculture) fellowship FX This work was supported in part by the Intramural Research Program of the NIDCR, National Institutes of Health, Bethesda, Md., USA. Edwige Van der Heiden was the recipient of a FRIA (Fonds de la Recherche pour l'Industrie et l'Agriculture) fellowship. We thank Eric Anderson, Noel Whittaker and Andreas Pikis for mass spectrometry data and technical assistance. We thank Regine Freichels for the gift of LacD enzyme. NR 40 TC 0 Z9 0 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 EI 1660-2412 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2015 VL 25 IS 2-3 BP 106 EP 119 DI 10.1159/000370115 PG 14 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA CM6XO UT WOS:000357834900004 PM 26159072 ER PT J AU Herman, JP Bogadhi, AR Krauzlis, RJ AF Herman, James P. Bogadhi, Amarender R. Krauzlis, Richard J. TI Effects of spatial cues on color-change detection in humans SO JOURNAL OF VISION LA English DT Article DE spatial attention; color; change detection ID VISUAL-MOTION; CHROMATIC MECHANISMS; ATTENTION; VISION; ORIENTATION; EVOLUTION; CONTRAST; SENSITIVITY; PERFORMANCE; ADAPTATION AB Studies of covert spatial attention have largely used motion, orientation, and contrast stimuli as these features are fundamental components of vision. The feature dimension of color is also fundamental to visual perception, particularly for catarrhine primates, and yet very little is known about the effects of spatial attention on color perception. Here we present results using novel dynamic color stimuli in both discrimination and color-change detection tasks. We find that our stimuli yield comparable discrimination thresholds to those obtained with static stimuli. Further, we find that an informative spatial cue improves performance and speeds response time in a color-change detection task compared with an uncued condition, similar to what has been demonstrated for motion, orientation, and contrast stimuli. Our results demonstrate the use of dynamic color stimuli for an established psychophysical task and show that color stimuli are well suited to the study of spatial attention. C1 [Herman, James P.; Bogadhi, Amarender R.; Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Herman, JP (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49 Room 2A50, Bethesda, MD 20892 USA. EM hermanj@gmail.com OI Herman, James/0000-0001-6916-2807 FU National Eye Institute Intramural Research Program at the National Institutes of Health FX This work was supported by the National Eye Institute Intramural Research Program at the National Institutes of Health. NR 38 TC 1 Z9 1 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2015 VL 15 IS 6 AR 3 DI 10.1167/15.6.3 PG 16 WC Ophthalmology SC Ophthalmology GA CM7GK UT WOS:000357858600003 PM 26047359 ER PT J AU Huang, PH Ren, LQ Nama, N Li, SX Li, P Yao, XL Cuento, RA Wei, CH Chen, YC Xie, YL Nawaz, AA Alevy, YG Holtzman, MJ Mccoy, JP Levinec, SJ Huang, TJ AF Huang, Po-Hsun Ren, Liqiang Nama, Nitesh Li, Sixing Li, Peng Yao, Xianglan Cuento, Rosemarie A. Wei, Cheng-Hsin Chen, Yuchao Xie, Yuliang Nawaz, Ahmad Ahsan Alevy, Yael G. Holtzman, Michael J. Mccoy, J. Philip Levinec, Stewart J. Huang, Tony Jun TI An acoustofluidic sputum liquefier SO LAB ON A CHIP LA English DT Article ID SURFACE ACOUSTIC-WAVES; CIRCULATING TUMOR-CELLS; MICROFLUIDIC PLATFORM; OSCILLATING BUBBLES; DRUG DISCOVERY; SHARP-EDGES; TUBERCULOSIS; CHIP; DIAGNOSTICS; SEPARATION AB We demonstrate the first microfluidic-based on-chip liquefaction device for human sputum samples. Our device is based on an acoustofluidic micromixer using oscillating sharp edges. This acoustofluidic sputum liquefier can effectively and uniformly liquefy sputum samples at a throughput of 30 mu L min(-1). Cell viability and integrity are maintained during the sputum liquefaction process. Our acoustofluidic sputum liquefier can be conveniently integrated with other microfluidic units to enable automated on-chip sputum processing and analysis. C1 [Huang, Po-Hsun; Ren, Liqiang; Nama, Nitesh; Li, Sixing; Li, Peng; Chen, Yuchao; Xie, Yuliang; Nawaz, Ahmad Ahsan; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA. [Li, Sixing] Penn State Univ, Huck Inst Life Sci, Cell & Dev Biol CDB Grad Program, University Pk, PA 16802 USA. [Yao, Xianglan; Cuento, Rosemarie A.; Mccoy, J. Philip; Levinec, Stewart J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Wei, Cheng-Hsin] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Xie, Yuliang; Huang, Tony Jun] Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA. [Alevy, Yael G.; Holtzman, Michael J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA. EM junhuang@psu.edu RI Huang, Po-Hsun/A-2713-2015; Ren, Liqiang/E-8953-2015; Li, Sixing/F-2383-2013; Li, Peng/B-3054-2013; Huang, Tony/A-1546-2009; Nama, Nitesh/E-9030-2014 OI Huang, Po-Hsun/0000-0001-9600-0141; Ren, Liqiang/0000-0003-0863-4609; Li, Peng/0000-0002-8332-7142; FU American Asthma Foundation (AAF) Scholar Award; National Science Foundation [IIP-1346440]; NHLBI Division of Intramural Research; NSF FX This research was supported by the American Asthma Foundation (AAF) Scholar Award, the National Science Foundation (IIP-1346440) and the NHLBI Division of Intramural Research. Components of this work were conducted at the Penn State node of the NSF-funded National Nanotechnology Infrastructure Network. NR 43 TC 11 Z9 11 U1 7 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2015 VL 15 IS 15 BP 3125 EP 3131 DI 10.1039/c5lc00539f PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CM9IU UT WOS:000358022900004 PM 26082346 ER PT S AU Boehm, KM Wang, SJ Burtt, KE Turkbey, B Weisenthal, S Pinto, P Choyke, P Wood, BJ Petrick, N Sahiner, B Summers, RM AF Boehm, Kevin M. Wang, Shijun Burtt, Karen E. Turkbey, Baris Weisenthal, Samuel Pinto, Peter Choyke, Peter Wood, Bradford J. Petrick, Nicholas Sahiner, Berkman Summers, Ronald M. BE Hadjiiski, LM Tourassi, GD TI Efficient Hilbert transform-based alternative to Tofts physiological models for representing MRI dynamic contrast-enhanced images in computer-aided diagnosis of prostate cancer SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Feature selection; prostate cancer; computer-aided diagnosis; multi-parametric MRI; DCE; Ktrans ID MANAGEMENT; TRACER AB In computer-aided diagnosis (CAD) systems for prostate cancer, dynamic contrast enhanced (DCE) magnetic resonance imaging is useful for distinguishing cancerous and benign tissue. The Tofts physiological model is a commonly used representation of the DCE image data, but the parameters require extensive computation. Hence, we developed an alternative representation based on the Hilbert transform of the DCE images. The time maximum of the Hilbert transform, a binary metric of early enhancement, and a pre-DCE value was assigned to each voxel and appended to a standard feature set derived from T2-weighted images and apparent diffusion coefficient maps. A cohort of 40 patients was used for training the classifier, and 20 patients were used for testing. The AUC was calculated by pooling the voxel-wise prediction values and comparing with the ground truth. The resulting AUC of 0.92 (95% CI [0.87 0.97]) is not significantly different from an AUC calculated using Tofts physiological models of 0.92 (95% CI [0.87 0.97]), as validated by a Wilcoxon signed rank test on each patient's AUC (p = 0.19). The time required for calculation and feature extraction is 11.39 seconds (95% CI [10.95 11.82]) per patient using the Hilbert-based feature set, two orders of magnitude faster than the 1319 seconds (95% CI [1233 1404]) required for the Tofts parameter-based feature set (p<0.001). Hence, the features proposed herein appear useful for CAD systems integrated into clinical workflows where efficiency is important. C1 [Boehm, Kevin M.; Wang, Shijun; Burtt, Karen E.; Weisenthal, Samuel; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Turkbey, Baris; Pinto, Peter; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Intervent Radiol Sect, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Petrick, Nicholas; Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 13 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94140S DI 10.1117/12.2082309 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600027 ER PT S AU Hoffman, J Liu, JM Turkbey, E Kim, L Summers, RM AF Hoffman, Joanne Liu, Jiamin Turkbey, Evrim Kim, Lauren Summers, Ronald M. BE Hadjiiski, LM Tourassi, GD TI Automatic Identification of IASLC-defined Mediastinal Lymph Node Stations on CT scans using Multi-atlas Organ Segmentation SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Lymph node station labeling; multi-atlas label fusion ID LUNG-CANCER AB Station-labeling of mediastinal lymph nodes is typically performed to identify the location of enlarged nodes for cancer staging. Stations are usually assigned in clinical radiology practice manually by qualitative visual assessment on CT scans, which is time consuming and highly variable. In this paper, we developed a method that automatically recognizes the lymph node stations in thoracic CT scans based on the anatomical organs in the mediastinum. First, the trachea, lungs, and spines are automatically segmented to locate the mediastinum region. Then, eight more anatomical organs are simultaneously identified by multi-atlas segmentation. Finally, with the segmentation of those anatomical organs, we convert the text definitions of the International Association for the Study of Lung Cancer (IASLC) lymph node map into patient-specific color-coded CT image maps. Thus, a lymph node station is automatically assigned to each lymph node. We applied this system to CT scans of 86 patients with 336 mediastinal lymph nodes measuring equal or greater than 10 mm. 84.8% of mediastinal lymph nodes were correctly mapped to their stations. C1 [Hoffman, Joanne; Liu, Jiamin; Turkbey, Evrim; Kim, Lauren; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94141R DI 10.1117/12.2082190 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600061 ER PT S AU Liu, JM Chang, K Kim, L Turkbey, E Lu, L Yao, JH Summers, RM AF Liu, Jiamin Chang, Kevin Kim, Lauren Turkbey, Evrim Lu, Le Yao, Jianhua Summers, Ronald M. BE Hadjiiski, LM Tourassi, GD TI Automated Segmentation of Thyroid Gland on CT images with Multi-atlas Label Fusion and Random Classification Forest SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Thyroid gland segmentation; multi-atlas label fusion; random classification forest AB The thyroid gland plays an important role in clinical practice, especially for radiation therapy treatment planning. For patients with head and neck cancer, radiation therapy requires a precise delineation of the thyroid gland to be spared on the pre-treatment planning CT images to avoid thyroid dysfunction. In the current clinical workflow, the thyroid gland is normally manually delineated by radiologists or radiation oncologists, which is time consuming and error prone. Therefore, a system for automated segmentation of the thyroid is desirable. However, automated segmentation of the thyroid is challenging because the thyroid is inhomogeneous and surrounded by structures that have similar intensities. In this work, the thyroid gland segmentation is initially estimated by multi-atlas label fusion algorithm. The segmentation is refined by supervised statistical learning based voxel labeling with a random forest algorithm. Multi-atlas label fusion (MALF) transfers expert-labeled thyroids from atlases to a target image using deformable registration. Errors produced by label transfer are reduced by label fusion that combines the results produced by all atlases into a consensus solution. Then, random forest (RF) employs an ensemble of decision trees that are trained on labeled thyroids to recognize features. The trained forest classifier is then applied to the thyroid estimated from the MALF by voxel scanning to assign the class-conditional probability. Voxels from the expert-labeled thyroids in CT volumes are treated as positive classes; background non-thyroid voxels as negatives. We applied this automated thyroid segmentation system to CT scans of 20 patients. The results showed that the MALF achieved an overall 0.75 Dice Similarity Coefficient (DSC) and the RF classification further improved the DSC to 0.81. C1 [Liu, Jiamin; Chang, Kevin; Kim, Lauren; Turkbey, Evrim; Lu, Le; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 8 TC 1 Z9 1 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 941413 DI 10.1117/12.2082204 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600037 ER PT S AU Stieger, J Burns, JE Yao, JH Summers, RM AF Stieger, James Burns, Joseph E. Yao, Jianhua Summers, Ronald M. BE Hadjiiski, LM Tourassi, GD TI Dynamic Cortex Stripping For Vertebra Evaluation SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE CAD; Image Processing; CBR; Volume Rendering AB Vertebral cortex removal through cancellous bone reconstruction (CBR) algorithms on CT has been shown to enhance the detection rate of bone metastases by radiologists and reduce average reading time per case. Removal of the cortical bone provides an unobstructed view of the inside of vertebrae without any anomalous distractions. However, these algorithms rely on the assumption that the cortical bone of vertebrae can be removed without the identification of the endosteal cortical margin. We present a method for the identification of the endosteal cortical margin based on vertebral models and CT intensity information. First, triangular mesh models are created using the marching cubes algorithm. A search region is established along the normal of the surface and the image gradient is calculated at every point along the search region. The location with the greatest image gradient is selected as the corresponding point on the endosteal cortical margin. In order to analyze the strength of this method, ground truth and control models were also created. Our method was shown to significantly reduce the average error from 0.80 mm +/-0.14 mm to 0.65 mm +/-0.17 mm (p < 0.0001) when compared to erosion. This method can potentially improve CBR algorithms, which improve visualization of cancellous bone lesions such as metastases, by more accurately identifying the inner wall of the vertebral cortex. C1 [Stieger, James; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. [Burns, Joseph E.] Univ Calif Irvine, Sch Med, Dept Radiol Sci, Irvine, CA 92717 USA. RP Stieger, J (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94143D DI 10.1117/12.2082434 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600114 ER PT S AU Wong, KCL Tee, M Chen, M Bluemke, DA Summers, RM Yao, JH AF Wong, Ken C. L. Tee, Michael Chen, Marcus Bluemke, David A. Summers, Ronald M. Yao, Jianhua BE Hadjiiski, LM Tourassi, GD TI Myocardial strain estimation from CT: towards computer-aided diagnosis on infarction identification SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Cardiac computed tomography; cardiac deformation recovery; computer-aided diagnosis; finite element methods; hyperelastic biomechanical model; myocardial infarction; myocardial strain estimation ID MEDICAL IMAGES; HEART; DEFORMATION; MODELS; MRI AB Regional myocardial strains have the potential for early quantification and detection of cardiac dysfunctions. Although image modalities such as tagged and strain-encoded MRI can provide motion information of the myocardium, they are uncommon in clinical routine. In contrary, cardiac CT images are usually available, but they only provide motion information at salient features such as the cardiac boundaries. To estimate myocardial strains from a CT image sequence, we adopted a cardiac biomechanical model with hyperelastic material properties to relate the motion on the cardiac boundaries to the myocardial deformation. The frame-to-frame displacements of the cardiac boundaries are obtained using B-spline deformable image registration based on mutual information, which are enforced as boundary conditions to the biomechanical model. The system equation is solved by the finite element method to provide the dense displacement field of the myocardium, and the regional values of the three principal strains and the six strains in cylindrical coordinates are computed in terms of the American Heart Association nomenclature. To study the potential of the estimated regional strains on identifying myocardial infarction, experiments were performed on cardiac CT image sequences of ten canines with artificially induced myocardial infarctions. The leave-one-subject-out cross validations show that, by using the optimal strain magnitude thresholds computed from ROC curves, the radial strain and the first principal strain have the best performance. C1 [Wong, Ken C. L.; Tee, Michael; Bluemke, David A.; Summers, Ronald M.; Yao, Jianhua] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Chen, Marcus] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Tee, Michael] Univ Oxford, Inst Biomed Engn, Oxford, England. RP Yao, JH (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM ken.wong@nih.gov; jyao@cc.nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 19 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 941434 DI 10.1117/12.2081464 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600107 ER PT S AU Xu, T Huang, XL Kim, E Long, LR Antani, S AF Xu, Tao Huang, Xiaolei Kim, Edward Long, L. Rodney Antani, Sameer BE Hadjiiski, LM Tourassi, GD TI Multi-Test Cervical Cancer Diagnosis with Missing Data Estimation SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Cervical dysplasia; automated screening; disease classification; missing data estimation ID CERVICOGRAPHY; LESIONS; TRIAGE AB Cervical cancer is a leading most common type of cancer for women worldwide. Existing screening programs for cervical cancer suffer from low sensitivity. Using images of the cervix (cervigrams) as an aid in detecting pre-cancerous changes to the cervix has good potential to improve sensitivity and help reduce the number of cervical cancer cases. In this paper, we present a method that utilizes multi-modality information extracted from multiple tests of a patient's visit to classify the patient visit to be either low-risk or high-risk. Our algorithm integrates image features and text features to make a diagnosis. We also present two strategies to estimate the missing values in text features: Image Classifier Supervised Mean Imputation (ICSMI) and Image Classifier Supervised Linear Interpolation (ICSLI). We evaluate our method on a large medical dataset and compare it with several alternative approaches. The results show that the proposed method with ICSLI strategy achieves the best result of 83.03% specificity and 76.36% sensitivity. When higher specificity is desired, our method can achieve 90% specificity with 62.12% sensitivity. C1 [Xu, Tao; Huang, Xiaolei] Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. [Kim, Edward] Villanova Univ, Dept Comp Sci, Villanova, PA 19085 USA. [Long, L. Rodney; Antani, Sameer] Natl Lib Med, Commun Engn Branch, Bethesda, MD 20894 USA. RP Xu, T (reprint author), Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94140X DI 10.1117/12.2080871 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600031 ER PT J AU Tekola-Ayele, F Rotimi, CN AF Tekola-Ayele, Fasil Rotimi, Charles N. TI Translational Genomics in Low- and Middle-Income Countries: Opportunities and Challenges SO PUBLIC HEALTH GENOMICS LA English DT Article DE Genomics; Translational research; Genomic medicine; Next-generation sequencing; Genetic testing; Family health history; Global health ID SICKLE-CELL-DISEASE; CHRONIC KIDNEY-DISEASE; APOL1 RISK VARIANTS; GENETIC-VARIATION; HEPATITIS-C; ETHIOPIAN POPULATION; PREVENTIVE MEDICINE; ASTHMATIC-CHILDREN; AFRICA EXPERIENCE; FAMILY-HISTORY AB Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low- and middle-income countries (LMIC) have participated minimally in genomic research for several reasons including the lack of coherent national policies, the limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genonne Project, and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomic research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and sociocultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomic research, we advocate that large-scale genomic research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and sociocultural uniqueness. These policies should encourage international collaboration and promote the link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC. 2015 S.Karger AG, Basel C1 [Tekola-Ayele, Fasil; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Tekola-Ayele, F (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 South Dr, Bethesda, MD 20892 USA. EM ayeleft@mail.nih.gov; rotimic@mail.nih.gov OI Tekola-Ayele, Fasil/0000-0003-4194-9370 FU National Human Genome Research Institute, NIH, in the Center for Research on Genomics and Global Health (CRGGH); National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; NIH [1ZIAHG200362] FX The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health (NIH). The authors are supported by the Intramural Research Program of the National Human Genome Research Institute, NIH, in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the NIH (1ZIAHG200362). NR 46 TC 7 Z9 7 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2015 VL 18 IS 4 BP 242 EP 247 DI 10.1159/000433518 PG 6 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA CN0MS UT WOS:000358108300007 PM 26138992 ER PT S AU Heffner, K Kaas, CS Kumar, A Baycin-Hizal, D Betenbaugh, M AF Heffner, Kelley Kaas, Christian Schroeder Kumar, Amit Baycin-Hizal, Deniz Betenbaugh, Michael BE AlRubeai, M TI Proteomics in Cell Culture: From Genomics to Combined 'Omics for Cell Line Engineering and Bioprocess Development SO ANIMAL CELL CULTURE SE Cell Engineering LA English DT Article; Book Chapter DE Proteomics; Genomics; Transcriptomics; Metabolomics; Bioprocess development; Cell line engineering; Bioinformatics ID HAMSTER OVARY CELLS; CHO-CELLS; 2-DIMENSIONAL ELECTROPHORESIS; SAMPLE PREPARATION; MASS-SPECTROMETRY; SODIUM-BUTYRATE; MESSENGER-RNA; AMINO-ACIDS; GROWTH-RATE; EXPRESSION AB The genetic sequencing of Chinese hamster ovary cells has initiated a systems biology era for biotechnology applications. In addition to genomics, critical 'omics data sets also include proteomics, transcriptomics and metabolomics. Recently, the use of proteomics in cell lines for recombinant protein production has increased significantly because proteomics can track changes in protein levels for different cell lines over time, which can be advantageous for bioprocess development and optimization. Specifically, the identification of proteins that affect cell culture processes can aid efforts in media development and cell line engineering to improve growth or productivity, delay the onset of apoptosis, or utilize nutrients efficiently. Mass-spectrometry based and other proteomics methods can provide for the detection of thousands of proteins from cell culture and bioinformatics analysis serves to identify and quantify protein levels. Optimizations of sample preparations and database development, including a detailed CHO proteome now available, have improved the quantity and accuracy of identified proteins. The applications are widespread and expanding, thus suggesting numerous applications of proteomics and combined 'omics experiments in coming years. C1 [Heffner, Kelley; Kumar, Amit; Baycin-Hizal, Deniz; Betenbaugh, Michael] Johns Hopkins Univ, Chem & Biomol Engn, Baltimore, MD 21218 USA. [Kaas, Christian Schroeder] Tech Univ Denmark, Network Engn Eukaryot Cell Factories, DK-2800 Lyngby, Denmark. [Kumar, Amit] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD USA. RP Betenbaugh, M (reprint author), Johns Hopkins Univ, Chem & Biomol Engn, Baltimore, MD 21218 USA. EM beten@jhu.edu NR 53 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1389-6946 BN 978-3-319-10320-4; 978-3-319-10319-8 J9 CELL ENG PY 2015 VL 9 BP 591 EP 614 DI 10.1007/978-3-319-10320-4_19 D2 10.1007/978-3-319-10320-4 PG 24 WC Cell & Tissue Engineering SC Cell Biology GA BD0XP UT WOS:000357817100020 ER PT S AU Skau, CT Waterman, CM AF Skau, Colleen T. Waterman, Clare M. BE Dill, KA TI Specification of Architecture and Function of Actin Structures by Actin Nucleation Factors SO ANNUAL REVIEW OF BIOPHYSICS, VOL 44 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE formin; Arp2/3; contractile ring; stress fiber; lamellipodium ID CLATHRIN-MEDIATED ENDOCYTOSIS; FORMIN HOMOLOGY-2 DOMAIN; ARP2/3 COMPLEX; CONTRACTILE RING; MYOSIN-II; MITOCHONDRIAL FISSION; BARBED END; ADHESIVE CONTACTS; FOCAL ADHESIONS; STRESS FIBERS AB The actin cytoskeleton is essential for diverse processes in mammalian cells; these processes range from establishing cell polarity to powering cell migration to driving cytokinesis to positioning intracellular organelles. How these many functions are carried out in a spatiotemporally regulated manner in a single cytoplasm has been the subject of much study in the cytoskeleton field. Recent work has identified a host of actin nucleation factors that can build architecturally diverse actin structures. The biochemical properties of these factors, coupled with their cellular location, likely define the functional properties of actin structures. In this article, we describe how recent advances in cell biology and biochemistry have begun to elucidate the role of individual actin nucleation factors in generating distinct cellular structures. We also consider how the localization and orientation of actin nucleation factors, in addition to their kinetic properties, are critical to their ability to build a functional actin cytoskeleton. C1 [Skau, Colleen T.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM colleen.skau@nih.gov; watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775 FU Intramural NIH HHS NR 141 TC 12 Z9 12 U1 3 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1844-4 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2015 VL 44 BP 285 EP 310 DI 10.1146/annurev-biophys-060414-034308 PG 26 WC Biophysics SC Biophysics GA BD0LD UT WOS:000357297800013 PM 26098516 ER PT S AU Forrest, LR AF Forrest, Lucy R. BE Dill, KA TI Structural Symmetry in Membrane Proteins SO ANNUAL REVIEW OF BIOPHYSICS, VOL 44 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE oligomer; internal repeats; inverted-topology repeats; asymmetry; alternating access ID X-RAY-STRUCTURE; RESPIRATORY COMPLEX I; FAMILY INTRAMEMBRANE PROTEASE; INWARD-FACING CONFORMATION; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; ABC TRANSPORTER AB Symmetry is a common feature among natural systems, including protein structures. A strong propensity toward symmetric architectures has long been recognized for water-soluble proteins, and this propensity has been rationalized from an evolutionary standpoint. Proteins residing in cellular membranes, however, have traditionally been less amenable to structural studies, and thus the prevalence and significance of symmetry in this important class of molecules is not as well understood. In the past two decades, researchers have made great strides in this area, and these advances have provided exciting insights into the range of architectures adopted by membrane proteins. These structural studies have revealed a similarly strong bias toward symmetric arrangements, which were often unexpected and which occurred despite the restrictions imposed by the membrane environment on the possible symmetry groups. Moreover, membrane proteins disproportionately contain internal structural repeats resulting from duplication and fusion of smaller segments. This article discusses the types and origins of symmetry in membrane proteins and the implications of symmetry for protein function. C1 NINDS, Computat Struct Biol Grp, Porter Neurosci Ctr, NIH, Rockville, MD 20852 USA. RP Forrest, LR (reprint author), NINDS, Computat Struct Biol Grp, Porter Neurosci Ctr, NIH, Rockville, MD 20852 USA. EM lucy.forrest@nih.gov FU Intramural NIH HHS NR 168 TC 13 Z9 13 U1 8 U2 30 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1844-4 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2015 VL 44 BP 311 EP 337 DI 10.1146/annurev-biophys-051013-023008 PG 27 WC Biophysics SC Biophysics GA BD0LD UT WOS:000357297800014 PM 26098517 ER PT J AU Wolford, JE Tewari, KS AF Wolford, Juliet E. Tewari, Krishnansu S. TI US FDA oncology drug approvals in 2014 SO FUTURE ONCOLOGY LA English DT Review DE accelerated approval; cancer drugs; orphan drug designation; priority review; US FDA; regulatory approval ID OLAPARIB MAINTENANCE THERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; OVARIAN-CANCER; ADVANCED MELANOMA; ATTRITION RATES; PHASE-3 TRIAL; DOUBLE-BLIND; MULTICENTER; BEVACIZUMAB AB Cancer is a close second to heart disease for cause of death in the USA, and could soon surpass heart disease as the population ages and the incidence of cancer continues to increase. While heart disease can be addressed through behavior modification and education (e. g., smoking cessation, dietary changes, exercises that promote cardiovascular fitness), pharmacology and improved surgical devices and methods, cancer ultimately requires improved and novel drug treatments to bring mortality rates down. In 2014, the US FDA approved 17 drugs and/or drug combinations in 12 disease sites for a total of 19 indications in melanoma, hematologic malignancies, gastrointestinal carcinoma, non-small-cell lung cancer, gynecologic malignancies and lymphoma/lymphoproliferative disorders. C1 [Wolford, Juliet E.; Tewari, Krishnansu S.] Univ Calif Irvine, Med Ctr, Chao Family NCI Designated Comprehens Canc Ctr, Orange, CA 92868 USA. RP Tewari, KS (reprint author), Univ Calif Irvine, Med Ctr, Chao Family NCI Designated Comprehens Canc Ctr, 101 City Dr South,Bldg 56, Orange, CA 92868 USA. EM ktewari@uci.edu NR 35 TC 2 Z9 2 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 13 BP 1931 EP 1945 DI 10.2217/FON.15.106 PG 15 WC Oncology SC Oncology GA CM5QI UT WOS:000357743000010 PM 26039742 ER PT J AU Parekh, VI Modali, SD Desai, SS Agarwal, SK AF Parekh, Vaishali I. Modali, Sita D. Desai, Shruti S. Agarwal, Sunita K. TI Consequence of Menin Deficiency in Mouse Adipocytes Derived by In Vitro Differentiation SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; ACTIVATED-RECEPTOR-GAMMA; EMBRYONIC STEM-CELLS; ADIPOSE CONVERSION; GENE; TUMORS; EXPRESSION; PITUITARY; METHYLATION; DELETION AB Lipoma in patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome is a type of benign fat-cell tumor that has biallelic inactivation of MEN1 that encodes menin and could serve as a model to investigate normal and pathologic fat-cell ( adipocyte) proliferation and function. The role of menin and its target genes in adipocytes is not known. We used in vitro differentiation to derive matched normal and menin-deficient adipocytes from wild type (WT) and menin-null (Men1-KO) mouse embryonic stem cells (mESCs), respectively, or 3T3-L1 cells without or with menin knockdown to investigate cell size, lipid content, and gene expression changes. Adipocytes derived from Men1-KO mESCs or after menin knockdown in 3T3-L1 cells showed a 1.5-1.7-fold increase in fat-cell size. Global gene expression analysis of mESC-derived adipocytes showed that lack of menin downregulated the expression of many differentially methylated genes including the tumor suppressor long noncoding RNA Meg3 but upregulated gene expression from the prolactin gene family locus. Our results show that menin deficiency leads to fat-cell hypertrophy and provide model systems that could be used to study the regulation of fat-cell size. C1 [Parekh, Vaishali I.; Modali, Sita D.; Desai, Shruti S.; Agarwal, Sunita K.] NIDDKD, NIH, Metab Dis Branch, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIDDKD, NIH, Metab Dis Branch, Bethesda, MD 20892 USA. EM sunitaa@mail.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU Intramural Research Program of the NIH, NIDDK [1ZIADK075035-03] FX The authors are grateful to Settara Chandrasekarappa of the NHGRI for kindly providing the WT and Men1-KO mESCs. They thank the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) genomics core facility (Chithra Keembiyehetty and Weiping Chen) for their advice and help in generating microarray data. This work was supported by the Intramural Research Program of the NIH, NIDDK (SKA; Project no. 1ZIADK075035-03). All the gene expression microarray data generated for this study are deposited in the NCBI GEO repository under accession no. GSE65859. NR 36 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2015 AR 149826 DI 10.1155/2015/149826 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM6OG UT WOS:000357807600001 ER PT J AU Soliman, SE Bassily, RW El-Sokkary, RI Nashed, MA AF Soliman, Sameh E. Bassily, Rafik W. El-Sokkary, Ramadan I. Nashed, Mina A. TI A Convenient Synthesis of Partially Benzylated Derivative of beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-beta-D-Glcp-1-OBn as a Versatile Building Block for Sialyl Lewis X Antigens SO LETTERS IN ORGANIC CHEMISTRY LA English DT Article DE Carbohydrates; Building block; Oxazoline coupling; Cyclic orthoester; Sialyl Le(x) ID GANGLIOSIDE; SELECTINS; CERAMIDE; ADHESION; LIGANDS; RESIDUE; SUGARS AB Synthesis of the trisaccharide, benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranosyl-(1 -> 3)-2,4,6-tri-O-benzyl-beta-D-galactopyranosyl-(1 -> 4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (9), was achieved from building block derivatives of the component mono-and disaccharide units. Initially the benzyl lactoside acceptor 3, which has a free hydroxyl group at position O-3', was prepared via selective opening of the 3',4'-cyclic orthoester derivative 2. The glucosaminyl donor, 2-methyl (3,4,6-tri-O-acetyl-1,2-dideoxy-alpha-D-glucopyrano)-[2',1':4,5]-2-oxazoline (4), was coupled to 3 affording the trisaccharide glycoside 5 in a good yield. Successive de-O-acetylation (5 -> 6), benzylidenation (6 -> 7), benzylation (7 -> 8) and reductive opening of the benzylidene acetal function of 8 gave the target trisaccharide 9, which is a useful building block for the construction of complex oligosaccharides. C1 [Soliman, Sameh E.; Bassily, Rafik W.; El-Sokkary, Ramadan I.; Nashed, Mina A.] Univ Alexandria, Dept Chem, Fac Sci, Alexandria 21321, Egypt. [Soliman, Sameh E.] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. RP Nashed, MA (reprint author), Univ Alexandria, Dept Chem, Fac Sci, POB 426, Alexandria 21321, Egypt. EM mina4na@yahoo.com NR 22 TC 0 Z9 0 U1 2 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1786 EI 1875-6255 J9 LETT ORG CHEM JI Lett. Org. Chem. PY 2015 VL 12 IS 6 BP 413 EP 417 PG 5 WC Chemistry, Organic SC Chemistry GA CM4YF UT WOS:000357691900007 ER PT J AU Vanderwert, RE Simpson, EA Paukner, A Suomi, SJ Fox, NA Ferrari, PF AF Vanderwert, Ross E. Simpson, Elizabeth A. Paukner, Annika Suomi, Stephen J. Fox, Nathan A. Ferrari, Pier F. TI Early Social Experience Affects Neural Activity to Affiliative Facial Gestures in Newborn Nonhuman Primates SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Mirror neuron; Plasticity; Sensitive period; Action perception; Mu rhythm; Infants; Communication; Neonatal imitation; Electroencephalogram; Mother-infant interactions ID NEONATAL IMITATION; MU-RHYTHM; SENSITIVE PERIODS; MIRROR MECHANISM; FACE PERCEPTION; INFANTS; BRAIN; EEG; SYSTEM; DESYNCHRONIZATION AB A fundamental issue in cognitive neuroscience is how the brain encodes the actions and intentions of others. The discovery of an action-production-perception mechanism underpinning such a capacity advanced our knowledge of how these processes occur; however, no study has examined how the early postnatal environment may shape action-production-perception. Here, we examined the effects of social experience on action-production-perception in 3-day-old rhesus macaques that were raised either with or without their biological mothers. We measured the neonatal imitation skills and brain electrical activity responses, while infants produced and observed facial gestures. We hypothesized that early social experiences may shape brain activity, as assessed via electroencephalogram suppression in the a band (5-7 Hz in infants, known as the mu rhythm) during action observation, and lead to more proficient imitation skills. Consistent with this hypothesis, the infants reared by their mothers were more likely to imitate lipsmacking (LS) - a natural, affiliative gesture - and exhibited greater mu rhythm desynchronization while viewing LS gestures than the nursery-reared infants. These effects were not found in response to tongue protrusion, a meaningless gesture, or a nonsocial control. These data suggest that socially enriched early experiences in the first days after birth increase brain sensitivity to socially relevant actions. (C) 2015 S. Karger AG, Basel C1 [Vanderwert, Ross E.] Childrens Hosp Boston, Div Dev Med, Labs Cognit Neurosci, Boston, MA USA. [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, Child Dev Lab, College Pk, MD 20742 USA. [Simpson, Elizabeth A.; Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, IT-431000 Parma, Italy. RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Neurosci, Via Volturno 39, IT-431000 Parma, Italy. EM pierfrancesco.ferrari@unipr.it OI Vanderwert, Ross/0000-0002-2280-8401; Simpson, Elizabeth/0000-0003-2715-2533 FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [P01 HD064653] NR 53 TC 3 Z9 3 U1 1 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2015 VL 37 IS 3 BP 243 EP 252 DI 10.1159/000381538 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CL5XW UT WOS:000357039300005 PM 26022835 ER PT S AU Xiao, S Shiloach, J Grisshammer, R AF Xiao, Su Shiloach, Joseph Grisshammer, Reinhard BE Prazeres, DMF Martins, SAM TI Construction of Recombinant HEK293 Cell Lines for the Expression of the Neurotensin Receptor NTSR1 SO G PROTEIN-COUPLED RECEPTOR SCREENING ASSAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE G protein-coupled receptor (GPCR); Recombinant expression; Inducible mammalian cell line; HEK293 cells; T-REx(TM)-inducible expression system; Stable clone selection; Suspension culture; Neurotensin receptor; NTSR1 ID HIGH-LEVEL EXPRESSION; INTEGRAL MEMBRANE-PROTEINS; TETRACYCLINE RESISTANCE; MAMMALIAN-CELLS; OVEREXPRESSION; RHODOPSIN; REPRESSOR; GENE AB G protein-coupled receptors (GPCRs) are associated with a wide array of diseases and are targets of most of the medicines sold worldwide. Despite their clinical importance, only 25 unique GPCR structures have been determined as of April 2014. The first step for structural studies is to establish the expression of correctly folded, functional receptors in recombinant host cells at quantities to allow subsequent purification and crystallization trials. Here we describe the T-REx(TM)-inducible expression system to construct and select a stable HEK293 cell line for high-level expression of functional neurotensin receptor type I (NTSR1). We also present the protocols used for the adaptation of the cells into suspension culture, as well as the optimization of the induction parameters for NTSR1 expression, which led to 1 mg of purified NTSR1 per liter suspension culture in bioreactors. C1 [Xiao, Su; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Xiao, Su] Johns Hopkins Univ, Dept Chem & Biomol Engn, Bethesda, MD USA. [Grisshammer, Reinhard] NINDS, Membrane Prot Struct & Funct Unit, Rockville, MD USA. RP Xiao, S (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. RI Grisshammer, Reinhard/C-3089-2015 FU Intramural NIH HHS NR 19 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2336-6; 978-1-4939-2335-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1272 BP 51 EP 64 DI 10.1007/978-1-4939-2336-6_4 D2 10.1007/978-1-4939-2336-6 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BD0RC UT WOS:000357597500005 PM 25563176 ER PT B AU Spruijt-Metz, D Nilsen, W Pavel, M AF Spruijt-Metz, Donna Nilsen, Wendy Pavel, Misha BE Adibi, S TI mHealth for Behavior Change and Monitoring SO MHEALTH MULTIDISCIPLINARY VERTICALS LA English DT Article; Book Chapter ID RANDOMIZED-CONTROLLED-TRIAL; SMOKING-CESSATION SUPPORT; DISEASE PREVENTION; HEALTH-PROMOTION; SELF-MANAGEMENT; UNITED-STATES; OBESITY; INTERVENTIONS; TECHNOLOGY; APPS C1 [Spruijt-Metz, Donna] Univ So Calif, MHlth Collaboratory, Ctr Econ & Social Res, Los Angeles, CA 90089 USA. [Spruijt-Metz, Donna] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Spruijt-Metz, Donna] Univ So Calif, Keck Sch Med, Responsible Conduct Res, Los Angeles, CA 90033 USA. [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Washington, DC USA. [Nilsen, Wendy] Natl Sci Fdn, Smart & Connected Hlth Program, Div Informat & Intelligent Syst CISE IIS, Washington, DC 20550 USA. [Pavel, Misha] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. [Pavel, Misha] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. RP Spruijt-Metz, D (reprint author), Univ So Calif, MHlth Collaboratory, Ctr Econ & Social Res, Los Angeles, CA 90089 USA. NR 73 TC 1 Z9 1 U1 1 U2 6 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-1481-9; 978-1-4822-1480-2 PY 2015 BP 119 EP 132 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BC7ZB UT WOS:000355422300009 ER PT S AU Cozzitorto, JA Jimbo, M Chand, S Blanco, F Lal, S Gilbert, M Winter, JM Gorospe, M Brody, JR AF Cozzitorto, Joseph A. Jimbo, Masaya Chand, Saswati Blanco, Fernando Lal, Shruti Gilbert, Melissa Winter, Jordan M. Gorospe, Myriam Brody, Jonathan R. BE Nakagawa, S Hirose, T TI Studying RNA-Binding Protein Interactions with Target mRNAs in Eukaryotic Cells: Native Ribonucleoprotein Immunoprecipitation (RIP) Assays SO NUCLEAR BODIES AND NONCODING RNAS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNA-binding proteins; Ribonucleoprotein immunoprecipitation (RIP); RNA; Post-transcriptional gene regulation; RIP-seq AB Post-transcriptional regulation of mRNA can potently dictate protein expression patterns in eukaryotic cells. This mode of regulation occurs through cis-acting regulatory regions in the mRNA transcript that mediate direct interactions with trans-acting RNA-binding proteins (RBPs). This mRNA/protein interaction can be studied in numerous ways that range from in vitro to in vivo through messenger ribonucleoprotein immunoprecipitation (mRNP-IP or RIP) assays. This modified immunoprecipitation approach is an important and sensitive method to determine the regulation of gene expression by specific RBPs under different cellular stressors. C1 [Cozzitorto, Joseph A.; Jimbo, Masaya; Chand, Saswati; Blanco, Fernando; Lal, Shruti; Gilbert, Melissa; Winter, Jordan M.; Brody, Jonathan R.] Thomas Jefferson Univ, Dept Surg, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. [Gorospe, Myriam] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cozzitorto, JA (reprint author), Thomas Jefferson Univ, Dept Surg, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. OI Lal, Shruti/0000-0002-2091-4307 NR 6 TC 4 Z9 4 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2253-6; 978-1-4939-2252-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1262 BP 239 EP 246 DI 10.1007/978-1-4939-2253-6_14 D2 10.1007/978-1-4939-2253-6 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BD0TO UT WOS:000357692500015 PM 25555585 ER PT J AU Sullivan, EV Noronha, A AF Sullivan, Edith V. Noronha, Antonio TI Translating Alcohol Research Into Practice SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material C1 [Sullivan, Edith V.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Noronha, Antonio] NIAAA, Div Neurosci & Behav, Rockville, MD 20852 USA. RP Sullivan, EV (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2015 VL 37 IS 1 BP 1 EP 3 PG 3 WC Substance Abuse SC Substance Abuse GA CL5LF UT WOS:000357000700001 ER PT J AU Lovinger, DM Kash, TL AF Lovinger, David M. Kash, Thomas L. TI Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Review DE Alcohol consumption; ethanol exposure; alcohol use disorder; relapse; brain; neuroplasticity; synaptic function; synaptic plasticity; striatum; stria terminalis; bed nucleus of the stria terminalis ID LONG-TERM DEPRESSION; CORTICOSTRIATAL SYNAPTIC PLASTICITY; PAVLOVIAN-INSTRUMENTAL TRANSFER; NR2B-CONTAINING NMDA RECEPTORS; CEREBRAL HEMISPHERE REGULATION; TYROSINE-PHOSPHATASE ALPHA; ALCOHOL-DRINKING BEHAVIOR; VENTRAL TEGMENTAL AREA; DORSOMEDIAL STRIATUM; GABAERGIC TRANSMISSION AB Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction. Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake, The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder. C1 [Lovinger, David M.; Kash, Thomas L.] NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 USA. FU Division of Intramural Clinical and Biological Research of NIAAA; NIH [AA-019454, AA-020911, AA-011605] FX Some of the work discussed in this manuscript, and the preparation of the manuscript were supported by the Division of Intramural Clinical and Biological Research of NIAAA (D.M.L.) and by NIH grants AA-019454, AA-020911, AA-011605 to Thomas L. Kash. NR 112 TC 4 Z9 4 U1 0 U2 10 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2015 VL 37 IS 1 BP 109 EP 124 PG 16 WC Substance Abuse SC Substance Abuse GA CL5LF UT WOS:000357000700009 PM 26259092 ER PT J AU Skolnick, P White, D Acri, JB AF Skolnick, Phil White, David Acri, Jane B. TI Emerging Targets for Stimulant Use Disorders: Where To Invest In An Era Of Constrained Resources? SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Editorial Material ID METHAMPHETAMINE DEPENDENCE; DOUBLE-BLIND; TRIAL; MULTISITE; BUPROPION; EFFICACY C1 [Skolnick, Phil; White, David; Acri, Jane B.] NIDA, NIH, Bethesda, MD 20892 USA. RP Skolnick, P (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 6 BP 691 EP 691 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CL3XY UT WOS:000356886800002 PM 26073937 ER PT J AU Bachtell, R Hutchinson, MR Wang, XH Rice, KC Maier, SF Watkins, LR AF Bachtell, Ryan Hutchinson, Mark R. Wang, Xiaohui Rice, Kenner C. Maier, Steven F. Watkins, Linda R. TI Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4 SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE (+)-naloxone; (+)-naltrexone; alcohol; cocaine; drug reward; drug reinforcement; morphine; opioid; psychostimulants; reinstatement ID NF-KAPPA-B; MESOLIMBIC DOPAMINE SYSTEM; GLIAL-CELL MODULATORS; MORPHINE-TOLERANCE; NEUROPATHIC PAIN; PSYCHOSTIMULANT ABUSE; INDUCED NEUROTOXICITY; OPIOID ANALGESIA; GENE-EXPRESSION; BRAIN-DAMAGE AB There is growing recognition that glial proinflammatory activation importantly contributes to the rewarding and reinforcing effects of a variety of drugs of abuse, including cocaine, methamphetamine, opioids, and alcohol. It has recently been proposed that glia are recognizing, and becoming activated by, such drugs as a CNS immunological response to these agents being xenobiotics; that is, substances foreign to the brain. Activation of glia, primarily microglia, by various drugs of abuse occurs via toll like receptor 4 (TLR4). The detection of such xenobiotics by TLR4 results in the release of glial neuroexcitatory and neurotoxic substances. These glial products of TLR4 activation enhance neuronal excitability within brain reward circuitry, thereby enhancing their rewarding and reinforcing effects. Indeed, selective pharmacological blockade of TLR4 activation, such as with the non-opioid TLR4 antagonist (+)-naltrexone, suppresses a number of indices of drug reward/reinforcement. These include: conditioned place preference, self-administration, drug-primed reinstatement, incubation of craving, and elevations of nucleus accumbens shell dopamine. Notably, TLR4 blockade fails to alter self-administration of food, indicative of a selective effect on drugs of abuse. Genetic disruption of TLR4 signaling recapitulates the effects of pharmacological TLR4 blockade, providing converging lines of evidence of a central importance of TLR4. Taken together, multiple lines of evidence converge to raise TLR4 as a promising therapeutic target for drug abuse. C1 [Bachtell, Ryan; Wang, Xiaohui; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Bachtell, Ryan; Wang, Xiaohui; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA. [Hutchinson, Mark R.] Univ Adelaide, ARC Ctr Excellence Nanoscale Biophoton, Sch Med Sci, Discipline Physiol, Adelaide, SA 5005, Australia. [Wang, Xiaohui] Univ Colorado, BioFrontiers, Dept Chem & Biochem, Boulder, CO 80309 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA. RP Bachtell, R (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. EM ryan.bachtell@colorado.edu RI Wang, Xiaohui/B-8126-2011; OI Wang, Xiaohui/0000-0002-3415-5612; Hutchinson, Mark/0000-0003-2154-5950 FU NIH [R01 DA023132, DA033358]; DoD grant [PR110146]; Australian Research Council Research Fellowship [DP110100297] FX This work was supported in part by NIH R01 DA023132 and DA033358, DoD grant PR110146 and Australian Research Council Research Fellowship (DP110100297). NR 71 TC 7 Z9 8 U1 1 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 6 BP 692 EP 699 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CL3XY UT WOS:000356886800003 PM 26022268 ER PT J AU Skolnick, P White, D Acri, JB AF Skolnick, Phil White, David Acri, Jane B. TI Synopsis of Expert Opinions and Conclusions SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Editorial Material ID RECEPTOR C1 [Skolnick, Phil; White, David; Acri, Jane B.] NIDA, NIH, Bethesda, MD 20892 USA. RP Skolnick, P (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM jacri@nida.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 6 BP 773 EP 776 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CL3XY UT WOS:000356886800013 PM 26073938 ER PT J AU Beard, JD Kamel, F AF Beard, John D. Kamel, Freya TI Military Service, Deployments, and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology and Survival SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE amyotrophic lateral sclerosis; Gulf War; incidence; military personnel; mortality; motor neuron disease; occupational exposure; veterans ID GULF-WAR VETERANS; MOTOR-NEURON DISEASE; PROGNOSTIC-FACTORS; NATIONAL REGISTRY; RISK-FACTORS; HEXANUCLEOTIDE REPEAT; PARKINSONS-DISEASE; US VETERANS; FAR-EAST; ALS AB Rates of amyotrophic lateral sclerosis (ALS) have been reported to be higher among US military veterans, who currently number more than 21 million, but the causal factor(s) has not been identified. We conducted a review to examine the weight of evidence for associations between military service, deployments, and exposures and ALS etiology and survival. Thirty articles or abstracts published through 2013 were reviewed. Although the current evidence suggests a positive association with ALS etiology, it is too limited to draw firm conclusions regarding associations between military service and ALS etiology or survival. Some evidence suggests that deployment to the 1990-1991 Persian Gulf War may be associated with ALS etiology, but there is currently no strong evidence that any particular military exposure is associated with ALS etiology. Future studies should address the limitations of previous ones, such as reliance on mortality as a surrogate for incidence, a dearth of survival analyses, lack of clinical data, low statistical power, and limited exposure assessment. The Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis (GENEVA) Study is one such study, but additional research is needed to determine whether military-related factors are associated with ALS and to assess potential prevention strategies. C1 [Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kamel@niehs.nih.gov OI Kamel, Freya/0000-0001-5052-6615 FU Intramural Research Program of the National Institute of Environmental Health Sciences [Z01 ES049005]; National Institute of Environmental Health Sciences [T32ES007018]; National Institute for Occupational Safety and Health [T42OH00867302] FX This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (grant Z01 ES049005). J.D.B. was also supported by training grants from the National Institute of Environmental Health Sciences (grant T32ES007018) and the National Institute for Occupational Safety and Health (grant T42OH00867302). NR 77 TC 15 Z9 15 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2015 VL 37 IS 1 BP 55 EP 70 DI 10.1093/epirev/mxu001 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL3ZX UT WOS:000356892800005 PM 25365170 ER PT J AU Fliedner, SMJ Yang, CZ Thompson, E Abu-Asab, M Hsu, CM Lampert, G Eiden, L Tischler, AS Wesley, R Zhuang, ZP Lehnert, H Pacak, K AF Fliedner, Stephanie M. J. Yang, Chunzhang Thompson, Eli Abu-Asab, Mones Hsu, Chang-Mei Lampert, Gary Eiden, Lee Tischler, Arthur S. Wesley, Robert Zhuang, Zhengping Lehnert, Hendrik Pacak, Karel TI Potential therapeutic target for malignant paragangliomas: ATP synthase on the surface of paraganglioma cells SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Cell surface ATP synthase; paraganglioma; pheochromocytoma; resveratrol; mouse pheochromocytoma cells ID CANCER CHEMOPREVENTIVE AGENT; HEALTHY-VOLUNTEERS; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; CLINICAL-TRIALS; BETA-SUBUNIT; LUNG-CANCER; TUMOR-CELLS; RESVERATROL; MITOCHONDRIAL AB F1FoATP synthase (ATP synthase) is a ubiquitous enzyme complex in eukaryotes. In general it is localized to the mitochondrial inner membrane and serves as the last step in the mitochondrial oxidative phosphorylation of ADP to ATP, utilizing a proton gradient across the inner mitochondrial membrane built by the complexes of the electron transfer chain. However some cell types, including tumors, carry ATP synthase on the cell surface. It was suggested that cell surface ATP synthase helps tumor cells thriving on glycolysis to survive their high acid generation. Angiostatin, aurovertin, resveratrol, and antibodies against the alpha and beta subunits of ATP synthase were shown to bind and selectively inhibit cell surface ATP synthase, promoting tumor cell death. Here we show that ATP synthase beta (ATP5B) is present on the cell surface of mouse pheochromocytoma cells as well as tumor cells of human SDHB-derived paragangliomas (PGLs), while being virtually absent on chromaffin primary cells from bovine adrenal medulla by confocal microscopy. The cell surface location of ATP5B was verified in the tissue of an SDHB-derived PGL by immunoelectron microscopy. Treatment of mouse pheochromocytoma cells with resveratrol as well as ATP5B antibody led to statistically significant proliferation inhibition. Our data suggest that PGLs carry ATP synthase on their surface that promotes cell survival or proliferation. Thus, cell surface ATP synthase may present a novel therapeutic target in treating metastatic or inoperable PGLs. C1 [Fliedner, Stephanie M. J.; Thompson, Eli; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Fliedner, Stephanie M. J.; Lehnert, Hendrik] Univ Med Ctr Schleswig Holstein, Dept Med 1, D-23538 Lubeck, Germany. [Yang, Chunzhang; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NEI, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. [Hsu, Chang-Mei; Eiden, Lee] NIMH, Sect Mol Neurosci, NIH, Bethesda, MD 20892 USA. [Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA 02111 USA. [Wesley, Robert] NIH, Dept Hlth & Human Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Fliedner, SMJ (reprint author), Univ Med Ctr Schleswig Holstein, Dept Med 1, Campus Lubeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM stephanie.fliedner@uksh.de FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Pheo-Para Alliance FX We are indebted to V. Schram, L. Holtzelaw, and L. Dye from the NICHD imaging core facility for their expert assistance in microscopy imaging. This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD and supported by the institute's imaging core facility. AST was supported by a grant from the Pheo-Para Alliance www.pheo-para-alliance.org/. NR 61 TC 4 Z9 4 U1 2 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2015 VL 5 IS 4 BP 1558 EP 1570 PG 13 WC Oncology SC Oncology GA CK8NV UT WOS:000356495900024 PM 26101719 ER PT J AU Bailey, RL West, KP Black, RE AF Bailey, Regan L. West, Keith P., Jr. Black, Robert E. TI The Epidemiology of Global Micronutrient Deficiencies SO ANNALS OF NUTRITION AND METABOLISM LA English DT Article DE Epidemiology; Micronutrient deficiencies; Vitamins; Minerals ID NEURAL-TUBE DEFECTS; IODINE-DEFICIENCY; INDONESIAN CHILDREN; FOOD FORTIFICATION; THYROID-FUNCTION; NUTRITION STATUS; PREGNANT-WOMEN; UNITED-STATES; IRON; SUPPLEMENTATION AB Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those <5 years of age. Folic acid taken in early pregnancy can prevent neural tube defects. Folate is essential for DNA synthesis and repair, and deficiency results in macrocytic anemia. Vitamin A deficiency is the leading cause of blindness worldwide and also impairs immune function and cell differentiation. Single MNDs rarely occur alone; often, multiple MNDs coexist. The long-term consequences of MNDs are not only seen at the individual level but also have deleterious impacts on the economic development and human capital at the country level. Perhaps of greatest concern is the cycle of MNDs that persists over generations and the intergenerational consequences of MNDs that we are only beginning to understand. Prevention of MNDs is critical and traditionally has been accomplished through supplementation, fortification, and food-based approaches including diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions. (C) 2015 National Institutes of Health (NIH). Annals of Nutrition and Metabolism published by S. Karger AG, Basel C1 [Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Bailey, Regan L.; West, Keith P., Jr.; Black, Robert E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Nutr, Baltimore, MD USA. RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Suite 3B01, Bethesda, MD 20892 USA. EM baileyr@mail.nih.gov NR 91 TC 27 Z9 29 U1 11 U2 40 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2015 VL 66 SU 2 BP 22 EP 33 DI 10.1159/000371618 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CL0DS UT WOS:000356609900004 PM 26045325 ER PT J AU Chibucos, K Wofford, SJ Moore, PA AF Chibucos, K. Wofford, S. J. Moore, P. A. TI Hierarchical decision making: resource distribution exhibits stronger effect on crayfish dominance relationships and shelter occupation than prior social experience and resource ownership SO BEHAVIOUR LA English DT Article DE crayfish; dominance; prior residence; resource ownership; shelter; social status; status reversal ID ORCONECTES-RUSTICUS; AGGRESSIVE INTERACTIONS; ANIMAL CONTESTS; INDIVIDUAL RECOGNITION; AGONISTIC BEHAVIOR; SIGNAL CRAYFISH; BODY-SIZE; WINNER; DYNAMICS; COMMUNICATION AB The outcome of agonistic interactions is critical to the acquisition of vital resources. These behaviours can be influenced by several intrinsic and extrinsic factors, and multi-faceted studies are necessary for ecologically relevant studies. The aim of this study was to combine the effects of past social experience, resource ownership, and the distribution of shelter resources to examine the combination of these effects on various measures of agonism in crayfish (Orconectes rusticus). Crayfish were assigned to one of three social conditioning treatments (naive, subordinate, dominant) and then introduced to an arena where they were assigned to a resident or intruder treatment. An intruder shelter was then positioned 20, 60 or 120 cm from the resident shelter. We found that resource distribution (shelter distance) played a larger role in influencing agonistic behaviour than did past social experience or current social status. C1 [Chibucos, K.] Eunice K Shiver Inst Child Hlth & Human Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Chibucos, K.; Wofford, S. J.; Moore, P. A.] Bowling Green State Univ, Dept Biol Sci, Lab Sensory Ecol, Bowling Green, OH 43403 USA. RP Moore, PA (reprint author), Bowling Green State Univ, Dept Biol Sci, Lab Sensory Ecol, Bowling Green, OH 43403 USA. EM pmoore@bgsu.edu NR 56 TC 1 Z9 1 U1 10 U2 24 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 EI 1568-539X J9 BEHAVIOUR JI Behaviour PY 2015 VL 152 IS 7-8 BP 1063 EP 1082 DI 10.1163/1568539X-00003292 PG 20 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA CK4KS UT WOS:000356193300010 ER PT J AU Cha, J Hwang, JM Jo, HJ Seo, SW Na, DL Lee, JM AF Cha, Jungho Hwang, Jung-Min Jo, Hang Joon Seo, Sang Won Na, Duk L. Lee, Jong-Min TI Assessment of Functional Characteristics of Amnestic Mild Cognitive Impairment and Alzheimer's Disease Using Various Methods of Resting-State FMRI Analysis SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID LOW-FREQUENCY FLUCTUATION; DEFAULT MODE; REGIONAL HOMOGENEITY; BRAIN ACTIVITY; BASE-LINE; MRI; CONNECTIVITY; NETWORK; AMPLITUDE AB Resting-state functional magnetic resonance imaging (RS FMRI) has been widely used to analyze functional alterations in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) patients. Although many clinical studies of aMCI and AD patients using RS FMRI have been undertaken, conducting a meta-analysis has not been easy because of seed selection bias by the investigators. The purpose of our study was to investigate the functional differences in aMCI and AD patients compared with healthy subjects in a meta-analysis. Thus, a multimethod approach using regional homogeneity, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and global brain connectivity was used to investigate differences between three groups based on previously published data. According to the choice of RS FMRI approach used, the patterns of functional alteration were slightly different. Nevertheless, patients with aMCI and AD displayed consistently decreased functional characteristics with all approaches. All approaches showed that the functional characteristics in the left parahippocampal gyrus were decreased in AD patients compared with healthy subjects. Although some regions were slightly different according to the different RS FMRI approaches, patients with aMCI and AD showed a consistent pattern of decreased functional characteristics with all approaches. C1 [Cha, Jungho; Hwang, Jung-Min; Lee, Jong-Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea. [Jo, Hang Joon] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Seo, Sang Won; Na, Duk L.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul 135710, South Korea. RP Lee, JM (reprint author), Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea. EM jmlee@bme.hanyang.ac.kr OI Cha, Jungho/0000-0003-1189-2051; Jo, Hang Joon/0000-0002-9180-3831 FU National Research Foundation of Korea (NRF) Grant - Korea government (MEST) [2011-0028333] FX This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MEST) (2011-0028333). NR 36 TC 3 Z9 4 U1 0 U2 5 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 907464 DI 10.1155/2015/907464 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CL1OC UT WOS:000356712300001 ER PT J AU Zang, YF Zuo, XN Milham, M Hallett, M AF Zang, Yu-Feng Zuo, Xi-Nian Milham, Michael Hallett, Mark TI Toward a Meta-Analytic Synthesis of the Resting-State fMRI Literature for Clinical Populations SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material ID SPONTANEOUS BRAIN ACTIVITY; FLUCTUATION; DEPRESSION; AMPLITUDE; NETWORKS; DISORDER; CHILDREN C1 [Zang, Yu-Feng] Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou 310015, Zhejiang, Peoples R China. [Zang, Yu-Feng] Hangzhou Normal Univ, Zhejiang Key Lab Res Assessment Cognit Impairment, Hangzhou 310015, Zhejiang, Peoples R China. [Zuo, Xi-Nian] Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China. [Zuo, Xi-Nian] Chinese Acad Sci, Magnet Resonance Imaging Res Ctr, Inst Psychol, Beijing 100101, Peoples R China. [Milham, Michael] ChildMind Inst, Ctr Developing Brain, New York, NY 10022 USA. [Milham, Michael] Nathan S Kline Inst Psychiat Res, Ctr Biomed Imaging & Neuromodulat, Orangeburg, NY 10962 USA. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Zang, YF (reprint author), Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou 310015, Zhejiang, Peoples R China. EM zangyf@gmail.com NR 23 TC 0 Z9 0 U1 1 U2 6 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 435265 DI 10.1155/2015/435265 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CL1DY UT WOS:000356684000001 ER PT J AU Achyut, BR Bader, D Robles, A Darawarlee, W Harris, C Ried, T Yang, L AF Achyut, B. R. Bader, David Robles, Ana Darawarlee, Wanga Harris, Curtis Ried, Thomas Yang, Li TI Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-beta signaling SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Achyut, B. R.; Robles, Ana; Darawarlee, Wanga; Harris, Curtis; Ried, Thomas; Yang, Li] NCI, Bethesda, MD 20892 USA. [Bader, David] Baylor Univ, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B48 DI 10.1158/1538-7445.CHTME14-B48 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300098 ER PT J AU Byrd, TT Fousek, K Grada, Z Aviles-Padilla, K Bielamowicz, K Gottschalk, S St Croix, B Fletcher, B Hegde, M Ahmed, N AF Byrd, Tiara T. Fousek, Kristen Grada, Zakaria Aviles-Padilla, Kevin Bielamowicz, Kevin Gottschalk, Stephen St Croix, Bradley Fletcher, Bradley Hegde, Meenakshi Ahmed, Nabil TI Co-targeting the tumor and its associated vasculature in glioblastoma SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Byrd, Tiara T.; Fousek, Kristen; Grada, Zakaria; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Baylor Coll Med, Houston, TX 77030 USA. [St Croix, Bradley] NCI, Frederick, MD 21701 USA. [Fletcher, Bradley] Univ Florida, Gainesville, FL USA. RI Grada , Zakaria /B-9760-2016 NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B74 DI 10.1158/1538-7445.CHTME14-B74 PG 2 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300116 ER PT J AU Chen, L Choyke, P Clarke, R Bhujwalla, Z Wang, Y AF Chen, Li Choyke, Peter Clarke, Robert Bhujwalla, Zaver Wang, Yue TI Unsupervised deconvolution of dynamic imaging reveals intratumor vascular heterogeneity and repopulation dynamics SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Chen, Li; Wang, Yue] Virginia Tech, Arlington, VA USA. [Choyke, Peter] NCI, Bethesda, MD 20892 USA. [Clarke, Robert] Georgetown Univ, Washington, DC USA. [Bhujwalla, Zaver] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA A10 DI 10.1158/1538-7445.CHTME14-A10 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300010 ER PT J AU Jensen-Taubman, S Bourboulia, D Han, HY Moss, LS Wei, BY Stetler-Stevenson, WG AF Jensen-Taubman, Sandra Bourboulia, Dimitra Han, Huiying Moss, Laurie Shuman Wei, Beiyang Stetler-Stevenson, William G. TI TIMP-2 mediated growth inhibition of human glioma U87MG is accompanied by elevated IGFBP7 and FSP-1/S100A4 expression at the tumor/stroma interface SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Jensen-Taubman, Sandra; Han, Huiying; Moss, Laurie Shuman; Wei, Beiyang; Stetler-Stevenson, William G.] NCI, Bethesda, MD 20892 USA. [Bourboulia, Dimitra] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B79 DI 10.1158/1538-7445.CHTME14-B79 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300120 ER PT J AU Tang, BW Raviv, A Esposito, D Daniel, C Nghiem, BT Garfield, S Lim, L Mannan, P Robles, A Smith, W Zimmerberg, J Ravin, R Wakefield, L AF Tang, Binwu Raviv, Asaf Esposito, Dominic Daniel, Catherine Nghiem, Bao Tram Garfield, Susan Lim, Langston Mannan, Poonam Robles, Ana Smith, William Zimmerberg, Joshua Ravin, Rea Wakefield, Lalage TI A novel reporter system with potential for in situ assessment of tumor microenvironmental effects on cancer stem cells SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Tang, Binwu; Raviv, Asaf; Daniel, Catherine; Nghiem, Bao Tram; Garfield, Susan; Lim, Langston; Mannan, Poonam; Robles, Ana; Wakefield, Lalage] NCI, Bethesda, MD 20892 USA. [Esposito, Dominic] Frederick Natl Lab Canc Res, Frederick, MD USA. [Smith, William] Suburban Hosp, Bethesda, MD USA. [Zimmerberg, Joshua; Ravin, Rea] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B45 DI 10.1158/1538-7445.CHTME14-B45 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300096 ER PT J AU Liu, JY Lin, PC Zhou, BHP AF Liu, Jingyi Lin, Pengnian Charles Zhou, Binhua P. TI Inflammation Fuels Tumor Progress and Metastasis SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Epithelial-mesenchymal transition; inflammation; metastasis ID EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER PATIENTS; ENDOPLASMIC-RETICULUM STRESS; FACTOR-KAPPA-B; POTENTIAL THERAPEUTIC TARGET; UNFOLDED PROTEIN RESPONSE; SAETHRE-CHOTZEN-SYNDROME; E-CADHERIN REPRESSION; REGULATORY T-CELLS; BASAL-LIKE SUBTYPE AB Inflammation is a beneficial response that can remove pathogens, repair injured tissue and restore homeostasis to damaged tissues and organs. However, increasing evidence indicate that chronic inflammation plays a pivotal role in tumor development, as well as progression, metastasis, and resistance to chemotherapy. We will review the current knowledge regarding the contribution of inflammation to epithelial mesenchymal transition. We will also provide some perspectives on the relationship between ER-stress signals and metabolism, and the role of these processes in the development of inflammation. C1 [Liu, Jingyi] Chinese Acad Med Sci, Inst Hematol & Blood Dis Hosp, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China. [Liu, Jingyi] Peking Union Med Coll, Tianjin 300020, Peoples R China. [Liu, Jingyi; Zhou, Binhua P.] Univ Kentucky, Sch Med, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA. [Liu, Jingyi; Zhou, Binhua P.] Univ Kentucky, Sch Med, Markey Canc Ctr, Lexington, KY 40506 USA. [Lin, Pengnian Charles] Natl Canc Inst, Ctr Canc Res, Frederick, MD 21702 USA. RP Zhou, BHP (reprint author), Dept Mol & Cellular Biochem, 741 South Limestone St, Lexington, KY 40536 USA. EM peter.zhou@uky.edu FU NIH (RO1s) [CA125454, CA188118]; DOD Breakthrough Award [BC140733P1]; Mary Kay Ash Foundation; National Natural Science Foundation of China [81402432] FX We apologize to the many authors whose studies are important but could not be cited due to space limitation. Our study is supported by the grants from NIH (RO1s CA125454 and CA188118), DOD Breakthrough Award (BC140733P1), the Mary Kay Ash Foundation (to B.P. Zhou), and the National Natural Science Foundation of China (81402432 to J Liu). NR 141 TC 1 Z9 1 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2015 VL 21 IS 21 BP 3032 EP 3040 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CK2YQ UT WOS:000356081900014 PM 26004407 ER PT J AU Xu, AJ Niciu, MJ Lundin, NB Luckenbaugh, DA Ionescu, DF Richards, EM Voort, JLV Ballard, ED Brutsche, NE Machado-Vieira, R Zarate, CA AF Xu, Annie J. Niciu, Mark J. Lundin, Nancy B. Luckenbaugh, David A. Ionescu, Dawn F. Richards, Erica M. Voort, Jennifer L. Vande Ballard, Elizabeth D. Brutsche, Nancy E. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression SO NEURAL PLASTICITY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; ADD-ON TRIAL; MAJOR DEPRESSION; NEUROTROPHIC FACTOR; MOOD STABILIZERS; DISORDER; INHIBITION; ALPHA; CARBAMAZEPINE; ANTAGONISTS AB Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 +/- 0.15 mEq/L) or valproate (n = 13, 79.6 +/- 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Asberg Depression Rating Scale (MADRS)-was assessed before infusion and at numerous postinfusion time points. Both lithium (F-1,F-118 = 152.08, p < 0.001, and d = 2.27) and valproate (F-1,F-128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F-1,F-28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithiummay not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression. C1 [Xu, Annie J.] New York Med Coll, Valhalla, NY 10595 USA. [Niciu, Mark J.; Lundin, Nancy B.; Luckenbaugh, David A.; Richards, Erica M.; Ballard, Elizabeth D.; Brutsche, Nancy E.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Ionescu, Dawn F.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Voort, Jennifer L. Vande] Mayo Clin, Dept Psychiat, Rochester, MN 55905 USA. [Voort, Jennifer L. Vande] Mayo Clin, Psychol Serv, Rochester, MN 55905 USA. RP Zarate, CA (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, 10 Ctr Dr,Bldg 10-CRC, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI Ionescu, Dawn/K-5675-2015; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA); 7SE Inpatient Mood and Anxiety Disorders Research Unit of the IRP-NIMH-NIH FX The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA), and thank the 7SE Inpatient Mood and Anxiety Disorders Research Unit of the IRP-NIMH-NIH for their support. Ioline Henter (NIMH) provided excellent editorial assistance. NR 40 TC 2 Z9 2 U1 1 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 858251 DI 10.1155/2015/858251 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CL1PD UT WOS:000356715100001 ER PT J AU Lee, CT Bendriem, RM Freed, WJ AF Lee, Chun-Ting Bendriem, Raphael M. Freed, William J. TI A new technique for modeling neuronal connectivity using human pluripotent stem cells SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Neocortex; dopamine; human; pluripotent stem cell; differentiation; embryonic stem cell; neuronal projections ID IN-VITRO MODEL; ADENOASSOCIATED VIRUS VECTORS; DOPAMINE NEURONS; MPP+ TOXICITY; TARGET-CELLS; DIFFERENTIATION; SCHIZOPHRENIA; TRANSDUCTION; SURVIVAL; CULTURES AB Purpose: We describe a technique for independently differentiating neocortical and mesencephalic dopaminergic (mDA) neurons from a single human pluripotent stem cell (hPSC) line, and subsequently allowing the two cell types to interact and form connections. Methods: Dopaminergic and neocortical progenitors were differentiated in separate vessels, then separately seeded into the inner and outer compartments of specialized cell culture vessels designed for in vitro studies of wound healing. Cells were further differentiated using dopamine-specific and neocortex-specific trophic factors, respectively. The barrier was then removed, and differentiation was continued for three weeks in the presence of BDNF. Results: After three weeks of differentiation, neocortical and mDA cell bodies largely remained in the areas into which they had been seeded, and the gap between the mDA and neocortical neuron populations could still be discerned. Abundant tyrosine hydroxylase (TH)-positive projections had extended from the area of the inner chamber to the outer chamber neocortical area. Conclusions: We have developed a hPSC-based system for producing connections between neurons from two brain regions, neocortex and midbrain. Future experiments could employ modifications of this method to examine connections between any two brain regions or neuronal subtypes that can be produced from hPSCs in vitro. C1 [Lee, Chun-Ting; Bendriem, Raphael M.; Freed, William J.] NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, NIH, Baltimore, MD 21224 USA. RP Lee, CT (reprint author), NIDA, Intramural Res Program, 333 Cassell Dr,Triad Bldg,Room 3305, Baltimore, MD 21224 USA. EM clee@mail.nih.gov FU IRP of NIDA, NIH FX Research supported by the IRP of NIDA, NIH. We thank Brandon K. Harvey and the Optogenetics and Transgenic Technology Core, IRP, NIDA, NIH, for providing the AAV-eGFP vector, Ora Dillon-Carter for helpful suggestions regarding cell culture techniques, and Cindy Ambriz for assistance in preparing the manuscript. NR 40 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2015 VL 33 IS 3 BP 347 EP 356 DI 10.3233/RNN-140488 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CK9CU UT WOS:000356538900009 PM 25835555 ER PT S AU Westrate, LM Lee, JE Prinz, WA Voeltz, GK AF Westrate, L. M. Lee, J. E. Prinz, W. A. Voeltz, G. K. BE Kornberg, RD TI Form Follows Function: The Importance of Endoplasmic Reticulum Shape SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 84 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE endoplasmic reticulum; structure; dynamics; virus; neurodegeneration ID HEREDITARY SPASTIC PARAPLEGIA; RNA VIRUS-REPLICATION; FAMILY ENCODING RETICULONS; PLASMA MEMBRANE JUNCTIONS; ER NETWORK FORMATION; GENE FAMILY; ALZHEIMERS-DISEASE; SARCOPLASMIC-RETICULUM; GENOMIC ORGANIZATION; VIRAL REPLICATION AB The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. Ihese studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure. C1 [Westrate, L. M.; Lee, J. E.; Voeltz, G. K.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80303 USA. [Prinz, W. A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Prinz, WA (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM prinzw@helix.nih.gov; gia.voeltz@colorado.edu FU Intramural NIH HHS; NCI NIH HHS [F32 CA174158, F32CA174158]; NIGMS NIH HHS [GM083977] NR 146 TC 25 Z9 25 U1 7 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0884-1 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2015 VL 84 BP 791 EP 811 DI 10.1146/annurev-biochem-072711-163501 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BC8LD UT WOS:000355765300030 PM 25580528 ER PT J AU Subramaniam, M Taylor, NG St Jean, B Follman, R Kodama, C Casciotti, D AF Subramaniam, Mega Taylor, Natalie Greene St Jean, Beth Follman, Rebecca Kodama, Christie Casciotti, Dana TI As simple as that?: tween credibility assessment in a complex online world SO JOURNAL OF DOCUMENTATION LA English DT Article DE Digital literacy; Health literacy; Credibility assessment; Digital youth; Health information seeking; Information seeking behavior ID INFORMATION-SEEKING BEHAVIOR; COGNITIVE AUTHORITY; DECISION-MAKING; SEARCH ROLES; WEB; LITERACIES; RESOURCES; WANT; INTERNET; SCHOOL AB Purpose - The purpose of this paper is to focus on disadvantaged tweens' (ages 11 through 13) strategies for making predictive and evaluative judgments of the credibility of health information online. More specifically, this paper identifies the features of Google search results pages and web sites that signal credibility (or lack thereof) to this population and the reasons behind their perceptions. Design/methodology/approach - The authors employed an ethnographic approach (using various types of data collection methods) targeted to generate in-depth descriptions of tweens making predictive and evaluative judgments of credibility, focussing on the ways in which these tweens naturally assess the credibility of online information. Findings - The research has yielded novel findings concerning the types of factors that influence disadvantaged tweens' credibility assessment strategies, such as limited English-language vocabularies, lack of familiarity with perhaps otherwise well-known sources, and forced reliance on (and/or general preference for) non-textual modalities, such as audio and video. Practical implications - The findings indicate a need for implementing digital literacy programs in a naturalized setting, building on tweens' existing heuristics and thereby resulting in strategies that are simultaneously compatible with their natural inclinations within the online environment and likely to consistently lead them to accurate credibility-related judgments. Originality/value - This study provides novel insights into how disadvantaged tweens interact with online health information in a natural context, and offers invaluable information regarding the ways in which credibility assessment processes should be facilitated within formal or informal digital literacy programs. C1 [Subramaniam, Mega; Taylor, Natalie Greene; St Jean, Beth; Follman, Rebecca; Kodama, Christie] Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. [Casciotti, Dana] US Natl Lib Med, Bethesda, MD USA. RP Subramaniam, M (reprint author), Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. EM mmsubram@umd.edu FU National Library of Medicine FX The authors would like to thank the National Library of Medicine for providing the funding that makes the HackHealth program possible. The authors would also like to thank all of the school librarians and tweens with whom we work in the hopes of improving the future overall health of our society. The authors would like to thank the librarians who worked with us in this project. Our humble gratitude to the tweens we worked with and their parents who consented to their participation in HackHealth. Special thanks to Dr June Ahn who provided feedback on the paper, and Faith Ambrosini who assisted the team in data collection and formatting. This material is based upon work supported by the National Library of Medicine. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Library of Medicine. NR 58 TC 2 Z9 2 U1 3 U2 11 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 0022-0418 EI 1758-7379 J9 J DOC JI J. Doc. PY 2015 VL 71 IS 3 BP 550 EP 571 DI 10.1108/JD-03-2014-0049 PG 22 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA CK0VA UT WOS:000355922100008 ER PT J AU Lapi, D Mastantuono, T Cesarelli, M D'Addio, G Gorbach, A Starita, N Verone, P Colantuoni, A AF Lapi, D. Mastantuono, T. Cesarelli, M. D'Addio, G. Gorbach, A. Starita, N. Verone, P. Colantuoni, A. TI ISCHEMIA REPERFUSION BLOOD FLOW OSCILLATORY PATTERNS IN SINGLE VESSELS ON RAT PIAL MICROCIRCULATION SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract CT Joint Meeting of the European-Society-for-Microcirculation (ESM) and European-Vascular-Biology-Organisation (EVBO) CY JUN 03-06, 2015 CL Pisa, ITALY SP European Soc Microcirculat, European Vasc Biol Org C1 [Lapi, D.; Mastantuono, T.; Starita, N.; Verone, P.; Colantuoni, A.] Univ Naples Federico II, Dept Clin Med & Surg, Federico II Univ Med Sch, Naples, Italy. [Cesarelli, M.] Univ Naples Federico II, Dept Biochem Elect & TLC Engn, Naples, Italy. [D'Addio, G.] S Maugeri Fdn, Rehabil Inst Telese Terme BN, Benevento, Italy. [Gorbach, A.] NIBIB, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 EI 1423-0135 J9 J VASC RES JI J. Vasc. Res. PY 2015 VL 52 SU 1 BP 39 EP 40 PG 2 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA CK1OC UT WOS:000355975600114 ER PT S AU Chen, M Jog, A Carass, A Prince, JL AF Chen, Min Jog, Amod Carass, Aaron Prince, Jerry L. BE Ourselin, S Styner, MA TI Using image synthesis for multi-channel registration of different image modalities SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Multi-modal image registration; Multi-channel image registration; Magnetic resonance imaging; Image synthesis ID CROSS-CORRELATION; BRAIN IMAGES; NORMALIZATION; REGRESSION AB This paper presents a multi-channel approach for performing registration between magnetic resonance (MR) images with different modalities. In general, a multi-channel registration cannot be used when the moving and target images do not have analogous modalities. In this work, we address this limitation by using a random forest regression technique to synthesize the missing modalities from the available ones. This allows a single channel registration between two different modalities to be converted into a multi-channel registration with two monomodal channels. To validate our approach, two openly available registration algorithms and five cost functions were used to compare the label transfer accuracy of the registration with (and without) our multi-channel synthesis approach. Our results show that the proposed method produced statistically significant improvements in registration accuracy (at an alpha level of 0.001) for both algorithms and all cost functions when compared to a standard multi-modal registration using the same algorithms with mutual information. C1 [Chen, Min; Jog, Amod; Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Dept ECE, Image Anal & Commun Lab, Baltimore, MD 21218 USA. [Chen, Min] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA. [Carass, Aaron] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. RP Chen, M (reprint author), Johns Hopkins Univ, Dept ECE, Image Anal & Commun Lab, Baltimore, MD 21218 USA. EM mchen55@jhu.edu OI Carass, Aaron/0000-0003-4939-5085 NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94131Q DI 10.1117/12.2082373 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800060 ER PT S AU Cohen, T Widdows, D Rindflesch, T AF Cohen, Trevor Widdows, Dominic Rindflesch, Thomas BE Atmanspacher, H Bergomi, C Filk, T Kitto, K TI Expansion-by-Analogy: A Vector Symbolic Approach to Semantic Search SO QUANTUM INTERACTION (QI 2014) SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 8th International Conference on Quantum Interaction (QI) CY JUN 30-JUL 03, 2014 CL Collegium Helveticum, Filzbach, SWITZERLAND HO Collegium Helveticum DE Distributional semantics; Information retrieval; Vector symbolic architectures AB In this paper, we develop an approach to semantic search that utilizes high-dimensional vector representations to infer the nature of the relationship between query concepts and other concepts in relevant documents. We do so by incorporating outside knowledge drawn from tens of millions of concept-relation-concept triplets, known as semantic predications, extracted from the biomedical literature using a Natural Language Processing (NLP) system called SemRep. Inference is accomplished in high-dimensional space using Expansion-by-Analogy, a novel analogical approach to pseudo-relevance feedback, in which the relationships between query concepts and other concepts in documents they occur in guide the query expansion process. The semantic vector based approaches developed in this work show improvements in performance over a baseline bag-of-concepts model, and these improvements are most pronounced on queries that are not conducive to keyword-based search. C1 [Cohen, Trevor] Univ Texas Houston, Sch Biomed Informat Houston, Houston, TX 77030 USA. [Widdows, Dominic] Microsoft Bing, Redmond, WA USA. [Rindflesch, Thomas] Natl Lib Med, Bethesda, MD USA. RP Cohen, T (reprint author), Univ Texas Houston, Sch Biomed Informat Houston, Houston, TX 77030 USA. EM trevor.cohen@uth.tmc.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-15930-0; 978-3-319-15931-7 J9 LECT NOTES COMPUT SC PY 2015 VL 8951 BP 54 EP 66 DI 10.1007/978-3-319-15931-7_5 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BC8JK UT WOS:000355731900005 ER PT J AU Marfeo, EE Eisen, S Ni, PS Rasch, EK Rogers, ES Jette, A AF Marfeo, Elizabeth E. Eisen, Sue Ni, Pengsheng Rasch, Elizabeth K. Rogers, E. Sally Jette, Alan TI Do claimants over-report behavioral health dysfunction when filing for work disability benefits? SO WORK-A JOURNAL OF PREVENTION ASSESSMENT & REHABILITATION LA English DT Article DE Work disability; behavioral health; disability evaluation ID QUALITY-OF-LIFE; ONCOLOGISTS RECOGNITION; INTERRATER RELIABILITY; AGREEMENT; PATIENT; CANCER; PHYSICIANS; INSURANCE; CARE AB BACKGROND: Questions exist related to the best way to use medical evidence relative to self-report as part of the SSA disability determination process. OBJECTIVE: To examine concordance between provider and claimant responses along the four dimensions of work related behavioral health functioning: Social Interactions, Mood and Emotions, Behavioral Control, and Self-Efficacy. METHODS: Using secondary data from a larger study, which collected data on individuals reporting difficulties with work (claimants) due to mental conditions, 39 items were completed by claimants and their healthcare provider. Inter-rater agreement was assessed using three techniques: Cohen's kappa, percent absolute agreement, and folded mountain plots. RESULTS: A sample of 65 dyads was obtained. Inter-rater agreement was low for most items (k = 0.0-0.20) with a minority of items having fair agreement (k = 0.21-0.40) Percent agreement was fair: Mood and Emotions (46%), Self-Efficacy (44%), Behavioral Control (39%) and Social Interactions (38%). Overall, providers reported lower functioning compared to claimants for the Behavioral Control and Self-Efficacy scales; the reverse trend held for the Mood and Emotions scale. CONCLUSIONS: Results indicate discordance between provider and claimant report of behavioral health functioning. Understanding reasons for and approaches to reconciling the inconsistencies between claimant and provider perspectives is a complex task. These findings have implications for how best to assess mental and behavioral-health related work disability in the absence of an established gold standard measure. C1 [Marfeo, Elizabeth E.; Ni, Pengsheng; Jette, Alan] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA. [Eisen, Sue] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Rasch, Elizabeth K.] NIH, Rehabil Med Dept, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Rogers, E. Sally] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. RP Marfeo, EE (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St T5W, Boston, MA 02118 USA. EM emarfeo@bu.edu FU SSA-NIH Interagency Agreements under NIH [HHSN269200900004C, HHSN269201 000011C, HHSN269201100009I]; NIH intramural research program FX Funding for this project was provided through SSA-NIH Interagency Agreements under NIH Contract # HHSN269200900004C, NIH Contract # HHSN269201 000011C, and NIH Contract # HHSN269201100009I and through the NIH intramural research program. NR 29 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1051-9815 EI 1875-9270 J9 WORK JI Work PY 2015 VL 51 IS 2 BP 187 EP 194 DI 10.3233/WOR-141847 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK2TN UT WOS:000356065900004 PM 24594538 ER PT J AU Maya-Hoyos, M Leguizamon, J Marino-Ramirez, L Soto, CY AF Maya-Hoyos, Milena Leguizamon, John Marino-Ramirez, Leonardo Soto, Carlos Y. TI Sliding Motility, Biofilm Formation, and Glycopeptidolipid Production in Mycobacterium colombiense Strains SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SURFACTANT-PRODUCING MICROORGANISMS; AVIUM-COMPLEX; RHAMNOSYLTRANSFERASE GENE; GENOME SEQUENCE; SP-NOV.; SMEGMATIS; IDENTIFICATION; TUBERCULOSIS; EXPRESSION; VARIANTS AB Mycobacterium colombiense is a novel member of the Mycobacterium avium complex, which produces respiratory and disseminated infections in immunosuppressed patients. Currently, the morphological and genetic bases underlying the phenotypic features of M. colombiense strains remain unknown. In the present study, we demonstrated that M. colombiense strains displaying smooth morphology show increased biofilm formation on hydrophobic surfaces and sliding on motility plates. Thin-layer chromatography experiments showed that M. colombiense strains displaying smooth colonies produce large amounts of glycolipids with a chromatographic behaviour similar to that of the glycopeptidolipids (GPLs) of M. avium. Conversely, we observed a natural rough variant of M. colombiense (57B strain) lacking pigmentation and exhibiting impaired sliding, biofilm formation, and GPL production. Bioinformatics analyses revealed a gene cluster that is likely involved in GPL biosynthesis in M. colombiense CECT 3035. RT-qPCR experiments showed that motile culture conditions activate the transcription of genes possibly involved in key enzymatic activities of GPL biosynthesis. C1 [Maya-Hoyos, Milena; Leguizamon, John; Soto, Carlos Y.] Univ Nacl Colombia, Fac Sci, Dept Chem, Bogota, Colombia. [Marino-Ramirez, Leonardo] NCBI, Computat Biol Branch, NLM, NIH, Bethesda, MD 20894 USA. [Marino-Ramirez, Leonardo] Pan Amer Bioinformat Inst, Santa Martat, Magdalena, Colombia. RP Soto, CY (reprint author), Univ Nacl Colombia, Fac Sci, Dept Chem, Carrera 30,45-03 Ciudad Univ, Bogota, Colombia. EM cysotoo@unal.edu.co OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU "Division de Investigacion Bogota (DIB)"-Vicerrectoria de Investigacion, Universidad Nacional de Colombia [16060, 14837, 14337]; Academic Direction, Universidad Nacional de Colombia; "Jovenes Investigadores e Innovadores" Program, Colciencias, Colombia; Intramural Research Program of the National Institutes of Health, National Library of Medicine; National Center for Biotechnology Information (NCBI) FX This work was supported through funding from the "Division de Investigacion Bogota (DIB)"-Vicerrectoria de Investigacion, Universidad Nacional de Colombia (Grants 16060, 14837, and 14337). Milena Maya-Hoyos received a fellowship from the Academic Direction, Universidad Nacional de Colombia, and the "Jovenes Investigadores e Innovadores" Program, Colciencias, Colombia. This research was also supported in part through the Intramural Research Program of the National Institutes of Health, National Library of Medicine and National Center for Biotechnology Information (NCBI). NR 42 TC 4 Z9 4 U1 1 U2 7 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 419549 DI 10.1155/2015/419549 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CJ9FY UT WOS:000355809100001 ER PT J AU Salmaninejad, A Estiar, MA Gill, RK Shih, JH Hewitt, S Jeon, HS Fukuoka, J Shilo, K Shakoori, A Jen, J AF Salmaninejad, Arash Estiar, Mehrdad Asghari Gill, Rajbir K. Shih, Joanna H. Hewitt, Stephen Jeon, Hyo-Sung Fukuoka, Junya Shilo, Konstantin Shakoori, Abbas Jen, Jin TI Expression Analysis of p16, c-Myc, and mSin3A in Non-small Cell Lung Cancer by Computer Aided Scoring and Analysis (CASA) SO CLINICAL LABORATORY LA English DT Article DE tissue microarray; immunohistochemistry; Computer Aided Scoring and Analysis (CASA); NSCLC ID HIERARCHICAL NAIVE-BAYES; TISSUE MICROARRAYS; BREAST-CANCER; HER-2/NEU EXPRESSION; CDNA MICROARRAY; VALIDATION; CARCINOMA; IMMUNOHISTOCHEMISTRY; ASSOCIATION; COMPLEXES AB Background: Immunohistochemical analysis (IHC) of tissue microarray (TMA) slides enables large sets of tissue samples to be analyzed simultaneously on a single slide. However, manual evaluation of small cores on a TMA slide is time consuming and error prone. Methods: We describe a computer aided scoring and analysis (CASA) method to allow facile and reliable scoring of IHC staining using TMA containing 300 non-small cell lung cancer (NSCLC) cases. In the two previous published papers utilizing our TMA slides of lung cancer we examined 18 proteins involved in the chromatin machinery. We developed our study using more proteins of the chromatin complex and several transcription factors that facilitate the chromatin machinery. Then, a total of 78 antibodies were evaluated by CASA to derive a normalized intensity value that correlated with the overall staining status of the targeting protein. The intensity values for TMA cores were then examined for association to clinical variables and predictive significance individually and with other factors. Results: Using our TMA, the intensity of several protein pairs were significantly correlated with an increased risk of death in NSCLC. These included c-Myc with p16, mSin3A with p16 and c-Myc with mSinA. Predictive values of these pairs remained significant when evaluated based on standard IHC scores. Conclusions: Our results demonstrate the usefulness of CASA as a valuable tool for systematic assessment of TMA slides to identify potential predictive biomarkers using a large set of primary human tissues. C1 [Salmaninejad, Arash; Estiar, Mehrdad Asghari; Shakoori, Abbas] Univ Tehran Med Sci, Canc Inst Iran, Dept Med Genet, Tehran 13145158, Iran. [Gill, Rajbir K.; Shakoori, Abbas] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Shih, Joanna H.; Shakoori, Abbas] NCI, Bethesda, MD 20892 USA. [Hewitt, Stephen] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Jeon, Hyo-Sung] Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Daegu, South Korea. [Fukuoka, Junya] Nagasaki Univ, Grad Sch Biomed Sci, Dept Pathol, Nagasaki 852, Japan. [Shilo, Konstantin] Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. [Jen, Jin] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Shakoori, A (reprint author), Univ Tehran Med Sci, Canc Inst Iran, Dept Med Genet, Keshavarz Blvd, Tehran 13145158, Iran. EM shakooria@tums.ac.ir; Jen.Jin@mayo.edu RI Shilo, Konstantin/E-4084-2011; OI Hewitt, Stephen/0000-0001-8283-1788; S, K/0000-0002-6702-3130 FU intramural research funds to the Center for Cancer Research at the National Cancer Institute FX We express our gratitude to the physicians who contributed to the primary tissue samples through the Armed Force Institute of Pathology (AFIP) and to AFIP for making updated follow-up and clinical information available for this study. We also thank members of LHC for critical discussions through the course of this study. This work was supported by the intramural research funds to the Center for Cancer Research at the National Cancer Institute. All authors participated in developing the content of this manuscript, preparing and reviewing the draft versions, and approving the final version. NR 44 TC 3 Z9 3 U1 1 U2 1 PU CLIN LAB PUBL PI HEIDELBERG PA IM BREITSPIEL 15, HEIDELBERG, D-69126, GERMANY SN 1433-6510 J9 CLIN LAB JI Clin. Lab. PY 2015 VL 61 IS 5-6 BP 549 EP 559 DI 10.7754/Clin.Lab.2014.141125 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CJ8VQ UT WOS:000355782000015 PM 26118188 ER PT J AU Savage, MJ Holder, DJ Wu, GX Kaplow, J Siuciak, JA Potter, WZ AF Savage, Mary J. Holder, Daniel J. Wu, Guoxin Kaplow, June Siuciak, Judith A. Potter, William Z. CA Fdn Natl Inst Hlth FNIH Biomarkers TI Soluble BACE-1 Activity and sA beta PP beta Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE ADNI; Alzheimer's disease; amyloid-beta; amyloid-beta protein precursor; BACE1; cerebrospinal fluid; ELISA; mild cognitive impairment; sA beta PP beta; sBACE1; secretase ID AMYLOID PRECURSOR PROTEIN; SECRETASE ACTIVITY; ALPHA-SECRETASE; SITE; CNS; EXPRESSION; BIOMARKERS; DECREASE; PEPTIDE; BRAIN AB beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-beta (A beta) N-terminus from the amyloid-beta protein precursor (A beta PP), the first step in A beta formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sA beta PP beta, the N-terminal secreted product of BACE1 (sBACE1) activity on A beta PP. Here, sBACE1 enzymatic activity and secreted A beta PP beta (sA beta PP beta) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sA beta PP beta demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF A beta peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF A beta(42) and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sA beta PP beta concentrations can be used to differentiate between healthy elderly and AD individuals. C1 [Savage, Mary J.; Holder, Daniel J.; Wu, Guoxin] Merck & Co Inc, West Point, PA USA. [Kaplow, June] Eisai, Woodcliff Lake, NJ USA. [Siuciak, Judith A.; Potter, William Z.] NIMH, Bethesda, MD 20892 USA. RP Savage, MJ (reprint author), Merck Res Labs, Mol Biomarkers & Diagnost, RY50-1D-131,126 E Lincoln Ave, Rahway, NJ 07065 USA. EM mary_savage@merck.com RI Siuciak, Judith/K-2759-2016 OI Siuciak, Judith/0000-0002-3945-3555 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd, Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare;; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 36 TC 3 Z9 3 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 46 IS 2 BP 431 EP 440 DI 10.3233/JAD-142778 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CJ8GY UT WOS:000355739400013 PM 25790831 ER PT J AU Vaish, A Krueger, S Dimitriou, M Majkrzak, C Vanderah, DJ Chen, L Gawrisch, K AF Vaish, Amit Krueger, Susan Dimitriou, Michael Majkrzak, Charles Vanderah, David J. Chen, Lei Gawrisch, Klaus TI Enhancing the platinum atomic layer deposition infiltration depth inside anodic alumina nanoporous membrane SO JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A LA English DT Article ID ANGLE NEUTRON-SCATTERING; POROUS ALUMINA; GAS SEPARATION; NANOTUBES; FILMS AB Nanoporous platinum membranes can be straightforwardly fabricated by forming a Pt coating inside the nanopores of anodic alumina membranes (AAO) using atomic layer deposition (ALD). However, the high-aspect-ratio of AAO makes Pt ALD very challenging. By tuning the process deposition temperature and precursor exposure time, enhanced infiltration depth along with conformal coating was achieved for Pt ALD inside the AAO templates. Cross-sectional scanning electron microscopy/energy dispersive x-ray spectroscopy and small angle neutron scattering were employed to analyze the Pt coverage and thickness inside the AAO nanopores. Additionally, one application of platinum-coated membrane was demonstrated by creating a high-density protein-functionalized interface. (C) 2014 American Vacuum Society. C1 [Vaish, Amit; Krueger, Susan; Dimitriou, Michael; Majkrzak, Charles] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Vanderah, David J.] NIST, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. [Chen, Lei] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA. [Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Vaish, A (reprint author), NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. EM anv@udel.edu; lei.chen@nist.gov FU National Institute of Standards and Technology-American Recovery and Reinvestment Act (NIST-ARRA); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX A.V. acknowledges the National Institute of Standards and Technology-American Recovery and Reinvestment Act (NIST-ARRA) fellowship for supporting this work. K.G. acknowledges support from the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. The authors acknowledge Andreas Heilmann and Annika Thormann of Fraunhofer IWM Halle for useful discussions. Certain commercial equipment, instruments, or materials are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. Research was performed in part at the NIST Center for Nanoscale Science and Technology. NR 26 TC 2 Z9 2 U1 5 U2 18 PU A V S AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0734-2101 EI 1520-8559 J9 J VAC SCI TECHNOL A JI J. Vac. Sci. Technol. A PD JAN PY 2015 VL 33 IS 1 AR 01A148 DI 10.1116/1.4904398 PG 6 WC Materials Science, Coatings & Films; Physics, Applied SC Materials Science; Physics GA CJ8FK UT WOS:000355735400048 ER PT J AU Hooten, NN Ejiogu, N Zonderman, AB Evans, MK AF Hooten, Nicole Noren Ejiogu, Ngozi Zonderman, Alan B. Evans, Michele K. TI Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women SO MEDIATORS OF INFLAMMATION LA English DT Article ID CORONARY-ARTERY-DISEASE; NEUROTROPHIC FACTOR; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS; LIFE-SPAN; HEALTH; RISK; ASSOCIATION; ANGIOGENESIS AB Background. Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2' deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age-and race-matched with low (<3mg/L), mid (>3-20mg/L), and high (>20mg/L) hsCRP (n = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP. C1 [Hooten, Nicole Noren; Ejiogu, Ngozi; Zonderman, Alan B.; Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIA, Lab Epidemiol & Populat Sci, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM me42v@nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institutes of Health; National Institute on Aging FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The authors wish to thank Mike Nalls for genotyping analysis, the HANDLS staff for care of participants and sample acquisition, Althaf Lohani for technical assistance, and various colleagues for valuable discussions and critical reading of the paper. NR 34 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2015 AR 516783 DI 10.1155/2015/516783 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CJ9OD UT WOS:000355831000001 ER PT S AU Djima, KAY Simonelli, LD Conningham, D Czaja, W AF Djima, Karamatou A. Yacoubou Simonelli, Lucia D. Conningham, Denise Czaja, Wojcicech BE Ourselin, S Styner, MA TI Detection of Anomaly In Human Retina using Laplacian Eigenmaps and Vectorized Matched Filtering SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm ID DIMENSIONALITY REDUCTION; WAVELET AB We present a novel method for automated anomaly detection on autofluorescent data provided by the National Institute of Health (NIH). This is motivated by the need for new tools to improve the capability of diagnosing macular degeneration in its early stages, track the progression over time, and test the effectiveness of new treatment methods. In previous work, macular anomalies have been detected automatically through multiscale analysis procedures such as wavelet analysis or dimensionality reduction algorithms followed by a classification algorithm, e.g., Support Vector Machine. The method that we propose is a Vectorized Matched Filtering (VMF) algorithm combined with Laplacian Eigenmaps (LE), a nonlinear dimensionality reduction algorithm with locality preserving properties. By applying LE, we are able to represent the data in the form of eigenimages, some of which accentuate the visibility of anomalies. We pick significant eigenimages and proceed with the VMF algorithm that classifies anomalies across all of these eigenimages simultaneously. To evaluate our performance, we compare our method to two other schemes: a matched filtering algorithm based on anomaly detection on single images and a combination of PCA and VMF. LE combined with VMF algorithm performs best, yielding a high rate of accurate anomaly detection. This shows the advantage of using a nonlinear approach to represent the data and the effectiveness of VMF, which operates on the images as a data cube rather than individual images. C1 [Djima, Karamatou A. Yacoubou; Simonelli, Lucia D.; Czaja, Wojcicech] Univ Maryland, Dept Math, College Pk, MD 20742 USA. [Conningham, Denise] NEI, Bethesda, MD 20892 USA. RP Djima, KAY (reprint author), Univ Maryland, Dept Math, College Pk, MD 20742 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94132F DI 10.1117/12.2082482 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800084 ER PT S AU Plassard, AJ Hinton, KE Venkatraman, V Gonzalez, C Resnick, SM Landman, BA AF Plassard, Andrew J. Hinton, Kendra E. Venkatraman, Vijay Gonzalez, Christopher Resnick, Susan M. Landman, Bennett A. BE Ourselin, S Styner, MA TI Bootstrapping White Matter Segmentation, Eve plus SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Multi-Atlas Segmentation; Diffusion Tensor Imaging; White Matter ID MULTI-ATLAS SEGMENTATION; PERFORMANCE; FUSION AB Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary. C1 [Landman, Bennett A.] Vanderbilt Univ, Elect Engn, Nashville, TN 37235 USA. [Hinton, Kendra E.] Vanderbilt Univ, Psychol, Nashville, TN 37235 USA. [Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M.] NIA, NIH, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94133E DI 10.1117/12.2081613 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800117 ER PT S AU Roth, HR Farag, A Lu, L Turkbey, EB Summers, RM AF Roth, Holger R. Farag, Amal Lu, Le Turkbey, Evrim B. Summers, Ronald M. BE Ourselin, S Styner, MA TI Deep convolutional networks for pancreas segmentation in CT imaging SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE deep learning; convolutional neural networks; computed tomography; segmentation; pancreas; abdomen; computer-aided detection; superpixel ID NEURAL-NETWORK AB Automatic organ segmentation is an important prerequisite for many computer-aided diagnosis systems. The high anatomical variability of organs in the abdomen, such as the pancreas, prevents many segmentation methods from achieving high accuracies when compared to state-of-the-art segmentation of organs like the liver, heart or kidneys. Recently, the availability of large annotated training sets and the accessibility of affordable parallel computing resources via GPUs have made it feasible for "deep learning" methods such as convolutional networks (Cony Nets) to succeed in image classification tasks. These methods have the advantage that used classification features are trained directly from the imaging data. We present a fully-automated bottom-up method for pancreas segmentation in computed tomography (CT) images of the abdomen. The method is based on hierarchical coarse-to-fine classification of local image regions (superpixels). Superpixels are extracted from the abdominal region using Simple Linear Iterative Clustering (SLIC). An initial probability response map is generated, using patch-level confidences and a two-level cascade of random forest classifiers, from which superpixel regions with probabilities larger 0.5 are retained. These retained superpixels serve as a highly sensitive initial input of the pancreas and its surroundings to a Cony Net that samples a bounding box around each superpixel at different scales (and random non-rigid deformations at training time) in order to assign a more distinct probability of each superpixel region being pancreas or not. We evaluate our method on CT images of 82 patients (60 for training, 2 for validation, and 20 for testing). Using Cony Nets we achieve maximum Dice scores of an average 68% +/- 10% (range, 43-80%) in testing. This shows promise for accurate pancreas segmentation, using a deep learning approach and compares favorably to state-of-the-art methods. C1 [Roth, Holger R.; Farag, Amal; Lu, Le; Turkbey, Evrim B.; Summers, Ronald M.] NIH, Imaging Biomakers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Roth, HR (reprint author), NIH, Imaging Biomakers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM holger.roth@nih.gov; rms@nih.gov NR 15 TC 1 Z9 1 U1 6 U2 23 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94131G DI 10.1117/12.2081420 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800050 ER PT S AU Roy, S Jog, A Magrath, E Butman, JA Pham, DL AF Roy, Snehashis Jog, Amod Magrath, Elizabeth Butman, John A. Pham, Dzung L. BE Ourselin, S Styner, MA TI Cerebral Microbleed Segmentation from Susceptibility Weighted Images SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE TBI; microbleed; brain; SWI; microhemorrhage ID RADIAL SYMMETRY; MR-IMAGES; REGISTRATION AB Cerebral microbleeds (CMB) are a common marker of traumatic brain injury. Accurate detection and quantification of the CMBs are important for better understanding the progression and prognosis of the injury. Previous microbleed detection methods have suffered from a high rate of false positives, which is time consuming to manually correct. In this paper, we propose a fully automatic, example-based method to segment CMBs from susceptibility-weighted (SWI) scans, where examples from an already segmented template SWI image are used to detect CMBs in a new image. First, multiple radial symmetry transforms (RST) are performed on the template SWI to detect small ellipsoidal structures, which serve as potential microbleed candidates. Then 3D patches from the SWI and its RSTs are combined to form a feature vector at each voxel of the image. A random forest regression is trained using the feature vectors, where the dependent variable is the binary segmentation voxel of the template. Once the regression is learnt, it is applied to a new SWI scan, whose feature vectors contain patches from SWI and its RSTs. Experiments on 26 subjects with mild to severe brain injury show a CMB detection sensitivity of 85.7%, specificity 99.5%, and a false positive to true positive ratio of 1.73, which is competitive with published methods while providing a significant reduction in computation time. C1 [Roy, Snehashis; Magrath, Elizabeth; Butman, John A.; Pham, Dzung L.] Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Roy, Snehashis; Magrath, Elizabeth; Pham, Dzung L.] Henry Jackson Fdn, Bethesda, MD USA. [Jog, Amod] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Roy, S (reprint author), Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. NR 32 TC 1 Z9 1 U1 2 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94131E DI 10.1117/12.2082237 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800048 ER PT S AU Roy, S Wilkes, S Diaz-Arrastia, R Butman, JA Pham, DL AF Roy, Snehashis Wilkes, Sean Diaz-Arrastia, Ramon Butman, John A. Pham, Dzunug L. BE Ourselin, S Styner, MA TI Intraparenchymal Hemorrhage Segmentation from Clinical Head CT of Patients with Traumatic Brain Injury SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE CT; TBI; intraparenchymal hemorrhage; brain; sparsity ID COMPUTED-TOMOGRAPHY; LINEAR-EQUATIONS; SET AB Quantification of hemorrhages in head computed tomography (CT) images from patients with traumatic brain injury (TBI) has potential applications in monitoring disease progression and better understanding of the pathophysiology of TBI. Although manual segmentations can provide accurate measures of hemorrhages, the processing time and inter-rater variability make it infeasible for large studies. In this paper, we propose a fully automatic novel pipeline for segmenting intraparenchymal hemorrhages (IPH) from clinical head CT images. Unlike previous methods of model based segmentation or active contour techniques, we rely on relevant and matching examples from already segmented images by trained raters. The CT images are first skull-stripped. Then example patches from an "atlas" CT and its manual segmentation are used to learn a two-class sparse dictionary for hemorrhage and normal tissue. Next, for a given "subject" CT, a subject patch is modeled as a sparse convex combination of a few atlas patches from the dictionary. The same convex combination is applied to the atlas segmentation patches to generate a membership for the hemorrhages at each voxel. Hemorrhages are segmented from 25 subjects with various degrees of TBI. Results are compared with segmentations obtained from an expert rater. A median Dice coefficient of 0.85 between automated and manual segmentations is achieved. A linear fit between automated and manual volumes show a slope of 1.0047, indicating a negligible bias in volume estimation. C1 [Roy, Snehashis; Wilkes, Sean; Diaz-Arrastia, Ramon; Butman, John A.; Pham, Dzunug L.] Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Roy, Snehashis; Pham, Dzunug L.] Henry Jackson Fdn, Bethesda, MD USA. [Wilkes, Sean; Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD 20814 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Roy, S (reprint author), Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. RI Wilkes, Sean/E-8162-2015 OI Wilkes, Sean/0000-0002-9768-6971 NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 941301 DI 10.1117/12.2082199 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800016 ER PT S AU Sak, M Duric, N Littrup, P Bey-Knight, L Krycia, M Sherman, ME Boyd, N Gierach, GL AF Sak, Mark Duric, Neb Littrup, Peter Bey-Knight, Lisa Krycia, Mark Sherman, Mark E. Boyd, Norman Gierach, Gretchen L. BE Bosch, JG Duric, N TI Comparison of breast density measurements made using ultrasound tomography and mammography SO MEDICAL IMAGING 2015: ULTRASONIC IMAGING AND TOMOGRAPHY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Ultrasonic Imaging and Tomography CY FEB 22-23, 2015 CL Orlando, FL SP Alpin Med Syst, Modus Med Devices Inc, Bruker, ALIO Ind, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc North America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm, SPIE DE Ultrasound tomography; Breast density; Breast cancer risk; Mammography; Sound speed ID TISSUE DENSITY; CANCER RISK AB Women with elevated mammographic percent density, defined as the ratio of fibroglandular tissue area to total breast area on a mammogram are at an increased risk of developing breast cancer. Ultrasound tomography (UST) is an imaging modality that can create tomographic sound speed images of a patient's breast, which can then be used to measure breast density. These sound speed images are useful because physical tissue density is directly proportional to sound speed. The work presented here updates previous results that compared mammographic breast density measurements with UST breast density measurements within an ongoing study. The current analysis has been expanded to include 158 women with negative digital mammographic screens who then underwent a breast UST scan. Breast density was measured for both imaging modalities and preliminary analysis demonstrated strong and positive correlations (Spearman correlation coefficient r(s) = 0.703). Additional mammographic and UST related imaging characteristics were also analyzed and used to compare the behavior of both imaging modalities. Results suggest that UST can be used among women with negative mammographic screens as a quantitative marker of breast density that may avert shortcomings of mammography. C1 [Sak, Mark; Duric, Neb; Littrup, Peter; Bey-Knight, Lisa; Gierach, Gretchen L.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Duric, Neb; Littrup, Peter; Krycia, Mark] Delphinus Med Technol, Plymouth, MI 48170 USA. [Sherman, Mark E.] NCI, Canc Prevent Div, Breast & Gynecol Canc Res Grp, Bethesda, MD 20892 USA. [Boyd, Norman] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. RP Sak, M (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA. RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 NR 17 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-509-4 J9 PROC SPIE PY 2015 VL 9419 AR 94190R DI 10.1117/12.2082802 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8EU UT WOS:000355579600019 ER PT J AU Hao, EK Mukhopadhyay, P Cao, ZX Erdelyi, K Holovac, E Liaudet, L Lee, WS Hasko, G Mechoulam, R Pacher, P AF Hao, Enkui Mukhopadhyay, Partha Cao, Zongxian Erdelyi, Katalin Holovac, Eileen Liaudet, Lucas Lee, Wen-Shin Hasko, Gyoergy Mechoulam, Raphael Pacher, Pal TI Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis SO MOLECULAR MEDICINE LA English DT Article ID INDUCED CARDIOTOXICITY; CELL-DEATH; ENDOCANNABINOID SYSTEM; OXIDATIVE STRESS; HEART-FAILURE; CARDIAC MITOCHONDRIA; RADICAL FORMATION; MURINE MODELS; NITRIC-OXIDE; MICE AB Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury. C1 [Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdelyi, Katalin; Holovac, Eileen; Lee, Wen-Shin; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hao, Enkui] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Cardiol, Jinan 250100, Peoples R China. [Liaudet, Lucas] Univ Hosp Med Ctr, Dept Intens Care Med, Lausanne, Switzerland. [Lee, Wen-Shin] Natl Yang Ming Univ, Sch Med, Taipei Vet Gen Hosp, Div Gen Med,Dept Med, Taipei 112, Taiwan. [Hasko, Gyoergy] Rutgers State Univ, New Jersey Med Sch, Dept Surg, Newark, NJ 07102 USA. [Mechoulam, Raphael] Hebrew Univ Jerusalem, Fac Med, Dept Med Chem & Nat Prod, Jerusalem, Israel. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural Research Program of National Institutes of Health/NIAAA; Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism FX This study was supported by the Intramural Research Program of National Institutes of Health/NIAAA. P Pacher is grateful to George Kunos, Scientific Director of NIAAA, for continuous support, and dedicates this study to collaborator and friend, Itai Bab. The study also was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (to P Pacher). NR 45 TC 3 Z9 3 U1 5 U2 11 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PY 2015 VL 21 DI 10.2119/molmed.2014.00261 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CJ8CM UT WOS:000355726900004 PM 25569804 ER PT J AU Turbyville, TJ Holderfield, M AF Turbyville, Thomas J. Holderfield, Matthew TI Progress in targeting RAF kinases for cancer therapy SO PERSONALIZED MEDICINE LA English DT Editorial Material DE BRAF; melanoma cancer; RAF ID B-RAF; C-RAF; INHIBITORS; BRAF; MELANOMA; DIMERIZATION; VEMURAFENIB; PATHWAY; GROWTH; DIMERS AB "... responses are only observed in BRAF-mutated melanomas, which account for less than 1% of the total cancer patient population." C1 [Turbyville, Thomas J.; Holderfield, Matthew] Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD 21701 USA. RP Holderfield, M (reprint author), Frederick Natl Lab Canc Res, Canc Res Technol Program, 8560 Progress Dr, Frederick, MD 21701 USA. EM matthew.holderfield@afnlcr.nih.gov NR 19 TC 1 Z9 1 U1 2 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PY 2015 VL 12 IS 3 BP 183 EP 186 DI 10.2217/PME.15.1 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CJ8LI UT WOS:000355751600002 ER PT J AU Willis, GB AF Willis, Gordon B. TI RESEARCH SYNTHESIS THE PRACTICE OF CROSS-CULTURAL COGNITIVE INTERVIEWING SO PUBLIC OPINION QUARTERLY LA English DT Article ID DIVERSE POPULATIONS; QUESTIONNAIRE; DESIGN AB Cross-cultural cognitive interviewing (CCCI) has increasingly been practiced across a range of cultures, languages, and countries, in an effort to establish cross-cultural equivalence of survey questions and other materials, to detect sources of difficulties in answering survey questions for particular subgroups, and to detect problems related to translation from source to target languages. Although descriptions of such studies have proliferated in both the published and unpublished literatures, there has been little effort to reconcile discrepant views, approaches, and findings. The current synthesis reviews 32 CCCI studies located in peer-reviewed journals and books, along with key unpublished sources, to characterize these investigations in terms of their purpose, procedures, and findings. Based on a number of trends in this emergent field, conclusions are made concerning appropriate methods for cognitive testing of cross-cultural instruments, and recommendations are made for future practices that will serve to advance the CCCI field. C1 [Willis, Gordon B.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. RP Willis, GB (reprint author), NCI, BRP, DCCPS, 9609 Med Ctr Dr,Room 3E358,MSC 9762, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov NR 71 TC 1 Z9 1 U1 5 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0033-362X EI 1537-5331 J9 PUBLIC OPIN QUART JI Public Opin. Q. PY 2015 VL 79 SU 1 SI SI BP 359 EP 395 DI 10.1093/poq/nfu092 PG 37 WC Communication; Political Science; Social Sciences, Interdisciplinary SC Communication; Government & Law; Social Sciences - Other Topics GA CJ2KO UT WOS:000355313500007 ER PT J AU Wing, S Rider, LG Johnson, JR Miller, FW Matteson, EL Crowson, CS Gabriel, SE AF Wing, Simon Rider, Lisa G. Johnson, Jay R. Miller, Federick W. Matteson, Eric L. Crowson, Cynthia S. Gabriel, Sherine E. TI Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence? SO BMJ OPEN LA English DT Article ID GEOMAGNETIC-ACTIVITY; AURORAL ELECTROJET; OLMSTED COUNTY; NURSES HEALTH; EPIDEMIOLOGY; FLUCTUATIONS; MINNESOTA; MELATONIN; FIELDS; RISK AB Objective: To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods: We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results: The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5-7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA incidence power spectrum main peak is broader (8-11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions: AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases. C1 [Wing, Simon] Johns Hopkins Univ, Laurel, MD 20723 USA. [Rider, Lisa G.; Miller, Federick W.] NIEHS, NIH, Environm Autoimmun Grp, Clin Res Branch, Bethesda, MD USA. [Johnson, Jay R.] Princeton Univ, Princeton, NJ 08544 USA. [Matteson, Eric L.; Crowson, Cynthia S.; Gabriel, Sherine E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Matteson, Eric L.; Crowson, Cynthia S.; Gabriel, Sherine E.] Mayo Clin, Div Rheumatol, Dept Internal Med, Rochester, MN USA. RP Wing, S (reprint author), Johns Hopkins Univ, Laurel, MD 20723 USA. EM simon.wing@jhuapl.edu OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIH [NIAMS R01 AR046849, NIA R01 AG034676]; NIH, National Institute of Environmental Health Sciences; NSF [ATM-0802715, AGS-1058456, ATM09002730, AGS1203299]; NASA [NNX13AE12G, NNH09AM53I, NN09AK63I, NNH11AR07I]; DOE [DE-AC02-09CH11466] FX This work was funded from NIH grants (NIAMS R01 AR046849, NIA R01 AG034676). This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. This work has also benefited from the works funded by NSF grants (ATM-0802715, AGS-1058456, ATM09002730, AGS1203299), NASA grants (NNX13AE12G, NNH09AM53I, NN09AK63I, NNH11AR07I), and DOE contract (DE-AC02-09CH11466). NR 44 TC 2 Z9 2 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 5 AR e006636 DI 10.1136/bmjopen-2014-006636 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CI3LB UT WOS:000354648100007 PM 25979866 ER PT B AU Fu, Y Patterson, GH AF Fu, Yan Patterson, George H. BE Cambi, A Lidke, DS TI Development of Optical Highlighter Fluorescent Proteins and Their Applications in Super-Resolution Fluorescence Microscopy SO CELL MEMBRANE NANODOMAINS: FROM BIOCHEMISTRY TO NANOSCOPY LA English DT Article; Book Chapter ID STRUCTURAL BASIS; RECONSTRUCTION MICROSCOPY; CORRELATION SPECTROSCOPY; LOCALIZATION MICROSCOPY; DIFFRACTION-LIMIT; RATIONAL DESIGN; PLASMA-MEMBRANE; MARKER PROTEIN; CELL-MEMBRANES; RED C1 [Fu, Yan; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA. RP Fu, Y (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA. NR 101 TC 0 Z9 0 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-0991-4; 978-1-4822-0989-1 PY 2015 BP 305 EP 340 PG 36 WC Nanoscience & Nanotechnology; Microscopy SC Science & Technology - Other Topics; Microscopy GA BC7RI UT WOS:000355166700015 ER PT J AU Barker, DJ Simmons, SJ West, MO AF Barker, David J. Simmons, Steven J. West, Mark O. TI Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings SO CURRENT NEUROPHARMACOLOGY LA English DT Review DE Addiction; affect; emotion; stimulant; ultrasonic vocalizations ID BASAL EXTRACELLULAR DOPAMINE; REINSTATES COCAINE-SEEKING; SELF-ADMINISTERED COCAINE; RAT NUCLEUS-ACCUMBENS; ADULT RATS; INDIVIDUAL-DIFFERENCES; LABORATORY RATS; METHAMPHETAMINE-SEEKING; DISTRESS VOCALIZATIONS; AMPHETAMINE EXPOSURE AB The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter-and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals' initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures. C1 [Barker, David J.] NIDA, Neuronal Networks Sect, NIH, Baltimore, MD 21224 USA. [Barker, David J.; West, Mark O.] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Simmons, Steven J.] Temple Univ, Sch Med, Ctr Subst Abuse Res, Philadelphia, PA 19122 USA. RP Barker, DJ (reprint author), NIDA, Neuronal Networks Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM David.Barker@nih.gov FU National Institute on Drug Abuse [NIDA DA006886, DA029873]; Intramural Research Program of the National Institute on Drug Abuse; National Research Service Award [DA032270]; NIDA training grant [T32DA007237] FX We thank Drs. Roy Wise, David Root, Rachel Poole, John Muschamp for their feedback on the present manuscript. We would like to acknowledge grant support from the National Institute on Drug Abuse (NIDA DA006886, DA029873, MOW) and support from the Intramural Research Program of the National Institute on Drug Abuse (DJB). DJB was supported by a National Research Service Award (DA032270). SJS was supported by a NIDA training grant (T32DA007237, Ellen Unterwald). NR 144 TC 7 Z9 7 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2015 VL 13 IS 2 BP 193 EP 210 PG 18 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CJ1CP UT WOS:000355219900005 PM 26411762 ER PT J AU Berger, VW AF Berger, V. W. TI Failure to Look Beyond Blocks Is a Mistake SO METHODS OF INFORMATION IN MEDICINE LA English DT Letter DE Chronological bias; maximal procedure; permuted blocks; selection bias ID RANDOMIZATION AB Tamm and Hilgers [1] are to be congratulated for bringing more attention to a rather important issue in trial design, namely chronological bias. Far too many researchers use permuted blocks without even recognizing that chronological bias is the reason they do it. Only armed with the rationale can we hope to enter an informed discussion regard. ing the merits, or lack thereof, for using permuted block randomization in actual trials. But chronological bias is only part of the story. If it were the entire story, then there would be a rather easy solution. We could just use blocks of size two, or even alternate treatment groups. But we can't, and the reason we can't is selection bias. The two are at odds, as the solution to chronological bias is a small block size, and the solution to selection bias is a large block size [2, 3]. At least this would be the case if we were limited to using permuted blocks. Fortunately, we are not. C1 NCI, NIH, Rockville, MD 20850 USA. RP Berger, VW (reprint author), NCI, NIH, Rockville, MD 20850 USA. EM vb78c@nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2015 VL 54 IS 3 BP 290 EP 290 DI 10.3414/ME15-04-0002 PG 1 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CI8YO UT WOS:000355057800016 PM 25762507 ER PT J AU Machado-Vieira, R Frey, BN Andreazza, AC Quevedo, J AF Machado-Vieira, Rodrigo Frey, Benicio N. Andreazza, Ana C. Quevedo, Joao TI Translational Research in Bipolar Disorders SO NEURAL PLASTICITY LA English DT Editorial Material ID MOOD DISORDERS; PSYCHIATRY; BIOMARKERS; LITHIUM; IMPACT; STATE C1 [Machado-Vieira, Rodrigo] Natl Inst Mental Hlth, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20852 USA. [Frey, Benicio N.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3K7, Canada. [Frey, Benicio N.] St Josephs Healthcare, Mood Disorders Program, Hamilton, ON L8N 3K7, Canada. [Frey, Benicio N.] St Josephs Healthcare, Womens Hlth Concerns Clin, Hamilton, ON L8N 3K7, Canada. [Andreazza, Ana C.] Univ Toronto, Dept Pharmacol & Therapeut, Toronto, ON M5S 1A8, Canada. [Andreazza, Ana C.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada. [Andreazza, Ana C.] Ctr Addict & Mental Hlth, Toronto, ON M5S 1A8, Canada. [Quevedo, Joao] Univ Texas Houston, Med Sch Houston, Ctr Expt Models Psychiat, Dept Psychiat & Behav Sci, Houston, TX 77054 USA. [Quevedo, Joao] Univ Southern Santa Catarina, Grad Program Hlth Sci, Neurosci Lab, Hlth Sci Unit, Criciuma, SC, Brazil. RP Machado-Vieira, R (reprint author), Natl Inst Mental Hlth, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20852 USA. EM machadovieirar@mail.nih.gov; joao.l.dequevedo@uth.tmc.edu RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Quevedo, Joao/E-5491-2013 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Quevedo, Joao/0000-0003-3114-6611 NR 13 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 576978 DI 10.1155/2015/576978 PG 3 WC Neurosciences SC Neurosciences & Neurology GA CJ4JI UT WOS:000355450500001 ER PT J AU Balansky, R Ganchev, G Iltcheva, M Nikolov, M La Maestra, S Micale, RT D'Agostini, F Steele, VE De Flora, S AF Balansky, Roumen Ganchev, Gancho Iltcheva, Marietta Nikolov, Manasi La Maestra, Sebastiano Micale, Rosanna T. D'Agostini, Francesco Steele, Vernon E. De Flora, Silvio TI Modulation by Licofelone and Celecoxib of Experimentally Induced Cancer and Preneoplastic Lesions in Mice Exposed to Cigarette Smoke SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Celecoxib; chemoprevention; cigarette smoke; licofelone; lung tumors ID LUNG-CANCER; FORMER SMOKERS; HISTOPATHOLOGICAL ALTERATIONS; PULMONARY INFLAMMATION; N-ACETYLCYSTEINE; RISK; CHEMOPREVENTION; CYCLOOXYGENASE-2; TUMORIGENESIS; INHIBITOR AB Chronic inflammation plays a crucial role in cigarette smoke-related carcinogenesis. Accordingly, anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), provide a rational strategy in cancer chemoprevention. We assayed celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and licofelone, an inhibitor of COX-1, COX-2, and 5lipoxygenase (5-LOX), for the ability to modulate carcinogenesis in neonatal mice exposed to mainstream cigarette smoke (MCS) for 4 months and thereafter kept in filtered air for 3.5 months. A preliminary toxicity study and a chemoprevention study involved the use of 591 Swiss H mice. Exposure to MCS caused a variety of pulmonary emphysema, alveolar and bronchial epithelial hyperplasias, proliferation of blood vessels, microadenomas, adenomas and malignant tumors, as well as kidney tubular and urinary bladder papillary epithelial hyperplasias. Celecoxib (1600 mg/kg diet) and even better licofelone (960 mg/kg diet) were able to significantly attenuate the MCS-induced alterations of inflammatory nature, including pulmonary emphysema, alveolar epithelial hyperplasias and microadenomas and urinary tract hyperplastic lesions when given to mice according to a protocol that mimics an intervention in current smokers. Moreover, celecoxib attenuated the yield of lung adenomas and both NSAIDs showed some involvement in lowering the progression to cancer in the lung. Celecoxib exhibited some protective effects even when given according to a protocol involving its administration after discontinuation of exposure to MCS. However, both agents and especially celecoxib showed some hepatotoxicity and affected survival and body weight gain of mice when administered to MCS-exposed mice in the long term. C1 [Balansky, Roumen; La Maestra, Sebastiano; Micale, Rosanna T.; D'Agostini, Francesco; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Nikolov, Manasi] Natl Oncol Ctr, Sofia 1756, Bulgaria. [Steele, Vernon E.] NCI, Canc Prevent Div, Rockville, MD 20892 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it FU US National Cancer Institute [HHSN-261200433000C]; Bulgarian Ministry of Science - National Science Fund [BIN-1]; Hasumi Science Foundation Bulgaria FX This work was supported by the US National Cancer Institute (HHSN-261200433000C), the Bulgarian Ministry of Science - National Science Fund (BIN-1), and the Hasumi Science Foundation Bulgaria. NR 48 TC 3 Z9 3 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2015 VL 15 IS 3 BP 188 EP 195 PG 8 WC Oncology SC Oncology GA CI0VU UT WOS:000354458000003 PM 25687474 ER PT S AU Song, YS Lee, SH Park, BH Kim, SH Hwang, WS Kim, DY AF Song, Young Sik Lee, Sang Hak Park, Byoung Hee Kim, Soo Hyeok Hwang, Won Sang Kim, Dug Young BE Farkas, DL Nicolau, DV Nicolau, RC TI Cholesterol efflux monitoring in macrophage form cells by using fluorescence lifetime imaging SO IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES XIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XIII CY FEB 09-11, 2015 CL San Francisco, CA SP SPIE DE fluorescence lifetime; cholesterol efflux; macrophage; AMD; analog mean delay; foam cell ID ORGANIZATION; DYNAMICS AB Macrophages play a key role in atherosclerotic plaque destabilization and rupture, since they accumulate large amounts of lipid through the uptake of modified lipoproteins which results in foam cell formation. Cholesterol efflux is the process of removing cholesterol from macrophages in the subintima of the vessel wall, and efflux mechanism in a cell is one of the critical issues for the prevention of cardiovascular diseases. High density lipoproteins (HDL) stimulate cholesterol efflux from macrophage foam cells in the arterial wall. Radioisotope-labeled cholesterol analysis method is well known conventional method for observing cholesterol efflux. The major drawback of this method is its long and complicated process. Fluorescence intensity imaging schemes are replacing the radioisotope-labeled method in recent years for cholesterol efflux monitoring. Various spectroscopic methods are also adapted for cholesterol efflux imaging. Here we present a fluorescence lifetime imaging method for more quantitative observation of cholesterol efflux process in macrophages, which enables us to observe cholesterol level changes with various conditions. We used J774 macrophage cell and 25-NBD-cholesterol which is a famous cholesterol specific dye. Our lifetime imaging results clearly show cholesterol efflux rate very effectively. We believe that fluorescence lifetime analysis is new and very powerful for cholesterol imaging or monitoring. C1 [Song, Young Sik; Hwang, Won Sang; Kim, Dug Young] Yonsei Univ, Dept Phys, Seoul, South Korea. [Lee, Sang Hak; Park, Byoung Hee] Yonsei Univ, Coll Med, Dept Internal Med, Div Cardiol,Severance Cardiovasc Hosp, Seoul, South Korea. [Kim, Soo Hyeok] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Song, YS (reprint author), Yonsei Univ, Dept Phys, 50 Yonsei Ro, Seoul, South Korea. EM dykim1@yonsei.ac.kr NR 7 TC 0 Z9 0 U1 3 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-418-9 J9 PROC SPIE PY 2015 VL 9328 AR 932808 DI 10.1117/12.2078996 PG 6 WC Cell & Tissue Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Cell Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6MB UT WOS:000354105000005 ER PT B AU Frawley, R Germolec, D van Loveren, H AF Frawley, Rachel Germolec, Dori van Loveren, Henk BE Corsini, E VanLoveren, H TI Use of Toxicogenomics in Immunotoxicology SO MOLECULAR IMMUNOTOXICOLOGY LA English DT Article; Book Chapter ID GENE-EXPRESSION PROFILES; BLOOD MONONUCLEAR-CELLS; SELECTION IN-VIVO; 3 DIFFERENT SENSITIZERS; AURICULAR LYMPH-NODES; OF-THE-ART; DENDRITIC CELLS; IMMUNE-SYSTEM; T-CELLS; RNA-SEQ C1 [Frawley, Rachel; Germolec, Dori] NIEHS, Natl Toxicol Program, Morrisville, NC 27560 USA. [van Loveren, Henk] Maastricht Univ, Dept Toxicogen, NL-6200 MD Maastricht, Netherlands. [van Loveren, Henk] Natl Inst Publ Hlth & Environm, Lab Hlth Protect Res, Utrecht, Netherlands. RP Frawley, R (reprint author), NIEHS, Natl Toxicol Program, Morrisville, NC 27560 USA. NR 174 TC 0 Z9 0 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-67696-5; 978-3-527-33519-0 PY 2015 BP 27 EP 66 PG 40 WC Toxicology SC Toxicology GA BC7MJ UT WOS:000354998200004 ER PT J AU Opina, AC Wong, KJ Griffiths, GL Turkbey, BI Bernardo, M Nakajima, T Kobayashi, H Choyke, PL Vasalatiy, O AF Opina, Ana Christina Wong, Karen J. Griffiths, Gary L. Turkbey, Baris I. Bernardo, Marcelino Nakajima, Takahito Kobayashi, Hisataka Choyke, Peter L. Vasalatiy, Olga TI Preparation and long-term biodistribution studies of a PAMAM dendrimer G5-Gd-BnDOTA conjugate for lymphatic imaging SO NANOMEDICINE LA English DT Article DE biodistribution; dendrimers; G5-Gd-BnDOTA; lymphatic imaging; MRI c-ontrast agent; PAMAM G5 ID MRI CONTRAST AGENTS; MAGNETIC-RESONANCE; POLYAMIDOAMINE DENDRIMER; LANTHANIDE(III) COMPLEXES; DOTA COMPLEXES; DYNAMICS; NMR; SPECTROSCOPY; ISOMERS; CORE AB Aims: To demonstrate the use of gadolinium (Gd)-labeled dendrimers as lymphatic imaging agents and establish the long-term biodistribution (90-day) of this type of agent in mice. Materials & methods: A G5-Gd-BnDOTA dendrimer was prepared and injected into mice and monkeys for MR lymphangiography, and long-term biodistribution of the conjugate was studied. Results: Administration of G5-Gd-BnDOTA in mice demonstrated a rapid uptake in the deep lymphatic system while injection in monkeys showed enhanced internal iliac nodes, indicating its general utility for lymphatic tracking. Biodistribution studies to 90 days showed that gadolinium conjugate is slowly being eliminated from the liver and other organs. Conclusion: The use of G5-Gd-BnDOTA holds great promise for lymphatic imaging, but its slow clearance from the body might hamper its eventual clinical translation. C1 [Opina, Ana Christina; Vasalatiy, Olga] NHLBI, Imaging Probe Dev Ctr, Rockville, MD 20850 USA. [Wong, Karen J.; Turkbey, Baris I.; Bernardo, Marcelino; Nakajima, Takahito; Kobayashi, Hisataka; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Griffiths, Gary L.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. RP Vasalatiy, O (reprint author), NHLBI, Imaging Probe Dev Ctr, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM vasalatiyo@nhlbi.nih.gov FU National Cancer Institute, NIH [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under Contract no. HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 48 TC 8 Z9 8 U1 7 U2 20 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 9 BP 1423 EP 1437 DI 10.2217/NNM.14.113 PG 15 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CI6OG UT WOS:000354879000006 PM 25392239 ER PT S AU Li, JW Minami, H Steward, E Ma, T Mohar, D Robertson, C Shung, KK Zhou, QF Patel, PM Chen, ZP AF Li, Jiawen Minami, Hataka Steward, Earl Ma, Teng Mohar, Dilbahar Robertson, Claire Shung, K. Kirk Zhou, Qifa Patel, Pranav M. Chen, Zhongping BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Nuttal, A Richter, CP Skala, MC Dewhirst, MW Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI Ideal flushing agents for integrated optical acoustic imaging systems SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XI CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, Assoc Res Otolaryngol DE Optical coherence tomography; ultrasound; attenuation; multimodality imaging ID COHERENCE TOMOGRAPHY AB An increased number of integrated optical acoustic intravascular imaging systems have been researched and hold great hope for accurate diagnosing of vulnerable plaques and for guiding atherosclerosis treatment. However, in any intravascular environment, vascular lumen is filled with blood, which is a high-scattering source for optical and high frequency ultrasound signals. Blood must be flushed away to make images clear. To our knowledge, no research has been performed to find the ideal flushing agent that works for both optical and acoustic imaging techniques. We selected three solutions, mannitol, dextran and iohexol, as flushing agents because of their image-enhancing effects and low toxicities. Quantitative testing of these flushing agents was performed in a closed loop circulation model and in vivo on rabbits. C1 [Li, Jiawen; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92617 USA. [Li, Jiawen; Minami, Hataka; Chen, Zhongping] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. [Steward, Earl; Mohar, Dilbahar; Patel, Pranav M.] Univ Calif Irvine, Sch Med, Irvine, CA 92868 USA. [Ma, Teng; Shung, K. Kirk; Zhou, Qifa] Univ So Calif, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Robertson, Claire] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. RP Li, JW (reprint author), Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd, Irvine, CA 92617 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-393-9 J9 PROC SPIE PY 2015 VL 9303 AR 93032Z DI 10.1117/12.2074696 PG 6 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BC6PW UT WOS:000354366400047 ER PT S AU Lloyd, WR Sinder, BP Salemi, J Ominsky, MS Marini, JC Caird, MS Morris, MD Kozloff, KM AF Lloyd, William R. Sinder, Benjamin P. Salemi, Joseph Ominsky, Michael S. Marini, Joan C. Caird, Michelle S. Morris, Michael D. Kozloff, Kenneth M. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Nuttal, A Richter, CP Skala, MC Dewhirst, MW Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI Tissue level material composition and mechanical properties in Brtl/plus mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XI CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, Assoc Res Otolaryngol DE Osteogenesis imperfecta; Brtl/ plus mice; sclerostin antibody; Raman spectroscopy; nanoindentation; tissue level composition ID BONE MASS; STRENGTH; CHILDREN AB Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (SclAb), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment. C1 [Lloyd, William R.; Morris, Michael D.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Sinder, Benjamin P.; Caird, Michelle S.; Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. [Sinder, Benjamin P.; Salemi, Joseph; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Ominsky, Michael S.] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA. [Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Lloyd, WR (reprint author), Univ Michigan, Dept Chem, 930 N Univ, Ann Arbor, MI 48109 USA. NR 25 TC 0 Z9 0 U1 3 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-393-9 J9 PROC SPIE PY 2015 VL 9303 AR 93033U DI 10.1117/12.2080261 PG 6 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BC6PW UT WOS:000354366400054 ER PT J AU Vegh, RB Bloch, DA Bommarius, AS Verkhovsky, M Pletnev, S Iwai, H Bochenkova, AV Solntsev, KM AF Vegh, Russell B. Bloch, Dmitry A. Bommarius, Andreas S. Verkhovsky, Michael Pletnev, Sergei Iwai, Hideo Bochenkova, Anastasia V. Solntsev, Kyril M. TI Hidden photoinduced reactivity of the blue fluorescent protein mKalama1 SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID STATE PROTON-TRANSFER; PHOTOACTIVE YELLOW PROTEIN; CORRELATION SPECTROSCOPY; GFP-CHROMOPHORE; SOLVATED ELECTRONS; ENERGY LANDSCAPE; STRUCTURAL BASIS; GROUND-STATE; GREEN; DYNAMICS AB Understanding the photoinduced dynamics of fluorescent proteins is essential for their applications in bioimaging. Despite numerous studies on the ultrafast dynamics, the delayed response of these proteins, which often results in population of kinetically trapped dark states of various origins, is largely unexplored. Here, by using transient absorption spectroscopy spanning the time scale from picoseconds to seconds, we reveal a hidden reactivity of the bright blue-light emitting protein mKalama1 previously thought to be inert. This protein shows no excited-state proton transfer during its nanosecond excited-state lifetime; however, its tyrosine-based chromophore undergoes deprotonation coupled to non-radiative electronic relaxation. Such deprotonation causes distinct optical absorption changes in the broad UV-to-NIR spectral range (ca. 300-800 nm); the disappearance of the transient absorption signal has a complex nature and spans the whole microsecond-to-second time scale. The mechanisms underlying the relaxation kinetics are disclosed based on the X-ray structural analysis of mKalama1 and the high-level electronic structure calculations of proposed intermediates in the photocycle. We conclude that the non-radiative excited-state decay includes two major branches: internal conversion coupled to intraprotein proton transfer, where a conserved residue E222 serves as the proton acceptor; and ionization induced by two consecutive resonant absorption events, followed by deprotonation of the chromophore radical cation to bulk solvent through a novel water-mediated proton-wire pathway. Our findings open up new perspectives on the dynamics of fluorescent proteins as tracked by its optical transient absorption in the time domain extending up to seconds. C1 [Vegh, Russell B.; Bommarius, Andreas S.; Solntsev, Kyril M.] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA. [Vegh, Russell B.; Bommarius, Andreas S.] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA. [Vegh, Russell B.; Bommarius, Andreas S.] Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA. [Bloch, Dmitry A.; Verkhovsky, Michael; Iwai, Hideo] Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, Helsinki 00014, Finland. [Pletnev, Sergei] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA. [Pletnev, Sergei] Leidos Biomed Res Inc, Basic Res Program, Argonne, IL 60439 USA. [Bochenkova, Anastasia V.] Aarhus Univ, Dept Phys & Astron, Aarhus, Denmark. [Bochenkova, Anastasia V.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia. RP Bochenkova, AV (reprint author), Aarhus Univ, Dept Phys & Astron, Aarhus, Denmark. EM bochenkova@phys.au.dk; solntsev@gatech.edu RI Iwai, Hideo/A-6416-2009; Bochenkova, Anastasia/G-2090-2015 OI Iwai, Hideo/0000-0001-7376-5264; Bochenkova, Anastasia/0000-0003-4101-3564 FU U.S. National Science Foundation [CHE-1213047, CHE-1465036]; U.S. National Institutes of Health [R21EB009976-01, HHSN26120080001E]; Intramural Research Program of the NIH; U.S. National Cancer Institute, Center for Cancer Research; Academy of Finland; Sigrid Juselius Foundation; Biocenter Finland; Biocentrum Helsinki; Russian Foundation for Basic Research (RFBR) [14-03-00887]; Marie Curie FP7 CIG Grant FX This work was supported by the U.S. National Science Foundation (CHE-1213047 and CHE-1465036, K.M.S.), the U.S. National Institutes of Health (R21EB009976-01, A.S.B. and HHSN26120080001E, S.P.), the Intramural Research Program of the NIH, U.S. National Cancer Institute, Center for Cancer Research (S.P.), the Academy of Finland, the Sigrid Juselius Foundation, Biocenter Finland, and Biocentrum Helsinki (D.A.B., M.V., and H.I.), as well as by the Russian Foundation for Basic Research (RFBR No. 14-03-00887, A.V.B.) and a Marie Curie FP7 CIG Grant (A.V.B.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This work was granted access to the HPC resources of the Leibniz and RZG Supercomputing Centers (Garching, Germany) made available within the FP7 DECI/PRACE-2IP initiative, as well as to the Lomonosov Supercomputing Center at Moscow State University. Crystallization was performed at the Crystallization Core Facility, Institute of Biotechnology, Helsinki University. Seija Maki and Jesper Omig are greatly acknowledged for their excellent assistance in the crystallization, as well as Dr Konstantin Kogan for the data collection, and the staff at the DIAMOND synchrotron beamline for their support. We thank Laren Tolbert, Robert Dickson and Konstantin Lukyanov for stimulating discussions. We are grateful to the members of Joseph Perry's group for the help with fs TA measurements. We thank Marten Wikstrom for hosting two research visits of RBV to Helsinki, providing access to their equipment, and for his interest in this study. We would like to dedicate this work to the memory of Dmitry Bloch and Michael Verkhovsky. NR 69 TC 4 Z9 4 U1 2 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2015 VL 17 IS 19 BP 12472 EP 12485 DI 10.1039/c5cp00887e PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CH7DH UT WOS:000354195300008 PM 25805012 ER PT S AU Ghysels, A Van Speybroeck, V Van Neck, D Brookst, BR Waroquier, M AF Ghysels, An Van Speybroeck, Veronique Van Neck, Dimitri Brookst, Bernard R. Waroquier, Michel BE Simos, TE Maroulis, G TI Normal Mode Analysis of Macromolecular Systems with the Mobile Block Hessian Method SO PROCEEDINGS OF THE INTERNATIONAL CONFERENCE OF COMPUTATIONAL METHODS IN SCIENCES AND ENGINEERING 2010 (ICCMSE-2010) SE AIP Conference Proceedings LA English DT Proceedings Paper CT International Conference of Computational Methods in Sciences and Engineering (ICCMSE) CY OCT 03-08, 2010 CL Kos, GREECE SP European Soc Computat Methods Sci, Engn & Technol DE NMA; vibrational analysis; IR spectrum; reduced dimension; partial optimization AB Until recently, normal mode analysis (NMA) was limited to small proteins, not only because the required energy minimization is a computationally exhausting task, but also because NMA requires the expensive diagonalization of a 3N(a) x 3N(a) matrix with N-a the number of atoms. A series of simplified models has been proposed, in particular the Rotation-Translation Blocks (RTB) method by Tama et al. for the simulation of proteins. It makes use of the concept that a peptide chain or protein can be seen as a subsequent set of rigid components, i.e. the peptide units. A peptide chain is thus divided into rigid blocks with six degrees of freedom each. Recently we developed the Mobile Block Hessian (MBH) method, which in a sense has similar features as the RTB method. The main difference is that MBH was developed to deal with partially optimized systems. The position/orientation of each block is optimized while the internal geometry is kept fixed at a plausible - but not necessarily optimized - geometry. This reduces the computational cost of the energy minimization. Applying the standard NMA on a partially optimized structure however results in spurious imaginary frequencies and unwanted coordinate dependence. The MBH avoids these unphysical effects by taking into account energy gradient corrections. Moreover the number of variables is reduced, which facilitates the diagonalization of the Hessian. In the original implementation of MBH, atoms could only be part of one rigid block. The MBH is now extended to the case where atoms can be part of two or more blocks. Two basic linkages can be realized: (1) blocks connected by one link atom, or (2) by two link atoms, where the latter is referred to as the hinge type connection. In this work we present the MBH concept and illustrate its performance with the crambin protein as an example. C1 [Ghysels, An; Van Speybroeck, Veronique; Van Neck, Dimitri; Waroquier, Michel] Univ Ghent, Ctr Mol Modeling, B-9052 Zwijnaarde, Belgium. [Brookst, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20851 USA. RP Ghysels, A (reprint author), Univ Ghent, Ctr Mol Modeling, Technol Pk 903, B-9052 Zwijnaarde, Belgium. RI Ghysels, An/M-9095-2015 NR 7 TC 0 Z9 0 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1282-8 J9 AIP CONF PROC PY 2015 VL 1642 BP 559 EP 562 DI 10.1063/14906742 PG 4 WC Physics, Applied SC Physics GA BC7GK UT WOS:000354845400113 ER PT J AU Wang, Z Zhang, MR Wang, L Wang, SJ Kang, F Li, GQ Jacobson, O Niu, G Yang, WD Wang, J Chen, XY AF Wang, Zhe Zhang, Mingru Wang, Liang Wang, Shengjun Kang, Fei Li, Guoquan Jacobson, Orit Niu, Gang Yang, Weidong Wang, Jing Chen, Xiaoyuan TI Prospective Study of Ga-68-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients SO THERANOSTICS LA English DT Article DE Ga-68-NOTA-NFB; internal dosimetry; CXCR4; glioma; PET/CT ID CHEMOKINE RECEPTOR CXCR4; PET; EXPRESSION; AGENT; ANTAGONIST; TRACER; CXCL12 AB Purpose: The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, Ga-68-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients. Methods: Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after Ga-68-NOTA-NFB injection (mean dose, 182.4 +/- 3.7 MBq (4.93 +/- 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both Ga-68-NOTA-NFB and F-18-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining. Results: Ga-68-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 +/- 32.5 mu Sv/MBq) and liver (119.3 +/- 25.0 mu Sv/MBq). The mean effective dose was 25.4 +/- 6.1 mu Sv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of Ga-68-NOTA-NFB PET/CT in glioma tissues were 4.11 +/- 2.90 (range, 0.45-8.21) and 9.21 +/- 8.75 (range, 3.66-24.88), respectively, while those of F-18-FDG PET/CT were 7.34 +/- 2.90 (range, 3.50-12.27) and 0.86 +/- 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent Ga-68-NOTA-NFB uptake. Conclusion: With a favorable radiation dosimetry profile, Ga-68-NOTA-NFB is safe for clinical imaging. Compared to F-18-FDG PET/CT, Ga-68-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients. C1 [Wang, Zhe; Zhang, Mingru; Wang, Shengjun; Kang, Fei; Li, Guoquan; Yang, Weidong; Wang, Jing] Fourth Mil Med Univ, Xijing Hosp, Dept Nucl Med, Xian 710032, Peoples R China. [Wang, Liang] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurosurg, Xian 710032, Peoples R China. [Jacobson, Orit; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Wang, J (reprint author), Fourth Mil Med Univ, Xijing Hosp, Dept Nucl Med, Xian 710032, Peoples R China. EM wangjing@fmmu.edu.cn; shawn.chen@nih.gov FU Key Program of National Natural Science Foundation of China [81230033]; Major State Basic Research Development Program [2011CB707704]; Major Instrument of National Natural Science Foundation Research Project [81227901]; National Natural Science Foundation of China [81371594, 81401442, 81371596]; International Cooperation Program of Xijing Hospital [XJZT13G02]; Key Science and Technology Program of Shaanxi Province, China [2013K12-03-05] FX This work was supported by the Key Program of National Natural Science Foundation of China (Grant No. 81230033), the Major State Basic Research Development Program (Grant No. 2011CB707704), the Major Instrument of National Natural Science Foundation Research Project (Grant No. 81227901), the National Natural Science Foundation of China (Grant No. 81371594, 81401442, 81371596), the International Cooperation Program of Xijing Hospital (Grant No. XJZT13G02), a Key Science and Technology Program of Shaanxi Province, China (Grant No. 2013K12-03-05). The authors are grateful to Zhiyong Quan, Zhiping Yang, Jin Zeng, Mingxuan Zhao, and Ming Zhang at the Department of Nuclear Medicine, Xijing Hospital, for performing the PET/CT scans and collecting data. We also thank Yi Li from the Department of Neurosurgery, Tangdu Hospital, for immunohistochemical analysis, and Jing Li, from the Department of Pathology, Xijing Hospital, for pathological analysis. NR 26 TC 5 Z9 5 U1 5 U2 12 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 8 BP 882 EP 889 DI 10.7150/thno.12303 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CI7QT UT WOS:000354959900008 PM 26000059 ER PT J AU Gartrell, K Trinkoff, AM Storr, CL Wilson, ML Gurses, AP AF Gartrell, K. Trinkoff, A. M. Storr, C. L. Wilson, M. L. Gurses, A. P. TI Testing the Electronic Personal Health Record Acceptance Model by Nurses for Managing Their Own Health A Cross-sectional Survey SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Personal health record; nurse; data privacy and security; health promotion; technology acceptance model ID HOSPITAL INFORMATION-SYSTEMS; DIABETES SELF-MANAGEMENT; TECHNOLOGY ACCEPTANCE; USER ACCEPTANCE; PERCEIVED USEFULNESS; FAMILY PHYSICIANS; MEDICAL RECORDS; PATIENTS ACCESS; CARE RECORD; PATIENT USE AB Background: To our knowledge, no evidence is available on health care professionals' use of electronic personal health records (ePHRs) for their health management. We therefore focused on nurses' personal use of ePHRs using a modified technology acceptance model. Objectives: To examine (1) the psychometric properties of the ePHR acceptance model, (2) the associations of perceived usefulness, ease of use, data privacy and security protection, and perception of self as health-promoting role models to nurses' own ePHR use, and (3) the moderating influences of age, chronic illness and medication use, and providers' use of electronic health record (EHRs) on the associations between the ePHR acceptance constructs and ePHR use. Methods: A convenience sample of registered nurses, those working in one of 12 hospitals in the Maryland and Washington, DC areas and members of the nursing informatics community (AMIA and HIMSS), were invited to respond to an anonymous online survey; 847 responded. Multiple logistic regression identified associations between the model constructs and ePHR use, and the moderating effect. Results: Overall, ePHRs were used by 47%. Sufficient reliability for all scales was found. Three constructs were significantly related to nurses' own ePHR use after adjusting for covariates: usefulness, data privacy and security protection, and health-promoting role model. Nurses with providers that used EHRs who perceived a higher level of data privacy and security protection had greater odds of ePHR use than those whose providers did not use EHRs. Older nurses with a higher self-perception as health-promoting role models had greater odds of ePHR use than younger nurses. Conclusions: Nurses who use ePHRs for their personal health might promote adoption by the general public by serving as health-promoting role models. They can contribute to improvements in patient education and ePHR design, and serve as crucial resources when working with their individual patients. C1 [Gartrell, K.] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. [Trinkoff, A. M.; Storr, C. L.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Wilson, M. L.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Gurses, A. P.] Johns Hopkins Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD USA. RP Gartrell, K (reprint author), NIH, Bldg 10,Room 6-2551 10 Ctr Dr,MSC 1504, Bethesda, MD 20892 USA. EM kyungsook.gartrell@nih.gov FU American Nursing Informatics Association Scholarship Award; Graduate Assistance in Areas of National Need fellowship from the University of Maryland School of Nursing FX This work was supported by the American Nursing Informatics Association Scholarship Award and by the Graduate Assistance in Areas of National Need fellowship from the University of Maryland School of Nursing. The authors would like to thank the nurses who participated in the survey. The authors also would like thank the editorial assistance of the National Institutes of Health Fellows Editorial Board. NR 91 TC 0 Z9 0 U1 6 U2 24 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2015 VL 6 IS 2 BP 224 EP 247 DI 10.4338/ACI-2014-11-RA-0107 PG 24 WC Medical Informatics SC Medical Informatics GA CI3AE UT WOS:000354619000002 PM 26171072 ER PT J AU Ellsworth, MA Homan, JM Cimino, JJ Peters, SG Pickering, BW Herasevich, V AF Ellsworth, M. A. Homan, J. M. Cimino, J. J. Peters, S. G. Pickering, B. W. Herasevich, V. TI Point-of-Care Knowledge-Based Resource Needs of Clinicians A Survey from a Large Academic Medical Center SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Electronic health records; evidence-based medicine; information storage and retrieval; point of care technology; user-computer interface ID PHYSICIANS INFORMATION NEEDS; QUESTIONS; RESIDENTS; RETRIEVAL; OPPORTUNITIES; LIBRARIANS; UPTODATE; SUPPORT; SYSTEMS; TRIAL AB Objective: To better understand the literature searching preferences of clinical providers we conducted an institution-wide survey assessing the most preferred knowledge searching techniques. Materials and Methods: A survey regarding literature searching preferences was sent to 1862 unique clinical providers throughout Mayo Clinic. The survey consisted of 25 items asking respondents to select which clinical scenarios most often prompt literature searches as well as identify their most preferred knowledge resources. Results: A total of 450 completed surveys were returned and analyzed (24% response rate). 48% of respondents perform literature searches for more than half of their patient interactions with 91% of all searches occurring either before or within 3 hours of the patient interaction. When a search is performed 57% of respondents prefer synthesized information sources as compared to only 13% who prefer original research. 82% of knowledge searches are performed on a workstation or office computer while just 10% occur on a mobile device or at home. Conclusion: Providers in our survey demonstrate a need to answer clinical questions on a regular basis, especially in the diagnosis and therapy domains. Responses suggest that most of these searches occur using synthesized knowledge sources in the patient care setting within a very short time from the patient interaction. C1 [Ellsworth, M. A.] Mayo Clin, Div Neonatal Med, Rochester, MN USA. [Homan, J. M.] Mayo Clin, Mayo Clin Libraries, Rochester, MN USA. [Cimino, J. J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. [Cimino, J. J.] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Peters, S. G.] Mayo Clin, Div Pulm & Crit Care, Rochester, MN USA. [Pickering, B. W.; Herasevich, V.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Pickering, B. W.; Herasevich, V.] Mayo Clin, Multidisciplinary Epidemiol & Translat Res Intens, Rochester, MN USA. RP Ellsworth, MA (reprint author), Div Neonatal Med, 200 1st St SW, Rochester, MN 55905 USA. EM ellsworth.marc@mayo.edu OI Cimino, James/0000-0003-4101-1622 NR 36 TC 2 Z9 2 U1 1 U2 9 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2015 VL 6 IS 2 BP 305 EP 317 DI 10.4338/ACI-2014-11-RA-0104 PG 13 WC Medical Informatics SC Medical Informatics GA CI3AE UT WOS:000354619000007 PM 26171077 ER PT B AU Alter, KE Nahab, FB Karp, BI AF Alter, Katharine E. Nahab, Fatta B. Karp, Barbara I. BE Alter, KE Wilson, NA TI Pharmacology of Botulinum Neurotoxins SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter ID TOXIN TYPE-A; PLACEBO-CONTROLLED TRIAL; UPPER-LIMB SPASTICITY; THORACIC OUTLET SYNDROME; TENSION-TYPE HEADACHE; RANDOMIZED CONTROLLED-TRIAL; MYOFASCIAL PAIN SYNDROME; BENIGN ESSENTIAL BLEPHAROSPASM; AMYOTROPHIC-LATERAL-SCLEROSIS; HEMIPLEGIC SHOULDER PAIN C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurosci, Miami, FL 33136 USA. [Karp, Barbara I.] NINDS, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 628 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 2 EP + PG 50 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100001 ER PT B AU Alter, KE Nahab, FB AF Alter, Katharine E. Nahab, Fatta B. BE Alter, KE Wilson, NA TI Comparison of Botulinum Neurotoxin Products SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurosci, Miami, FL 33136 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 10 EP 18 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100002 ER PT B AU Alter, KE Lungu, C AF Alter, Katharine E. Lungu, Codrin BE Alter, KE Wilson, NA TI Neurotoxin Storage, Reconstitution, Handling, and Dilution SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 19 EP 28 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100003 ER PT B AU Alter, KE Munin, MC AF Alter, Katharine E. Munin, Michael C. BE Alter, KE Wilson, NA TI Guidance Techniques for Botulinum Neurotoxin Injections SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Munin, Michael C.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 29 EP 37 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100004 ER PT B AU Bohart, Z Koelbel, S Alter, KE AF Bohart, Zachary Koelbel, Stephen Alter, Katharine E. BE Alter, KE Wilson, NA TI Phenol Nerve Blocks SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Bohart, Zachary; Koelbel, Stephen] Braintree Rehabil Hosp, Spast Program, Braintree, MA 02184 USA. [Bohart, Zachary] Braintree Rehabil Hosp, Neurorehabil Clin, Braintree, MA USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. RP Bohart, Z (reprint author), Braintree Rehabil Hosp, Spast Program, Braintree, MA 02184 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 38 EP 43 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100005 ER PT B AU Alter, KE Karp, BI AF Alter, Katharine E. Karp, Barbara I. BE Alter, KE Wilson, NA TI Benign Essential Blepharospasm SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Karp, Barbara I.] NINDS, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 50 EP 58 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100006 ER PT B AU Alter, KE Karp, BI AF Alter, Katharine E. Karp, Barbara I. BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Therapy for Hemifacial Spasm SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Karp, Barbara I.] NINDS, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 59 EP 67 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100007 ER PT B AU Alter, KE Karp, BI AF Alter, Katharine E. Karp, Barbara I. BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Injections for Oromandibular Dystonias SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Karp, Barbara I.] NINDS, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 68 EP 74 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100008 ER PT B AU Alter, KE Munin, MC Downie, SA AF Alter, Katharine E. Munin, Michael C. Downie, Sherry A. BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Injections for Cervical Dystonia SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Munin, Michael C.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Downie, Sherry A.] Yeshiva Univ, Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY USA. [Downie, Sherry A.] Yeshiva Univ, Albert Einstein Coll Med, Dept Phys Med & Rehabil, Bronx, NY USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 79 EP 93 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100009 ER PT B AU Alter, KE Simpson, D Elovic, E AF Alter, Katharine E. Simpson, David Elovic, Elie BE Alter, KE Wilson, NA TI Botulinum Neurotoxin for the Treatment of Idiopathic Primary Focal Limb Dystonia SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Simpson, David] Mt Sinai Med Ctr, Neurol, New York, NY 10029 USA. [Simpson, David] Mt Sinai Med Ctr, Clin Neurophysiol Labs, New York, NY 10029 USA. [Simpson, David] Mt Sinai Med Ctr, Neuromuscular Div, New York, NY 10029 USA. [Simpson, David] Mt Sinai Med Ctr, Dept Neurol, NeuroAIDS Program, New York, NY 10029 USA. [Elovic, Elie] HealthSouth Rehabil Utah, Sandy, UT USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 97 EP 120 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100010 ER PT B AU Alter, KE McGuire, J Nichols, S AF Alter, Katharine E. McGuire, John Nichols, Stephen BE Alter, KE Wilson, NA TI Botulinum Neurotoxin for Treatment of Muscle Overactivity Associated with Upper Motor Neuron Syndromes SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [McGuire, John] Froedtert Hosp, Med Coll Wisconsin, Milwaukee, WI USA. [Nichols, Stephen] Mt Washington Pediat Hosp, Baltimore, MD USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 121 EP 177 PG 57 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100011 ER PT B AU Alter, KE Lungu, C AF Alter, Katharine E. Lungu, Codrin BE Alter, KE Wilson, NA TI Botulinum Neurotoxin for the Treatment of Trunk Dystonia/Camptocormia SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 178 EP 187 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100012 ER PT B AU Alter, KE Ghosh, P AF Alter, Katharine E. Ghosh, Pritha BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Injections for the Treatment of Tremor SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Ghosh, Pritha] George Washington Univ, Med Fac Associates, Dept Neurol, Movement Disorders Program, Washington, DC USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 188 EP 206 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100013 ER PT B AU Alter, KE AF Alter, Katharine E. BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Therapy for Problematic Sialorrhea SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 210 EP 220 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100014 ER PT B AU Alter, KE Lungu, C AF Alter, Katharine E. Lungu, Codrin BE Alter, KE Wilson, NA TI Botulinum Neurotoxin Therapy for Hyperhidrosis SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 221 EP 230 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100015 ER PT B AU Alter, KE Lea, DA AF Alter, Katharine E. Lea, Dallas A., II BE Alter, KE Wilson, NA TI Botulinum Neurotoxin for Urologic Conditions SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Lea, Dallas A., II] Lea Med Partners LLC, Silver Spring, MD USA. [Lea, Dallas A., II] Lea Med Therapies, Silver Spring, MD USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 232 EP 240 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100016 ER PT B AU Alter, KE Ghosh, P AF Alter, Katharine E. Ghosh, Pritha BE Alter, KE Wilson, NA TI Botulinum Neurotoxins for the Treatment of Headache SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Ghosh, Pritha] George Washington Univ, Med Fac Associates, Dept Neurol, Movement Disorders Program, Washington, DC USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 243 EP 258 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100017 ER PT B AU Alter, KE Wilson, NA AF Alter, Katharine E. Wilson, Nicole A. BE Alter, KE Wilson, NA TI Botulinum Neurotoxin for Musculoskeletal Pain Conditions SO BOTULINUM NEUROTOXIN INJECTION MANUAL LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Wilson, Nicole A.] Roth Affin LLC, St Louis, MO USA. [Wilson, Nicole A.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-042-6 PY 2015 BP 260 EP 284 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA BC3SC UT WOS:000351888100018 ER PT J AU Kamal, MA Mushtaq, G Greig, NH AF Kamal, Mohammad A. Mushtaq, Gohar Greig, Nigel H. TI Current Update on Synopsis of miRNA Dysregulation in Neurological Disorders SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article; Proceedings Paper CT 181st Annual Meeting of the American-Association-for-the-Advancement-of-Science (AAAS) CY FEB 12-16, 2015 CL San Jose, CA SP Amer Assoc Advancement Sci DE Alzheimer disease; amyotrophic lateral sclerosis; autism; Huntington disease; microRNA; neurodegeneration; Parkinson's disease; postmortem brain tissue; schizophrenia ID AMYOTROPHIC-LATERAL-SCLEROSIS; AUTISM SPECTRUM DISORDERS; SPORADIC ALZHEIMERS-DISEASE; MICRORNA EXPRESSION PROFILE; ALPHA-SYNUCLEIN EXPRESSION; LYMPHOBLASTOID CELL-LINES; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; THERAPEUTIC TARGETS AB Aberrant expression of microRNAs (miRNAs) has been implicated in various neurological disorders (NDs) of the central nervous system such as Alzheimer disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, schizophrenia and autism. If dysregulated miRNAs are identified in patients suffering from NDs, this may serve as a biomarker for the earlier diagnosis and monitoring of disease progression. Identifying the role of miRNAs in normal cellular processes and understanding how dysregulated miRNA expression is responsible for their neurological effects is also critical in the development of new therapeutic strategies for NDs. miRNAs hold great promise from a therapeutic point of view especially if it can be proved that a single miRNA has the ability to influence several target genes, making it possible for the researchers to potentially modify a whole disease phenotype by modulating a single miRNA molecule. Hence, better understanding of the mechanisms by which miRNA play a role in the pathogenesis of NDs may provide novel targets to scientists and researchers for innovative therapies. C1 [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. [Mushtaq, Gohar] King Abdulaziz Univ, Coll Sci, Dept Biochem, Jeddah 21589, Saudi Arabia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Kamal, MA (reprint author), King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia. EM prof.makamal@lycos.com; gmushtaq2000@yahoo.com RI Mushtaq, Gohar/G-5504-2015; OI Mushtaq, Gohar/0000-0003-4880-4035; Kamal, Mohammad Amjad/0000-0003-0088-0565 NR 106 TC 3 Z9 3 U1 3 U2 12 PU BENTHAM SCIENCE PUBL PI BUSUM PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 4 BP 492 EP 501 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CH6XG UT WOS:000354179100010 PM 25714967 ER PT S AU Gavrielidesl, MA Gallas, BD Hewitt, SM AF Gavrielidesl, Marios A. Gallas, Brandon D. Hewitt, Stephen M. BE Gurcan, MN Madabhushi, A TI Uncertainty in the assessment of immunohistochemical staining with optical and digital microscopy: lessons from a reader study SO MEDICAL IMAGING 2015: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Digital Pathology CY FEB 25-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker ID SURGICAL PATHOLOGY; VIRTUAL MICROSCOPY; BREAST-CANCER; SLIDE; TELEPATHOLOGY; DIAGNOSIS; RECOMMENDATIONS; VALIDATION; GUIDELINE; ROUTINE AB We recently completed a reader study to compare optical and digital pathology (DP) for the assessment of two tissue-based biomarkers with immunohistochemistry. Eight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, 97 cores each), using digital and optical microscopy. All reviews took place in a single office, using the same microscope, same computer/color calibrated monitor combination, and the same ambient light, in order to eliminate sources of variability due to these parameters. Agreement analysis was performed using the Kendall's tau-b metric and percent correct agreement. Results showed relatively high overall inter-observer and inter-modality agreement. However, significant uncertainty was observed for the whole slide evaluation with 95% confidence intervals (CI) in the order of 0.30 for the Kendall's tau-b metric, despite taking care to reduce sources of uncertainty. For the better-sampled TMAs, CIs were in the order of 0.15. It can be deduced that the sample size of 25 slides for each biomarker was not adequate even though it is in line with recent guidelines for the validation of DP from the College of American Pathologists (20 slides for immunohistochemistry without specifying task). Significant uncertainty was observed in our study, despite controlling for several variables. Further work is needed to identify sources of uncertainty for observer tasks in DP, and to account for it in study designs to assess DP. C1 [Gavrielidesl, Marios A.; Gallas, Brandon D.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gavrielidesl, MA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 25 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-510-0 J9 PROC SPIE PY 2015 VL 9420 AR 94200V DI 10.1117/12.2082243 PG 12 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6QB UT WOS:000354372500028 ER PT S AU Kwaki, JT Hewitt, SM Xu, S Pinto, PA Wood, B AF Kwaki, Jin Tae Hewitt, Stephen M. Xu, Sheng Pinto, Peter A. Wood, Bradford BE Gurcan, MN Madabhushi, A TI Nucleus Detection using Gradient Orientation Information and Linear Least Squares Regression SO MEDICAL IMAGING 2015: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Digital Pathology CY FEB 25-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker DE Nucleus segmentation; overlapping nuclei; gradient orientation; linear least squares regression; greedy search; multiview boosting; prostate ID ACTIVE CONTOURS; SEGMENTATION; IMAGES AB Computerized histopathology image analysis enables an objective, efficient, and quantitative assessment of digitized histopathology images. Such analysis often requires an accurate and efficient detection and segmentation of histological structures such as glands, cells and nuclei. The segmentation is used to characterize tissue specimens and to determine the disease status or outcomes. The segmentation of nuclei, in particular, is challenging due to the overlapping or clumped nuclei. Here, we propose a nuclei seed detection method for the individual and overlapping nuclei that utilizes the gradient orientation or direction information. The initial nuclei segmentation is provided by a multiview boosting approach. The angle of the gradient orientation is computed and traced for the nuclear boundaries. Taking the first derivative of the angle of the gradient orientation, high concavity points (junctions) are discovered. False junctions are found and removed by adopting a greedy search scheme with the goodness-of-fit statistic in a linear least squares sense. Then, the junctions determine boundary segments. Partial boundary segments belonging to the same nucleus are identified and combined by examining the overlapping area between them. Using the final set of the boundary segments, we generate the list of seeds in tissue images. The method achieved an overall precision of 0.89 and a recall of 0.88 in comparison to the manual segmentation. C1 [Kwaki, Jin Tae; Xu, Sheng; Wood, Bradford] NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.; Wood, Bradford] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kwaki, JT (reprint author), NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. EM jintae.kwak@nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-510-0 J9 PROC SPIE PY 2015 VL 9420 AR 94200N DI 10.1117/12.2081413 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6QB UT WOS:000354372500020 ER PT S AU Dehghan, E Lu, KK Yan, PK Tahmasebi, A Xu, S Wood, BJ Abi-Jaoudeh, N Venkatesan, A Kruecker, J AF Dehghan, Ehsan Lu, Kongkuo Yan, Pingkun Tahmasebi, Amir Xu, Sheng Wood, Bradford J. Abi-Jaoudeh, Nadine Venkatesan, Aradhana Kruecker, Jochen BE Yaniv, ZR Webster, RJ TI Surface-based registration of liver in ultrasound and CT SO MEDICAL IMAGING 2015: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 22-24, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Siemens, Natl Diagnost Imaging DE Multi-modality fusion; image registration; liver-diaphragm surface; image-guided intervention; ultrasound; computed tomography; electromagnetic tracking AB Ultrasound imaging is an attractive modality for real-time image-guided interventions. Fusion of US imaging with a diagnostic imaging modality such as CT shows great potential in minimally invasive applications such as liver biopsy and ablation. However, significantly different representation of liver in US and CT turns this image fusion into a challenging task, in particular if some of the CT scans may be obtained without contrast agents. The liver surface, including the diaphragm immediately adjacent to it, typically appears as a hyper-echoic region in the ultrasound image if the proper imaging window and depth setting are used. The liver surface is also well visualized in both contrast and non-contrast CT scans, thus making the diaphragm or liver surface one of the few attractive common features for registration of US and non-contrast CT. We propose a fusion method based on point-to-volume registration of liver surface segmented in CT to a processed electromagnetically (EM) tracked US volume. In this approach, first, the US image is pre-processed in order to enhance the liver surface features. In addition, non-imaging information from the EM-tracking system is used to initialize and constrain the registration process. We tested our algorithm in comparison with a manually corrected vessel-based registration method using 8 pairs of tracked US and contrast CT volumes. The registration method was able to achieve an average deviation of 12.8mm from the ground truth measured as the root mean square Euclidean distance for control points distributed throughout the US volume. Our results show that if the US image acquisition is optimized for imaging of the diaphragm, high registration success rates are achievable. C1 [Dehghan, Ehsan; Lu, Kongkuo; Yan, Pingkun; Tahmasebi, Amir; Kruecker, Jochen] Philips Res North Amer, Briarcliff Manor, NY 10510 USA. [Xu, Sheng; Wood, Bradford J.; Abi-Jaoudeh, Nadine; Venkatesan, Aradhana] NIH, Dept Radiol, Bethesda, MD 20892 USA. [Xu, Sheng; Wood, Bradford J.; Abi-Jaoudeh, Nadine; Venkatesan, Aradhana] NIH, Imaging Sci Clin Ctr, Bethesda, MD 20892 USA. RP Dehghan, E (reprint author), Philips Res North Amer, 345 Scarborough Rd, Briarcliff Manor, NY 10510 USA. EM ehsan.dehghan@philips.com NR 8 TC 0 Z9 0 U1 0 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-505-6 J9 PROC SPIE PY 2015 VL 9415 AR 941522 DI 10.1117/12.2082160 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6PU UT WOS:000354365300071 ER PT S AU Yaniv, Z AF Yaniv, Ziv BE Yaniv, ZR Webster, RJ TI Which Pivot Calibration? SO MEDICAL IMAGING 2015: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 22-24, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Siemens, Natl Diagnost Imaging DE calibration; localization and tracking technologies; validation and evaluation ID KNEE REPLACEMENT; SIMULATOR; TRACKING; SYSTEM AB Estimating the location of a tracked tool's tip relative to its Dynamic Reference Frame (DRF) and localizing a specific point in a tracking system's coordinate frame are fundamental tasks in image-guided procedures. The most common approach to estimating these values is by pivoting a tool around a fixed point. The transformations from the tracking system's frame to the tool's DRF are the input. The output is the translation from the DRF to the tool's tip and the translation from the tracker's frame to the pivoting point. While the input and output are unique, there are multiple mathematical formulations for performing this estimation task. The question is, are these formulations equivalent in terms of precision and accuracy? In this work we empirically evaluate three common formulations, a geometry based sphere fitting formulation and two algebraic formulations. In addition we evaluate robust variants of these formulations using the RANSAC framework. Our evaluation shows that the algebraic formulations yield estimates that are more precise and accurate than the sphere fitting formulation. Using the Vicra optical tracking system from Northern Digital Inc., we observed that the algebraic approaches have a mean(std) precision of 0.25(0.11)mm localizing the pivoting point relative to the tracked DRF, and yield a fiducial registration error with a mean(std) 0.15(0.08)mm when registering a precisely constructed divot phantom to the localized points in the tracking system's frame. The sphere fitting formulation yielded less precise and accurate results with a mean(std) of 0.35(0.21)mm for precision and 0.25(0.14)mm for accuracy. The robust versions of these formulations yield similar results even when the data is contaminated with 30% outliers. C1 NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Yaniv, Z (reprint author), NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. EM zivyaniv@nih.gov RI Yaniv, Ziv/Q-1177-2015 OI Yaniv, Ziv/0000-0003-0315-7727 NR 19 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-505-6 J9 PROC SPIE PY 2015 VL 9415 AR 941527 DI 10.1117/12.2081348 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6PU UT WOS:000354365300075 ER PT J AU Ghosh, A Jana, M Modi, K Babu, S Gonzalez, FJ Sims, KB Berry-Kravis, E Pahan, K AF Ghosh, A. Jana, M. Modi, K. Babu, S. Gonzalez, F. J. Sims, K. B. Berry-Kravis, E. Pahan, K. TI Induction of Lysosomal Biogenesis by Activating Peroxisome Proliferator-Activated Receptor alpha SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 22nd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 30-MAY 02, 2015 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Ghosh, A.; Jana, M.; Modi, K.; Babu, S.; Pahan, K.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Gonzalez, F. J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sims, K. B.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Berry-Kravis, E.] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA. [Berry-Kravis, E.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Berry-Kravis, E.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Pahan, K.] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2015 VL 24 IS 4 SI SI BP 758 EP 759 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CH3KD UT WOS:000353928700037 ER PT J AU Michino, M Free, RB Doyle, TB Sibley, DR Shi, L AF Michino, Mayako Free, R. Benjamin Doyle, Trevor B. Sibley, David R. Shi, Lei TI Structural basis for Na+-sensitivity in dopamine D2 and D3 receptors SO CHEMICAL COMMUNICATIONS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BINDING-SITE CREVICE; ALLOSTERIC MODULATION; SODIUM-BINDING; PIVOTAL ROLE; ANTAGONIST; INHIBITION; MEMBRANE; RESIDUES; AFFINITY AB To understand the structural basis for the Na+-sensitivity of ligand binding to dopamine D2-like receptors, using computational analysis in combination with binding assays, we identified interactions critical in propagating the impact of Na+ on receptor conformations and on the ligand-binding site. Our findings expand the pharmacologically-relevant conformational spectrum of these receptors. C1 [Michino, Mayako; Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Michino, Mayako; Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Intramural Res Program, NIH, Baltimore, MD USA. [Free, R. Benjamin; Doyle, Trevor B.; Sibley, David R.] NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. [Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA. RP Shi, L (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. EM les2007@med.cornell.edu FU Intramural NIH HHS [Z01 NS002263-32] NR 24 TC 4 Z9 4 U1 1 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2015 VL 51 IS 41 BP 8618 EP 8621 DI 10.1039/c5cc02204e PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA CH7FH UT WOS:000354200500011 PM 25896577 ER PT J AU Kano, S Yuan, M Cardarelli, RA Maegawa, G Higurashi, N Gaval-Cruz, M Wilson, AM Tristan, C Kondo, MA Chen, Y Koga, M Obie, C Ishizuka, K Seshadri, S Srivastava, R Kato, TA Horiuchi, Y Sedlak, TW Lee, Y Rapoport, JL Hirose, S Okano, H Valle, D O'Donnell, P Sawa, A Kai, M AF Kano, S. Yuan, M. Cardarelli, R. A. Maegawa, G. Higurashi, N. Gaval-Cruz, M. Wilson, A. M. Tristan, C. Kondo, M. A. Chen, Y. Koga, M. Obie, C. Ishizuka, K. Seshadri, S. Srivastava, R. Kato, T. A. Horiuchi, Y. Sedlak, T. W. Lee, Y. Rapoport, J. L. Hirose, S. Okano, H. Valle, D. O'Donnell, P. Sawa, A. Kai, M. TI Clinical Utility of Neuronal Cells Directly Converted from Fibroblasts of Patients for Neuropsychiatric Disorders: Studies of Lysosomal Storage Diseases and Channelopathy SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Direct conversion; induced neuronal cells; iN cells; lysosomal storage diseases; channelopathy; polyglutamine diseases ID PLURIPOTENT STEM-CELLS; IPSC-DERIVED NEURONS; FUNCTIONAL-NEURONS; OXIDATIVE STRESS; HUMAN BRAIN; EPILEPSY; MICE; MODEL; INTERNEURONS; GANGLIOSIDE AB Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies. C1 [Kano, S.; Wilson, A. M.; Tristan, C.; Kondo, M. A.; Chen, Y.; Koga, M.; Ishizuka, K.; Seshadri, S.; Srivastava, R.; Horiuchi, Y.; Sedlak, T. W.; Sawa, A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Sawa, A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Yuan, M.; Kai, M.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21287 USA. [Maegawa, G.; Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Obie, C.; Valle, D.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. [Cardarelli, R. A.; Gaval-Cruz, M.; O'Donnell, P.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [O'Donnell, P.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Lee, Y.; Rapoport, J. L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Higurashi, N.; Hirose, S.] Fukuoka Univ, Sch Med, Dept Pediat, Fukuoka 8140180, Japan. [Okano, H.] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. [Kato, T. A.] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 8128582, Japan. RP O'Donnell, P (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. EM odon002@umaryland.edu; asawa1@jhmi.edu; mkai2@jhmi.edu RI Hidokano, Hideyuki/J-5973-2013; Kondo, Mari/N-2461-2015; U-ID, Kyushu/C-5291-2016; Ishizuka, Koko/L-2071-2014; Kano, Shin-ichi/F-4144-2015; OI Kano, Shin-ichi/0000-0002-5171-3436; Cardarelli, Ross/0000-0002-3692-6708; Kondo, Mari/0000-0001-7960-2888; Maegawa, Gustavo/0000-0001-6933-4138 FU National Institute of Health [Maryland Stem Cell Research Fund] [MH069853, MH084018, MH085226, MH088753, NS071535, MH098689, MH093458]; National Tay-Sachs and Allied Diseases Association; Brain and Behavioral Foundation; Stanley Foundation; SR foundation; Hammerschlag Family; Research grant for Central Research Institute for the Molecular Pathomechanisms of Epilepsy of Fukuoka University; [21249062]; [23659529]; [22791011] FX We thank Drs. P. Talalay, Y. Nakagawa, and M. Li for critical reading of the manuscript and discussion; Drs. A. George, H. Miyoshi, P. Osten, and S. Kugler for reagents; Ms. Y. Lema for help in organizing the manuscript. This work was supported by the National Institute of Health [MH069853, MH084018, MH085226, and MH088753 to A. S., MH085226 to P.O., NS071535 and MH098689 to G.M., and MH093458 to S.K.; the Maryland Stem Cell Research Fund to M.K., P.O., and A. S.]; the National Tay-Sachs and Allied Diseases Association to G.M.; the Brain and Behavioral Foundation to A. S.; Stanley Foundation to A. S.; the SR foundation to A. S.; the Hammerschlag Family to S.K.; Grant-in-Aids for Scientific Research in Japan [# 21249062, # 23659529 to S. H. and # 22791011 to N.H.]; Research grant for Central Research Institute for the Molecular Pathomechanisms of Epilepsy of Fukuoka University to S. H. and N.H. NR 30 TC 4 Z9 4 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 2 BP 138 EP 145 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH3HH UT WOS:000353919900005 PM 25732146 ER PT J AU Ng, TB Cheung, RCF Ng, CCW Fang, EF Wong, JH AF Ng, Tzi Bun Cheung, Randy Chi Fai Ng, Charlene Cheuk Wing Fang, Evandro Fei Wong, Jack Ho TI A Review of Fish Lectins SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE Fish; lectins; mucus; roe; serum ID C-TYPE LECTIN; TROUT ONCORHYNCHUS-MYKISS; RHAMNOSE-BINDING LECTIN; ZEBRAFISH DANIO-RERIO; B-SPECIFIC LECTIN; RAINBOW-TROUT; SERUM LECTIN; ROE LECTIN; STRUCTURAL-CHARACTERIZATION; RACHYCENTRON-CANADUM AB Lectins have been reported from various tissues of a diversity of fish species including Japanese eel, conger eel, electric eel, bighead carp, gibel carp, grass carp, Arabian Gulf catfish, channel catfish, blue catfish, catfish, pike perch, perch, powan, zebrafish, toxic moray, cobia fish, steelhead trout, Japanese trout, Atlantic salmon, chinook salmon, olive rainbow smelt, rainbow smelt, whitespotted charr, tilapia, blue gourami, ayu, Potca fish, Spanish mackerel, gilt head bream, tench, roach, rudd, common skate, and sea lamprey. The tissues from which the lectins were isolated comprise gills, eggs, electric organ, stomach, intestine, and liver. Lectins have also been isolated from skin, mucus serum, and plasma. The lectins differ in molecular weight, number of subunits, glycosylation, sugar binding specificity and amino acid sequence. Their activities include antimicrobial, antitumor, immunoregulatory and a role in development. C1 [Ng, Tzi Bun; Cheung, Randy Chi Fai; Ng, Charlene Cheuk Wing; Wong, Jack Ho] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA. RP Ng, TB (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Kwee Seong Integrated Biomed Sci Bldg, Shatin, Hong Kong, Peoples R China. EM b021770@mailserv.cuhk.edu.hk; b577724@mailserv.cuhk.edu.hk; evandrofang@nih.gov; b111509@mailserv.cuhk.edu.hk NR 92 TC 2 Z9 2 U1 4 U2 26 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 EI 1875-5550 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PY 2015 VL 16 IS 4 BP 337 EP 351 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CH4CD UT WOS:000353978100010 PM 25929869 ER PT S AU Chon, B Tokumasu, F Lee, JY Allen, DW Rice, JP Hwang, J AF Chon, Bonghwan Tokumasu, Fuyuki Lee, Ji Youn Allen, David W. Rice, Joseph P. Hwang, Jeeseong BE Allen, DW Bouchard, JP TI Making Digital Phantoms with Spectral and Spatial Light Modulators for Quantitative Applications of Hyperspectral Optical Medical Imaging Devices SO DESIGN AND PERFORMANCE VALIDATION OF PHANTOMS USED IN CONJUNCTION WITH OPTICAL MEASUREMENT OF TISSUE VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue VII CY FEB 07, 2015 CL San Francisco, CA SP SPIE DE hyperspectral imaging; optical imaging standard; digital phantom; molecular imaging; single cell imaging; scatter imaging; spatial light modulator ID PLASMODIUM-FALCIPARUM; SYSTEM AB We present a procedure to generate digital phantoms with a hyperspectral image projector (HIP) consisting of two liquid crystal on silicon (LCoS) spatial light modulators (SLMs). The digital phantoms are 3D image data cubes of the spatial distribution of spectrally resolved abundances of intracellular light-absorbing oxy-hemoglobin molecules in single erythrocytes. Spectrally and spatially resolved image data indistinguishable from the real scene may be used as standards to calibrate image sensors and validate image analysis algorithms for their measurement quality, performance consistency, and inter-laboratory comparisons for quantitative biomedical imaging applications. C1 [Chon, Bonghwan; Lee, Ji Youn; Hwang, Jeeseong] NIST, Quantum Elect & Photon Div, Boulder, CO 80305 USA. [Tokumasu, Fuyuki] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Allen, David W.; Rice, Joseph P.] NIST, Sensor Sci Div, Gaithersburg, MD 20899 USA. RP Chon, B (reprint author), NIST, Quantum Elect & Photon Div, Boulder, CO 80305 USA. OI Tokumasu, Fuyuki/0000-0003-2790-1071 NR 21 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-415-8 J9 PROC SPIE PY 2015 VL 9325 AR 93250C DI 10.1117/12.2085237 PG 7 WC Cell & Tissue Engineering; Biophysics; Optics SC Cell Biology; Biophysics; Optics GA BC6EX UT WOS:000353883600008 ER PT S AU Wang, JT Ghassemi, P Melchiorri, A Ramella-Roman, J Mathews, SA Coburn, J Sorg, B Chen, Y Pfefer, J AF Wang, Jianting Ghassemi, Pejhman Melchiorri, Anthony Ramella-Roman, Jessica Mathews, Scott A. Coburn, James Sorg, Brian Chen, Yu Pfefer, Joshua BE Allen, DW Bouchard, JP TI 3D Printed Biomimetic Vascular Phantoms for Assessment of Hyperspectral Imaging Systems SO DESIGN AND PERFORMANCE VALIDATION OF PHANTOMS USED IN CONJUNCTION WITH OPTICAL MEASUREMENT OF TISSUE VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue VII CY FEB 07, 2015 CL San Francisco, CA SP SPIE DE 3D printing; biomimetic vascular phantoms; biophotonic imaging; hyperspectral reflectance imaging; tissue oximetry ID TISSUE OPTICAL-PROPERTIES; OXYGEN-SATURATION; TURBID MEDIA; RETINA AB The emerging technique of three-dimensional (3D) printing provides a revolutionary way to fabricate objects with biologically realistic geometries. Previously we have performed optical and morphological characterization of basic 3D printed tissue-simulating phantoms and found them suitable for use in evaluating biophotonic imaging systems. In this study we assess the potential for printing phantoms with irregular, image-defined vascular networks that can be used to provide clinically-relevant insights into device performance. A previously acquired fundus camera image of the human retina was segmented, embedded into a 3D matrix, edited to incorporate the tubular shape of vessels and converted into a digital format suitable for printing. A polymer with biologically realistic optical properties was identified by spectrophotometer measurements of several commercially available samples. Phantoms were printed with the retinal vascular network reproduced as similar to 1.0 mm diameter channels at a range of depths up to similar to 3 mm. The morphology of the printed vessels was verified by volumetric imaging with mu-CT. Channels were filled with hemoglobin solutions at controlled oxygenation levels, and the phantoms were imaged by a near-infrared hyperspectral reflectance imaging system. The effect of vessel depth on hemoglobin saturation estimates was studied. Additionally, a phantom incorporating the vascular network at two depths was printed and filled with hemoglobin solution at two different saturation levels. Overall, results indicated that 3D printed phantoms are useful for assessing biophotonic system performance and have the potential to form the basis of clinically-relevant standardized test methods for assessment of medical imaging modalities. C1 [Wang, Jianting; Ghassemi, Pejhman; Coburn, James; Pfefer, Joshua] US FDA, Silver Spring, MD 20993 USA. [Wang, Jianting; Melchiorri, Anthony; Chen, Yu] Univ Maryland, College Pk, MD 20742 USA. [Ramella-Roman, Jessica] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA. [Mathews, Scott A.] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA. [Sorg, Brian] NCI, NIH, Rockville, MD 20852 USA. RP Wang, JT (reprint author), US FDA, Silver Spring, MD 20993 USA. EM Joshua.Pfefer@fda.hhs.gov NR 21 TC 1 Z9 1 U1 5 U2 10 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-415-8 J9 PROC SPIE PY 2015 VL 9325 AR 932508 DI 10.1117/12.2084720 PG 9 WC Cell & Tissue Engineering; Biophysics; Optics SC Cell Biology; Biophysics; Optics GA BC6EX UT WOS:000353883600005 ER PT J AU Jones, RR Hogrefe, C Fitzgerald, EF Hwang, SA Ozkaynak, H Garcia, VC Lin, S AF Jones, Rena R. Hogrefe, Christian Fitzgerald, Edward F. Hwang, Syni-An Oezkaynak, Haluk Garcia, Valerie C. Lin, Shao TI Respiratory hospitalizations in association with fine PM and its components in New York State SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; PARTICULATE AIR-POLLUTION; SHORT-TERM ASSOCIATIONS; CASE-CROSSOVER; CARDIORESPIRATORY DISEASES; ADMISSIONS; PM2.5; PARTICLES; ASTHMA; MODEL AB Despite observed geographic and temporal variation in particulate matter (PM)-related health morbidities, only a small number of epidemiologic studies have evaluated the relation between PM2.5 chemical constituents and respiratory disease. Most assessments are limited by inadequate spatial and temporal resolution of ambient PM measurements and/or by their approaches to examine the role of specific PM components on health outcomes. In a case-crossover analysis using daily average ambient PM2.5 total mass and species estimates derived from the Community Multiscale Air Quality (CMAQ) model and available observations, we examined the association between the chemical components of PM (including elemental and organic carbon, sulfate, nitrate, ammonium, and other remaining) and respiratory hospitalizations in New York State. We evaluated relationships between levels (low, medium, high) of PM constituent mass fractions, and assessed modification of the PM2.5-hospitalization association via models stratified by mass fractions of both primary and secondary PM components. In our results, average daily PM2.5 concentrations in New York State were generally lower than the 24-hr average National Ambient Air Quality Standard (NAAQS). Year-round analyses showed statistically significant positive associations between respiratory hospitalizations and PM2.5 total mass, sulfate, nitrate, and ammonium concentrations at multiple exposure lags (0.5-2.0% per interquartile range [IQR] increase). Primarily in the summer months, the greatest associations with respiratory hospitalizations were observed per IQR increase in the secondary species sulfate and ammonium concentrations at lags of 1-4 days (1.0-2.0%). Although there were subtle differences in associations observed between mass fraction tertiles, there was no strong evidence to support modification of the PM2.5-respiratory disease association by a particular constituent. We conclude that ambient concentrations of PM2.5 and secondary aerosols including sulfate, ammonium, and nitrate were positively associated with respiratory hospitalizations, although patterns varied by season. Exposure to specific fine PM constituents is a plausible risk factor for respiratory hospitalization in New York State.Implications: The association between ambient concentrations of PM2.5 components has been evaluated in only a small number of epidemiologic studies with refined spatial and temporal scale data. In New York State, fine PM and several of its constituents, including sulfate, ammonium, and nitrate, were positively associated with respiratory hospitalizations. Results suggest that PM species relationships and their influence on respiratory endpoints are complex and season dependent. Additional work is needed to better understand the relative toxicity of PM species, and to further explore the role of co-pollutant relationships and exposure prediction error on observed PM-respiratory disease associations. C1 [Jones, Rena R.; Hwang, Syni-An; Lin, Shao] New York State Dept Hlth, Ctr Environm Hlth, Albany, NY USA. [Jones, Rena R.; Fitzgerald, Edward F.; Hwang, Syni-An; Lin, Shao] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. [Hogrefe, Christian; Oezkaynak, Haluk; Garcia, Valerie C.] US EPA, Raleigh, NC USA. RP Jones, RR (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6906 Med Ctr Dr Room 6E124, Rockville, MD 20850 USA. EM rena.jones@nih.gov OI Lin, Shao/0000-0002-5535-7504 NR 36 TC 6 Z9 6 U1 2 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1096-2247 EI 2162-2906 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PY 2015 VL 65 IS 5 BP 559 EP 569 DI 10.1080/10962247.2014.1001500 PG 11 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA CH5AU UT WOS:000354047100007 PM 25947314 ER PT S AU Hamblin, MR de Sousa, MVP Arany, PR Carroll, JD Patthoff, D AF Hamblin, Michael R. Pires de Sousa, Marcelo Victor Arany, Praveen R. Carroll, James D. Patthoff, Donald BE Hamblin, MR Carroll, JD Arany, P TI Low Level Laser (Light) Therapy and Photobiomodulation: The Path Forward SO MECHANISMS FOR LOW-LIGHT THERAPY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy X CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, THOR Photomedicine Ltd DE low level laser (light) therapy; LLLT; photobiomodulation; mechanism of action; mitochondria; TRP ion channels; new indications; new light sources ID NEAR-INFRARED LIGHT; POTENTIAL TRP CHANNELS; BIPHASIC DOSE-RESPONSE; MPTP-TREATED MICE; BONE-MARROW; MOUSE MODEL; STEM-CELLS; NEUROPROTECTION; DEGENERATION; INFLAMMATION AB Low level laser (light) therapy (LLLT) also known as photobiomodulation (PBM) therapy has been practiced for almost fifty years, and hundreds of positive clinical trials and thousands of laboratory studies have been published. Despite these impressive accomplishments LLLT has still not reached the stage of acceptance by mainstream medicine. The reasons for this were discussed at a recent Optical Society of America (OSA) Incubator meeting in Washington DC in 2014. Uncertainty about mechanisms was highlighted, and this paper will describe the current thinking. To drive LLLT towards mainstream medicine, we need better guidelines with standardized protocols and consistent parameters. Studies should be published in higher impact scientific and medical journals. Companies should avoid false promises and deceptive marketing, and physicians should receive a clearly defined return on investment with insurance reimbursement. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Pires de Sousa, Marcelo Victor] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Sao Paulo, Brazil. [Arany, Praveen R.] NIDCR, NIH, Bethesda, MD USA. [Carroll, James D.] THOR Photomed Ltd, Chesham, England. [Patthoff, Donald] Gen Dent, Martinsburg, WV USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 58 TC 2 Z9 2 U1 3 U2 10 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-399-1 J9 PROC SPIE PY 2015 VL 9309 AR 930902 DI 10.1117/12.2084049 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6EU UT WOS:000353877400002 ER PT J AU Hanaoka, H Nakajima, T Sato, K Watanabe, R Phung, Y Gao, W Harada, T Kim, I Paik, CH Choyke, PL Ho, M Kobayashi, H AF Hanaoka, Hirofumi Nakajima, Takahito Sato, Kazuhide Watanabe, Rira Phung, Yen Gao, Wei Harada, Toshiko Kim, Insook Paik, Chang H. Choyke, Peter L. Ho, Mitchell Kobayashi, Hisataka TI Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel SO NANOMEDICINE LA English DT Article DE Glypican-3; hepatoma; monoclonal antibody; nab-paxlitaxel; nanodelivery; photocyanine dye; photoimmunotherapy ID THERAPEUTIC TARGET; CANCER; ANTIBODIES; EXPRESSION; MARKER AB Aim: Effectiveness of Glypican-3 (GPC3)-targeted photoimmunotherapy (PIT) combined with the nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for hepatocellular carcinoma was evaluated. Materials & methods: GPC3 expressing A431/G1 cells were incubated with a phthalocyanine-derivative, IRDye700DX (IR700), conjugated to an anti-GPC3 antibody, IR700-YP7 and exposed to near-infrared light. Therapeutic experiments combining GPC3-targeted PIT with nab-paclitaxel were performed in A431/G1 tumor-bearing mice. Results: IR700-YP7 bound to A431/G1 cells and induced rapid target-specific necrotic cell death by near-infrared light exposure in vitro. IR700-YP7 accumulated in A431/G1 tumors. Tumor growth was inhibited by PIT compared with nontreated control. Additionally, PIT dramatically increased nabpaclitaxel delivery and enhanced the therapeutic effect. Conclusion: PIT targeting GPC3 combined with nab-paclitaxel is a promising method for treating hepatocellular carcinoma. C1 [Hanaoka, Hirofumi; Nakajima, Takahito; Sato, Kazuhide; Watanabe, Rira; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Phung, Yen; Gao, Wei; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick Natl Lab, Frederick, MD 21702 USA. [Paik, Chang H.] NIH, Nucl Med Dept, Warren Grant Magnuson Clin Ctr, Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU NIH, National Cancer Institute, Center for Cancer Research; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH; National Cancer Institute, NIH [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. KS is supported with JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. In addition, this project has been funded in whole or in part with Federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 18 TC 5 Z9 5 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 7 BP 1139 EP 1147 DI 10.2217/NNM.14.194 PG 9 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CH0MF UT WOS:000353713700010 PM 25929570 ER PT J AU Mello, EA Cohen, LG dos Anjos, SM Conti, J Andrade, KNF Moll, FT Marins, T Fernandes, CA Rodrigues, W Conforto, AB AF Mello, Eduardo Arruda Cohen, Leonardo G. dos Anjos, Sarah Monteiro Conti, Juliana Andrade, Karina Nocelo F. Moll, Fernanda Tovar Marins, Theo Fernandes, Corina A. Rodrigues, Waldyr, Jr. Conforto, Adriana Bastos TI Increase in Short-Interval Intracortical Facilitation of the Motor Cortex after Low-Frequency Repetitive Magnetic Stimulation of the Unaffected Hemisphere in the Subacute Phase after Stroke SO NEURAL PLASTICITY LA English DT Article ID RANDOMIZED-TRIAL; RTMS; HEMIPARESIS; THERAPY; HAND; INHIBITION; PLASTICITY; SYSTEM; BRAIN AB Low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere (UH-LF-rTMS) in patients with stroke can decrease interhemispheric inhibition from the unaffected to the affected hemisphere and improve hand dexterity and strength of the paretic hand. The objective of this proof-of-principle study was to explore, for the first time, effects of UH-LF-rTMS as add-on therapy to motor rehabilitation on short-termintracortical inhibition (SICI) and intracortical facilitation (ICF) of the motor cortex of the unaffected hemisphere (M1(UH)) in patients with ischemic stroke. Eighteen patients were randomized to receive, immediately before rehabilitation treatment, either active or sham UH-LF-rTMS, during two weeks. Resting motor threshold (rMT), SICI, and ICF weremeasured in M1(UH) before the first session and after the last session of treatment. There was a significant increase in ICF in the active group compared to the sham group after treatment, and there was no significant differences in changes in rMT or SICI. ICF is a measure of intracortical synaptic excitability, with a relative contribution of spinal mechanisms. ICF is typically upregulated by glutamatergic agonists and downregulated by gabaergic antagonists. The observed increase in ICF in the active group, in this hypothesis-generating study, may be related to M1(UH) reorganization induced by UH-LF-rTMS. C1 [Mello, Eduardo Arruda; dos Anjos, Sarah Monteiro; Conti, Juliana; Andrade, Karina Nocelo F.; Fernandes, Corina A.; Rodrigues, Waldyr, Jr.; Conforto, Adriana Bastos] Univ Sao Paulo, Hosp & Clin, Clin Hosp, Neurol Clin Div, BR-05403010 Sao Paulo, SP, Brazil. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, NIH, Bethesda, MD 20892 USA. [Moll, Fernanda Tovar; Marins, Theo] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21941902 Rio De Janeiro, RJ, Brazil. [Moll, Fernanda Tovar; Marins, Theo] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, BR-21941902 Rio De Janeiro, RJ, Brazil. [Moll, Fernanda Tovar; Marins, Theo] DOr Inst Res & Educ IDOR, BR-22281032 Rio De Janeiro, RJ, Brazil. [Conforto, Adriana Bastos] Hosp Israelita Albert Einstein, Inst Ensino & Pesquisa, BR-05601901 Sao Paulo, Brazil. RP Conforto, AB (reprint author), Univ Sao Paulo, Hosp & Clin, Clin Hosp, Neurol Clin Div, Ave Dr Eneas C Aguiar 255-5084, BR-05403010 Sao Paulo, SP, Brazil. EM adriana.conforto@gmail.com RI DOS ANJOS, SARAH/G-9277-2015 OI DOS ANJOS, SARAH/0000-0002-7792-862X NR 29 TC 4 Z9 4 U1 1 U2 4 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 407320 DI 10.1155/2015/407320 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CH8US UT WOS:000354312200001 ER PT J AU Apetoh, L Smyth, MJ Drake, CG Abastado, JP Apte, RN Ayyoub, M Blay, JY Bonneville, M Butterfield, LH Caignard, A Castelli, C Cavallo, F Celis, E Chen, LP Colombo, MP Comin-Anduix, B Coukos, G Dhodapkar, MV Dranoff, G Frazer, IH Fridman, WH Gabrilovich, DI Gilboa, E Gnjatic, S Jager, D Kalinski, P Kaufman, HL Kiessling, R Kirkwood, J Knuth, A Liblau, R Lotze, MT Lugli, E Marincola, F Melero, I Melief, CJ Mempel, TR Mittendorf, EA Odun, K Overwijk, WW Palucka, AK Parmiani, G Ribas, A Romero, P Schreiber, RD Schuler, G Srivastava, PK Tartour, E Valmori, D van der Burg, SH van der Bruggen, P van den Eynde, BJ Wang, E Zou, WP Whiteside, TL Speiser, DE Pardoll, DM Restifo, NP Anderson, AC AF Apetoh, Lionel Smyth, Mark J. Drake, Charles G. Abastado, Jean-Pierre Apte, Ron N. Ayyoub, Maha Blay, Jean-Yves Bonneville, Marc Butterfield, Lisa H. Caignard, Anne Castelli, Chiara Cavallo, Federica Celis, Esteban Chen, Lieping Colombo, Mario P. Comin-Anduix, Begona Coukos, Georges Dhodapkar, Madhav V. Dranoff, Glenn Frazer, Ian H. Fridman, Wolf-Herve Gabrilovich, Dmitry I. Gilboa, Eli Gnjatic, Sacha Jaeger, Dirk Kalinski, Pawel Kaufman, Howard L. Kiessling, Rolf Kirkwood, John Knuth, Alexander Liblau, Roland Lotze, Michael T. Lugli, Enrico Marincola, Francesco Melero, Ignacio Melief, Cornelis J. Mempel, Thorsten R. Mittendorf, Elizabeth A. Odun, Kunle Overwijk, Willem W. Palucka, Anna Karolina Parmiani, Giorgio Ribas, Antoni Romero, Pedro Schreiber, Robert D. Schuler, Gerold Srivastava, Pramod K. Tartour, Eric Valmori, Danila van der Burg, Sjoerd H. van der Bruggen, Pierre van den Eynde, Benoit J. Wang, Ena Zou, Weiping Whiteside, Theresa L. Speiser, Daniel E. Pardoll, Drew M. Restifo, Nicholas P. Anderson, Ana C. TI Consensus nomenclature for CD8(+) T cell phenotypes in cancer SO ONCOIMMUNOLOGY LA English DT Article DE anergy; anticancer immunity; CD8(+) T cells; cytotoxicity; exhaustion; effector; IFN gamma; senescence; stemness ID CHRONIC VIRAL-INFECTION; ANTIGEN-LOSS VARIANTS; TUMOR-SPECIFIC CTL; ANTITUMOR IMMUNITY; REPLICATIVE SENESCENCE; MELANOMA PATIENTS; INTERFERON-GAMMA; DENDRITIC CELLS; IN-VITRO; INHIBITORY RECEPTORS C1 [Apetoh, Lionel] INSERM, UMR 866, Dijon, France. [Apetoh, Lionel] Ctr Georges Francois Leclerc, Dijon, France. [Apetoh, Lionel] Univ Bourgogne, Dijon, France. [Smyth, Mark J.] QIMR Berghofer Med Res Inst, Herston, Qld, Australia. [Drake, Charles G.; Pardoll, Drew M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Abastado, Jean-Pierre] Inst Rech Int Servier, Suresnes, France. [Apte, Ron N.] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol, Immunol & Genet, Beer Sheva, Israel. [Ayyoub, Maha; Valmori, Danila] INSERM, U1102, Equipe Labellisee Ligue Canc, Inst Cancerol Ouest, Nantes St Hreblain, France. [Blay, Jean-Yves] Canc Res Ctr Lyon, INSERM UMR 1052, CNRS UMR 5286, Ctr Leon Berard, Lyon, France. [Blay, Jean-Yves] Dept Med Oncol, Lyon, France. [Bonneville, Marc] CRCNA, INSERM U892, CNRS UMR 6299, Nantes, France. [Bonneville, Marc] Inst Merienx, Lyon, France. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Med, Pittsburgh, PA USA. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA. [Caignard, Anne] INSERM UMR 1116, Paris, France. [Castelli, Chiara] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Unit Immunotherapy Human Tumor, Milan, Italy. [Cavallo, Federica] Univ Turin, Ctr Mol Biotechnol, Dept Mol Biotechnol & Hlth Sci, I-10124 Turin, Italy. [Celis, Esteban] Georgia Regents Univ, Ctr Canc, Canc Immunol, Inflammat & Tolerance Program, Augusta, GA USA. [Chen, Lieping] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Chen, Lieping] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Colombo, Mario P.] Fdn IRCCS Ist Nazl Tumori, Mol Immunol Unit, Dept Expt Oncol & Mol Med, Milan, Italy. [Comin-Anduix, Begona; Ribas, Antoni] Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr Los Angels, Los Angeles, CA 90024 USA. [Coukos, Georges; Romero, Pedro; Speiser, Daniel E.] Univ Lausanne, Dept Oncol, Ludwig Ctr Canc Res, CH-1015 Lausanne, Switzerland. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn; Anderson, Ana C.] Harvard Univ, Sch Med, Boston, MA USA. [Frazer, Ian H.] Univ Queensland, Brisbane, Qld 4072, Australia. [Fridman, Wolf-Herve] Univ Paris 05, Cordeliers Res Ctr, Paris, France. [Gabrilovich, Dmitry I.] Wistar Inst Anat & Biol, Translat Tumor Immunol, Philadelphia, PA 19104 USA. [Gilboa, Eli] Univ Miami, Miller Sch Med, Dodson Interdisciplinary Immunotherapy Inst, Dept Microbiol & Immunol,Sylvester Comprehens Can, Miami, FL USA. [Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Jaeger, Dirk] Univ Heidelberg Hosp, Internal Med 4, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany. [Kalinski, Pawel] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Kaufman, Howard L.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Kiessling, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Kirkwood, John] Univ Pittsburgh, Dept Med, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA. [Kirkwood, John] Univ Pittsburgh, Inst Canc, Melanoma & Skin Canc Program, Pittsburgh, PA USA. [Knuth, Alexander] Natl Ctr Canc Care & Res, Doha, Qatar. [Liblau, Roland] INSERM UMR 1043, Toulouse, France. [Liblau, Roland] CNRS, U5282, Toulouse, France. [Liblau, Roland] Univ Toulouse, UPS, Ctr Physiopathol Toulouse Purpan, Toulouse, France. [Liblau, Roland] CHU Toulouse Purpan, Toulouse, France. [Lotze, Michael T.] Univ Pittsburgh, Sch Hlth Sci, Hillman Canc Ctr, Pittsburgh, PA USA. [Lugli, Enrico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy. [Marincola, Francesco; Wang, Ena] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Melero, Ignacio] Univ Navarra, Div Oncol, Ctr Appl Med Res & Clin, E-31080 Pamplona, Spain. [Melief, Cornelis J.] Leiden Univ, ISA Pharmaceut, NL-2300 RA Leiden, Netherlands. [Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Mittendorf, Elizabeth A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Odun, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Odun, Kunle] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Overwijk, Willem W.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Palucka, Anna Karolina] Jackson Lab Genom Med, Farmington, CT USA. [Parmiani, Giorgio] Univ Hosp, Div Med Oncol & Immunotherapy, Siena, Italy. [Schreiber, Robert D.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Schuler, Gerold] Univ Klinikum Erlangen, Dept Dermatol, Erlangen, Germany. [Srivastava, Pramod K.] Univ Connecticut, Ctr Hlth, Carole & Ray Neag Comprehens Canc Ctr, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT USA. [Tartour, Eric] Univ Paris 05, Sorbonne Paris Cite, INSERM U970, Dept Clin Oncol, Paris, France. [Tartour, Eric] Serv Immunol Biol, Hop Europeen Georges Pompidou, Paris, France. [Valmori, Danila] Univ Nantes, Fac Med, F-44035 Nantes, France. [van der Burg, Sjoerd H.] Leiden Univ, Med Ctr, Leiden, Netherlands. [van der Bruggen, Pierre; van den Eynde, Benoit J.] Catholic Univ Louvain, Brussels Branch, Ludwig Inst Canc Res, Duve Inst, B-1200 Brussels, Belgium. [Zou, Weiping] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Whiteside, Theresa L.] Univ Pittsburgh, Dept Pathol, Inst Canc, Immunol & Otolaryngol, Pittsburgh, PA USA. [Restifo, Nicholas P.] Natl Canc Inst, NIH, Bethesda, MD USA. [Anderson, Ana C.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. RP Apetoh, L (reprint author), INSERM, UMR 866, Dijon, France. EM lionel.apetoh@inserm.fr; acanderson@partners.org RI Caignard, Anne/F-8159-2013; Valmori, Danila/K-2439-2015; Smyth, Mark/H-8709-2014; Apetoh, Lionel/G-3310-2014; Blay, Jean-Yves/N-3966-2016; Ayyoub, Maha/A-2074-2017; castelli, chiara/K-6899-2012; Cavallo, Federica/C-5666-2011; OI Smyth, Mark/0000-0001-7098-7240; Apetoh, Lionel/0000-0002-2774-438X; Blay, Jean-Yves/0000-0001-7190-120X; castelli, chiara/0000-0001-6891-8350; Colombo, Mario Paolo/0000-0003-0042-7955; Cavallo, Federica/0000-0003-4571-1060; MELERO BERMEJO, IGNACIO/0000-0002-1360-348X FU American Cancer Society [RSG-11-057-02-LIB]; National Health and Medical Research Council of Australia [628623]; French National Research Agency [ANR-13-JSV3-0001] FX Work in the author's laboratories is supported by grants from the American Cancer Society (RSG-11-057-02-LIB to A.C.A.), the National Health and Medical Research Council of Australia (628623 to MJS), and the French National Research Agency (ANR-13-JSV3-0001 to L.A.). Due to space and other limitations, it is not possible to include all other sources of financial support. NR 97 TC 14 Z9 14 U1 2 U2 20 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 4 AR e998538 DI 10.1080/2162402X.2014.998538 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CH7NS UT WOS:000354224400020 PM 26137416 ER PT J AU Goldstone, AE Chen, Z Perry, MJ Kannan, K Louis, GMB AF Goldstone, Alexandra E. Chen, Zhen Perry, Melissa J. Kannan, Kurunthachalam Louis, Germaine M. Buck TI Urinary bisphenol A and semen quality, the LIFE Study SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Bisphenol A; DNA fragmentation; Endocrine disruptors; Fecundity; Fertility; Semen; Sperm; Sperm chromatin structure assay ID SPERM CHROMATIN INTEGRITY; REPRODUCTIVE HORMONES; DNA FRAGMENTATION; HUMAN-FERTILITY; HUMAN EXPOSURE; MEN; HEALTH; INFERTILITY; DAMAGE; LEVEL AB Bisphenol A (BPA), a high-production volume industrial chemical found in several consumer products, has been negatively associated with sperm quality. This study aimed to estimate the association between BPA and 35 measures of semen quality among reproductive aged men recruited from 16 counties in Michigan and Texas, 2005-2009. Of 501 enrolled males, 418 (83.4%) provided a urine sample and at least one semen sample. Linear and logistic regression models assessed the association between urinary BPA levels and individual semen quality endpoints. Generalized estimating equations were used to account for repeated measures of semen quality and adjusted models accounted for 11 a priori covariates. Geometric mean total urinary BPA concentration among participants was 0.55 ng/mL (95% CI 0.49-0.63). A negative relation between BPA and DNA fragmentation was the sole significant finding in adjusted linear regression (beta = -0.0544, p = 0.035) and suggestive of less sperm DNA damage. Published by Elsevier Inc. C1 [Goldstone, Alexandra E.; Perry, Melissa J.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC USA. [Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Div Environm Hlth Sci, Albany, NY USA. [Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (contracts #N01-HD-3-3355, N01-HD-3-3356, and N01-HD-3-3358). Semen samples were analyzed under a Memorandum of Understanding with NICHD by the Reproductive Health Assessment Team, Biomonitoring and Health Assessments Branch, National Institute for Occupational Safety and Health. NR 40 TC 9 Z9 10 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN PY 2015 VL 51 BP 7 EP 13 DI 10.1016/j.reprotox.2014.11.003 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA CH6NH UT WOS:000354152800002 PM 25462789 ER PT J AU Wright, DL Afeiche, MC Ehrlich, S Smith, K Williams, PL Chavarro, JE Batsis, M Toth, TL Hauser, R AF Wright, Diane L. Afeiche, Myriam C. Ehrlich, Shelley Smith, Kristen Williams, Paige L. Chavarro, Jorge E. Batsis, Maria Toth, Thomas L. Hauser, Russ TI Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Mercury (Hg); Oocyte; Fertilization; In vitro fertilization (IVF); Implantation; Human ID BISPHENOL-A CONCENTRATIONS; LIVE-BIRTH-RATES; OCCUPATIONAL EXPOSURE; REPRODUCTIVE HEALTH; SEAFOOD CONSUMPTION; HEAVY-METALS; TOXIC METALS; CADMIUM; BLOOD; FISH AB Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median = 0.62 ppm, range: 0.03-5.66 ppm) correlated with fish intake (r = 0.59), and exceeded the recommended EPA reference of 1 ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wright, Diane L.; Batsis, Maria; Toth, Thomas L.; Hauser, Russ] Harvard Univ, Sch Med, Vincent Dept Obstet & Gynecol Serv, Div Reprod Med & IVF,Massachusetts Gen Hosp,Ferti, Boston, MA USA. [Afeiche, Myriam C.; Smith, Kristen; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Ehrlich, Shelley] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Williams, Paige L.; Chavarro, Jorge E.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Batsis, Maria] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Batsis, Maria] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. RP Wright, DL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. EM dwright4@mgh.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institutes of Health (NIH) [ES009718, ES000002, T32ES007069] FX Work supported by grants ES009718, ES000002, and T32ES007069 from the National Institutes of Health (NIH). NR 38 TC 2 Z9 2 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN PY 2015 VL 51 BP 125 EP 132 DI 10.1016/j.reprotox.2015.01.003 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA CH6NH UT WOS:000354152800015 PM 25601638 ER PT J AU Kim, HJ Park, Y Bae, HB Choi, SH AF Kim, Hyun Jung Park, Yeonjoon Bae, Hyung Bin Choi, Sang H. TI High-Electron-Mobility SiGe on Sapphire Substrate for Fast Chipsets SO ADVANCES IN CONDENSED MATTER PHYSICS LA English DT Article ID METAL-OXIDE-SEMICONDUCTOR; FIELD-EFFECT TRANSISTORS; STRAINED SI; SILICON; GE; DENSITY; ALLOYS; GROWTH AB High-quality strain-relaxed SiGe films with a low twin defect density, high electron mobility, and smooth surface are critical for device fabrication to achieve designed performance. The mobilities of SiGe can be a few times higher than those of silicon due to the content of high carrier mobilities of germanium (p-type Si: 430 cm(2)/V.s, p-type Ge: 2200 cm(2)/V.s, n-type Si: 1300 cm(2)/V.s, and n-type Ge: 3000 cm(2)/V.s at 10(16) per cm 3 doping density). Therefore, radio frequency devices which are made with rhombohedral SiGe on c-plane sapphire can potentially run a few times faster than RF devices on SOS wafers. NASA Langley has successfully grown highly ordered single crystal rhombohedral epitaxy using an atomic alignment of the [111] direction of cubic SiGe on top of the [0001] direction of the sapphire basal plane. Several samples of rhombohedrally grown SiGe on c-plane sapphire show high percentage of a single crystalline over 95% to 99.5%. The electron mobilities of the tested samples are between those of single crystals Si and Ge. The measured electron mobility of 95% single crystal SiGe was 1538 cm(2)/V.s which is between 350 cm(2)/V.s (Si) and 1550 cm(2)/V.s (Ge) at 6 x 10(17)/cm(3) doping concentration. C1 [Kim, Hyun Jung; Park, Yeonjoon] NIA, Hampton, VA 23666 USA. [Bae, Hyung Bin] Korea Adv Inst Sci & Technol, KAIST Res Anal Ctr KARA, Taejon 305701, South Korea. [Choi, Sang H.] NASA Langley Res Ctr, Hampton, VA 23681 USA. RP Kim, HJ (reprint author), NIA, 100 Explorat Way, Hampton, VA 23666 USA. EM hyunjung.kim@nasa.gov NR 42 TC 0 Z9 0 U1 2 U2 6 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-8108 EI 1687-8124 J9 ADV COND MATTER PHYS JI Adv. Condens. Matter Phys. PY 2015 AR 785415 DI 10.1155/2015/785415 PG 9 WC Physics, Condensed Matter SC Physics GA CH1MF UT WOS:000353785100001 ER PT J AU Kasahara, Y Arime, Y Hall, FS Uhl, GR Sora, I AF Kasahara, Y. Arime, Y. Hall, F. S. Uhl, G. R. Sora, I. TI Region-Specific Dendritic Spine Loss of Pyramidal Neurons in Dopamine Transporter Knockout Mice SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Basolateral amygdala; dendrite; GFP transgenic mouse; hippocampus; medial prefrontal cortex; motor cortex; pyramidal neuron; spine density ID PREPULSE INHIBITION DEFICITS; NMDA RECEPTOR HYPOFUNCTION; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; EXTRACELLULAR LEVELS; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; PLACE PREFERENCE; COCAINE REWARD; WORKING-MEMORY AB Dopamine transporter (DAT) knockout (KO) mice show numerous behavioral alterations, including hyperlocomotion, cognitive deficits, impulsivity and impairment of prepulse inhibition of the startle reflex (PPI), phenotypes that may be relevant to frontostriatal disorders such as schizophrenia. Dendritic spine changes of pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) are among the most replicated of findings in postmortem studies of schizophrenia. The mechanisms that account for dendritic changes in the DLPFC in schizophrenia are unclear. Here, we report basal spine density of pyramidal neurons in the medial prefrontal cortex (mPFC), the motor cortex, the CA1 region of the hippocampus, and the basolateral amygdala in DAT KO mice. Pyramidal neurons were visualized using DAT KO mice crossbred with a Thy1-GFP transgenic mouse line. We observed a significant decrease in spine density of pyramidal neurons in the mPFC and the CA1 region of the hippocampus in DAT KO mice compared to that in WT mice. On the other hand, no difference was observed in spine density of pyramidal neurons in the motor cortex or the basolateral amygdala between DAT genotypes. These results suggest that decreased spine density could cause hypofunction of the mPFC and the hippocampus, and contribute to the behavioral abnormalities observed in DAT KO mice, including cognitive deficits. This might suggest that aberrant dopaminergic signaling may trigger dystrophic changes in dendrites of hippocampal and prefrontocortical pyramidal neurons in schizophrenia. C1 [Kasahara, Y.; Arime, Y.; Sora, I.] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan. [Arime, Y.] Dokkyo Med Univ, Sch Med, Dept Biol Psychiat & Neurosci, Mibu, Tochigi, Japan. [Hall, F. S.; Uhl, G. R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH DHSS, Baltimore, MD USA. RP Sora, I (reprint author), Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Aoba Ku, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan. EM sora@med.tohoku.ac.jp RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU MHLW of Japan; MEXT of Japan; Smoking Research Foundation of Japan; SEISHIN Medical Research Foundation of Japan; National Institute on Drug Abuse, NIH/DHHS, USA FX This study was supported by a Grant-in-Aid for Health and Labour Science Research (Research on Pharmaceutical and Medical Safety) from MHLW of Japan; by Grants-in-Aid for Core Research for Evolutional Science and Technology (CREST), Global COE Program (Basic & Translational Research Center for Global Brain Science) from MEXT of Japan, Smoking Research Foundation of Japan, SEISHIN Medical Research Foundation of Japan and through funding from the Intramural Research Program of the National Institute on Drug Abuse, NIH/DHHS, USA (GRU and FSH). NR 70 TC 3 Z9 3 U1 2 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 3 BP 237 EP 244 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH3HM UT WOS:000353920400005 PM 25817859 ER PT J AU Takamatsu, Y Hagino, Y Sato, A Takahashi, T Nagasawa, SY Kubo, Y Mizuguchi, M Uhl, GR Sora, I Ikeda, K AF Takamatsu, Y. Hagino, Y. Sato, A. Takahashi, T. Nagasawa, S. Y. Kubo, Y. Mizuguchi, M. Uhl, G. R. Sora, I. Ikeda, K. TI Improvement of Learning and Increase in Dopamine Level in the Frontal Cortex by Methylphenidate in Mice Lacking Dopamine Transporter SO CURRENT MOLECULAR MEDICINE LA English DT Article DE ADHD; dopamine transporter; frontal cortex; knockout; learning; methylphenidate; norepinephrine transporter ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXTRACELLULAR DOPAMINE; PREFRONTAL CORTEX; NOREPINEPHRINE TRANSPORTER; PARKINSONS-DISEASE; AVOIDANCE STRATEGY; KNOCKOUT MICE; SHUTTLE-BOX; RAT-BRAIN AB The symptoms of attention-deficit/hyperactivity disorder (ADHD) are characterized by inattention and hyperactivity-impulsivity. It is a common childhood neurodevelopmental disorder that often persists into adulthood. Improvements in ADHD symptoms using psychostimulants have been recognized as a paradoxical calming effect. The psychostimulant methylphenidate (MPH) is currently used as the first-line medication for the management of ADHD. Recent studies have drawn attention to altered dopamine-mediated neurotransmission in ADHD, particularly reuptake by the dopamine transporter (DAT). This hypothesis is supported by the observation that DAT knockout mice exhibit marked hyperactivity that is responsive to acute MPH treatment. However, other behaviors relevant to ADHD have not been fully clarified. In the present study, we observed learning impairment in shuttle-box avoidance behavior together with hyperactivity in a novel environment in DAT knockout mice. Methylphenidate normalized these behaviors and enhanced escape activity in the tail suspension test. Interestingly, the effective dose of MPH increased extracellular dopamine in the prefrontal cortex but not striatum, suggesting an important role for changes in prefrontal dopamine in ADHD. Research that uses C1 [Takamatsu, Y.; Hagino, Y.; Sato, A.; Takahashi, T.; Nagasawa, S. Y.; Ikeda, K.] Tokyo Metropolitan Inst Med Sci, Addict Subst Project, Tokyo 1568506, Japan. [Sato, A.] Univ Tokyo, Grad Sch Med, Dept Pediat, Tokyo 1138655, Japan. [Sato, A.; Nagasawa, S. Y.; Mizuguchi, M.] Univ Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo 1130033, Japan. [Kubo, Y.; Sora, I.] Tohoku Univ, Int Res Inst Disaster Sci, Dept Disaster Psychiat, Sendai, Miyagi 9808579, Japan. [Uhl, G. R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Sora, I.] Kobe Univ, Grad Sch Med, Dept Psychiat, Kobe, Hyogo 6500017, Japan. RP Ikeda, K (reprint author), Tokyo Metropolitan Inst Med Sci, Addict Subst Project, Setagaya Ku, 2-1-6 Kamikitazawa, Tokyo 1568506, Japan. EM ikeda-kz@igakuken.or.jp FU Ministry of Health, Labour and Welfare (MHLW) of Japan [H21-3jiganippan-011, H22-Iyaku-015, H25-Iyaku-020]; JSPS KAKENHI [20602020, 20390162, 22790518, 23390377, 24659490, 24659549]; MEXT KAKENHI [25116532]; Smoking Research Foundation; Astellas Foundation for Research on Metabolic Disorders FX We acknowledge Dr. Hiroaki Niki for supporting this study, Ms. Junko Hasegawa, Ms. Satomi Soma, Ms. Etsuko Kamegaya, and Ms. Yurie Nakamoto for technical assistance, and Mr. Michael Arends for assistance with editing the manuscript. This research was supported by grants from the Ministry of Health, Labour and Welfare (MHLW) of Japan (H21-3jiganippan-011, H22-Iyaku-015, and H25-Iyaku-020), JSPS KAKENHI Grant Numbers 20602020, 20390162, 22790518, 23390377, 24659490, 24659549, MEXT KAKENHI Grant Number 25116532, Smoking Research Foundation, and Astellas Foundation for Research on Metabolic Disorders. NR 53 TC 2 Z9 2 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2015 VL 15 IS 3 BP 245 EP 252 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH3HM UT WOS:000353920400006 PM 25817856 ER PT J AU Gu, XQ Song, YL Chai, YF Lu, F Gonzalez, FJ Fan, GR Qi, YP AF Gu, Xueqin Song, Yunlong Chai, Yifeng Lu, Feng Gonzalez, Frank J. Fan, Guorong Qi, Yunpeng TI GC-MS metabolomics on PPAR alpha-dependent exacerbation of colitis SO MOLECULAR BIOSYSTEMS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; AMINO-ACID-METABOLISM; GAS CHROMATOGRAPHY/MASS SPECTROMETRY; ULCERATIVE-COLITIS; URIC-ACID; SACCHAROMYCES-CEREVISIAE; H-1-NMR SPECTROSCOPY; THREONINE ALDOLASE; HEART-FAILURE; MICE AB Fenofibrate, a peroxisome proliferator-activated receptor a (PPAR alpha) agonist, was found to exacerbate inflammation and tissue injury in experimental acute colitis mice. Through lipidomics analysis, bioactive sphingolipids were significantly up-regulated in the colitis group. In this study, to provide further insight into the PPAR alpha-dependent exacerbation of colitis, gas chromatography-mass spectrometry (GC/MS) based metabolomics was employed to investigate the serum and colon of dextran sulfate sodium (DSS)-induced colitis mice treated with fenofibrate, with particular emphasis on changes in low-molecular-weight metabolites. With the aid of multivariate analysis and metabolic pathway analysis, potential metabolite markers in the amino acid metabolism, urea cycle, purine metabolism, and citrate cycle were highlighted, such as glycine, serine, threonine, malic acid, isocitric acid, uric acid, and urea. The level changes of these metabolites in either serum or colons of colitis mice were further potentiated following fenofibrate treatment. Accordingly, the expression of threonine aldolase and phosphoserine aminotransferase 1 was significantly up-regulated in colitis mice and further potentiated in fenofibrate/DSS-treated mice. It was revealed that beyond the control of lipid metabolism, PPARa also shows effects on the above pathways, resulting in enhanced protein catabolism and energy expenditure, increased bioactive sphingolipid metabolism and proinflammatory state, which were possibly related to the exacerbated colitis. C1 [Gu, Xueqin; Song, Yunlong; Chai, Yifeng; Lu, Feng; Fan, Guorong; Qi, Yunpeng] Second Mil Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 200433, Peoples R China. [Gu, Xueqin; Qi, Yunpeng] Fujian Univ Chinese Tradit Med, Fuzhou 350122, Fujian, Peoples R China. [Gonzalez, Frank J.] NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Fan, GR (reprint author), Second Mil Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 200433, Peoples R China. EM guorfan@outlook.com; qiyunpeng@smmu.edu.cn FU National Science and Technology Major Project of the Ministry of Science and Technology of China [2013ZX09103-001-014]; Li-Shi-Zhen Young Scientist Project of School of Pharmacy at the Second Military Medical University, Shanghai, China FX This study was supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (2013ZX09103-001-014), and Li-Shi-Zhen Young Scientist Project of School of Pharmacy at the Second Military Medical University, Shanghai, China. NR 47 TC 3 Z9 3 U1 2 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2015 VL 11 IS 5 BP 1329 EP 1337 DI 10.1039/c5mb00048c PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG4AD UT WOS:000353221100012 PM 25790429 ER PT S AU Wong, RSL AF Wong, Rosemary S. L. BE Kessel, DH Hasan, T TI NIH and NCI Grant-Related Changes During Fiscal Years 2014/2015 SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXIV CY FEB 07-09, 2015 CL San Francisco, CA SP SPIE C1 NCI, Radiat Res Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA. RP Wong, RSL (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-398-4 J9 PROC SPIE PY 2015 VL 9308 AR 93080E DI 10.1117/12.2083933 PG 3 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6CO UT WOS:000353802500008 ER PT J AU Helton, SG Lohoff, FW AF Helton, Sarah G. Lohoff, Falk W. TI Serotonin pathway polymorphisms and the treatment of major depressive disorder and anxiety disorders SO PHARMACOGENOMICS LA English DT Review DE antidepressants; anxiety disorders; biomarker; genetics; pharmacogenetics; serotonin; treatment response ID CATECHOL-O-METHYLTRANSFERASE; OBSESSIVE-COMPULSIVE DISORDER; GENE PROMOTER POLYMORPHISM; MONOAMINE-OXIDASE-A; ANTIDEPRESSANT TREATMENT RESPONSE; TERM TREATMENT RESPONSE; LATE-LIFE DEPRESSION; FAMILY-BASED ASSOCIATION; 5-HT2A RECEPTOR GENE; ASTERISK-D REPORT AB While antidepressants are widely used to treat major depressive disorder and anxiety disorders, only half of the patients will respond to antidepressant treatment and only a third of patients will experience a remission of symptoms. Identification of genetic biomarkers that predict antidepressant treatment response could thus greatly improve current clinical practice by providing guidance on which drug to use for which patient. Most antidepressant drugs for the treatment of depression and anxiety disorders have effects on the serotonergic neurotransmitter system; thus, genetic polymorphisms in the genes involved in this pathway represent logical candidates for investigation. This article reviews recent findings on the pharmacogenetics of antidepressant drugs with a focus on serotonergic pathway polymorphisms and discusses future clinical applications. C1 [Helton, Sarah G.; Lohoff, Falk W.] NIAAA, Sect Clin Genom & Expt Therapeut CGET, LCTS, NIH, Bethesda, MD 20892 USA. RP Lohoff, FW (reprint author), NIAAA, Sect Clin Genom & Expt Therapeut CGET, LCTS, NIH, Bethesda, MD 20892 USA. EM falk.lohoff@nih.gov RI Lohoff, Falk/M-7951-2016 NR 148 TC 7 Z9 9 U1 6 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PY 2015 VL 16 IS 5 BP 541 EP 553 DI 10.2217/PGS.15.15 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG8UV UT WOS:000353590800011 PM 25916524 ER PT J AU Wilmut, I Leslie, S Martin, NG Peschanski, M Rao, M Trounson, A Turner, D Turner, ML Yamanaka, S Taylor, CJ AF Wilmut, Ian Leslie, Stephen Martin, Nicholas G. Peschanski, Marc Rao, Mahendra Trounson, Alan Turner, David Turner, Marc L. Yamanaka, Shinya Taylor, Craig J. TI Development of a global network of induced pluripotent stem cell haplobanks SO REGENERATIVE MEDICINE LA English DT Editorial Material DE allogeneic; global; haplobank; HLA-matching; iPSC; rejection; transplantation ID IPS CELLS; TRANSPLANTATION; BANKING; LINES; DONOR C1 [Wilmut, Ian] Univ Edinburgh, Edinburgh BioQuarter, MRC Ctr Regenerat Med,Scottish Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland. [Leslie, Stephen] Univ Melbourne, Murdoch Childrens Res Inst, Stat Genet, Parkville, Vic 3052, Australia. [Leslie, Stephen] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3052, Australia. [Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Peschanski, Marc] INSERM, AFM, UMR861, I Stem, F-91030 Evry, France. [Peschanski, Marc] UEVE, UMR861, F-91030 Evry, France. [Rao, Mahendra] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA. [Trounson, Alan] Monash Prince Henrys Hudson Inst Med Res, Clayton, Vic 3168, Australia. [Turner, David] Royal Infirm Edinburgh NHS Trust, SNBTS, Lead H&I Diag Serv, Edinburgh EH16 4SA, Midlothian, Scotland. [Turner, Marc L.] SNBTS HeadQuarters, Edinburgh EH17 7QT, Midlothian, Scotland. [Yamanaka, Shinya] Kyoto Univ, Ctr iPS Cell Res & Applicat, Kyoto 6068507, Japan. [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Taylor, Craig J.] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Histocompatibil & Immunogenet, Cambridge CB2 0QQ, England. [Taylor, Craig J.] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Tissue Typing Lab, Cambridge CB2 0QQ, England. RP Wilmut, I (reprint author), Univ Edinburgh, Edinburgh BioQuarter, MRC Ctr Regenerat Med,Scottish Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland. EM ian.wilmut@ed.ac.uk NR 14 TC 8 Z9 8 U1 2 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 EI 1746-076X J9 REGEN MED JI Regen. Med. PY 2015 VL 10 IS 3 BP 235 EP 238 DI 10.2217/RME.15.1 PG 4 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA CH0MO UT WOS:000353714700003 PM 25933231 ER PT J AU Davila-Torres, J Chowell, G Borja-Aburto, VH Viboud, C Grajalez-Muniz, C Miller, MA AF Davila-Torres, Javier Chowell, Gerardo Borja-Aburto, Victor H. Viboud, Cecile Grajalez-Muniz, Concepcion Miller, Mark. A. TI Intense Seasonal A/H1N1 Influenza in Mexico, Winter 2013-2014 SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE A/H1N1 influenza pandemic; Influenza vaccine; Age distribution; Transmissibility; Drift; Immunity ID A H1N1 VIRUS; AGE DISTRIBUTION; EPIDEMIOLOGIC CHARACTERIZATION; WAVE; MORTALITY; TRANSMISSIBILITY; COPENHAGEN; PNEUMONIA; DEATHS AB Background and Aims. A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013-2014 following a mild 2012-2013 A/H3N2 influenza season. Methods. We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013-2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system. Results. A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October I, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 years and lower among younger age groups for the 2013-2014 A/H1N1 season compared to the previous A/H1N1 season in 2011-2012 (chi(2) test, p <0.001). The reproduction number for the winter 2013-2014 influenza season in central Mexico was estimated at 1.3-1.4, in line with that reported for the 2011-2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009. Conclusions. We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013-March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011-2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics. (C) 2015 IMSS. Published by Elsevier Inc. C1 [Davila-Torres, Javier; Borja-Aburto, Victor H.] Mexican Inst Social Secur, Direct Med Benefits, Mexico City, DF, Mexico. [Chowell, Gerardo; Viboud, Cecile; Miller, Mark. A.] Fogarty Int Ctr, Div Epidemiol & Populat Studies, NIH, Bethesda, MD USA. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci, Tempe, AZ USA. [Grajalez-Muniz, Concepcion] Mexican Inst Social Secur, Coordinat Epidemiol Surveillance & Contingency Su, Mexico City, DF, Mexico. RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, 4791 W Harrison St, Chandler, AZ 85226 USA. EM gchowell@asu.edu FU International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services FX IMSS was responsible for the influenza surveillance system and data gathering. This report was conducted in the context of the MISMS (Multinational Influenza Seasonal Mortality Study), an ongoing international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, U.S. National Institutes of Health (http://www.origem.info/misms/index.php). The MISMS study is funded by the International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services. NR 30 TC 1 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 EI 1873-5487 J9 ARCH MED RES JI Arch. Med. Res. PD JAN PY 2015 VL 46 IS 1 BP 63 EP 70 DI 10.1016/j.arcmed.2014.11.005 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG2IQ UT WOS:000353098500009 PM 25446618 ER PT J AU Kang, MG Jang, MJ Lee, SY Kim, HR Choi, SY Shin, JH Suh, SP Ryang, DW Shin, MG AF Kang, Min-Gu Jang, Min-Joong Lee, Seung-Yeob Kim, Hye-Ran Choi, Seok-Yong Shin, Jong-Hee Suh, Soon-Pal Ryang, Dong-Wook Shin, Myung-Geun TI Feasible Quantitative Detection of Cytomegalovirus from Urine Sediment in Stem Cell Transplant Patients SO CLINICAL LABORATORY LA English DT Article DE urine sediment; quantitative PCR; cytomegalovirus ID BLOOD; RECIPIENTS; INFECTION; DISEASE AB Background: Urine is an important source for the detection of infections caused by CMV in stem cell transplant patients. Currently, there is no agreement about the type of urine specimen. In order to investigate which is the better specimen type for quantitative detection of CMV, we compared the results from urine supernatant and sediment from the same patients. Methods: Seventy urine specimens were collected from patients with hematological disorders or solid tumors. After performing shell vial culture, residual urine specimens were centrifuged. Then, 10 mL of each urine supernatant and sediment were taken and immediately frozen at -70 degrees C. Afterwards, archived urine specimens were thawed at room temperature and CMV-quantitative PCR was performed on both the supernatant and sediment fraction of urine. The results from each patient were reviewed for CMV antigenemia, blood shell vial culture, CMV-IgM or IgG, and clinical symptoms. Results: CMV-qPCR results for the urine sediment fraction revealed a significant difference (p = 0.012) between the active CMV infection group and the latent CMV infection group. In addition, receiver operating characteristic curves for active CMV infection revealed that CMV-qPCR using urine sediment produced more accurate results than urine supernatant. Conclusions: These findings suggest that the sediment fraction of urine is a more suitable specimen in CMV-qPCR testing. C1 [Kang, Min-Gu; Jang, Min-Joong; Lee, Seung-Yeob; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Dept Lab Med, Hwasun, South Korea. [Kang, Min-Gu; Jang, Min-Joong; Lee, Seung-Yeob; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Hwasun, South Korea. [Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Environm Hlth Ctr Childhood Leukemia & Canc, Hwasun, South Korea. [Kim, Hye-Ran; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Choi, Seok-Yong] Chonnam Natl Univ, Ctr Biomed Human Resources, Brain Korea Project 21, Gwangju, South Korea. RP Shin, MG (reprint author), Chonnam Natl Univ, Sch Med, Dept Lab Med, 160 Ilsim Ri, Hwasun Gun 519809, Jeollanam Do, South Korea. EM mgshin@chonnam.ac.kr FU National Research Foundation of Korea (NRF); Korean government (MEST) [2011-0015304]; Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology (MEST) [2011-0030034]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-002436] FX This study was supported by the National Research Foundation of Korea (NRF) and grants funded by the Korean government (MEST) (No.: 2011-0015304), the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (No.: 2011-0030034), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No.: 2010-002436). NR 12 TC 0 Z9 0 U1 0 U2 0 PU CLIN LAB PUBL PI HEIDELBERG PA IM BREITSPIEL 15, HEIDELBERG, D-69126, GERMANY SN 1433-6510 J9 CLIN LAB JI Clin. Lab. PY 2015 VL 61 IS 3-4 BP 299 EP 306 DI 10.7754/Clin.Lab.2014.140810 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CG1BU UT WOS:000353008800012 PM 25974996 ER PT S AU Eggers, SDZ Horn, AKE Roeber, S Hartig, W Nair, G Reich, DS Leigh, RJ AF Eggers, Scott D. Z. Horn, Anja K. E. Roeber, Sigrun Haertig, Wolfgang Nair, Govind Reich, Daniel S. Leigh, R. John BE Braaten, D TI Saccadic palsy following cardiac surgery: a review and new hypothesis SO Dizziness and Balance Disorders SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE supranuclear gaze palsy; omnipause neurons; burst neurons; PPRF; RIMLF; eye movements ID ASCENDING AORTA DISSECTION; SYNDROME RESEMBLING PSP; OCULAR MOTOR APRAXIA; EXTRACELLULAR-MATRIX; EYE-MOVEMENTS; OMNIPAUSE NEURONS; PERINEURONAL NETS; BURST NEURONS; VERTICAL SACCADES; FEEDBACK-CONTROL AB The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction-such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN. C1 [Eggers, Scott D. Z.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Horn, Anja K. E.] Univ Munich, Inst Anat & Cell Biol 1, Munich, Germany. [Horn, Anja K. E.; Roeber, Sigrun] Univ Munich, German Ctr Vertigo & Balance Disorders, Munich, Germany. [Roeber, Sigrun] Univ Munich, Inst Neuropathol & Prion Res, Munich, Germany. [Haertig, Wolfgang] Univ Leipzig, Paul Flechsig Inst Brain Res, D-04109 Leipzig, Germany. [Nair, Govind; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA. [Leigh, R. John] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. RP Eggers, SDZ (reprint author), Mayo Clin, Dept Neurol, 200 First St SW, Rochester, MN 55905 USA. EM eggers.scott@mayo.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Intramural NIH HHS [ZIA NS003119-05] NR 43 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1343 BP 113 EP 119 DI 10.1111/nyas.12666 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA BC5NT UT WOS:000353404000013 PM 25721480 ER PT S AU Koonin, EV Krupovic, M Yutin, N AF Koonin, Eugene V. Krupovic, Mart Yutin, Natalya BE Witzany, G TI Evolution of double-stranded DNA viruses of eukaryotes: from bacteriophages to transposons to giant viruses SO DNA HABITATS AND THEIR RNA INHABITANTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on DNA Habitats and Their RNA Inhabitants CY JUL 03-05, 2014 CL Salzburg, AUSTRIA DE Polintons; Megavirales; virus evolution; capsid proteins; translation ID ORTHOLOGOUS GENES; GENOME EVOLUTION; ORIGIN; DOMAIN; MIMIVIRUS; VIROPHAGE; PROTEINS; ELEMENTS; FAMILIES; LIFE AB Diverse eukaryotes including animals and protists are hosts to a broad variety of viruses with double-stranded (ds) DNA genomes, from the largest known viruses, such as pandoraviruses and mimiviruses, to tiny polyomaviruses. Recent comparative genomic analyses have revealed many evolutionary connections between dsDNA viruses of eukaryotes, bacteriophages, transposable elements, and linear DNA plasmids. These findings provide an evolutionary scenario that derives several major groups of eukaryotic dsDNA viruses, including the proposed order "Megavirales," adenoviruses, and virophages from a group of large virus-like transposons known as Polintons (Mavericks). The Polintons have been recently shown to encode two capsid proteins, suggesting that these elements lead a dual lifestyle with both a transposon and a viral phase and should perhaps more appropriately be named polintoviruses. Here, we describe the recently identified evolutionary relationships between bacteriophages of the family Tectiviridae, polintoviruses, adenoviruses, virophages, large and giant DNA viruses of eukaryotes of the proposed order "Megavirales," and linear mitochondrial and cytoplasmic plasmids. We outline an evolutionary scenario under which the polintoviruses were the first group of eukaryotic dsDNA viruses that evolved from bacteriophages and became the ancestors of most large DNA viruses of eukaryotes and a variety of other selfish elements. Distinct lines of origin are detectable only for herpesviruses (from a different bacteriophage root) and polyoma/papillomaviruses (from single-stranded DNA viruses and ultimately from plasmids). Phylogenomic analysis of giant viruses provides compelling evidence of their independent origins from smaller members of the putative order "Megavirales," refuting the speculations on the evolution of these viruses from an extinct fourth domain of cellular life. C1 [Koonin, Eugene V.; Yutin, Natalya] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Krupovic, Mart] Inst Pasteur, Unite Biol Mol Gene Extremophiles, Paris, France. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Krupovic, Mart/I-4209-2012 OI Krupovic, Mart/0000-0001-5486-0098 FU U.S. Department of Health and Human Services FX E.V.K. and N.Y. are supported by intramural funds of the U.S. Department of Health and Human Services (to the National Library of Medicine). NR 79 TC 16 Z9 16 U1 4 U2 21 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1341 BP 10 EP 24 DI 10.1111/nyas.12728 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BC5AA UT WOS:000353112000003 PM 25727355 ER PT S AU Jalasvuori, M Koonin, EV AF Jalasvuori, Matti Koonin, Eugene V. BE Witzany, G TI Classification of prokaryotic genetic replicators: between selfishness and altruism SO DNA HABITATS AND THEIR RNA INHABITANTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on DNA Habitats and Their RNA Inhabitants CY JUL 03-05, 2014 CL Salzburg, AUSTRIA DE bacteria; archaea; prokaryotes; classification; replicators; cell vehicles ID TOXIN-ANTITOXIN SYSTEMS; RESTRICTION-MODIFICATION SYSTEMS; DOUBLE-STRANDED DNA; COMPARATIVE GENOMICS; VIRUS WORLD; PHAGE BAM35; BACTERIA; EVOLUTION; ELEMENTS; ARCHAEA AB Prokaryotes harbor a variety of genetic replicators, including plasmids, viruses, and chromosomes, each having different effects on the phenotype of the hosting cell. Here, we propose a classification for replicators of bacteria and archaea on the basis of their horizontal-transfer potential and the type of relationships (mutualistic, symbiotic, commensal, or parasitic) that they have with the host cell vehicle. Horizontal movement of replicators can be either active or passive, reflecting whether or not the replicator encodes the means to mediate its own transfer from one cell to another. Some replicators also have an infectious extracellular state, thus separating viruses from other mobile elements. From the perspective of the cell vehicle, the different types of replicators form a continuum from genuinely mutualistic to completely parasitic replicators. This classification provides a general framework for dissecting prokaryotic systems into evolutionarily meaningful components. C1 [Jalasvuori, Matti] Univ Jyvaskyla, Dept Biol & Environm Sci, Ctr Excellence Biol Interact, Jyvaskyla 40014, Finland. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Jalasvuori, M (reprint author), Univ Jyvaskyla, Dept Biol & Environm Sci, POB 35, Jyvaskyla 40014, Finland. EM matti.jalasvuori@jyu.fi FU Intramural NIH HHS [Z01 LM000073-12] NR 62 TC 5 Z9 5 U1 1 U2 7 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1341 BP 96 EP 105 DI 10.1111/nyas.12696 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BC5AA UT WOS:000353112000010 PM 25703428 ER PT J AU Bargi-Souza, P Kucka, M Bjelobaba, I Tomic, M Janjic, MM Nunes, MT Stojilkovic, SS AF Bargi-Souza, Paula Kucka, Marek Bjelobaba, Ivana Tomic, Melanija Janjic, Marija M. Nunes, Maria Tereza Stojilkovic, Stanko S. TI Loss of Basal and TRH-Stimulated Tshb Expression in Dispersed Pituitary Cells SO ENDOCRINOLOGY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; RAT ANTERIOR-PITUITARY; BETA-SUBUNIT GENE; INTRACELLULAR CALCIUM; CENTRAL HYPOTHYROIDISM; THYROID-HORMONE; BIOLOGICAL-ACTIVITY; RECEPTOR-BINDING; MESSENGER-RNA; IN-VITRO AB This study addresses the in vivo and in vitro expression pattern of three genes that are operative in the thyrotroph subpopulation of anterior pituitary cells: glycoprotein alpha-chain (Cga), thyroid-stimulating hormone beta-chain (Tshb), and TRH receptor (Trhr). In vivo, the expression of Cga and Tshb was robust, whereas the expression of Trhr was low. In cultured pituitary cells, there was a progressive decline in the expression of Cga, Tshb, and Trhr. The expression of Tshb could not be reversed via pulsatile or continuous TRH application in variable concentrations and treatment duration or by the removal of thyroid and steroid hormones from the sera. In parallel, the expression of CGA and TSHB proteins declined progressively in pituitary cells from both sexes. The lack of the effect of TRH on Tshb expression was not related to the age of pituitary cultures and the presence of functional TRH receptors. In cultured pituitary fragments, there was also a rapid decline in expression of these genes, but TRH was able to induce transient Tshb expression. In vivo, thyrotrophs were often in close proximity to each other and to somatotroph and folliculostellate cell networks and especially to the lactotroph cell network; such an organization pattern was lost in vitro. These observations suggest that the lack of influence of anterior pituitary architecture and/or intrapituitary factors probably accounts for the loss of basal and TRH-stimulated Tshb expression in dispersed pituitary cells. C1 [Bargi-Souza, Paula; Kucka, Marek; Bjelobaba, Ivana; Tomic, Melanija; Janjic, Marija M.; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, NIH, Sect Cellular Signaling, Bethesda, MD 20892 USA. [Bargi-Souza, Paula; Nunes, Maria Tereza] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP, Brazil. RP Stojilkovic, SS (reprint author), Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM paulascj@gmail.com; mkucka@gmail.com; bjelobabai@mail.nih.gov; tomicm@mail.nih.gov; marija.janjic@nih.gov; mtnunes@icb.usp.br; stojilks@mail.nih.gov RI Tomic, Melanija/C-3371-2016; OI Bargi-Souza, Paula/0000-0001-7746-0636 FU Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Procedure) [12/06643-8]; Intramural Research Program of the Eunice Kennedy Shiver National Institute of Child Health and Human Development, National Institutes of Health; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico FX This work was supported by the Sao Paulo Research Foundation (the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Procedure 12/06643-8) through a grant to P.B.-S. and by a grant from the Intramural Research Program of the Eunice Kennedy Shiver National Institute of Child Health and Human Development, National Institutes of Health (to I.B., M.K., M.T., and S.S.S.). M.T.N. is the recipient of a fellowship from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. NR 53 TC 7 Z9 7 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2015 VL 156 IS 1 BP 242 EP 254 DI 10.1210/en.2014-1281 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG2TA UT WOS:000353126800025 PM 25356823 ER PT J AU Manku, G Wang, Y Merkbaoui, V Boisvert, A Ye, XY Blonder, J Culty, M AF Manku, Gurpreet Wang, Yan Merkbaoui, Vanessa Boisvert, Annie Ye, Xiaoying Blonder, Josip Culty, Martine TI Role of Retinoic Acid and Platelet-Derived Growth Factor Receptor Cross Talk in the Regulation of Neonatal Gonocyte and Embryonal Carcinoma Cell Differentiation SO ENDOCRINOLOGY LA English DT Article ID F9 TERATOCARCINOMA CELLS; RAT TESTIS; SIGNALING PATHWAYS; ENDODERM DIFFERENTIATION; PRIMITIVE ENDODERM; ESTROGEN EXPOSURE; PARIETAL ENDODERM; BASEMENT-MEMBRANE; KINASE INHIBITOR; STEM-CELLS AB Neonatal gonocytes are direct precursors of spermatogonial stem cells, the cell pool that supports spermatogenesis. Although unipotent in vivo, gonocytes express pluripotency genes common with embryonic stem cells. Previously, we found that all-trans retinoic acid (RA) induced the expression of differentiation markers and a truncated form of platelet-derived growth factor receptor (PDGFR)beta in rat gonocytes, as well as in F9 mouse embryonal carcinoma cells, an embryonic stem cell-surrogate that expresses somatic lineage markers in response to RA. The present study is focused on identifying the signaling pathways involved in RA-induced gonocyte and F9 cell differentiation. Mitogen-activated protein kinase kinase (MEK) 1/2 activation was required during F9 cell differentiation towards somatic lineage, whereas its inhibition potentiated RA-induced Stra8 expression, suggesting that MEK1/2 acts as a lineage specification switch in F9 cells. In both cell types, RA increased the expression of the spermatogonial/premeiotic marker Stra8, which is in line with F9 cells being at a stage before somatic-germline lineage specification. Inhibiting PDGFR kinase activity reduced RA-induced Stra8 expression. Interestingly, RA increased the expression of PDGFR alpha variant forms in both cell types. Together, these results suggest a potential cross talk between RA and PDGFR signaling pathways in cell differentiation. RA receptor-alpha inhibition partially reduced RA effects on Stra8 in gonocytes, indicating that RA acts in part via RA receptor-alpha. RA-induced gonocyte differentiation was significantly reduced by inhibiting SRC (v-src avian sarcoma [Schmidt-Ruppin A-2] viral oncogene) and JAK2/STAT5 (Janus kinase 2/signal transducer and activator of transcription 5) activities, implying that these signaling molecules play a role in gonocyte differentiation. These results suggest that gonocyte and F9 cell differentiation is regulated via cross talk between RA and PDGFRs using different downstream pathways. C1 [Manku, Gurpreet; Merkbaoui, Vanessa; Boisvert, Annie; Culty, Martine] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada. [Manku, Gurpreet; Culty, Martine] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1A4, Canada. [Manku, Gurpreet; Culty, Martine] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada. [Wang, Yan] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. [Ye, Xiaoying; Blonder, Josip] NCI, Prot Characterizat Lab, Canc Res Technol Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Culty, M (reprint author), McGill Univ, Ctr Hlth, Montreal Gen Hosp, Res Inst, 1650 Cedar Ave,Room C10-148, Montreal, PQ H3G 1A4, Canada. EM martine.culty@mcgill.ca FU Natural Sciences and Engineering Research Council of Canada [386038-2013]; Royal Victoria Hospital Foundation, Montreal; Centre for the Study of Reproduction, McGill University; Division of Endocrinology and Metabolism (McGill University Health Centre); Reseau Quebecois en Reproduction; Le Fonds de la Recherche en Sante du Quebec FX This work was supported in part by a Natural Sciences and Engineering Research Council of Canada Discovery Grant 386038-2013 and an award from the Royal Victoria Hospital Foundation, Montreal (M.C.); and by funds from the Centre for the Study of Reproduction, McGill University, the Division of Endocrinology and Metabolism (McGill University Health Centre), and the Reseau Quebecois en Reproduction (G.M.). The Research Institute of McGill University Health Centre is supported in part by a Center grant from Le Fonds de la Recherche en Sante du Quebec. NR 63 TC 5 Z9 5 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2015 VL 156 IS 1 BP 346 EP 359 DI 10.1210/en.2014-1524 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG2TA UT WOS:000353126800034 PM 25380237 ER PT J AU Karageorgiadis, AS Papadakis, GZ Biro, J Keil, MF Lyssikatos, C Quezado, MM Merino, M Schrump, DS Kebebew, E Patronas, NJ Hunter, MK Alwazeer, MR Karaviti, LP Balazs, AE Lodish, MB Stratakis, CA AF Karageorgiadis, Alexander S. Papadakis, Georgios Z. Biro, Juliana Keil, Meg F. Lyssikatos, Charalampos Quezado, Martha M. Merino, Maria Schrump, David S. Kebebew, Electron Patronas, Nicholas J. Hunter, Maya K. Alwazeer, Mouhammad R. Karaviti, Lefkothea P. Balazs, Andrea E. Lodish, Maya B. Stratakis, Constantine A. TI Ectopic Adrenocorticotropic Hormone and Corticotropin-Releasing Hormone Co-Secreting Tumors in Children and Adolescents Causing Cushing Syndrome: A Diagnostic Dilemma and How to Solve It SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXPERIENCE; PITUITARY; CRH AB Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH-secreting tumors are discussed. Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH-secreting tumors during the period 2009-2014. Patients: Seven patients with ectopicACTH/CRHCS are included in this study with a median age 13.6 years (range 1-21), and 3 are female. Measurements: Clinical, biochemical, radiological features, treatment, and histological findings are described. Results: Seven patients were found to have ACTH/CRH-secreting tumors, all with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). Patients underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT, and PET scan; imaging with octreotide and 68 gallium DOTATATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH and CRH levels from additional sites. Three patients underwent trans-sphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. Three patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor. Conclusions: Ectopic ACTH/CRH co-secreting tumors are extremely rare in children and adolescents. The diagnosis of this condition is frequently missed and is sometimes confused with CD due to the effect of CRH on the pituitary. C1 [Karageorgiadis, Alexander S.; Biro, Juliana; Keil, Meg F.; Lyssikatos, Charalampos; Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Papadakis, Georgios Z.; Patronas, Nicholas J.] NIH, Sect Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Quezado, Martha M.; Merino, Maria] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Schrump, David S.] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Hunter, Maya K.] Randall Childrens Hosp Legacy Emanuel, Childrens Diabet & Endocrine Ctr, Portland, OR 97227 USA. [Alwazeer, Mouhammad R.; Karaviti, Lefkothea P.; Balazs, Andrea E.] Baylor Coll Med, Sect Diabet & Endocrinol, Dept Pediat, Houston, TX 77030 USA. RP Lodish, MB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM lodishma@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Laboratory of Pathology, Center for Cancer Research; Randall Children's Hospital at Legacy Emanuel, Children's Diabetes and Endocrine Center, Portland, OR; National Cancer Institute, National Institutes of Health, Bethesda, MD FX This work was supported by the intramural programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, and the Randall Children's Hospital at Legacy Emanuel, Children's Diabetes and Endocrine Center, Portland, OR. NR 14 TC 10 Z9 10 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2015 VL 100 IS 1 BP 141 EP 148 DI 10.1210/jc.2014-2945 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300062 PM 25291050 ER PT J AU Rosenquist, KJ Massaro, JM Pedley, A Long, MT Kreger, BE Vasan, RS Murabito, JM Hoffmann, U Fox, CS AF Rosenquist, Klara J. Massaro, Joseph M. Pedley, Alison Long, Michelle T. Kreger, Bernard E. Vasan, Ramachandran S. Murabito, Joanne M. Hoffmann, Udo Fox, Caroline S. TI Fat Quality and Incident Cardiovascular Disease, All-Cause Mortality, and Cancer Mortality SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; ADIPOSE-TISSUE; INSULIN-RESISTANCE; EXTRACELLULAR-MATRIX; RISK-FACTORS; US ADULTS; OBESITY; ASSOCIATION; OVERWEIGHT; SENSITIVITY AB Context: Cellular characteristics of fat quality have been associated with cardiometabolic risk and can be estimated by computed tomography (CT) attenuation. Objective: The aim was to determine the association between CT attenuation (measured in Hounsfield units [ HU]) and clinical outcomes. Methods: This was a prospective community-based cohort study using data from the Framingham Heart Study (n = 3324, 48% women, mean age 51 years) and Cox proportional hazard models. Main Outcomes: The primary outcomes of interest were incident cardiovascular disease (CVD) and all-cause mortality. The secondary outcomes of interest were incident cancer, non-CVD death, and cancer death. Results: There were 111 incident CVD events, 137 incident cancers, 85 deaths including 69 non-CVD deaths, and 45 cancer deaths in up to 23 047 person-years of follow-up. A1-SD increment in visceral adipose tissue (VAT) HU was inversely associated with incident CVD in the age-and sex-adjusted model (hazard ratio [HR] 0.78, P = .02) but not after multivariable adjustment (HR 0.83, P = .11). VAT HU was directly associated with all-cause mortality (multivariable HR 1.40, P = .003), which maintained significance after additional adjustment for body mass index (HR 1.53, P < .001) and VAT volume (HR 1.99, P < .001). Non-CVDdeath remained significant in all 3 models, including after adjustment for VAT volume (HR 1.97, P < .001). VAT HU was also associated with cancer mortality (HR 1.93, P = .002). Similar results were obtained for sc adipose tissue HU. Conclusions: Fat quality, as estimated by CT attenuation, is associated with all-cause mortality, non-CVD death, and cancer death. These associations highlight how indirect indices of fat quality can potentially add to a better understanding of obesity-related complications. C1 [Rosenquist, Klara J.; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Rosenquist, Klara J.; Long, Michelle T.; Kreger, Bernard E.; Vasan, Ramachandran S.; Murabito, Joanne M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Pedley, Alison; Long, Michelle T.; Fox, Caroline S.] Div Intramural Res, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Pedley, Alison; Long, Michelle T.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Long, Michelle T.] Boston Med Ctr, Sect Gastroenterol, Dept Med, Boston, MA 02118 USA. [Kreger, Bernard E.; Murabito, Joanne M.] Boston Med Ctr, Sect Gen Internal Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Hoffmann, Udo] Boston Med Ctr, Sect Prevent Med & Epidemiol & Cardiol, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Long, Michelle/0000-0001-6131-3981; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI's FHS [N01-HC-25195, ROI-HL-077477]; Whitaker Cardiovascular Institute [T32 HL007224] FX This research was conducted in part using data and resources from the Framingham Heart Study (FHS) of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and Boston University School of Medicine. This work was supported by the NHLBI's FHS (Contract N01-HC-25195) and ROI-HL-077477 (to R.S.V.). K.J. R. is supported through funding from the Whitaker Cardiovascular Institute (T32 HL007224). NR 40 TC 17 Z9 17 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2015 VL 100 IS 1 BP 227 EP 234 DI 10.1210/jc.2013-4296 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300072 PM 25226289 ER PT J AU Monticone, S Bandulik, S Stindl, J Zilbermint, M Dedov, I Mulatero, P Allgaeuer, M Lee, CCR Stratakis, CA Williams, TA Tiulpakov, A AF Monticone, Silvia Bandulik, Sascha Stindl, Julia Zilbermint, Mihail Dedov, Ivan Mulatero, Paolo Allgaeuer, Michael Lee, Chyi-Chia Richard Stratakis, Constantine A. Williams, Tracy A. Tiulpakov, Anatoly TI A Case of Severe Hyperaldosteronism Caused by a De Novo Mutation Affecting a Critical Salt Bridge Kir3.4 Residue SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALDOSTERONE-PRODUCING ADENOMAS; POTASSIUM CHANNEL; K+ CHANNEL; REMEDIABLE ALDOSTERONISM; ADRENAL-HYPERPLASIA; SELECTIVITY FILTER; ION SELECTIVITY; MOLECULAR-BASIS; HYPERTENSION; KCNJ5 AB Context: Familial hyperaldosteronism type III (FH-III) is a rare and clinically heterogeneous condition, that can display mild as well as severe phenotypes. Point mutations in the KCNJ5 gene, affecting the ion selectivity of the inward rectifier K+ channel 4 (Kir3.4), underlie the molecular basis of FH-III. Objective: The objective of the study was to investigate the effects of a de novo germline KCNJ5 mutation. Patients and Methods: We describe the case of a girl who came to medical attention at the age of 2 years because of polydipsia, polyuria, and failure to thrive. The patient, affected by hypertension and hypokalemia, was diagnosed with primary aldosteronism on the basis of extremely high aldosterone levels and suppressed plasma renin activity. Genomic DNA was isolated and KCNJ5 sequenced. Human adrenocortical cells were used as an in vitro model for the functional characterization of the mutant channel. Results: KCNJ5 sequencing in the index case and her parents revealed a de novo p.Glu145Gln germline mutation. The substitution resulted in Na+-dependent depolarization of adrenal cells and increased intracellular calcium concentration, which activated the transcription of NR4A2 and, in turn, CYP11B2. Pharmacological studies revealed that the mutant channel was insensitive to tertiapin-Q and calcium-channel blocker verapamil. Conclusions: Herein we report the identification of a novel KCNJ5 germline mutation responsible for severe hyperaldosteronism that presented in infancy with symptoms of diabetes insipidus. The findings of this study further elucidate the etiology of FH-III and expand our knowledge of this rare condition. C1 [Monticone, Silvia; Mulatero, Paolo; Williams, Tracy A.] Univ Turin, Div Internal Med, I-10124 Turin, Italy. [Monticone, Silvia; Mulatero, Paolo; Williams, Tracy A.] Univ Turin, Dept Med Sci, Hypertens Unit, I-10124 Turin, Italy. [Bandulik, Sascha; Stindl, Julia] Univ Regensburg, Med Cell Biol, D-93053 Regensburg, Germany. [Zilbermint, Mihail; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Zilbermint, Mihail; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Inter Inst Training Program, Bethesda, MD 20892 USA. [Allgaeuer, Michael; Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dedov, Ivan; Tiulpakov, Anatoly] Endocrinol Res Ctr, Dept Inherited Endocrine Disorders, Moscow 117036, Russia. RP Tiulpakov, A (reprint author), Endocrinol Res Ctr, Dept & Lab Inherited Endocrine Disorders, Ulitsa Dmitriya Ulianova 11, Moscow 117036, Russia. EM genes@endocrincentr.ru RI Dedov, Ivan/D-3729-2014; Bandulik, Sascha/L-7365-2015; OI Dedov, Ivan/0000-0002-8175-7886; Allgaeuer, Michael/0000-0003-4518-7887 FU Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Societa Italiana dell'Ipertensione Arteriosa; Italian Ministry of the Instruction, University and Research; Deutsche Forschungsgemeinschaft [FOR 1086]; Alfa-Endo Program of Charities Aid Foundation Russia - Alfa-Group; Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland FX We thank Christina Sterner (Medical Cell Biology, University of Regensburg, Germany) for her expert assistance. We acknowledge the support by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and its staff (Elena Belyavskaya, MD; and Charalambos Lyssikatos, among others).; This work was supported by 2013 by a fellowship from the Societa Italiana dell'Ipertensione Arteriosa to S.M.; P.M. is in receipt of a grant from the Italian Ministry of the Instruction, University and Research (grant ex-60%-2013); S.B. was supported by Deutsche Forschungsgemeinschaft (FOR 1086). This work was supported in part by Alfa-Endo Program of Charities Aid Foundation Russia funded by Alfa-Group and by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland. NR 19 TC 13 Z9 13 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2015 VL 100 IS 1 BP E114 EP E118 DI 10.1210/jc.2014-3636 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300030 PM 25322277 ER PT J AU Friedman, C Rubin, J Brown, J Buntin, M Corn, M Etheredge, L Gunter, C Musen, M Platt, R Stead, W Sullivan, K Van Houweling, D AF Friedman, Charles Rubin, Joshua Brown, Jeffrey Buntin, Melinda Corn, Milton Etheredge, Lynn Gunter, Carl Musen, Mark Platt, Richard Stead, William Sullivan, Kevin Van Houweling, Douglas TI Toward a science of learning systems: a research agenda for the high-functioning Learning Health System SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE learning health system; population health; system science; research agenda ID CARE AB Objective The capability to share data, and harness its potential to generate knowledge rapidly and inform decisions, can have transformative effects that improve health. The infrastructure to achieve this goal at scale-marrying technology, process, and policy-is commonly referred to as the Learning Health System (LHS). Achieving an LHS raises numerous scientific challenges. Materials and methods The National Science Foundation convened an invitational workshop to identify the fundamental scientific and engineering research challenges to achieving a national-scale LHS. The workshop was planned by a 12-member committee and ultimately engaged 45 prominent researchers spanning multiple disciplines over 2 days in Washington, DC on 11-12 April 2013. Results The workshop participants collectively identified 106 research questions organized around four system-level requirements that a high-functioning LHS must satisfy. The workshop participants also identified a new cross-disciplinary integrative science of cyber-social ecosystems that will be required to address these challenges. Conclusions The intellectual merit and potential broad impacts of the innovations that will be driven by investments in an LHS are of great potential significance. The specific research questions that emerged from the workshop, alongside the potential for diverse communities to assemble to address them through a 'new science of learning systems', create an important agenda for informatics and related disciplines. C1 [Friedman, Charles; Rubin, Joshua; Van Houweling, Douglas] Univ Michigan, Ann Arbor, MI 48109 USA. [Brown, Jeffrey; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Buntin, Melinda; Stead, William] Vanderbilt Univ, Nashville, TN 37235 USA. [Corn, Milton] Natl Lib Med, Bethesda, MD USA. [Etheredge, Lynn] George Washington Univ, Washington, DC 20052 USA. [Gunter, Carl] Univ Illinois, Urbana, IL 61801 USA. [Musen, Mark] Stanford Univ, Stanford, CA 94305 USA. [Sullivan, Kevin] Univ Virginia, Charlottesville, VA USA. RP Friedman, C (reprint author), Univ Michigan, Dept Learning Hlth Sci, 1111 E Catherine St, Ann Arbor, MI 48109 USA. EM cpfried@umich.edu FU National Science Foundation [IIS - 1249354] FX This work was supported by National Science Foundation grant number IIS - 1249354. NR 46 TC 9 Z9 9 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN PY 2015 VL 22 IS 1 BP 43 EP 50 DI 10.1136/amiajnl-2014-002977 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CF7YA UT WOS:000352771100007 PM 25342177 ER PT J AU Burke, HB Sessums, LL Hoang, A Becher, DA Fontelo, P Liu, F Stephens, M Pangaro, LN O'Malley, PG Baxi, NS Bunt, CW Capaldill, VF Chen, JM Cooper, BA Djuric, DA Hodge, JA Kane, S Magee, C Makary, ZR Mallory, RM Miller, T Saperstein, A Servey, J Gimbel, RW AF Burke, Harry B. Sessums, Laura L. Hoang, Albert Becher, Dorothy A. Fontelo, Paul Liu, Fang Stephens, Mark Pangaro, Louis N. O'Malley, Patrick G. Baxi, Nancy S. Bunt, Christopher W. Capaldill, Vincent F. Chen, Julie M. Cooper, Barbara A. Djuric, David A. Hodge, Joshua A. Kane, Shawn Magee, Charles Makary, Zizette R. Mallory, Renee M. Miller, Thomas Saperstein, Adam Servey, Jessica Gimbel, Ronald W. TI Electronic health records improve clinical note quality SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE QNOTE; electronic health record; clinical quality; clinical note; note quality ID MEDICAL-RECORD; DOCUMENTATION; CARE; PHYSICIANS; MILITARY; PERCEPTIONS; GENERATION; DIAGNOSES; ACCURACY; SYSTEMS AB Background and objective The clinical note documents the clinician's information collection, problem assessment, clinical management, and its used for administrative purposes. Electronic health records (EHRs) are being implemented in clinical practices throughout the USA yet it is not known whether they improve the quality of clinical notes. The goal in this study was to determine if EHRs improve the quality of outpatient clinical notes. Materials and methods A five and a half year longitudinal retrospective multicenter quantitative study comparing the quality of handwritten and electronic outpatient clinical visit notes for 100 patients with type 2 diabetes at three time points: 6 months prior to the introduction of the EHR (before-EHR), 6 months after the introduction of the EHR (after-EHR), and 5 years after the introduction of the EHR (5-year-EHR). QNOTE, a validated quantitative instrument, was used to assess the quality of outpatient clinical notes. Its scores can range from a low of 0 to a high of 100. Sixteen primary care physicians with active practices used QNOTE to determine the quality of the 300 patient notes. Results The before-EHR, after-EHR, and 5-year-EHR grand mean scores (SD) were 52.0 (18.4), 61.2 (16.3), and 80.4 (8.9), respectively, and the change in scores for before-EHR to after-EHR and before-EHR to 5-year-EHR were 18% (p<0.0001) and 55% (p<0.0001), respectively. All the element and grand mean quality scores significantly improved over the 5-year time interval. Conclusions The EHR significantly improved the overall quality of the outpatient clinical note and the quality of all its elements, including the core and non-core elements. To our knowledge, this is the first study to demonstrate that the EHR significantly improves the quality of clinical notes. C1 [Burke, Harry B.; Sessums, Laura L.; Hoang, Albert; Becher, Dorothy A.; Pangaro, Louis N.; O'Malley, Patrick G.; Magee, Charles] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Fontelo, Paul; Liu, Fang] Natl Lib Med, NIH, Bethesda, MD USA. [Stephens, Mark; Bunt, Christopher W.; Miller, Thomas; Saperstein, Adam; Servey, Jessica] Uniformed Serv Univ Hlth Sci, Dept Family, Bethesda, MD 20814 USA. [Baxi, Nancy S.; Capaldill, Vincent F.; Chen, Julie M.; Cooper, Barbara A.; Kane, Shawn; Makary, Zizette R.; Mallory, Renee M.] Walter Reed Natl Mil Med Ctr, Internal Med Serv, Bethesda, MD USA. [Djuric, David A.; Hodge, Joshua A.] Ft Belvoir Community Hosp, Ft Belvoir, VA USA. [Gimbel, Ronald W.] Clemson Univ, Dept Publ Hlth Sci, Clemson, SC USA. RP Burke, HB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, F Edward Hebert Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM harry.burke@usuhs.edu OI Bunt, Christopher/0000-0002-5130-6902 FU US Army Medical Research & Materials Command [W81XWH-08-2-0056] FX Extramural funding was provided by the US Army Medical Research & Materials Command, cooperative agreement W81XWH-08-2-0056. All of the authors are employed by the Uniformed Services University of the Health Sciences or another entity of the US Federal Government. There are no author financial affiliations associated with this manuscript other than those related to their government employment. NR 33 TC 6 Z9 7 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN PY 2015 VL 22 IS 1 BP 199 EP 205 DI 10.1136/amiajnl-2014-002726 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CF7YA UT WOS:000352771100021 PM 25342178 ER PT J AU Taylor, SI Blau, JE Rother, KI AF Taylor, Simeon I. Blau, Jenny E. Rother, Kristina I. TI Possible adverse effects of SGLT2 inhibitors on bone SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Editorial Material ID PHOSPHATE; DAPAGLIFLOZIN; SECRETION; FGF-23 C1 [Taylor, Simeon I.; Blau, Jenny E.; Rother, Kristina I.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Taylor, Simeon I.] Univ Maryland, Sch Med, Dept Med, Div Diabet Endocrinol & Nutr, Baltimore, MD 21201 USA. RP Taylor, SI (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM simeon.taylor@nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 11 TC 47 Z9 48 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JAN PY 2015 VL 3 IS 1 BP 8 EP 10 DI 10.1016/S2213-8587(14)70227-X PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG1KB UT WOS:000353030400009 PM 25523498 ER PT S AU Christensen, R Bokinsky, A Santella, A Wu, YC Marquina, J Kovacevic, I Kumar, A Winter, P McCreedy, E Mohler, W Bao, ZR Colon-Ramos, D Shroff, H AF Christensen, Ryan Bokinsky, Alexandra Santella, Anthony Wu, Yicong Marquina, Javier Kovacevic, Ismar Kumar, Abhishek Winter, Peter McCreedy, Evan Mohler, William Bao, Zhirong Colon-Ramos, Daniel Shroff, Hari BE Rollins, AM Fraser, SE Choma, MA TI An imaging and analysis toolset for the study of Caenorhabditis elegans neurodevelopment SO Optical Methods in Developmental Biology III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods in Developmental Biology III CY FEB 07-08, 2015 CL San Francisco, CA SP Nufern Inc, Physik Instrumente, ThorLabs Inc DE Caenorhabditis elegans; neurodevelopment; light sheet imaging ID PLANE ILLUMINATION MICROSCOPY; AXON GUIDANCE; BIOLOGY AB How an entire nervous system develops remains mysterious. We have developed a light-sheet microscope system to examine neurodevelopment in C. elegans embryos. Our system creates overlapping light sheets from two orthogonally positioned objectives, enabling imaging from the first cell division to hatching (similar to 14 hours) with 350 nm isotropic resolution. We have also developed computer algorithms to computationally straighten nematode embryos, facilitating data comparison and combination from multiple animals. We plan to use these tools to create an atlas showing the position and morphology of all neurons in the developing embryo. C1 [Christensen, Ryan; Wu, Yicong; Kumar, Abhishek; Winter, Peter; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA. [Bokinsky, Alexandra; McCreedy, Evan] NIH, Ctr Informat Technol, Biomed Imaging Res Serv Sect, Bethesda, MD 20892 USA. [Santella, Anthony; Kovacevic, Ismar] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA. [Marquina, Javier; Kumar, Abhishek; Colon-Ramos, Daniel] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, Dept Cell Biol, New Haven, CT 06536 USA. [Mohler, William] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. RP Shroff, H (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA. EM hari.shroff@nih.gov RI Shroff, Hari/E-7247-2016; OI Shroff, Hari/0000-0003-3613-8215; Bao, Zhirong/0000-0002-2201-2745 NR 13 TC 0 Z9 0 U1 4 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-424-0 J9 PROC SPIE PY 2015 VL 9334 AR 93340C DI 10.1117/12.2082394 PG 9 WC Developmental Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Developmental Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC5OC UT WOS:000353408400003 ER PT B AU Malik, N Shin, S Rao, MS AF Malik, Nasir Shin, Soojung Rao, Mahendra S. BE Moody, SA TI Genomic Analyses of Neural Stem Cells SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID GENE-EXPRESSION; MOLECULAR SIGNATURE; PROGENITOR CELLS; DNA METHYLATION; PRECURSOR CELLS; SPINAL-CORD; ES CELLS; ALLELIC VARIATION; MICRORNA TARGETS; NERVOUS-SYSTEM C1 [Malik, Nasir; Rao, Mahendra S.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Shin, Soojung] Invitrogen Corp, Carlsbad, CA USA. [Rao, Mahendra S.] Natl Inst Hlth Ctr Regenerat Med, Bethesda, MD USA. RP Malik, N (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 105 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 97 EP 113 DI 10.1016/B978-0-12-405945-0.00006-5 PG 17 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800007 ER PT B AU Feldman, B AF Feldman, Benjamin BE Moody, SA TI Taking the Middle Road: Vertebrate Mesoderm Formation and the Blastula-Gastrula Transition SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID NODAL-RELATED SIGNALS; EMBRYONIC STEM-CELLS; GERM-LAYER FORMATION; LEFT-RIGHT ASYMMETRY; NEURAL-TUBE DEFECTS; FIBROBLAST-GROWTH-FACTOR; XENOPUS NIEUWKOOP-CENTER; YOLK SYNCYTIAL LAYER; ONE-EYED PINHEAD; MOUSE EMBRYO C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. RP Feldman, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. NR 304 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 203 EP 236 DI 10.1016/B978-0-12-405945-0.00012-0 PG 34 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800013 ER PT B AU Chitnis, AB Nogare, DD AF Chitnis, Ajay B. Nogare, Damian Dalle BE Moody, SA TI Lessons from the Zebrafish Lateral Line System SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID REPORTER TRANSGENIC ZEBRAFISH; COLLECTIVE CELL-MIGRATION; WNT/BETA-CATENIN; TISSUE MIGRATION; PATTERN-FORMATION; SHEET MIGRATION; BETA-ARRESTIN; DANIO-RERIO; INNER-EAR; REGENERATION C1 [Chitnis, Ajay B.; Nogare, Damian Dalle] NICHD, Sect Neural Dev Dynam, Program Genom Differentiat, NIH, Bethesda, MD 20847 USA. RP Chitnis, AB (reprint author), NICHD, Sect Neural Dev Dynam, Program Genom Differentiat, NIH, Bethesda, MD 20847 USA. NR 71 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 265 EP 279 DI 10.1016/B978-0-12-405945-0.00015-6 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800016 ER PT B AU Mann, ZF Kelley, MW AF Mann, Zoe F. Kelley, Matthew W. BE Moody, SA TI Development of the Inner Ear SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID HAIR CELL-DEVELOPMENT; DEVELOPING MAMMALIAN COCHLEA; RETINOIC ACID; NOTCH LIGANDS; OTIC PLACODE; MICE LACKING; REGULATES DEVELOPMENT; AXIAL SPECIFICATION; SENSORY EPITHELIUM; PROSENSORY PATCHES C1 [Mann, Zoe F.; Kelley, Matthew W.] NIDCD, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Mann, ZF (reprint author), NIDCD, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NR 115 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 377 EP 391 DI 10.1016/B978-0-12-405945-0.00021-1 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800022 ER PT B AU Stratman, AN Yu, JXA Mulligan, TS Butler, MG Sause, ET Weinstein, BM AF Stratman, Amber N. Yu, Jianxin A. Mulligan, Timothy S. Butler, Matthew G. Sause, Eric T. Weinstein, Brant M. BE Moody, SA TI Blood Vessel Formation SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID ENDOTHELIAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; ARTERIAL-VENOUS DIFFERENTIATION; EMBRYONIC VASCULAR DEVELOPMENT; INHIBITS SPROUTING ANGIOGENESIS; AUTOSOMAL-DOMINANT ARTERIOPATHY; MUSCLE-CELL DIFFERENTIATION; COMMISSURAL AXON GUIDANCE; VEGF SIGNALING PATHWAY; LYMPHATIC VASCULATURE C1 [Stratman, Amber N.; Yu, Jianxin A.; Mulligan, Timothy S.; Butler, Matthew G.; Sause, Eric T.; Weinstein, Brant M.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Stratman, AN (reprint author), NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. NR 288 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 421 EP 449 DI 10.1016/B978-0-12-405945-0.00024-7 PG 29 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800025 ER PT B AU Yang, YZ AF Yang, Yingzi BE Moody, SA TI Formation of Vertebrate Limbs SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID APICAL ECTODERMAL RIDGE; BONE MORPHOGENETIC PROTEINS; DEVELOPING CHICK LIMB; PLANAR CELL POLARITY; SONIC-HEDGEHOG; FEEDBACK LOOP; SIGNALING CASCADE; FGF SIGNALS; CANDIDATE GENE; GREIG SYNDROME C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 113 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 531 EP 544 DI 10.1016/B978-0-12-405945-0.00029-6 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800030 ER PT B AU Douglas, NC Washkowitz, AJ Naiche, LA Papaioannou, VE AF Douglas, Nataki C. Washkowitz, Andrew J. Naiche, L. A. Papaioannou, Virginia E. BE Moody, SA TI T-Box Genes and Developmental Anomalies SO PRINCIPLES OF DEVELOPMENTAL GENETICS, 2ND EDITION LA English DT Article; Book Chapter ID HOLT-ORAM-SYNDROME; ULNAR-MAMMARY SYNDROME; CONGENITAL HEART-DISEASE; 22Q11 DELETION SYNDROME; LINKED CLEFT-PALATE; GENOTYPE-PHENOTYPE RELATIONSHIP; VENTRICULAR SEPTAL-DEFECTS; DIGEORGE-SYNDROME REGION; TRANSCRIPTION FACTOR; EXPRESSION ANALYSIS C1 [Douglas, Nataki C.; Washkowitz, Andrew J.; Papaioannou, Virginia E.] Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY 10027 USA. [Naiche, L. A.] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. RP Douglas, NC (reprint author), Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY 10027 USA. NR 150 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405923-8; 978-0-12-405945-0 PY 2015 BP 635 EP 652 DI 10.1016/B978-0-12-405945-0.00034-X PG 18 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BC2OS UT WOS:000351155800035 ER PT J AU Huo, L Guo, JX Dang, YH Lv, JQ Zheng, YJ Li, F Xie, QG Chen, XY AF Huo, Li Guo, Jinxia Dang, Yonghong Lv, Jinqiao Zheng, Youjing Li, Fang Xie, Qingguo Chen, Xiaoyuan TI Kinetic Analysis of Dynamic C-11-Acetate PET/CT Imaging as a Potential Method for Differentiation of Hepatocellular Carcinoma and Benign Liver Lesions SO THERANOSTICS LA English DT Article DE C-11-Acetate; dynamic PET; hepatocellular carcinoma; kinetic modeling; discriminant analysis ID POSITRON-EMISSION-TOMOGRAPHY; DISCRIMINANT-ANALYSIS; HEPATIC-TUMORS; MANAGEMENT; CANCER; DIAGNOSIS; CLASSIFICATION; SURVIVAL; TRACER AB Objective: The kinetic analysis of C-11-acetate PET provides more information than routine one time-point static imaging. This study aims to investigate the potential of dynamic C-11-acetate hepatic PET imaging to improve the diagnosis of hepatocellular carcinoma (HCC) and benign liver lesions by using compartmental kinetic modeling and discriminant analysis. Methods: Twenty-two patients were enrolled in this study, 6 cases were with well-differentiated HCCs, 7 with poorly-differentiated HCCs and 9 with benign pathologies. Following the CT scan, all patients underwent C-11-acetate dynamic PET imaging. A three-compartment irreversible dual-input model was applied to the lesion time activity curves (TACs) to estimate the kinetic rate constants K-1-k(3), vascular fraction (VB) and the coefficient alpha representing the relative hepatic artery (HA) contribution to the hepatic blood supply on lesions and non-lesion liver tissue. The parameter Ki (=K-1 x k(3)/(k(2) + k(3))) was calculated to evaluate the local hepatic metabolic rate of acetate (LHMAct). The lesions were further classified by discriminant analysis with all the above parameters. Results: K-1 and lesion to non-lesion standardized uptake value (SUV) ratio (T/L) were found to be the parameters best characterizing the differences among well-differentiated HCC, poorly-differentiated HCC and benign lesions in stepwise discriminant analysis. With discriminant functions consisting of these two parameters, the accuracy of lesion prediction was 87.5% for well-differentiated HCC, 50% for poorly-differentiated HCC and 66.7% for benign lesions. The classification was much better than that with SUV and T/L, where the corresponding classification accuracy of the three kinds of lesions was 57.1%, 33.3% and 44.4%. Conclusion: C-11-acetate kinetic parameter K-1 could improve the identification of HCC from benign lesions in combination with T/L in discriminant analysis. The discriminant analysis using static and kinetic parameters appears to be a very helpful method for clinical liver masses diagnosis and staging. C1 [Huo, Li; Dang, Yonghong; Lv, Jinqiao; Zheng, Youjing; Li, Fang] Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China. [Guo, Jinxia; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA. [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China. [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China. RP Li, F (reprint author), 1 Shuaifuyuan, Beijing 100730, Peoples R China. EM lifang@pumch.cn; shawn.chen@nih.gov FU National Natural Science Foundation of China [81071188, 81371596]; National Key Basic Research Program (973 Project) [2013CB733802]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported in part, by the National Natural Science Foundation of China (Grant No. 81071188, 81371596), by National Key Basic Research Program (973 Project) (2013CB733802), and by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 37 TC 2 Z9 4 U1 1 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 4 BP 371 EP 377 DI 10.7150/thno.10760 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VO UT WOS:000353063500004 PM 25699097 ER PT J AU Melemenidis, S Jefferson, A Ruparelia, N Akhtar, AM Xie, J Allen, D Hamilton, A Larkin, JR Perez-Balderas, F Smart, SC Muschel, RJ Chen, XY Sibson, NR Choudhury, RP AF Melemenidis, Stavros Jefferson, Andrew Ruparelia, Neil Akhtar, Asim M. Xie, Jin Allen, Danny Hamilton, Alastair Larkin, James R. Perez-Balderas, Francisco Smart, Sean C. Muschel, Ruth J. Chen, Xiaoyuan Sibson, Nicola R. Choudhury, Robin P. TI Molecular Magnetic Resonance Imaging of Angiogenesis In Vivo using Polyvalent Cyclic RGD-Iron Oxide Microparticle Conjugates SO THERANOSTICS LA English DT Article DE Tumour; angiogenesis; cRGDyK; microparticles; MRI; DCE ID REFERENCE REGION MODEL; ALPHA(V)BETA(3) INTEGRIN EXPRESSION; DCE-MRI DATA; ARG-GLY-ASP; TUMOR ANGIOGENESIS; CONTRAST AGENT; BLOOD-VESSELS; MOUSE MODEL; ENDOTHELIAL-CELLS; QUANTUM DOTS AB Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule alpha(v)beta(3) integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for alpha(v)beta(3), to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 mu m MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre-and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A significantly greater volume of MPIO-induced hypointensities were found in c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater reduction in mean tumour T-2* relaxation times than the control agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed immunohistochemically was significantly greater for c(RGDyK)-MPIO than c(RADyK)-MPIO injected animals, in both melanoma (P < 0.05) and colorectal (P < 0.0005) tumours. In both cases, binding of c(RGDyK)-MPIO co-localised with alpha(v)beta(3) expression. Comparison of RGD-targeted and dynamic contrast enhanced (DCE) MRI assessment of tumour perfusion indicated sensitivity to different vascular features. This study demonstrates specific binding of c(RGDyK)-MPIO to alpha(v)beta(3) expressing neo-vessels, with marked and quantifiable contrast and rapid clearance of unbound particles from the blood circulation compared to NPIO. Combination of this molecular MRI approach with conventional DCE MRI will enable integrated molecular, anatomical and perfusion tumour imaging. C1 [Jefferson, Andrew; Ruparelia, Neil; Akhtar, Asim M.; Choudhury, Robin P.] Univ Oxford, John Radcliffe Hosp, Div Cardiovasc Med, Radcliffe Dept Med, Oxford OX3 9DU, England. [Melemenidis, Stavros; Allen, Danny; Hamilton, Alastair; Larkin, James R.; Perez-Balderas, Francisco; Smart, Sean C.; Muschel, Ruth J.; Sibson, Nicola R.] Univ Oxford, Canc Res UK, Oxford, England. [Melemenidis, Stavros; Allen, Danny; Hamilton, Alastair; Larkin, James R.; Perez-Balderas, Francisco; Smart, Sean C.; Muschel, Ruth J.; Sibson, Nicola R.] Univ Oxford, Dept Oncol, MRC, Oxford Inst Radiat Oncol, Oxford, England. [Xie, Jin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Choudhury, RP (reprint author), John Radcliffe Hosp, Div Cardiovasc Med, Level 6,West Wing, Oxford OX3 9DU, England. EM robin.choudhury@cardiov.ox.ac.uk FU Cancer Research UK [C5255/A12678]; CR-UK & EPSRC Oxford Cancer Imaging Center; Wellcome Trust; British Heart Foundation Oxford Centre for Research Excellence; CR-UK & EPSRC Oxford Cancer Imaging Centre Studentship FX This work was funded by Cancer Research UK (grant number C5255/A12678), the CR-UK & EPSRC Oxford Cancer Imaging Center, the Wellcome Trust (Senior Research Fellowship to RC) and British Heart Foundation Oxford Centre for Research Excellence (NR). SM was funded by a CR-UK & EPSRC Oxford Cancer Imaging Centre Studentship. The authors would like to thank Dr Veerle Kersemans, Dr Sebastien Serres and Dr Manuel Sarmiento Soto for technical assistance. NR 56 TC 11 Z9 10 U1 2 U2 27 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 5 BP 515 EP 529 DI 10.7150/thno.10319 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VQ UT WOS:000353063800007 PM 25767618 ER PT J AU Zeng, WB Wang, XB Xu, PF Liu, G Eden, HS Chen, XY AF Zeng, Wenbin Wang, Xiaobo Xu, Pengfei Liu, Gang Eden, Henry S. Chen, Xiaoyuan TI Molecular Imaging of Apoptosis: From Micro to Macro SO THERANOSTICS LA English DT Review DE Apoptosis; Microscopic imaging assays; Macroscopic imaging probes; Clinical translation ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO EVALUATION; F-18-FLUOROBENZYL TRIPHENYL PHOSPHONIUM; EXPERIMENTAL CEREBRAL STROKE; RESONANCE ENERGY-TRANSFER; IRON-OXIDE NANOPARTICLES; DETECT PROTEASE ACTIVITY; TARGETED CONTRAST AGENT; RED FLUORESCENT PEPTIDE; INDUCED TUMOR APOPTOSIS AB Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. C1 [Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei] Cent S Univ, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China. [Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei] Cent S Univ, Mol Imaging Res Ctr, Changsha 410013, Hunan, Peoples R China. [Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Eden, Henry S.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Zeng, WB (reprint author), Cent S Univ, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China. EM wbzeng@hotmail.com; shawn.chen@nih.gov FU National Natural Science Foundation of China [30900377, 81271634]; Doctoral Fund of Ministry of Education of China [20120162110070]; Hunan Provincial Natural Science Foundation of China [12JJ1012]; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We acknowledge the financial support from The National Natural Science Foundation of China (No. 30900377 and 81271634), Doctoral Fund of Ministry of Education of China (No. 20120162110070), Hunan Provincial Natural Science Foundation of China (12JJ1012), and the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 221 TC 18 Z9 18 U1 4 U2 39 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 6 BP 559 EP 582 DI 10.7150/thno.11548 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VU UT WOS:000353064200002 PM 25825597 ER PT S AU De Obaldia, ME Bhandoola, A AF De Obaldia, Maria Elena Bhandoola, Avinash BE Littman, DR Yokoyama, WM TI Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages SO ANNUAL REVIEW OF IMMUNOLOGY VOL 33 SE Annual Review of Immunology LA English DT Review; Book Chapter DE T cell development; innate lymphoid cell development; transcription factors; lineage commitment; evolution of lymphocytes; enhancer regulation ID T-CELL DEVELOPMENT; ROR-GAMMA-T; HEMATOPOIETIC STEM-CELLS; NATURAL-KILLER-CELL; ORPHAN NUCLEAR RECEPTORS; DELTA-LIKE 4; EARLIEST THYMIC PROGENITORS; CHROMATIN STATE DYNAMICS; ANTIGEN-PRESENTING CELLS; GENE-EXPRESSION PROGRAM AB The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the trailscriptome level and express many elements of the core cell transcriptional program, including Notch, Gata3 T47, and Bd11b. We present our current understanding of the shared and distinct transcriptional regulatory mechanisms involved in the development of adaptive T lymphocytes and closely related ILCs. We discuss the possibility that a core set of transcriptional regulators common to ILCs and T cells establish enhancers that enable implementation of closely aligned effector pathways. Studies of the transcriptional regulation of lymphopoiesis will support the development of novel therapeutic approaches to correct early lymphoid developmental defects and aberrant lymphocyte function. C1 [De Obaldia, Maria Elena; Bhandoola, Avinash] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [De Obaldia, Maria Elena] Rockefeller Univ, Howard Hughes Med Inst, Lab Neurogenet & Behav, New York, NY 10065 USA. [Bhandoola, Avinash] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP De Obaldia, ME (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM mdeobaldia@mail.rockefeller.edu; avinash.bhandoola@nih.gov FU Intramural NIH HHS; NCI NIH HHS [T32 CA-009140, T32 CA009140]; NHLBI NIH HHS [HL11074103]; NIAID NIH HHS [AI059621, AI098428]; NIGMS NIH HHS [T32 GM-07229] NR 312 TC 34 Z9 34 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3033-0 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2015 VL 33 BP 607 EP 642 DI 10.1146/annurev-immunol-032414-112032 PG 36 WC Immunology SC Immunology GA BC4TF UT WOS:000352911900020 PM 25665079 ER PT S AU Grossman, Z Paul, WE AF Grossman, Zvi Paul, William E. BE Littman, DR Yokoyama, WM TI Dynamic Tuning of Lymphocytes: Physiological Basis, Mechanisms, and Function SO ANNUAL REVIEW OF IMMUNOLOGY VOL 33 SE Annual Review of Immunology LA English DT Review; Book Chapter DE adaptation; activation threshold; subthreshold interaction; self/nonself discrimination; reciprocal tuning; anergy; immune regulation; functional reprogramming; adaptive differentiation ID T-CELL HOMEOSTASIS; DENDRITIC CELLS; LIGAND DISCRIMINATION; ANTIGEN SENSITIVITY; SENSORY ADAPTATION; POSITIVE SELECTION; ADAPTIVE TOLERANCE; SELF-RECOGNITION; FOREIGN ANTIGEN; LOW-AFFINITY AB Dynamic tuning of cellular responsiveness as a result of repeated stimuli improves the ability of cells to distinguish physiologically meaningful signals from each other and from noise. In particular, lymphocyte activation thresholds are subject to tuning, which contributes to maintaining tolerance to self-antigens and persisting foreign antigens, averting autoimmunity and immune pathogenesis, but allowing responses to strong, structured perturbations that are typically associated with acute infection. Such tuning is also implicated in conferring flexibility to positive selection in the thymus, in controlling the magnitude of the immune response, and in generating memory cells. Additional functional properties are dynamically and differentially tuned in parallel via subthreshold contact interactions between developing or mature lymphocytes and self-antigen-presenting cells. these interactions facilitate and regulate lymphocyte viability, maintain their functional integrity, and influence their responses to foreign antigens and accessory signals, qualitatively and quantitatively. Bidirectional tuning of T cells and antigen-presenting cells leads to the definition of homeostatic set points, thus maximizing clonal diversity. C1 [Grossman, Zvi; Paul, William E.] NIAID, Lab Immunol, NIH, Bethesda, MD 20892 USA. [Grossman, Zvi] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Grossman, Z (reprint author), NIAID, Lab Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM grossmanz@niaid.nih.gov; wpaul@niaid.nih.gov NR 127 TC 12 Z9 12 U1 0 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3033-0 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2015 VL 33 BP 677 EP 713 DI 10.1146/annurev-immunol-032712-100027 PG 37 WC Immunology SC Immunology GA BC4TF UT WOS:000352911900022 PM 25665077 ER PT S AU de Jesus, AA Canna, SW Liu, Y Goldbach-Mansky, R AF de Jesus, Adriana Almeida Canna, Scott W. Liu, Yin Goldbach-Mansky, Raphaela BE Littman, DR Yokoyama, WM TI Molecular Mechanisms in Genetically Defined Autoinflammatory Diseases: Disorders of Amplified Danger Signaling SO ANNUAL REVIEW OF IMMUNOLOGY VOL 33 SE Annual Review of Immunology LA English DT Review; Book Chapter DE autoinflammatory diseases; IL-I-mediated autoinflammatory diseases; IFN-mediated autoinflammatorv diseases; cryopyrin-associated periodic syndromes; proteasome-associated autoinflammatory syndromes; inflammasomes in human disease; hereditary fever syndromes; macrophage activation syndrome ID FAMILIAL MEDITERRANEAN FEVER; MACROPHAGE ACTIVATION SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS; NF-KAPPA-B; AICARDI-GOUTIERES SYNDROME; LINKED LYMPHOPROLIFERATIVE DISEASE; PEDIATRIC GRANULOMATOUS ARTHRITIS; INFLAMMATORY-BOWEL-DISEASE; GAIN-OF-FUNCTION; CYCLIC GMP-AMP AB Patients with autoinflammatory diseases present with noninfectious fever Hares and systemic and/or disease-specific organ inflammation. Their excessive proinflammatory cytokine and chemokine responses can be life threatening and lead to organ damage over time. Studying such patients has revealed genetic defects that have helped unravel key innate immune pathways, including excessive IL-1 signaling, constitutive NF-kappa B activation, and, more recently, chronic type I IFN signaling. Discoveries of monogenic defects that lead to activation of proinflammatorv cytokines have inspired the use of anticytokine-directed treatment approaches that have been life changing for many patients and have led to the approval of IL-1 -blocking agents for a number of autoinflammatory conditions. In this review, we describe the genetically characterized autoinflammatory diseases, we summarize our understanding of the molecular pathways that drive clinical phenotypes and that continue to inspire the search for novel treatment targets. and we provide a conceptual framework for classification. C1 [de Jesus, Adriana Almeida; Canna, Scott W.; Liu, Yin; Goldbach-Mansky, Raphaela] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. RP de Jesus, AA (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov FU Intramural NIH HHS [Z99 AR999999, ZIA AR041138-12] NR 243 TC 33 Z9 34 U1 1 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3033-0 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2015 VL 33 BP 823 EP 874 DI 10.1146/annurev-immunol-032414-112227 PG 52 WC Immunology SC Immunology GA BC4TF UT WOS:000352911900026 PM 25706096 ER PT B AU Conde-Agudelo, A Romero, R Roberts, JM AF Conde-Agudelo, Agustin Romero, Roberto Roberts, James M. BE Taylor, RN Roberts, JM Cunningham, FG Lindheimer, MD TI Tests to Predict Preeclampsia SO CHESLEY'S HYPERTENSIVE DISORDERS IN PREGNANCY, 4TH EDITION LA English DT Article; Book Chapter ID UTERINE ARTERY DOPPLER; PLACENTAL GROWTH-FACTOR; HUMAN CHORIONIC-GONADOTROPIN; MATERNAL SERUM INHIBIN; FOR-GESTATIONAL-AGE; FREE BETA-HCG; EARLY-ONSET PREECLAMPSIA; CELL-FREE FETAL; PREGNANCY-INDUCED HYPERTENSION; CALCIUM CREATININE RATIO C1 [Conde-Agudelo, Agustin] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD 20847 USA. [Conde-Agudelo, Agustin] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Detroit, MI USA. [Romero, Roberto] NICHD, Obstet & Perinatol, Intramural Div, NIH,DHHS, Ann Arbor, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Roberts, James M.] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA. [Roberts, James M.] Univ Pittsburgh, Obstet Gynecol Reprod Sci & Epidemiol & Clin & Tr, Pittsburgh, PA USA. RP Conde-Agudelo, A (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD 20847 USA. NR 232 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-407945-8; 978-0-12-407866-6 PY 2015 BP 221 EP 251 DI 10.1016/B978-0-12-407866-6.00011-0 PG 31 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BC2OU UT WOS:000351157200014 ER PT B AU Kummer, A Dalal, M Chew, E Weber, M AF Kummer, Andrew Dalal, Monica Chew, Emily Weber, Marc BE Kimmel, PL Rosenberg, ME TI Ophthalmic Issues in Chronic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID TREATMENT DIABETIC-RETINOPATHY; INFANTILE NEPHROPATHIC CYSTINOSIS; RETINAL VESSEL DIAMETERS; RENAL TUBULAR-ACIDOSIS; STURGE-WEBER-SYNDROME; OCULAR MANIFESTATIONS; INTRAOCULAR-PRESSURE; MACULAR EDEMA; TUBULOINTERSTITIAL NEPHRITIS; CORNEAL CALCIFICATION C1 [Kummer, Andrew; Weber, Marc] Univ Minnesota, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. [Dalal, Monica; Chew, Emily] NEI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD USA. RP Kummer, A (reprint author), Univ Minnesota, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 237 EP 248 DI 10.1016/B978-0-12-411602-3.00020-2 PG 12 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600020 ER PT B AU Germino, GG Guay-Woodford, LM AF Germino, Gregory G. Guay-Woodford, Lisa M. BE Kimmel, PL Rosenberg, ME TI Polycystic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID CONGENITAL HEPATIC-FIBROSIS; PREIMPLANTATION GENETIC DIAGNOSIS; AUTOSOMAL-DOMINANT; MOLECULAR DIAGNOSTICS; EPITHELIAL-CELLS; PRIMARY CILIUM; LIVER-DISEASE; PRENATAL-DIAGNOSIS; PKHD1 MUTATIONS; MTOR PATHWAY C1 [Germino, Gregory G.] Johns Hopkins Univ, Sch Med, NIH, Bethesda, MD 20817 USA. [Guay-Woodford, Lisa M.] Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA. RP Germino, GG (reprint author), Johns Hopkins Univ, Sch Med, NIH, Bethesda, MD 20817 USA. NR 93 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 484 EP 500 DI 10.1016/B978-0-12-411602-3.00040-8 PG 17 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600040 ER PT B AU Cohen, SD Kopp, JB Cathro, H Kimmel, PL AF Cohen, Scott D. Kopp, Jeffrey B. Cathro, Helen Kimmel, Paul L. BE Kimmel, PL Rosenberg, ME TI Human Immunodeficiency Virus Infection and Chronic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID HIV-ASSOCIATED NEPHROPATHY; ACTIVE ANTIRETROVIRAL THERAPY; THROMBOTIC THROMBOCYTOPENIC PURPURA; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; TENOFOVIR DISOPROXIL FUMARATE; STAGE RENAL-DISEASE; HIV-1-ASSOCIATED NEPHROPATHY; RECENT PROGRESS; INJURY; COHORT C1 [Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. [Kopp, Jeffrey B.] Natl Inst Diabet Digest & Kidney Dis, Kidney Dis Sect, NIH, Bethesda, MD USA. [Cathro, Helen] Univ Virginia, Dept Pathol, Med Ctr, Charlottesville, VA 22903 USA. RP Cohen, SD (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. NR 81 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 534 EP 543 DI 10.1016/B978-0-12-411602-3.00044-5 PG 10 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600044 ER PT B AU Dreisbach, AW Flessner, MF AF Dreisbach, Albert W. Flessner, Michael F. BE Kimmel, PL Rosenberg, ME TI Drug Metabolism and Chronic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID CHRONIC-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; DOWN-REGULATION; SERUM CREATININE; PROTEIN-BINDING; PHARMACOKINETICS; TRANSPORT; CYTOCHROME-P450; HEMODIALYSIS; ACETYLATION C1 [Dreisbach, Albert W.] Univ Mississippi, Med Ctr, Div Nephrol, Jackson, MS 39216 USA. [Flessner, Michael F.] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Dreisbach, AW (reprint author), Univ Mississippi, Med Ctr, Div Nephrol, Jackson, MS 39216 USA. NR 45 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 674 EP 681 DI 10.1016/B978-0-12-411602-3.00055-X PG 8 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600055 ER PT B AU Flessner, MF AF Flessner, Michael F. BE Kimmel, PL Rosenberg, ME TI Preparing for Peritoneal Dialysis SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID RESIDUAL RENAL-FUNCTION; CHRONIC KIDNEY-DISEASE; DECISION-MAKING; INFECTION C1 Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. RP Flessner, MF (reprint author), Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 765 EP 770 DI 10.1016/B978-0-12-411602-3.00063-9 PG 6 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600063 ER PT B AU Furth, SL Moxey-Mims, M Ruebner, R AF Furth, Susan L. Moxey-Mims, Marva Ruebner, Rebecca BE Kimmel, PL Rosenberg, ME TI Chronic Kidney Disease in Children SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID CHRONIC-RENAL-FAILURE; PEDIATRIC LIVER-TRANSPLANTATION; LONG-TERM SURVIVORS; HEMATOPOIETIC-CELL TRANSPLANTATION; GROWTH-HORMONE TREATMENT; CARDIOVASCULAR-DISEASE; HEART-TRANSPLANTATION; RISK-FACTORS; ITALKID PROJECT; URINARY-TRACT C1 [Furth, Susan L.; Ruebner, Rebecca] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Moxey-Mims, Marva] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Furth, SL (reprint author), Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 130 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 813 EP 824 DI 10.1016/B978-0-12-411602-3.00067-6 PG 12 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600067 ER PT B AU Mattoo, TK Moxey-Mims, M AF Mattoo, Tej K. Moxey-Mims, Marva BE Kimmel, PL Rosenberg, ME TI Reflux Nephropathy SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID URINARY-TRACT-INFECTION; PRIMARY VESICOURETERAL REFLUX; ACID RENAL SCINTIGRAPHY; ACUTE PYELONEPHRITIS; ANTIBIOTIC-PROPHYLAXIS; SURGICAL-TREATMENT; BLOOD-PRESSURE; FOLLOW-UP; INTERNATIONAL REFLUX; YOUNG-CHILDREN C1 [Mattoo, Tej K.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Detroit, MI 48202 USA. [Moxey-Mims, Marva] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Mattoo, TK (reprint author), Wayne State Univ, Sch Med, Childrens Hosp Michigan, Detroit, MI 48202 USA. NR 82 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 825 EP 832 DI 10.1016/B978-0-12-411602-3.00068-8 PG 8 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600068 ER PT J AU Hauser, W Hoffmann, EM Wolfe, F Worthing, AB Stahl, N Rothenberg, R Walitt, B AF Haeuser, W. Hoffmann, E. -M. Wolfe, F. Worthing, A. B. Stahl, N. Rothenberg, R. Walitt, B. TI Self-reported childhood maltreatment, lifelong traumatic events and mental disorders in fibromyalgia syndrome: a comparison of US and German outpatients SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE fibromyalgia syndrome; childhood maltreatment; traumatic experiences; transcultural epidemiology; mental disorder ID POSTTRAUMATIC-STRESS-DISORDER; FUNCTIONAL SOMATIC SYNDROMES; PSYCHOMETRIC PROPERTIES; SEXUAL-ABUSE; METAANALYSIS; POPULATION; PREVALENCE; DEPRESSION; VERSION; PAIN AB Objective. The robustness of findings on retrospective self-reports of childhood maltreatment and lifetime traumatic experiences of adults with fibromyalgia syndrome (FMS) has not been demonstrated by transcultural studies. This is the first transcultural study to focus on the associations between FMS, childhood maltreatment, lifetime psychological traumas, and potential differences between countries adjusting for psychological distress. Methods. 71 age-and sex-matched US and German FMS outpatients were compared. Childhood maltreatment were assessed by the Childhood Trauma Questionnaire and potential, traumatic experiences by the trauma list of the Munich Composite International Diagnostic Interview. Potential posttraumatic stress disorder (PTSD) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV-TR symptom criteria by the Posttraumatic Diagnostic Scale. Potential depressive and anxiety disorder were assessed by the Patient Health Questionnaire PHQ4. Results. US and German patients did not significantly differ in the amount of self-reported childhood maltreatment (emotional, physical and sexual abuse or neglect) or in the frequency of lifetime traumatic experiences. No differences in the frequency of potential anxiety, depression, and PTSD were seen. Psychological distress fully accounted for group differences in emotional and sexual abuse and emotional and physical neglect. Conclusion. The study demonstrated the transcultural robustness of findings on the association of adult FMS with self-reports of childhood maltreatment and lifelong traumatic experiences. These associations are mainly explained by current psychological distress. C1 [Haeuser, W.] Klinikum Saarbrucken gGmbH, Dept Internal Med 1, D-66119 Saarbrucken, Germany. [Haeuser, W.; Hoffmann, E. -M.] Tech Univ Munich, Dept Psychosomat Med, D-80290 Munich, Germany. [Wolfe, F.] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Wolfe, F.] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Worthing, A. B.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Stahl, N.] Arthrit & Rheumatism Associates Grp Practice, Washington, DC USA. [Walitt, B.] MedStar Hlth Washington Hosp Ctr, Washington, DC USA. [Walitt, B.] NINR, NIH, Bethesda, MD 20892 USA. RP Hauser, W (reprint author), Klinikum Saarbrucken gGmbH, Dept Internal Med 1, Winterberg 1, D-66119 Saarbrucken, Germany. EM whaeuser@klinikum-saarbruecken.de FU Intramural Research program of the NIH; National Institute of Nursing Research; Georgetown Howard Universities Center for Clinical and Translational Science FX this research was supported (in part) by the Intramural Research program of the NIH, National Institute of Nursing Research and by the Georgetown Howard Universities Center for Clinical and Translational Science. NR 46 TC 2 Z9 2 U1 2 U2 8 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X EI 1593-098X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JAN-FEB PY 2015 VL 33 IS 1 SU 88 BP S86 EP S92 PG 7 WC Rheumatology SC Rheumatology GA CF8RI UT WOS:000352829200014 PM 25786049 ER PT J AU Steffens, S Pacher, P AF Steffens, Sabine Pacher, Pal TI The Activated Endocannabinoid System in Atherosclerosis: Driving Force or Protective Mechanism? SO CURRENT DRUG TARGETS LA English DT Article DE Cannabinoid receptor CB1; CB2; diacylglycerol lipase; eicosanoid; fatty acid amide hydrolase; monoacylglycerol lipase ID ACID AMIDE HYDROLASE; CB1 CANNABINOID RECEPTOR; REVERSE CHOLESTEROL TRANSPORT; MUSCLE-CELL PROLIFERATION; CORONARY-ARTERY-DISEASE; TRAUMATIC BRAIN-INJURY; CARDIOVASCULAR FUNCTION; NEOINTIMA FORMATION; HYPERTENSIVE-RATS; DENDRITIC CELLS AB Atherosclerosis and its major acute complications, myocardial infarction and stroke, are the leading causes of death and morbidity worldwide. Despite major advances in cardiovascular intervention and healthcare, improving preventive care and treatment remains a continuous mission for cardiovascular research. Within the last 10 to 15 years, the endocannabinoid system has emerged as an important lipid signaling system involved in many biological processes. Growing evidence suggests that an overactive endocannabinoid-CB1 receptor signaling promotes the development of cardiovascular risk factors such as obesity, insulin resistance and dyslipidemia. This prompted an increasing interest in studying the role of the endocannabinoid system in atherosclerosis. As opposed to the detrimental actions of CB1 signaling, the endocannabinoid-CB2 receptor axis exhibits an anti-inflammatory and atheroprotective role. We will review recent findings from experimental and clinical studies aimed at understanding the complex actions of endocannabinoid signaling in cardiovascular disease. This is followed by an outlook on emerging targets for possible therapeutic intervention. C1 [Steffens, Sabine] Univ Munich, Inst Cardiovasc Prevent, Munich, Germany. [Steffens, Sabine] Partner Site Munich Heart Alliance, German Ctr Cardiovasc Res DZHK, Munich, Germany. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Steffens, S (reprint author), Inst Cardiovasc Prevent, Pettenkoferstr 9, D-80336 Munich, Germany. EM sabine.steffens@med.uni-muenchen.de RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural Program of the NIAAA/NIH; Deutsche Forschungsgemeinschaft [STE1053/3-1, SFB1123 C01] FX The related research studies were supported by the Intramural Program of the NIAAA/NIH (to Pal Pacher) and the Deutsche Forschungsgemeinschaft (STE1053/3-1, SFB1123 C01 to Sabine Steffens). NR 117 TC 4 Z9 4 U1 1 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 EI 1873-5592 J9 CURR DRUG TARGETS JI Curr. Drug Targets PY 2015 VL 16 IS 4 BP 334 EP 341 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CF4IW UT WOS:000352513400005 PM 25469884 ER PT B AU Sylvetsky, AC Brown, RJ Rother, KI AF Sylvetsky, Allison C. Brown, Rebecca J. Rother, Kristina I. BE Goran, MI Tappy, L Le, KA TI Biological and Health Effects of Nonnutritive Sweeteners SO DIETARY SUGARS AND HEALTH LA English DT Article; Book Chapter ID HIGH-INTENSITY SWEETENER; BODY-MASS INDEX; ARTIFICIAL SWEETENERS; BEVERAGE CONSUMPTION; TASTE RECEPTORS; DIET SODA; GLUCOSE-HOMEOSTASIS; METABOLIC SYNDROME; PROSPECTIVE COHORT; PRETERM DELIVERY C1 [Sylvetsky, Allison C.; Brown, Rebecca J.; Rother, Kristina I.] NIDDKD, Sect Pediat Diabet & Metab, NIH, Bethesda, MD 20892 USA. RP Sylvetsky, AC (reprint author), NIDDKD, Sect Pediat Diabet & Metab, NIH, Bethesda, MD 20892 USA. OI Brown, Rebecca/0000-0002-2589-7382 NR 113 TC 0 Z9 0 U1 1 U2 16 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-9378-7; 978-1-4665-9377-0 PY 2015 BP 99 EP 113 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BC4WQ UT WOS:000352983800008 ER PT J AU Gong, SY Osei, ES Kaplan, D Chen, YH Meyerson, H AF Gong, Shunyou Osei, Ebenezer S. Kaplan, David Chen, Youhai H. Meyerson, Howard TI CD317 is over-expressed in B-cell chronic lymphocytic leukemia, but not B-cell acute lymphoblastic leukemia SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE CD317; B lymphocytes; chronic lymphocytic leukemia; acute lymphoblastic leukemia ID MULTIPLE-MYELOMA CELLS; ANTI-HM1.24 ANTIBODY; CARCINOMA XENOGRAFT; MONOCLONAL-ANTIBODY; ZAP-70 EXPRESSION; MOLECULAR-CLONING; GENE-EXPRESSION; IN-VIVO; ANTIGEN; HM1.24 AB CD317 was first identified as a multiple myeloma-associated antigen. Here we report the expression of CD317 in normal B cells and B-cell malignancies. In normal bone marrow, CD317 demonstrates a biphasic expression pattern, with higher expression on stage 1 and stage 3 hematogones, but not on stage 2 hematogones. CD317 is over-expressed in B-cell chronic lymphocytic leukemia, and appears associated with negative CD38 expression. Moreover, CD317 is barely detectable in B-cell acute lymphoblastic leukemia. Our results suggest that CD317 expression might be of prognostic significance for B-CLL, and CD317 could be used as a new marker for minimal residual disease detection in B-ALL. C1 [Gong, Shunyou; Osei, Ebenezer S.; Kaplan, David; Meyerson, Howard] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. [Gong, Shunyou; Chen, Youhai H.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Gong, SY (reprint author), NCI, Hematopathol Sect, NIH, Pathol Lab, 10 Ctr Dr,Room 2N113, Bethesda, MD 20892 USA. EM shunyou.gong@nih.gov; howard.meyerson@uhhospitals.org FU Case Western Reserve University Department of Pathology intramural research fund [2010-04]; National Institutes of Health, USA [AI-050059] FX This work was supported by the Case Western Reserve University Department of Pathology intramural research fund (2010-04, to S.G.), and National Institutes of Health, USA (AI-050059 to YHC). Contributions: S.G. and H.M. designed the study; S.G., E.S.O. performed the experiments; D.K. and Y.H.C provided important conceptual contribution to the study; S.G. analyzed the data and drafted the manuscript; H.M. critically revised the manuscript; all authors reviewed the manuscript and approved the final version. NR 39 TC 1 Z9 1 U1 1 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2015 VL 8 IS 2 BP 1613 EP 1621 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA CF2IU UT WOS:000352371800052 PM 25973046 ER PT J AU Bromwich, D Millum, J AF Bromwich, Danielle Millum, Joseph TI Disclosure and Consent to Medical Research Participation SO JOURNAL OF MORAL PHILOSOPHY LA English DT Article DE consent; informed consent; autonomy rights; disclosure; understanding; fraud; medical research; bioethics ID THERAPEUTIC MISCONCEPTION; INFORMED-CONSENT; DECISIONS AB Most regulations and guidelines require that potential research participants be told a great deal of information during the consent process. Many of these documents, and most of the scholars who consider the consent process, assume that all this information must be disclosed because it must all be understood. However, a wide range of studies surveying apparently competent participants in clinical trials around the world show that many do not understand key aspects of what they have been told. The standard view of the conditions for valid consent therefore implies that these people have failed to give valid consent to research participation. In this paper we argue that the standard view is false. The primary function of the requirement that researchers disclose information about a study is the avoidance of illegitimate control over someone's consent decision, which is a form of fraud.We derive the content and manner of appropriate disclosure by analysing the ways in which the manipulation of information can invalidate consent. Our analysis shows that the informational requirements for valid consent are conceptually distinct and thus unlikely to have identical contents. This implies that consent can be valid when not everything that ought to be disclosed by the person asking for consent is understood by the person who proffers it. C1 [Bromwich, Danielle] Univ Massachusetts, Dept Philosophy, Boston, MA 02125 USA. [Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Bromwich, D (reprint author), Univ Massachusetts, Dept Philosophy, Boston, MA 02125 USA. EM daniellebromwich@gmail.com; millumj@cc.nih.gov NR 42 TC 4 Z9 4 U1 5 U2 6 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 1740-4681 EI 1745-5243 J9 J MORAL PHILOS JI J. Moral Philos. PY 2015 VL 12 IS 2 BP 195 EP 219 DI 10.1163/17455243-4681027 PG 25 WC Ethics; Philosophy SC Social Sciences - Other Topics; Philosophy GA CF1UU UT WOS:000352334200004 ER PT J AU Putnam, K Robertson-Blackmore, E Sharkey, K Payne, J Bergink, V Munk-Olsen, T Deligiannidis, K Altemus, M Newport, J Apter, G Devouche, E Vikorin, A Magnusson, P Lichtenstein, P Penninx, B Buist, A Bilszta, J O'Hara, M Stuart, S Brock, R Roza, S Tiemeier, H Guille, C Epperson, CN Kim, D Schmidt, P Martinez, P Wisner, KL Stowe, Z Jones, I Rubinow, D Sullivan, P Meltzer-Brody, S AF Putnam, Karen Robertson-Blackmore, Emma Sharkey, Katherine Payne, Jennifer Bergink, Veerle Munk-Olsen, Trine Deligiannidis, Kristina Altemus, Margaret Newport, Jeffrey Apter, Gisele Devouche, Emmanuel Vikorin, Alexander Magnusson, Patrik Lichtenstein, Paul Penninx, Brenda Buist, Anne Bilszta, Justin O'Hara, Michael Stuart, Scott Brock, Rebecca Roza, Sabine Tiemeier, Henning Guille, Constance Epperson, C. Neill Kim, Deborah Schmidt, Peter Martinez, Pedro Wisner, Katherine L. Stowe, Zachary Jones, Ian Rubinow, David Sullivan, Patrick Meltzer-Brody, Samantha CA Postpartum Depression Action TI Heterogeneity of postpartum depression: a latent class analysis SO LANCET PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS; PERINATAL DEPRESSION; RISK-FACTORS; PREGNANCY; PREVALENCE; WOMEN; MODEL; MOTHERS; COHORT; PERIOD AB Background Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. Methods Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17 912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. Findings 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10.5), followed by those in class 2 (mean EPDS score 14.8) and those in class 3 (mean EPDS score 20.1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20.1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). Interpretation PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. C1 [Putnam, Karen; Rubinow, David; Meltzer-Brody, Samantha] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Robertson-Blackmore, Emma] Univ Florida, Dept Psychiat, Jacksonville, FL USA. [Sharkey, Katherine] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Psychiat, Providence, RI 02912 USA. [Payne, Jennifer] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 USA. [Bergink, Veerle; Roza, Sabine; Tiemeier, Henning] Erasmus MC, Dept Psychiat Psychol, Rotterdam, Netherlands. [Munk-Olsen, Trine] Aarhus Univ, Dept Econ & Business NCRR NCRR, Natl Ctr Integrated Register Based Res, DK-8000 Aarhus C, Denmark. [Deligiannidis, Kristina] Univ Massachusetts, Sch Med, Dept Psychiat, Amherst, MA 01003 USA. [Altemus, Margaret] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Newport, Jeffrey] Univ Miami, Dept Psychiat, Coral Gables, FL 33124 USA. [Apter, Gisele] Paris Diderot Univ, Erasme Hosp, Paris, France. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Penninx, Brenda] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Bilszta, Justin] Univ Melbourne, Womens Mental Hlth, Melbourne, Vic 3010, Australia. [Brock, Rebecca] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Guille, Constance] Med Univ S Carolina, Dept Psychiat, Charleston, SC USA. [Epperson, C. Neill; Kim, Deborah] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Schmidt, Peter; Martinez, Pedro] NIMH, Bethesda, MD USA. [Wisner, Katherine L.] Northwestern Univ, Feinberg Sch Med, Asher Ctr Study & Treatment Depress Disorders, Evanston, IL 60208 USA. [Stowe, Zachary] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Jones, Ian] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Meltzer-Brody, S (reprint author), Univ N Carolina, Dept Psychiat, Campus Box 7160, Chapel Hill, NC 27599 USA. EM meltzerb@med.unc.edu RI Apter, gisele/K-3383-2016; Deligiannidis, Kristina/C-3654-2014; Magnusson, Patrik/C-4458-2017; OI Apter, gisele/0000-0001-5185-1479; Deligiannidis, Kristina/0000-0001-7439-2236; Tiemeier, Henning/0000-0002-4395-1397; Viktorin, Alexander/0000-0003-2141-2816 FU National Institute of Mental Health [K23 MH085165-01A1, 1R01MH104468-01, K23MH080290, 5K23MH086689, K23 MH074799-01A2, 222963, MH50524 NIMH, 5R01MH60335, 5R01MH071825 NIMH, 5R01MH075921 NIMH, 5-2R01MH057102]; Brain & Behavior Research Foundation; ZonMW [10.000.1003]; NIMH [K23 MH097794]; NIH [UL1 TR000161]; Worcester Foundation for Biomedical Research; Pfizer Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression; French Ministry of Health [PHRC 98/001]; Mustela Foundation; Geestkracht program of the Netherlands Organisation for Health Research and Development [10-000-1002]; VU University Medical Centre; GGZ Geest; Arkin; Leiden University Medical Centre; GGZ Rivierduinen; University Medical Centre in Groningen; Lentis; GGZ Fries land; GGZ Drenthe; IQ Healthcare; Netherlands Institute for Health Services Research; Netherlands Institute of Mental Health and Addiction; South Carolina Clinical and Translational Research Institute [UL1 TR000062]; Building Interdisciplinary Research Careers in Women's Health [K12 HD055885]; National Institutes for Health [P50 MH-77928, P50 MH 68036]; National Centre for Mental Health Wales; [ZIA MH002865-09 BEB] FX The National Institute of Mental Health support SM-B (K23 MH085165-01A1), TM-O, DRR, PFS, and SM-B (1R01MH104468-01), ERB (K23MH080290), and a young investigator award from the Brain & Behavior Research Foundation), KMS (5K23MH086689, JP (K23 MH074799-01A2), VB (FP7-Health-2007 Project no 222963), MWO (MH50524 NIMH), KLW (5R01MH60335, NIMH, 5R01MH071825 NIMH, 5R01MH075921 NIMH, and 5-2R01MH057102), SJR and HT (ZonMW 10.000.1003, NIMH K23 MH097794, and NIH UL1 TR000161), and PJS (ZIA MH002865-09 BEB). KMD is supported by the Worcester Foundation for Biomedical Research. CNE is supported by Pfizer Pharmaceuticals and a young investigator award from the National Alliance for Research on Schizophrenia and Depression. GA and ED are supported by the French Ministry of Health (PHRC 98/001) and Mustela Foundation. BWP is supported by the Geestkracht program of the Netherlands Organisation for Health Research and Development (10-000-1002) and VU University Medical Centre, GGZ Geest, Arkin, Leiden University Medical Centre, GGZ Rivierduinen, University Medical Centre in Groningen, Lentis, GGZ Fries land, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services Research, and Netherlands Institute of Mental Health and Addiction. CG is supported by South Carolina Clinical and Translational Research Institute (UL1 TR000062) & Building Interdisciplinary Research Careers in Women's Health (K12 HD055885). ZNS is supported by the National Institutes for Health (P50 MH-77928 and P50 MH 68036). IJ is supported by the National Centre for Mental Health Wales. NR 35 TC 12 Z9 12 U1 5 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD JAN PY 2015 VL 2 IS 1 BP 59 EP 67 DI 10.1016/S2215-0366(14)00055-8 PG 9 WC Psychiatry SC Psychiatry GA CF6ZM UT WOS:000352705600025 ER PT J AU Tosh, DK Paoletta, S Chen, ZM Crane, S Lloyd, J Gao, ZG Gizewski, ET Auchampach, JA Salvemini, D Jacobson, KA AF Tosh, Dilip K. Paoletta, Silvia Chen, Zhoumou Crane, Steven Lloyd, John Gao, Zhan-Guo Gizewski, Elizabeth T. Auchampach, John A. Salvemini, Daniela Jacobson, Kenneth A. TI Structure-based design, synthesis by click chemistry and in vivo activity of highly selective A(3) adenosine receptor agonists SO MEDCHEMCOMM LA English DT Article ID NUCLEOSIDES; PAIN; LIGANDS; PURINE; RIBOSE; RAT AB 2-Arylethynyl derivatives of (N)-methanocarba adenosine 5'-uronamides are selective A(3)AR (adenosine receptor) agonists. Here we substitute a 1,2,3-triazol-1-yl linker in place of the rigid, linear ethynyl group to eliminate its potential metabolic liability. Docking of nucleosides containing possible short linker moieties at the adenine C2 position using a hybrid molecular model of the A(3)AR (based on the A(2A)AR agonist-bound structure) correctly predicted that a triazole would maintain the A(3)AR selectivity, due to its ability to fit a narrow cleft in the receptor. The analogues with various N-6 and C2-aryltriazolyl substitution were synthesized and characterized in binding (K-i at hA(3)AR 0.3-12 nM) and in vivo to demonstrate efficacy in controlling chronic neuropathic pain (chronic constriction injury). Among N-6-methyl derivatives, a terminal pyrimidin-2-yl group in 9 (MRS7116) increased duration of action (36% pain protection at 3 h) in vivo. N-6-Ethyl 5-chlorothien-2-yl analogue 15 (MRS7126) preserved in vivo efficacy (85% protection at 1 h) with short duration. Larger N6 groups, e.g. 17 (MRS7138, > 90% protection at 1 and 3 h), greatly enhanced in vivo activity. Thus, we have combined structure-based methods and phenotypic screening to identify nucleoside derivatives having translational potential. C1 [Tosh, Dilip K.; Paoletta, Silvia; Crane, Steven; Lloyd, John; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. [Chen, Zhoumou; Salvemini, Daniela] St Louis Univ Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. [Gizewski, Elizabeth T.; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Mol Recognit Sect, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kennethj@niddk.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases; NIH [R01 HL077707]; National Institute of Mental Health's Psychoactive Drug Screening Program [HHSN-271-200800025-C] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases, and NIH R01 HL077707). We thank Noel Whittaker (NIDDK) for mass spectral determinations. We thank Dr. Bryan L. Roth (Univ. North Carolina at Chapel Hill) and National Institute of Mental Health's Psychoactive Drug Screening Program (contract # HHSN-271-200800025-C) for screening data. NR 25 TC 6 Z9 6 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2015 VL 6 IS 4 BP 555 EP 563 DI 10.1039/c4md00571f PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CF9RK UT WOS:000352903400007 PM 26236460 ER PT J AU Yang, L Ni, L Duan, QL Wang, XX Chen, C Chen, S Chaugai, S Zeldin, DC Tang, JR Wang, DW AF Yang, Lei Ni, Li Duan, Quanlu Wang, Xingxu Chen, Chen Chen, Song Chaugai, Sandip Zeldin, D. C. Tang, Jia Rong Wang, Dao Wen TI CYP epoxygenase 2J2 prevents cardiac fibrosis by suppression of transmission of pro-inflammation from cardiomyocytes to macrophages SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE Cardiac fibrosis; Heart failure; Inflammation; EETs; CYP2J2 ID SOLUBLE EPOXIDE HYDROLASE; SPONTANEOUSLY HYPERTENSIVE-RATS; EPOXYEICOSATRIENOIC ACIDS; KAPPA-B; ENDOTHELIAL EXPRESSION; HEART-FAILURE; IN-VIVO; HYPERTROPHY; PRESSURE; INJURY AB Cytochrome P450 epoxygenase (CYP450)-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; but the underlying mechanism remains unclear. The present study aimed to elucidate how EETs regulated cardiac fibrosis in response to isoprenaline (Iso) or angiotensin (Ang) II. Cardiac-specific human CYP2J2 transgenic mice (Tr) and wild-type (WT) C57BL/6 littermates were infused with Iso- or Ang II. Two weeks after infusion, Tr mice showed more alleviative cardiac fibrosis and inflammation compared with WT mice. In vitro, we found Is or Ang II induced nuclear transfer of NF-kappa B p65 and inflammatory cytokines expression in cardiomyocytes. Furthermore, inflammation response emerged in macrophages cultured in cardiomyocytes-conditioned medium. When pretreatment with 14,15-EET in cardiomyocytes, the inflammatory response was markedly suppressed and the transmission of inflammation from cardiomyocytes to macrophages was reduced. In conclusion, CYP2J2 and EETs prevent cardiac fibrosis and cardiac dysfunction by suppressing transmission of pro-inflammation from cardiomyocytes to macrophages in heart, suggesting that elevation of EETs level could be a potential strategy to prevent cardiac fibrosis. (C) 2015 Elsevier Inc. All rights reserved. C1 [Yang, Lei; Ni, Li; Duan, Quanlu; Wang, Xingxu; Chen, Chen; Chaugai, Sandip; Tang, Jia Rong; Wang, Dao Wen] Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Yang, Lei; Ni, Li; Duan, Quanlu; Wang, Xingxu; Chen, Chen; Chaugai, Sandip; Tang, Jia Rong; Wang, Dao Wen] Huazhong Univ Sci & Technol, Gene Therapy Ctr, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Chen, Song] Huazhong Univ Sci & Technol, Dept Surg, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Zeldin, D. C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Tang, JR (reprint author), Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China. EM jrtang@tjh.tjmu.edu.cn; dwwang@tjh.tjmu.edu.cn FU National Basic Research Program (973) of China [2012CB518004]; National Natural Science Foundation of China [31130031, 81000097] FX This work was supported by a National Basic Research Program (973) of China (2012CB518004) and National Natural Science Foundation of China (Nos. 31130031 and 81000097). The authors would like to thank Dr. Darryl C. Zeldin for giving cardiac-specific human CYP2J2 transgenic mice as gift. NR 43 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 EI 2212-196X J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN-MAR PY 2015 VL 116 SI SI BP 64 EP 75 DI 10.1016/j.prostaglandins.2015.01.004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG2CR UT WOS:000353083000008 PM 25686540 ER PT J AU Niu, G Chen, XY AF Niu, Gang Chen, Xiaoyuan TI Lymphatic Imaging: Focus on Imaging Probes SO THERANOSTICS LA English DT Review DE Sentinel lymph node; contrast agent; PET; MRI; fluorescence; imaging ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; INTERSTITIAL MR LYMPHOGRAPHY; RECURRENT PROSTATE-CANCER; ULTRASOUND-MEDIATED GENE; DIFFUSION-WEIGHTED-MR; DUAL-MODALITY PET/CT; SENTINEL-NODE BIOPSY; CELL LUNG-CANCER AB In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored. Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging. In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents. Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration. Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs. C1 [Niu, Gang; Chen, Xiaoyuan] NIBIB, NIH, LOMIN, Bethesda, MD 20892 USA. RP Niu, G (reprint author), 35A Convent Dr Rm GD959, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 142 TC 7 Z9 8 U1 14 U2 40 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 7 BP 686 EP 697 DI 10.7150/thno.11862 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VX UT WOS:000353064500003 PM 25897334 ER PT J AU Sato, K Nagaya, T Choyke, PL Kobayashi, H AF Sato, Kazuhide Nagaya, Tadanobu Choyke, Peter L. Kobayashi, Hisataka TI Near Infrared Photoimmunotherapy in the Treatment of Pleural Disseminated NSCLC: Preclinical Experience SO THERANOSTICS LA English DT Article DE photoimmunotherapy; fluorescence thoracoscopy; pleural dissemination; bioluminescence imaging; fluorescence imaging ID IN-VIVO; LUNG-CANCER; PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODIES; OVARIAN-CANCER; TUMORS; TRIAL; IMMUNOCONJUGATE; EFFICACY; SURGERY AB Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors. C1 [Sato, Kazuhide; Nagaya, Tadanobu; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. K.S. is supported with JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. NR 32 TC 17 Z9 17 U1 1 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 7 BP 698 EP 709 DI 10.7150/thno.11559 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VX UT WOS:000353064500004 PM 25897335 ER PT J AU Ballard, ED Musci, RJ Tingey, L Goklish, N Larzelere-Hinton, F Barlow, A Cwik, M AF Ballard, Elizabeth D. Musci, Rashelle J. Tingey, Lauren Goklish, Novalene Larzelere-Hinton, Francene Barlow, Allison Cwik, Mary TI LATENT CLASS ANALYSIS OF SUBSTANCE USE AND AGGRESSIVE BEHAVIOR IN RESERVATION-BASED AMERICAN INDIAN YOUTH WHO ATTEMPTED SUICIDE SO AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH LA English DT Article ID HIGH-SCHOOL-STUDENTS; ALASKA NATIVE YOUTH; RISK-FACTORS; REPRESENTATIVE SAMPLE; PROTECTIVE-FACTORS; ADOLESCENTS; PREVENTION; SURVEILLANCE; SYSTEM; INTERVENTION AB American Indian (AI) adolescents who attempt suicide are heterogeneous. A latent class analysis was used to identify subgroups of reservation-based AI adolescents with recent suicide attempts. Indicators of class membership were substance abuse and aggressive behaviors; clinical correlates of subgroup membership included risky sexual behavior and recent exposure to suicidal behavior. Three subgroups were identi ied, representing low, medium, and high substance use and aggressive behavior. Suicide exposure was associated with membership in the lowest risk behavior subgroup; risky sexual behavior was associated with membership the highest risk behaviors subgroup. Findings suggest a continuum of risk behaviors in reservation-based AI youth who attempt suicide. C1 [Ballard, Elizabeth D.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Musci, Rashelle J.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Musci, Rashelle J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Tingey, Lauren; Goklish, Novalene; Larzelere-Hinton, Francene; Barlow, Allison; Cwik, Mary] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Amer Indian Hlth, Baltimore, MD USA. RP Cwik, M (reprint author), Johns Hopkins Univ, Ctr Amer Indian Hlth, Bloomberg Sch Publ Hlth, 415 North Washington St,Room 457, Baltimore, MD 21231 USA. EM mcwik1@jhu.edu NR 44 TC 1 Z9 1 U1 3 U2 14 PU UNIV PRESS COLORADO PI NIWOT PA PO BOX 849, NIWOT, CO 80544 USA SN 0893-5394 EI 1533-7731 J9 AM INDIAN ALASKA NAT JI Am. Indian Alsk. Nativ. Ment. Health Res. PY 2015 VL 22 IS 1 BP 77 EP 94 PG 18 WC Psychology, Clinical SC Psychology GA CF4HD UT WOS:000352508500004 PM 25768391 ER PT S AU Ernst, M Torrisi, S Balderston, N Grillon, C Hale, EA AF Ernst, Monique Torrisi, Salvatore Balderston, Nicholas Grillon, Christian Hale, Elizabeth A. BE Cannon, TD Widiger, T TI fMRI Functional Connectivity Applied to Adolescent Neurodevelopment SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 11 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE development; resting state; fMRI; networks; intrinsic functional connectivity ID RESTING-STATE FMRI; INDEPENDENT COMPONENT ANALYSIS; 10 SIMPLE RULES; HUMAN BRAIN; INHIBITORY CONTROL; SYSTEMS-MODEL; LIFE-SPAN; NETWORKS; BEHAVIOR; MRI AB The exponential rise in the number of functional brain connectivity studies, particularly those examining intrinsic functional connectivity (iFC) at rest, and the promises of this work for unraveling the ontogeny of functional neural systems motivate this review. Shortly before this explosion in functional connectivity research, developmental neuroscientists had proposed theories based on neural systems models to explain behavioral changes, particularly in adolescence. The current review presents recent advances in imaging in brain connectivity research, which provides a unique tool for the study of neural systems. Understanding the potential of neuroimaging for refining neurodevelopmental models of brain function requires a description of various functional connectivity approaches. In this review, we describe task-based and resting-state functional magnetic resonance imaging (fMRI) analytic strategies, but we focus on iFC findings from resting-state data to describe general developmental trajectories of brain network organization. Finally, we use the example of drug addiction to frame a discussion of psychopathology that emerges in adolescence. C1 [Ernst, Monique; Torrisi, Salvatore; Balderston, Nicholas; Grillon, Christian; Hale, Elizabeth A.] NIMH, NIH, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov; sam.torrisi@nih.gov; nicholas.balderston@nih.gov; grillonc@mail.nih.gov; elizabeth.hale@nih.gov OI Balderston, Nicholas/0000-0002-8565-1544 FU Intramural NIH HHS [Z01 MH002798-07] NR 93 TC 11 Z9 11 U1 6 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3911-1 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2015 VL 11 BP 361 EP 377 DI 10.1146/annurev-clinpsy-032814-112753 PG 17 WC Psychology, Clinical; Psychology SC Psychology GA BC3WH UT WOS:000352014000015 PM 25581237 ER PT J AU Zhang, H Tian, M Carrio, I Civelek, AC Fujibayashi, Y AF Zhang, Hong Tian, Mei Carrio, Ignasi Civelek, Ali Cahid Fujibayashi, Yasuhisa TI Molecular Image-Guided Theranostic and Personalized Medicine 2014 SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Zhang, Hong] Zhejiang Univ, Affiliated Hosp 2, Hangzhou 310003, Zhejiang, Peoples R China. [Tian, Mei] Zhejiang Univ, Hangzhou Binjiang Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Carrio, Ignasi] Autonomous Univ Barcelona, San Paul Hosp, Barcelona, Spain. [Civelek, Ali Cahid] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Fujibayashi, Yasuhisa] Natl Inst Radiol Sci, Chiba 260, Japan. RP Zhang, H (reprint author), Zhejiang Univ, Affiliated Hosp 2, Hangzhou 310003, Zhejiang, Peoples R China. EM hzhang21@gmail.com NR 0 TC 0 Z9 0 U1 3 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 258612 DI 10.1155/2015/258612 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CF2ZH UT WOS:000352416400001 ER PT J AU Kiyatkin, EA Sharma, HS AF Kiyatkin, Eugene A. Sharma, Hari S. TI Not Just the Brain: Methamphetamine Disrupts Blood-Spinal Cord Barrier and Induces Acute Glial Activation and Structural Damage of Spinal Cord Cells SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Albumin leakage; blood-spinal cord barrier; brain; cellular damage; glial fibrillary acidic protein; hyperthermia; metabolic brain activation; spinal cord ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; NEURODEGENERATIVE DISORDERS; ENVIRONMENTAL-TEMPERATURE; PARA-CHLOROPHENYLALANINE; TRAUMATIC INJURY; I-131 SODIUM; HYPERTHERMIA; EDEMA; PATHOPHYSIOLOGY AB Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29 degrees C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29 degrees C and brain hyperthermia reached pathological levels (>40 degrees C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure. C1 [Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Sharma, Hari S.] Uppsala Univ, Dept Surg Sci, Univ Hosp, SE-75421 Uppsala, Sweden. RP Sharma, HS (reprint author), Uppsala Univ, Univ Hosp, Anesthesiol & Intens Care Med, Dept Surg Sci, Frodingsgatan 12 28, SE-75421 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Sharma, Hari/G-4508-2016 FU Intramural Research Program of NIDA-NIH; Leaderal Foundation for Acute Medicine, Stavanger, Norway; NIDA Distinguished International Scientist Collaboration Award (NIH) FX This study was supported by the Intramural Research Program of NIDA-NIH, the Leaderal Foundation for Acute Medicine, Stavanger, Norway, and NIDA Distinguished International Scientist Collaboration Award (NIH) to Hari S. Sharma. The authors greatly appreciate editorial assistance and valuable suggestions of Dr. Ken T. Wakabayashi, technical assistance in conducting experiments and data analyses of Mari-Anne Carlsson, Inga Horte (Uppsala University) and Leon Brown (NIDA-IRP), and valuable help in constructing color figures of Suraj Sharma (Uppsala). NR 40 TC 2 Z9 2 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 2 BP 282 EP 294 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CF0FZ UT WOS:000352219800014 PM 25687701 ER PT J AU Egwuagu, CE Yu, CR AF Egwuagu, Charles E. Yu, Cheng-Rong TI Interleukin 35-Producing B Cells (i35-Breg): A New Mediator of Regulatory B-Cell Functions in CNS Autoimmune Diseases SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE interleukin 35; interleukin 10; regulatory B cell or Breg; interleukin 35-producing Breg or i35-Breg; autoimmunity; experimental autoimmune uveitis ID MARGINAL ZONE; MULTIPLE-SCLEROSIS; IL-12 FAMILY; BONE-MARROW; T-CELLS; LYMPHOCYTES; RECEPTOR; INFLAMMATION; MECHANISMS; STAT3 AB Neuroinflammation contributes to neuronal deficits in neurodegenerative CNS (central nervous system) autoimmune diseases, such as multiple sclerosis and uveitis. The major goal of most treatment modalities for CNS autoimmune diseases is to limit inflammatory responses in the CNS; immune-suppressive drugs are the therapy of choice. However, lifelong immunosuppression increases the occurrence of infections, nephrotoxicity, malignancies, cataractogenesis, and glaucoma, which can greatly impair quality of life for the patient. Biologics that target pathogenic T cells is an alternative approach that is gaining wide acceptance as indicated by the popularity of a variety of Food and Drug Administration (FDA)-approved anti-inflammatory compounds and humanized antibodies such as Zenapax, Etanercept, Remicade, anti-ICAM, rapamycin, or tacrolimus. B cells are also potential therapeutic targets because they provide costimulatory signals that activate pathogenic T cells and secrete cytokines that promote autoimmune pathology. B cells also produce autoreactive antibodies implicated in several organ-specific and systemic autoimmune diseases including lupus erythematosus, Graves' disease, and Hashimoto's thyroiditis. On the other hand, recent studies have led to the discovery of several regulatory B-cell (Breg) populations that suppress immune responses and autoimmum diseases. In this review, we present a brief overview of Breg phenotypes and in particular, the newly discovered IL35-producing regulatory B cell (i35-Breg). We discuss the critical roles played by i35-Bregs in regulating autoimmune diseases and the potential use of adoptive Breg therapy in CNS autoimmune diseases. C1 [Egwuagu, Charles E.; Yu, Cheng-Rong] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N109A, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 48 TC 5 Z9 7 U1 0 U2 5 PU BEGELL HOUSE INC PI DANBURY PA 50 NORTH ST, DANBURY, CT 06810 USA SN 1040-8401 EI 2162-6472 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2015 VL 35 IS 1 BP 49 EP 57 PG 9 WC Immunology SC Immunology GA CF7PY UT WOS:000352750000004 PM 25746047 ER PT J AU Williams, JA Tai, XG Hodes, RJ AF Williams, Joy A. Tai, Xuguang Hodes, Richard J. TI CD28-CD80/86 and CD40-CD40L Interactions Promote Thymic Tolerance by Regulating Medullary Epithelial Cell and Thymocyte Development SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE FoxP3; T regulatory; mTEC; negative selection; thymus; costimulation ID DOUBLE-POSITIVE THYMOCYTES; FOXP3 TRANSCRIPTION FACTOR; T-CELLS; NEGATIVE SELECTION; CD28 COSTIMULATION; CUTTING EDGE; B-CELLS; CD4(+)CD8(+) THYMOCYTES; NKT CELLS; DISTINCT MECHANISMS AB Development and central tolerance of T lymphocytes in the thymus requires both TCR signals and collaboration with signals generated through costimulatory molecule interactions. In this review, we discuss the importance of CD28-CD80/86 and CD40-CD40L costimulatory interactions in promoting normal thymic development. This discussion includes roles in the generation of a normal thymic medulla, in the development of specific T-cells subsets, including iNKT and T regulatory cells, and in the generation of a tolerant mature T-cell repertoire. We discuss recent contributions to the understanding of CD28-CD80/86 and CD40-CD40L costimulatory interactions in thymic development, and we highlight the ways in which the many important roles mediated by these interactions collaborate to promote normal thymic development. C1 [Williams, Joy A.; Tai, Xuguang; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM HodesR@mail.nih.gov NR 105 TC 0 Z9 1 U1 2 U2 5 PU BEGELL HOUSE INC PI DANBURY PA 50 NORTH ST, DANBURY, CT 06810 USA SN 1040-8401 EI 2162-6472 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2015 VL 35 IS 1 BP 59 EP 76 PG 18 WC Immunology SC Immunology GA CF7PY UT WOS:000352750000005 PM 25746048 ER PT J AU Zalazar, F De Luca, P Gardner, K Figg, WD Meiss, R Spallanzani, RG Vallecorsa, P Elguero, B Cotignola, J Vazquez, E De Siervi, A AF Zalazar, Florencia De Luca, Paola Gardner, Kevin Figg, William D. Meiss, Roberto Spallanzani, Raul G. Vallecorsa, Pablo Elguero, Belen Cotignola, Javier Vazquez, Elba De Siervi, Adriana TI Low Doses of CPS49 and Flavopiridol Combination as Potential Treatment for Advanced Prostate Cancer SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Article DE CPS49; flavopiridol; paclitaxel; prostate cancer; preclinical study; xenografts ID DEPENDENT KINASE INHIBITOR; THALIDOMIDE ANALOGS; PHASE-II; DOCETAXEL; PACLITAXEL; CARBOPLATIN; CHEMOTHERAPY; CARCINOMA; LEUKEMIA; THERAPY AB Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer and metastatic castration-resistant prostate cancer (CRPC) is a foremost cause of men cancer death around the world. The aim of this work was to investigate the selectivity and efficacy of new drug combinations for CRPC. We combined three compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole1,3( 2H)-dione (CPS49; redox-reactive thalidomide analog with anti-angiogenic properties) and flavopiridol (flavo: semisynthetic flavonoid that inhibits cyclin dependent kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell line. Furthermore, xenografts generated by inoculation of human prostate carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49 combination did not significantly reduce tumor growth in PC3 xenografts. Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination showed extensive areas of necrosis induced by the treatment. RT-qPCR array containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo combination showed that this treatment shut down the expression of several genes involved in adhesion, migration or invasion. In summary, the antitumor activity of CPS49 or flavopiridol was improved by the combination of these compounds and using half dose of that previously reported. Hence, CPS49-flavo combination is a promising new alternative for PCa therapy. C1 [Zalazar, Florencia; De Luca, Paola; De Siervi, Adriana] Consejo Nacl Invest Cient & Tecn, IBYME, Lab Oncol Mol & Nuevos Blancos Terapeut, Buenos Aires, DF, Argentina. [Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Meiss, Roberto; Vallecorsa, Pablo] Acad Nacl Med Buenos Aires, Dept Patol, Buenos Aires, DF, Argentina. [Elguero, Belen; Cotignola, Javier; Vazquez, Elba] Univ Buenos Aires, FCEN, CONICET, IQUIBICEN,Dept Quim Biol,Lab Inflamac & Canc, RA-1033 Buenos Aires, DF, Argentina. [Spallanzani, Raul G.] Consejo Nacl Invest Cient & Tecn, IBYME, Lab Fisiopatol Inmunidad Innata, RA-1033 Buenos Aires, DF, Argentina. RP De Siervi, A (reprint author), Consejo Nacl Invest Cient & Tecn, IBYME, Lab Oncol Mol & Nuevos Blancos Terapeut, Vuelta Obligado 2490,C1428ADN, Buenos Aires, DF, Argentina. EM adesiervi@qb.fcen.uba.ar RI Spallanzani, Raul German/B-7210-2016; Figg Sr, William/M-2411-2016; OI Spallanzani, Raul German/0000-0001-5402-3687; Cotignola, Javier/0000-0003-4473-9854 FU Argentinean Agency of Science and Technology (ANPCyT) [PICT 2006-00228, PICT 2006-00367, PICT 2010-00431, PICT 2012-374]; National Cancer Institute (Argentina); CONICET FX This research was supported by the Argentinean Agency of Science and Technology (ANPCyT PICT 2006-00228, PICT 2006-00367, PICT 2010-00431, PICT 2012-374) and National Cancer Institute (Argentina). E. Vazquez and A. De Siervi are members of the career of scientific researcher at the National Research Council (CONICET). P De Luca holds postdoctoral fellowship from CONICET. F Zalazar holds PhD scholarships from CONICET. These results are part of Florencia Zalazar's PhD thesis. NR 29 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 EI 1873-4316 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PY 2015 VL 16 IS 6 BP 553 EP 563 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CF4JG UT WOS:000352514600008 PM 25860066 ER PT J AU Dimitrov, L Hong, CS Yang, CZ Zhuang, ZP Heiss, JD AF Dimitrov, Lilia Hong, Christopher S. Yang, Chunzhang Zhuang, Zhengping Heiss, John D. TI New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES LA English DT Review DE IDH1 protein; glioma; DNA methylation; HIF1A protein; molecular targeted therapy; review ID ISOCITRATE DEHYDROGENASE 1; ACUTE MYELOID-LEUKEMIA; MUTANT IDH1; ONCOMETABOLITE 2-HYDROXYGLUTARATE; SECONDARY GLIOBLASTOMAS; CELL PROLIFERATION; GENETIC PATHWAYS; PROGNOSTIC VALUE; DNA METHYLATION; DIFFUSE GLIOMAS AB In the last five years, IDH1 mutations in human malignancies have significantly shaped the diagnosis and management of cancer patients. Ongoing intense research efforts continue to alter our understanding of the role of the IDH1 mutation in tumor formation. Currently, evidence suggests the IDH1 mutation to be an early event in tumorigenesis with multiple downstream oncogenic consequences including maintenance of a hypermethylator phenotype, alterations in HIF signalling, and disruption of collagen maturation contributing to a cancer-promoting extracellular matrix. The most recent reports elucidating these mechanisms is described in this review with an emphasis on the pathogenesis of the IDH1 mutation in glioma. Conflicting findings from various studies are discussed, in order to highlight areas warranting further research. Finally, the latest progress in developing novel therapies against the IDH1 mutation is presented, including recent findings from ongoing phase 1 clinical trials and the exciting prospect of vaccine immunotherapy targeting the IDH1 mutant protein. C1 [Dimitrov, Lilia] Barts & London Queen Marys Sch Med & Dent, London E1 2AD, England. [Dimitrov, Lilia; Hong, Christopher S.; Yang, Chunzhang; Zhuang, Zhengping; Heiss, John D.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov; heissj@ninds.nih.gov OI Heiss, John/0000-0002-3890-0165 FU National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH). NR 107 TC 14 Z9 17 U1 3 U2 15 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-1907 J9 INT J MED SCI JI Int. J. Med. Sci. PY 2015 VL 12 IS 3 BP 201 EP 213 DI 10.7150/ijms.11047 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CF2VS UT WOS:000352406400001 PM 25678837 ER PT J AU Ballard, ED Lally, N Nugent, AC Furey, ML Luckenbaugh, DA Zarate, CA AF Ballard, Elizabeth D. Lally, Niall Nugent, Allison C. Furey, Maura L. Luckenbaugh, David A. Zarate, Carlos A., Jr. TI Neural Correlates of Suicidal Ideation and Its Reduction in Depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE suicidal ideation; PET imaging; ketamine; depression ID STRUCTURAL BRAIN ABNORMALITIES; TREATMENT-RESISTANT DEPRESSION; RAPID ANTIDEPRESSANT RESPONSE; POSITRON-EMISSION-TOMOGRAPHY; PREFRONTAL CORTEX; MAJOR DEPRESSION; MOOD DISORDERS; KETAMINE; BEHAVIOR; SCALE AB Background: The neural correlates of suicidal ideation and its reduction after treatment are unknown. We hypothesized that increased regional cerebral glucose metabolism in the infralimbic cortex (Brodmann area 25), amygdala, and subgenual anterior cingulate cortex would be associated with suicidal ideation and its reduction after ketamine infusion. Methods: Medication-free patients (n = 19) with treatment-resistant major depressive disorder underwent positron emission tomography imaging at baseline and 230 minutes after an open-label ketamine infusion (0.5 mg/kg for 40 minutes). Results: Baseline suicidal ideation and regional cerebral glucose metabolism in the infralimbic cortex were significantly correlated (r = .59, P = .007); but not overall mood scores (r = -.07, P = .79). Reductions in suicidal ideation after ketamine infusion were correlated with decreased regional cerebral glucose metabolism in the infralimbic cortex (r = .54, P = .02). Metabolism in other areas of interest was not significantly correlated with suicidal ideation or depression. Conclusion: The infralimbic cortex may be implicated in suicidal ideation. C1 [Ballard, Elizabeth D.; Lally, Niall; Nugent, Allison C.; Furey, Maura L.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Lally, Niall] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. RP Ballard, ED (reprint author), NIMH, NIH, Bldg 10-CRC,7-5345, Bethesda, MD 20892 USA. EM elizabeth.ballard@nih.gov OI Nugent, Allison/0000-0003-2569-2480 FU Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); NARSAD; Brain and Behavior Mood Disorders FX Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator to C.A.Z., and by the Brain and Behavior Mood Disorders Research Award to C.A.Z. NR 31 TC 2 Z9 2 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JAN PY 2015 VL 18 IS 1 DI 10.1093/ijnp/pyu069 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CF4OE UT WOS:000352528600020 ER PT J AU Niciu, MJ Luckenbaugh, DA Ionescu, DF Richards, EM Vande Voort, JL Ballard, ED Brutsche, NE Furey, ML Zarate, CA AF Niciu, Mark J. Luckenbaugh, David A. Ionescu, Dawn F. Richards, Erica M. Vande Voort, Jennifer L. Ballard, Elizabeth D. Brutsche, Nancy E. Furey, Maura L. Zarate, Carlos A., Jr. TI Ketamine's Antidepressant Efficacy is Extended for at Least Four Weeks in Subjects with a Family History of an Alcohol Use Disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcohol use disorder; family history; ketamine; major depressive disorder; riluzole ID RESISTANT MAJOR DEPRESSION; D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; BIPOLAR DEPRESSION; TERM OUTCOMES; RATING-SCALE; DEPENDENCE; RILUZOLE; INFUSION; REPLICATION AB Background: A single subanesthetic infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant properties in treatment-resistant major depressive disorder (TRD). As a family history of an alcohol use disorder is a positive predictor of ketamine's antidepressant response and the strength of the association increases over time, we hypothesized that depressed subjects with a family history of an alcohol use disorder would have greater antidepressant durability and that riluzole would augment and/or extend ketamine's antidepressant efficacy. Methods: Fifty-two TRD subjects received an open-label infusion of ketamine (0.5 mg/kg over 40 minutes), and, four to six hours post-infusion, were randomized to either flexible-dose (100-200 mg/day) riluzole or placebo in the following proportions: Family History Positive (FHP) riluzole (n = 10), FHP placebo (n = 9), Family History Negative (FHN) riluzole (n = 16), and FHN placebo (n = 17). Results: FHP subjects randomized to placebo had a greater antidepressant response than FHN subjects; however, contrary to our initial hypothesis, there was no significant difference in antidepressant efficacy with riluzole. Although potentially underpowered, there was no difference in overall time-to-relapse based on randomization status (riluzole responders: n = 15, placebo responders: n = 17). Yet, time-to-relapse was longer in FHP placebo responders (n = 8) compared to FHN placebo responders (n = 9) with, again, no significant difference in time-to-relapse in FHP riluzole responders (n = 6) compared to FHN riluzole responders (n = 9). Conclusions: Ketamine's extended antidepressant durability in FHP TRD should be considered in the design and analysis of ketamine depression trials. C1 [Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Richards, Erica M.; Vande Voort, Jennifer L.; Ballard, Elizabeth D.; Brutsche, Nancy E.; Furey, Maura L.; Zarate, Carlos A., Jr.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. RP Niciu, MJ (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, 10 Ctr Dr,Bldg 10-CRC,Room 7-5545, Bethesda, MD 20892 USA. EM mark.niciu@nih.gov RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015 OI Niciu, Mark/0000-0002-5612-3021; FU Intramural Research Program of the National Institute of Mental Health and National Institutes of Health (IRP-NIMH-NIH); 7SE Inpatient Mood and Anxiety Disorders Research Unit of the NIMH-NIH; National Alliance for Research in Schizophrenia and Affective Disorders; Brain and Behavior Foundation FX The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Health and National Institutes of Health (IRP-NIMH-NIH), and thank the 7SE Inpatient Mood and Anxiety Disorders Research Unit of the NIMH-NIH for their support.; The authors gratefully acknowledge the support of the IRP-NIMH-NIH and the National Alliance for Research in Schizophrenia and Affective Disorders Independent Investigator Award and Brain and Behavior Foundation Bipolar Research Award (Dr Zarate). Salary support was also provided by the IRP-NIMH-NIH (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Ms. Brutsche, and Mr. Luckenbaugh). Other than the aforementioned, the IRP-NIMH-NIH played no other role. NR 46 TC 4 Z9 4 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JAN PY 2015 VL 18 IS 1 DI 10.1093/ijnp/pyu039 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CF4OE UT WOS:000352528600016 ER PT J AU Mookherjee, S Bhattacharjee, A Sengupta, M AF Mookherjee, Suddhasil Bhattacharjee, Ashima Sengupta, Mainak TI The Aging Eye SO JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material C1 [Mookherjee, Suddhasil] NEI, NIH, Bethesda, MD 20892 USA. [Bhattacharjee, Ashima] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sengupta, Mainak] Univ Calcutta, Dept Genet, Kolkata, India. RP Mookherjee, S (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM suddhasilmookherjee@gmail.com OI Sengupta, Mainak/0000-0002-4031-1810; Mookherjee, Suddhasil/0000-0003-2796-2659 NR 0 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2015 AR 832326 DI 10.1155/2015/832326 PG 2 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA CF2PQ UT WOS:000352389900001 ER PT J AU Seelaender, M Neto, JCR Pimentel, GD Goldszmid, RS Lira, FS AF Seelaender, M. Rosa Neto, J. C. Pimentel, G. D. Goldszmid, R. S. Lira, F. S. TI Inflammation in the Disease: Mechanism and Therapies 2014 SO MEDIATORS OF INFLAMMATION LA English DT Editorial Material C1 [Seelaender, M.] Univ Sao Paulo, Inst Biomed Sci, Canc Metab Res Grp, BR-05508000 Sao Paulo, SP, Brazil. [Rosa Neto, J. C.] Univ Sao Paulo, Inst Biomed Sci, Immunometab Res Grp, BR-05508000 Sao Paulo, SP, Brazil. [Pimentel, G. D.] State Univ Campinas UNICAMP, Dept Internal Med, BR-13083970 Campinas, SP, Brazil. [Goldszmid, R. S.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Bethesda, MD 21702 USA. [Lira, F. S.] State Univ Sao Paulo UNESP, Dept Phys Educ, Exercise & Immunometab Res Grp, BR-19060900 Presidente Prudente, SP, Brazil. RP Lira, FS (reprint author), State Univ Sao Paulo UNESP, Dept Phys Educ, Exercise & Immunometab Res Grp, BR-19060900 Presidente Prudente, SP, Brazil. EM fabiolira@fct.unesp.br RI Rosa Neto, Jose/I-8145-2015; seelaender, marilia/B-9101-2011 OI seelaender, marilia/0000-0002-9999-8020 NR 0 TC 0 Z9 0 U1 2 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2015 AR 169852 DI 10.1155/2015/169852 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CF3IR UT WOS:000352442400001 ER PT J AU Gold, PW Achado-Vieira, R Pavlatou, MG AF Gold, Phillip W. achado-Vieira, Rodrigo Pavlatou, Maria G. TI Clinical and Biochemical Manifestations of Depression: Relation to the Neurobiology of Stress SO NEURAL PLASTICITY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL RESPONSES; MAJOR DEPRESSION; MOOD DISORDERS; THERAPEUTIC IMPLICATIONS; TYROSINE-HYDROXYLASE; MESSENGER-RNA; UNITED-STATES; HEART-DISEASE; RAT-BRAIN AB Major depressive disorder (MDD) is a chronic, recurrent, and severe psychiatric disorder with high mortality and medical comorbidities. Stress-related pathways have been directly involved in the pathophysiology and treatment of MDD. The present paper provides an overview on the stress system as a model to understand key pathophysiological paradigms in MDD. These mechanisms involve behavioral, cognitive, and systemic manifestations and are also associated with the mechanisms of action of effective antidepressants. Aspects such as depression subtypes, inflammation, insulin resistance, oxidative stress, and prothrombotic states in critical brain circuits and periphery are critically appraised. Finally, new strategies for approaching treatment-resistant major depression and potential adverse effects associated with this complex and intricate network are highlighted. The authors used PubMed as the database for this review. Each author extracted relevant data and assessed the methodological quality of each study. C1 [Gold, Phillip W.; achado-Vieira, Rodrigo] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Pavlatou, Maria G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Gold, PW (reprint author), NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM philipgold@mail.nih.gov OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 55 TC 10 Z9 10 U1 3 U2 14 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 581976 DI 10.1155/2015/581976 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CF3CB UT WOS:000352424200001 ER PT J AU Pereira, BD Tortella, G Lafer, B Nunes, P Bensenor, IM Lotufo, PA Machado-Vieira, R Brunoni, AR AF Pereira Junior, Bernardo de Sampaio Tortella, Gabriel Lafer, Beny Nunes, Paula Bensenor, Isabela Martins Lotufo, Paulo Andrade Machado-Vieira, Rodrigo Brunoni, Andre R. TI The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase SO NEURAL PLASTICITY LA English DT Article ID DIRECT-CURRENT STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; WEEKLY SYMPTOMATIC STATUS; GENOME-WIDE ASSOCIATION; HEART-RATE-VARIABILITY; HUMAN MOTOR CORTEX; NEUROTROPHIC FACTOR; MAJOR DEPRESSION; EUTHYMIC PATIENTS AB Background. Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS. C1 [Pereira Junior, Bernardo de Sampaio; Tortella, Gabriel; Bensenor, Isabela Martins; Lotufo, Paulo Andrade; Brunoni, Andre R.] Univ Sao Paulo, Ctr Clin & Epidemiol Res, Univ Hosp, BR-05508000 Sao Paulo, Brazil. [Pereira Junior, Bernardo de Sampaio; Tortella, Gabriel; Bensenor, Isabela Martins; Lotufo, Paulo Andrade; Brunoni, Andre R.] Univ Sao Paulo, Interdisciplinary Ctr Appl Neuromodulat CINA, Univ Hosp, BR-05508000 Sao Paulo, Brazil. [Pereira Junior, Bernardo de Sampaio; Tortella, Gabriel; Brunoni, Andre R.] Univ Sao Paulo, Fac Med, SIN, Dept & Inst Psychiat, BR-05508000 Sao Paulo, Brazil. [Pereira Junior, Bernardo de Sampaio; Tortella, Gabriel; Machado-Vieira, Rodrigo; Brunoni, Andre R.] Univ Sao Paulo, Lab Neurosci LIM27, Dept & Inst Psychiat, BR-05508000 Sao Paulo, Brazil. [Lafer, Beny; Nunes, Paula] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, Bipolar Disorder Res Program, BR-05508000 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Brunoni, Andre R.] Univ Sao Paulo, Univ Hosp, BR-05508000 Sao Paulo, SP, Brazil. RP Brunoni, AR (reprint author), Univ Sao Paulo, Ctr Clin & Epidemiol Res, Univ Hosp, BR-05508000 Sao Paulo, Brazil. EM brunowsky@gmail.com RI Lafer, Beny/F-9390-2015; MACHADO-VIEIRA, RODRIGO/D-8293-2012; Lafer, Beny/C-1055-2012; Lotufo, Paulo/A-9843-2008; Villela Nunes, Paula/J-9532-2015 OI Lafer, Beny/0000-0002-6132-9999; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Russowsky Brunoni, Andre/0000-0002-6310-3571; Lafer, Beny/0000-0002-6132-9999; Lotufo, Paulo/0000-0002-4856-8450; Villela Nunes, Paula/0000-0001-5323-2110 FU NARSAD Young Investigation Grant from the Brain & Behavior Research Foundation [13/20493]; FAPESP Young Research Award from the Sao Paulo State Foundation [20911-5]; National Council for Scientific and Technological Development Grant (CNPq) [470904] FX This study is directly supported by a NARSAD Young Investigation Grant from the Brain & Behavior Research Foundation (Grant no. 13/20493). Bernardo de Sampaio Pereira Junior and Gabriel Tortella are supported by this grant. Andre R. Brunoni also receives grants from the 2012 FAPESP Young Research Award from the Sao Paulo State Foundation (Grant no. 20911-5) and a National Council for Scientific and Technological Development Grant (CNPq, Grant no. 470904). The authors are grateful to Cibele Soares and Rosa Rios, study nurses and coordinators, who are of invaluable help in executing the study. NR 73 TC 1 Z9 1 U1 3 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 684025 DI 10.1155/2015/684025 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CF3CE UT WOS:000352424500001 ER PT J AU Chen, WY Liu, SY Chang, YS Yin, JJ Yeh, HL Mouhieddine, TH Hadadeh, O Abou-Kheir, W Liu, YN AF Chen, Wei-Yu Liu, Shih-Yang Chang, Yung-Sheng Yin, Juan Juan Yeh, Hsiu-Lien Mouhieddine, Tarek H. Hadadeh, Ola Abou-Kheir, Wassim Liu, Yen-Nien TI MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer SO ONCOTARGET LA English DT Article DE Prostate cancer; bone metastasis; miR-34a; TCF7; BIRC5 ID EXPRESSION PROFILES; COLORECTAL-CANCER; GENE-EXPRESSION; C-MYC; K-RAS; APOPTOSIS; WNT; MUTATIONS; SURVIVIN; CELLS AB Aberrant activation of Ras and WNT signaling are key events that have been shown to be up-regulated in prostate cancer that has metastasized to the bone. However, the regulatory mechanism of combinatorial Ras and WNT signaling in advanced prostate cancer is still unclear. TCF7, a WNT signaling-related gene, has been implicated as a critical factor in bone metastasis, and here we show that TCF7 is a direct target of miR-34a. In samples of prostate cancer patients, miR-34a levels are inversely correlated with TCF7 expression and a WNT dependent gene signature. Ectopic miR-34a expression inhibited bone metastasis and reduced cancer cell proliferation in a Ras-dependent xenograft model. We demonstrate that miR-34a can directly interfere with the gene expression of the anti-proliferative BIRC5, by targeting BIRC5 3'UTR. Importantly, BIRC5 overexpression was sufficient to reconstitute anti-apoptotic signaling in cells expressing high levels of miR-34a. In prostate cancer patients, we found that BIRC5 levels were positively correlated with a Ras signaling signature expression. Our data show that the bone metastasis and anti-apoptotic effects found in Ras signaling-activated prostate cancer cells require miR-34a deficiency, which in turn aids in cell survival by activating the WNT and antiapoptotic signaling pathways thereby inducing TCF7 and BIRC5 expressions. C1 [Chen, Wei-Yu] Taipei Med Univ, Wan Fang Hosp, Dept Pathol, Taipei, Taiwan. [Chen, Wei-Yu] Taipei Med Univ, Sch Med, Dept Pathol, Coll Med, Taipei, Taiwan. [Liu, Shih-Yang] Tianjin Univ Tradit Chinese Med, Dept Acupuncture & Manipulat, Coll Int Educ, Tianjin, Peoples R China. [Chang, Yung-Sheng; Liu, Yen-Nien] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Coll Med Sci & Technol, Taipei, Taiwan. [Yin, Juan Juan] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Yeh, Hsiu-Lien] Natl Tsing Hua Univ, Inst Informat Syst & Applicat, Hsinchu, Taiwan. [Mouhieddine, Tarek H.; Hadadeh, Ola; Abou-Kheir, Wassim] Amer Univ Beirut, Fac Med, Dept Anat Cell Biol & Physiol Sci, Beirut, Lebanon. RP Abou-Kheir, W (reprint author), Amer Univ Beirut, Fac Med, Dept Anat Cell Biol & Physiol Sci, Beirut, Lebanon. EM wa12@aub.edu.lb; liuy@tmu.edu.tw FU Wan Fang Hospital [103TMU-WFH-05]; National Health Research Institutes of Taiwan [NHRI-EX103-10308BC]; Medical Practice Plan-MPP (AUB-FM); Lebanese National Council for Scientific Research (CNRS) FX This work was jointly supported by grants from the Wan Fang Hospital (103TMU-WFH-05), and National Health Research Institutes (NHRI-EX103-10308BC) of Taiwan to YNL, and partly supported by funding from the Medical Practice Plan-MPP (AUB-FM) and the Lebanese National Council for Scientific Research (CNRS) to WAK. We thank Dr. Ji-Hshiung Chen (Tzu Chi University, Taiwan) for reading the manuscript and for his comments and helpful suggestions. NR 56 TC 19 Z9 19 U1 1 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 1 PY 2015 VL 6 IS 1 BP 441 EP 457 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CE8BE UT WOS:000352065200035 PM 25436980 ER PT J AU Kathawala, RJ Wei, LY Anreddy, N Chen, K Patel, A Alqahtani, S Zhang, YK Wang, YJ Sodani, K Kaddoumi, A Ashby, CR Chen, ZS AF Kathawala, Rishil J. Wei, Liuya Anreddy, Nagaraju Chen, Kang Patel, Atish Alqahtani, Saeed Zhang, Yun-Kai Wang, Yi-Jun Sodani, Kamlesh Kaddoumi, Amal Ashby, Charles R., Jr. Chen, Zhe-Sheng TI The small molecule tyrosine kinase inhibitor NVP-BHG712 antagonizes ABCC10-mediated paclitaxel resistance: a preclinical and pharmacokinetic study SO ONCOTARGET LA English DT Article DE NVP-BHG712; ABCC10; ABC transporters; Paclitaxel; Tyrosine kinase inhibitors ID REVERSES MULTIDRUG-RESISTANCE; CELL LUNG-CANCER; G MEMBER 2; EFFLUX ACTIVITY; IN-VIVO; DRUG-RESISTANCE; ABCC10; AGENTS; EXPRESSION; ABCG2 AB Paclitaxel exhibits clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multi-drug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. Here, we determine the effect of NVP-BHG712, a specific EphB4 receptor inhibitor, on 1) paclitaxel resistance in HEK293 cells transfected with ABCC10, 2) the growth of tumors in athymic nude mice that received NVP-BHG712 and paclitaxel systemically and 3) the pharmacokinetics of paclitaxel in presence or absence of NVP-BHG712. NVP-BHG712 (0.5 mu M), in HEK293/ABCC10 cells, significantly enhanced the intracellular accumulation of paclitaxel by inhibiting the efflux activity of ABCC10 without altering the expression level of the ABCC10 protein. Furthermore, NVP-BHG712 (25 mg/kg, p.o., q3d x 6), in combination with paclitaxel (15 mg/kg, i.p., q3d x 6), significantly inhibited the growth of ABCC10-expressing tumors in athymic nude mice. NVP-BHG712 administration significantly increased the levels of paclitaxel in the tumors but not in plasma compared to paclitaxel alone. The combination of NVP-BHG712 and paclitaxel could serve as a novel and useful therapeutic strategy to attenuate paclitaxel resistance mediated by the expression of the ABCC10 transporter. C1 [Kathawala, Rishil J.; Wei, Liuya; Anreddy, Nagaraju; Patel, Atish; Zhang, Yun-Kai; Wang, Yi-Jun; Sodani, Kamlesh; Ashby, Charles R., Jr.; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY USA. [Wei, Liuya] Weifang Med Univ, Sch Pharm & Biol Sci, Weifang, Peoples R China. [Chen, Kang] Wayne State Univ Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. [Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Bethesda, MD USA. [Chen, Kang] Barbara Ann Karmanos Canc Inst, Tumor Biol & Microenvironm Program, Detroit, MI USA. [Chen, Kang] NIAID, Mucosal Immunol Studies Team, NIH, Bethesda, MD 20892 USA. [Alqahtani, Saeed; Kaddoumi, Amal] Univ Louisiana, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA USA. RP Chen, ZS (reprint author), St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY USA. EM ashbyc@stjohns.edu; chenz@stjohns.edu RI Wang, Yi-Jun/K-3218-2016; OI Anreddy, Nagaraju/0000-0001-8914-8404 NR 43 TC 8 Z9 8 U1 0 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 1 PY 2015 VL 6 IS 1 BP 510 EP 521 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CE8BE UT WOS:000352065200040 PM 25402202 ER PT J AU Kelly, CM Muzard, J Brooks, BR Lee, GU Buchete, NV AF Kelly, Catherine M. Muzard, Julien Brooks, Bernard R. Lee, Gil U. Buchete, Nicolae-Viorel TI Structure and dynamics of the fibronectin-III domains of Aplysia californica cell adhesion molecules SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID SEQUENCE CLEAVAGE SITES; SWISS-MODEL; SYNAPTIC PLASTICITY; FORCE SPECTROSCOPY; AMINO-ACIDS; GROWTH; PROTEINS; ELASTICITY; NCAM; SIMULATIONS AB Due to their homophilic and heterophilic binding properties, cell adhesion molecules (CAMs) such as integrin, cadherin and the immunoglobulin superfamily CAMs are of primary importance in cell-cell and cell-substrate interactions, signalling pathways and other crucial biological processes. We study the molecular structures and conformational dynamics of the two fibronectin type III (Fn-III) extracellular domains of the Aplysia californica CAM (apCAM) protein, by constructing and probing an atomically-detailed structural model based on apCAM's homology with other CAMs. The stability and dynamic properties of the Fn-III domains, individually and in tandem, are probed and analysed using all-atom explicit-solvent molecular dynamics (MD) simulations and normal mode analysis of their corresponding elastic network models. The refined structural model of the Fn-III tandem of apCAM reveals a specific pattern of amino acid interactions that controls the stability of the beta-sheet rich structure and could affect apCAM's response to physical or chemical changes of its environment. It also exposes the important role of several specific charged residues in modulating the structural properties of the linker segment connecting the two Fn-III domains, as well as of the inter-domain interface. C1 [Kelly, Catherine M.; Buchete, Nicolae-Viorel] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland. [Kelly, Catherine M.; Buchete, Nicolae-Viorel] Univ Coll Dublin, CASL, Dublin 4, Ireland. [Muzard, Julien; Lee, Gil U.] Univ Coll Dublin, Sch Chem & Chem Biol, UCD Nanomed Ctr, Dublin 4, Ireland. [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Buchete, NV (reprint author), Univ Coll Dublin, Sch Phys, Dublin 4, Ireland. EM buchete@ucd.ie RI Foundry, Molecular/G-9968-2014; Lee, Gil/P-8696-2016; Kelly, Catherine/D-6267-2014; OI Lee, Gil/0000-0002-7949-5848; Kelly, Catherine/0000-0002-9408-7463; Buchete, Nicolae-Viorel/0000-0001-9861-1157 FU University College Dublin Structured PhD Programme in Simulation Science - under the Programme for Research in Third Level Institutions (PRTLI) Cycle 5; European Regional Development Fund (ERDF); Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy [DE-AC02-05CH11231] FX The authors thank the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC), and the Biowulf cluster at the National Institutes of Health, USA (http://biowulf.nih.gov) for the provision of computational facilities and support. CMK and NVB would like to thank Frank McQuillan for useful initial discussions. This work was supported in part by the University College Dublin Structured PhD Programme in Simulation Science, funded under the Programme for Research in Third Level Institutions (PRTLI) Cycle 5 and co-funded by the European Regional Development Fund (ERDF). JM's work at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy, under Contract No. DE-AC02-05CH11231. NR 82 TC 2 Z9 2 U1 5 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2015 VL 17 IS 15 BP 9634 EP 9643 DI 10.1039/c4cp05307a PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CF0YN UT WOS:000352270700006 PM 25729787 ER PT J AU Manolio, TA AF Manolio, T. A. TI Genomic Medicine Programs of the National Human Genome Research Institute SO PUBLIC HEALTH GENOMICS LA English DT Meeting Abstract C1 [Manolio, T. A.] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2015 VL 18 SU 1 MA S01 BP 1 EP 1 PG 1 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA CF1NX UT WOS:000352314100002 ER PT J AU Gage, JC Schiffman, M Katki, HA Castle, PE Fetterman, B Wentzensen, N Poitras, NE Lorey, T Cheung, LC Kinney, WK AF Gage, Julia C. Schiffman, Mark Katki, Hormuzd A. Castle, Philip E. Fetterman, Barbara Wentzensen, Nicolas Poitras, Nancy E. Lorey, Thomas Cheung, Li C. Kinney, Walter K. TI Making Breast Cancer Molecular Subtypes Robust? Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CERVICAL-CANCER; COLPOSCOPY C1 [Gage, Julia C.; Schiffman, Mark; Katki, Hormuzd A.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Castle, Philip E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. [Cheung, Li C.] Informat Management Serv Inc, Calverton, MD USA. [Kinney, Walter K.] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. RP Gage, JC (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9772, Bethesda, MD 20892 USA. EM gagej@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju390 DI 10.1093/jnci/dju390 PG 2 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800033 ER PT J AU Bharucha, AE Dunivan, G Goode, PS Lukacz, ES Markland, AD Matthews, CA Mott, L Rogers, RG Zinsmeister, AR Whitehead, WE Rao, SSC Hamilton, FA AF Bharucha, Adil E. Dunivan, Gena Goode, Patricia S. Lukacz, Emily S. Markland, Alayne D. Matthews, Catherine A. Mott, Louise Rogers, Rebecca G. Zinsmeister, Alan R. Whitehead, William E. Rao, Satish S. C. Hamilton, Frank A. TI Epidemiology, Pathophysiology, and Classification of Fecal Incontinence: State of the Science Summary for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Workshop SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID QUALITY-OF-LIFE; PELVIC FLOOR DISORDERS; ACCIDENTAL BOWEL LEAKAGE; SACRAL NERVE-STIMULATION; NURSING-HOME RESIDENTS; AGED 40 YEARS; RISK-FACTORS; ANAL INCONTINENCE; ANORECTAL FUNCTION; ELDERLY-PATIENTS AB In August 2013, the National Institutes of Health sponsored a conference to address major gaps in our understanding of the epidemiology, pathophysiology, and management of fecal incontinence (FI) and to identify topics for future clinical research. This article is the first of a two-part summary of those proceedings. FI is a common symptom, with a prevalence that ranges from 7 to 15% in community-dwelling men and women, but it is often underreported, as providers seldom screen for FI and patients do not volunteer the symptom, even though the symptoms can have a devastating impact on the quality of life. Rough estimates suggest that FI is associated with a substantial economic burden, particularly in patients who require surgical therapy. Bowel disturbances, particularly diarrhea, the symptom of rectal urgency, and burden of chronic illness are the strongest independent risk factors for FI in the community. Smoking, obesity, and inappropriate cholecystectomy are emerging, potentially modifiable risk factors. Other risk factors for FI include advanced age, female gender, disease burden (comorbidity count, diabetes), anal sphincter trauma (obstetrical injury, prior surgery), and decreased physical activity. Neurological disorders, inflammatory bowel disease, and pelvic floor anatomical disturbances (rectal prolapse) are also associated with FI. The pathophysiological mechanisms responsible for FI include diarrhea, anal and pelvic floor weakness, reduced rectal compliance, and reduced or increased rectal sensation; many patients have multifaceted anorectal dysfunctions. The type (urge, passive or combined), etiology (anorectal disturbance, bowel symptoms, or both), and severity of FI provide the basis for classifying FI; these domains can be integrated to comprehensively characterize the symptom. Several validated scales for classifying symptom severity and its impact on the quality of life are available. Symptom severity scales should incorporate the frequency, volume, consistency, and nature (urge or passive) of stool leakage. Despite the basic understanding of FI, there are still major knowledge gaps in disease epidemiology and pathogenesis, necessitating future clinical research in FI. C1 [Bharucha, Adil E.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Dunivan, Gena; Rogers, Rebecca G.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Goode, Patricia S.; Markland, Alayne D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Lukacz, Emily S.] Univ Calif San Diego, Dept Reprod Med, Hlth Syst, La Jolla, CA 92093 USA. [Matthews, Catherine A.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Mott, Louise] Simon Fdn, Langley, BC, Canada. [Zinsmeister, Alan R.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Whitehead, William E.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Rao, Satish S. C.] Georgia Regents Univ, Dept Gastroenterol, Augusta, GA USA. [Hamilton, Frank A.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Bharucha, AE (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 First St SW, Rochester, MN 55905 USA. EM bharucha.adil@mayo.edu OI Markland, Alayne/0000-0002-6567-6744 FU NIH from the National Institutes of Health (NIH) [R01 DKDK78924]; Agency for Healthcare Research and Quality [R01 HS018695]; NIH [R21 DK096545] FX Bharucha was partly supported by NIH grants R01 DKDK78924 from the National Institutes of Health (NIH). Whitehead was partly supported by Agency for Healthcare Research and Quality grant R01 HS018695 and NIH grant R21 DK096545. NR 107 TC 33 Z9 33 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2015 VL 110 IS 1 BP 127 EP 136 DI 10.1038/ajg.2014.396 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5ZJ UT WOS:000351914700013 PM 25533002 ER PT J AU Whitehead, WE Rao, SSC Lowry, A Nagle, D Varma, M Bitar, KN Bharucha, AE Hamilton, FA AF Whitehead, William E. Rao, Satish S. C. Lowry, Ann Nagle, Deborah Varma, Madhulika Bitar, Khalil N. Bharucha, Adil E. Hamilton, Frank A. TI Treatment of Fecal Incontinence: State of the Science Summary for the National Institute of Diabetes and Digestive and Kidney Diseases Workshop SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID SACRAL NERVE-STIMULATION; RANDOMIZED CONTROLLED-TRIAL; MAGNETIC ANAL-SPHINCTER; ARTIFICIAL BOWEL SPHINCTER; TRIPLE-TARGET TREATMENT; QUALITY-OF-LIFE; LONG-TERM; BIOFEEDBACK THERAPY; ELECTRICAL-STIMULATION; EFFICACY AB This is the second of a two-part summary of a National Institutes of Health conference on fecal incontinence (FI) that summarizes current treatments and identifies research priorities. Conservative medical management consisting of patient education, fiber supplements or antidiarrheals, behavioral techniques such as scheduled toileting, and pelvic floor exercises restores continence in up to 25% of patients. Biofeedback, often recommended as first-line treatment after conservative management fails, produces satisfaction with treatment in up to 76% and continence in 55%; however, outcomes depend on the skill of the therapist, and some trials are less favorable. Electrical stimulation of the anal mucosa is ineffective, but continuous electrical pulsing of sacral nerves produces a >= 50% reduction in FI frequency in a median 73% of patients. Tibial nerve electrical stimulation with needle electrodes is promising but remains unproven. Sphincteroplasty produces short-term clinical improvement in a median 67%, but 5-year outcomes are poor. Injecting an inert bulking agent around the anal canal led to >= 50% reductions of FI in up to 53% of patients. Colostomy is used as a last resort because of adverse effects on quality of life. Several new devices are under investigation but not yet approved. FI researchers identify the following priorities for future research: (1) trials comparing the effectiveness, safety, and cost of current therapies; (2) studies addressing barriers to consulting for care; and (3) translational research on regenerative medicine. Unmet patient needs include FI in special populations (e.g., neurological disorders and nursing home residents) and improvements in behavioral treatments. C1 [Whitehead, William E.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27516 USA. [Whitehead, William E.] Univ N Carolina, Dept Obstet & Gynecol, Div Urogynecol & Reconstruct Pelv Floor Surg, Chapel Hill, NC 27516 USA. [Rao, Satish S. C.] Georgia Regents Univ, Dept Gastroenterol, Augusta, GA USA. [Lowry, Ann] Colon & Rectal Surg Associates Ltd, St Paul, MN USA. [Nagle, Deborah] Beth Israel Deaconess Med Ctr, Harvard Med Fac Phys, Dept Colon & Rectal Surg, Boston, MA 02215 USA. [Varma, Madhulika] Univ Calif San Francisco, Sect Colorectal Surg, San Francisco, CA 94143 USA. [Bitar, Khalil N.] Wake Forest Inst Regenerat Med, Dept Regenerat Med, Winston Salem, NC USA. [Bharucha, Adil E.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Hamilton, Frank A.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Whitehead, WE (reprint author), Univ N Carolina, Div Gastroenterol & Hepatol, Campus Box 7080, Chapel Hill, NC 27516 USA. EM William_Whitehead@med.unc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases FX National Institute of Diabetes and Digestive and Kidney Diseases provided financial assistance for the conference. NR 73 TC 13 Z9 13 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2015 VL 110 IS 1 BP 138 EP 146 DI 10.1038/ajg.2014.303 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5ZJ UT WOS:000351914700014 PM 25331348 ER PT J AU Murray, DM Cross, WP Simons-Morton, D Engel, J Portnoy, B Wu, J Watson, PA Olkkola, S AF Murray, David M. Cross, Wilma Peterman Simons-Morton, Denise Engel, Jody Portnoy, Barry Wu, Jessica Watson, Paris A. Olkkola, Susanne TI Enhancing the Quality of Prevention Research Supported by the National Institutes of Health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID UNITED-STATES; STRATEGY; DISEASE; DEATH AB As the nation's premier biomedical research agency, the National Institutes of Health(NIH) has supported most of the research that underlies the prevention services that are provided to citizens in the United States and around the world. Within the NIH, the Office of Disease Prevention (ODP) has as its mission to improve the public health by increasing the scope, quality, dissemination, and effect of prevention research supported by the NIH. In today's environment, the ODP needs to focus its efforts to address this mission. To do so, the ODP has developed a strategic plan for 2014 to 2018. We provide background on the ODP and key points from the strategic plan. C1 [Murray, David M.; Cross, Wilma Peterman; Simons-Morton, Denise; Engel, Jody; Portnoy, Barry; Wu, Jessica; Watson, Paris A.; Olkkola, Susanne] NIH, Off Dis Prevent, Rockville, MD 20892 USA. RP Murray, DM (reprint author), NIH, Prevent, 6100 Execut Blvd,2B03, Rockville, MD 20892 USA. EM david.murray2@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2015 VL 105 IS 1 BP 9 EP 12 DI 10.2105/AJPH.2014.302057 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE6BG UT WOS:000351920100018 ER PT J AU Neta, G Glasgow, RE Carpenter, CR Grimshaw, JM Rabin, BA Fernandez, ME Brownson, RC AF Neta, Gila Glasgow, Russell E. Carpenter, Christopher R. Grimshaw, Jeremy M. Rabin, Borsika A. Fernandez, Maria E. Brownson, Ross C. TI A Framework for Enhancing the Value of Research for Dissemination and Implementation SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OUTCOMES RESEARCH-INSTITUTE; BEHAVIOR-CHANGE INTERVENTIONS; HEALTH-PROMOTION PROGRAMS; SUBSTANCE-ABUSE TREATMENT; RE-AIM FRAMEWORK; CONSORT STATEMENT; RANDOMIZED-TRIALS; UNINTENDED CONSEQUENCES; PERSONALIZED MEDICINE; COMPLEX INTERVENTIONS AB A comprehensive guide that identifies critical evaluation and reporting elements necessary to move research into practice is needed. We propose a framework that highlights the domains required to enhance the value of dissemination and implementation research for end users. We emphasize the importance of transparent reporting on the planning phase of research in addition to delivery, evaluation, and long-term outcomes. We highlight key topics for which well-established reporting and assessment tools are underused (e.g., cost of intervention, implementation strategy, adoption) and where such tools are inadequate or lacking (e.g., context, sustainability, evolution) within the context of existing reporting guidelines. Consistent evaluation of and reporting on these issues with standardized approaches would enhance the value of research for practitioners and decision-makers. C1 [Neta, Gila] NCI, Implementat Sci, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA. [Glasgow, Russell E.] Univ Colorado, Dept Family Med, Denver, CO 80202 USA. [Glasgow, Russell E.] Univ Colorado, Colorado Hlth Outcomes Res Program, Denver, CO 80202 USA. [Carpenter, Christopher R.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA. [Grimshaw, Jeremy M.] Univ Ottawa, Clin Epidemiol Program, Ottawa Hosp Res Inst, Ottawa, ON K1N 6N5, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON K1N 6N5, Canada. [Rabin, Borsika A.] Univ Colorado, Sch Med, Dept Family Med, Denver, CO USA. [Rabin, Borsika A.] Kaiser Permanente Colorado, Inst Hlth Res, CRN Canc Commun Res Ctr, Denver, CO USA. [Fernandez, Maria E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. [Brownson, Ross C.] Prevent Res Ctr, St Louis, MO USA. [Brownson, Ross C.] Washington Univ, Brown Sch, St Louis, MO USA. [Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Neta, G (reprint author), NCI, Implementat Sci Team, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E442,MSC 9778, Rockville, MD 20850 USA. EM netagil@mail.nih.gov RI Carpenter, Christopher/E-3720-2013 OI Carpenter, Christopher/0000-0002-2603-7157 FU National Cancer Institute [1P20 CA137219] FX This work was partially funded by the National Cancer Institute, project 1P20 CA137219 (B. R.). J. M. Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. NR 108 TC 38 Z9 38 U1 13 U2 35 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2015 VL 105 IS 1 BP 49 EP 57 DI 10.2105/AJPH.2014.302206 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE6BG UT WOS:000351920100023 PM 25393182 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI Cognitive Dissonance in the Early Thirties: The League of Nations Health Organization Confronts the Worldwide Economic Depression SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Publ Hlth, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2015 VL 105 IS 1 BP 65 EP 65 DI 10.2105/AJPH.2014.302063 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE6BG UT WOS:000351920100026 PM 25393194 ER PT J AU Krauss, MR Harris, DR Abreu, T Ferreira, FG Ruz, NP Worrell, C Hazra, R AF Krauss, Margot R. Harris, D. Robert Abreu, Thalita Ferreira, Fabiana G. Ruz, Noris Pavia Worrell, Carol Hazra, Rohan CA NISDI Pediat Study Grp TI Tuberculosis in HIV-infected infants, children, and adolescents in Latin America SO BRAZILIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Thberculosis; HIV; Children; Latin America ID HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY TUBERCULOSIS; COINFECTION; IMPACT; DIAGNOSIS; COHORT; KENYA AB Objective: To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. Methods: A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. Results: Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. Conclusions: Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized. (C) 2014 Elsevier Editora Ltda. Este e um artigo Open Access sob a licenca de CC BY-NC-ND C1 [Krauss, Margot R.; Harris, D. Robert] Westat Corp, Rockville, MD 20850 USA. [Abreu, Thalita] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, BR-21941 Rio De Janeiro, RJ, Brazil. [Ferreira, Fabiana G.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Ruz, Noris Pavia] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Worrell, Carol; Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Krauss, MR (reprint author), Westat Corp, Rockville, MD 20850 USA. EM Margotkrauss@westat.com OI Harris, Donald/0000-0002-8262-3716 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, NICHD [HHSN267200800001C, N01-HD-8-0001] FX Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, NICHD Contract # HHSN267200800001C (NICHD Control # N01-HD-8-0001). NR 20 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER BRAZIL PI RIO DE JANEIRO PA R SETE SETEMBRO, 111-16, RIO DE JANEIRO, RJ 20050-006, BRAZIL SN 1413-8670 EI 1678-4391 J9 BRAZ J INFECT DIS JI Braz. J. Infect. Dis. PD JAN-FEB PY 2015 VL 19 IS 1 BP 23 EP 29 DI 10.1016/j.bjid.2014.08.007 PG 7 WC Infectious Diseases SC Infectious Diseases GA CE9MS UT WOS:000352168700004 PM 25307683 ER PT J AU Siniscalchi, A Bonci, A Mercuri, NB De Siena, A De Sarro, G Malferrari, G Diana, M Gallelli, L AF Siniscalchi, Antonio Bonci, Antonello Mercuri, Nicola Biagio De Siena, Antonia De Sarro, Giovambattista Malferrari, Giovanni Diana, Marco Gallelli, Luca TI Cocaine Dependence and Stroke: Pathogenesis and Management SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE Cocaine; hemorrhagic stroke; ischemic stroke; antineurotoxic agents; antithrombogenic agents; antivasospastic agents ID CEREBRAL BLOOD-FLOW; ANEURYSMAL SUBARACHNOID HEMORRHAGE; POSITRON EMISSION TOMOGRAPHY; ISCHEMIA-INDUCED RELEASE; SMOKING CRACK COCAINE; NEUROVASCULAR COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; MYOCARDIAL-INFARCTION; CALCIUM-CONCENTRATION; POSSIBLE MECHANISM AB Cocaine abuse remains a devastating medical problem for our society. Current concepts suggest that both hemorrhagic and ischemic stroke, particularly in young people, can result as a consequence of cocaine exposure. We provide an analysis of mechanisms of injury and a discussion of the pharmacological management of stroke following cocaine use. Preclinical research suggests that the cause of cocaine-mediated stroke is multifactorial and involves vasospasm, changes in cerebral vasculature, and platelet aggregation. We suggest that drugs able to induce vasospastic, thrombogenic, or neurotoxic effects of cocaine could be suitable as therapeutic agents. In contrast caution should be exerted when using anti-platelet and thrombolytic agents in cocaine users with stroke. C1 [Siniscalchi, Antonio] Annunziata Hosp, Div Neurol, Dept Neurosci, I-87100 Cosenza, Italy. [Bonci, Antonello] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mercuri, Nicola Biagio] Univ Roma Tor Vergata, IRCCS Fdn S Lucia, Rome, Italy. [Mercuri, Nicola Biagio] Univ Roma Tor Vergata, Dept Neurophysiopathol, Rome, Italy. [De Sarro, Giovambattista; Gallelli, Luca] Magna Graecia Univ Catanzaro, Clin Pharmacol & Pharmacovigilance Unit, Mater Domini Univ Hosp, Dept Hlth Sci,Sch Med, Catanzaro, Italy. [Diana, Marco] Santa Maria Nuova Hosp, Dept Neurol, Reggio Emilia, Italy. [Diana, Marco] Univ Sassari, Dept Chem & Pharm, G Minardi Lab Cognit Neurosci, I-07100 Sassari, Italy. RP Siniscalchi, A (reprint author), Annunziata Hosp, Dept Neurol, Via F Migliori 1, I-87100 Cosenza, Italy. EM anto.siniscalchi@libero.it RI Diana, Marco/D-1475-2011; OI Diana, Marco/0000-0002-6561-5642; Mercuri, Nicola B./0000-0001-6700-7491; De Sarro, Giovambattista/0000-0002-7629-6579 NR 121 TC 6 Z9 6 U1 3 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 EI 1875-5739 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PY 2015 VL 12 IS 2 BP 163 EP 172 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE5JD UT WOS:000351867500008 PM 25742568 ER PT J AU Boehringer, S Hilbers, FS Devilee, P Pfeiffer, R AF Boehringer, S. Hilbers, F. S. Devilee, P. Pfeiffer, R. TI Genotype Imputation of Family Data SO HUMAN HEREDITY LA English DT Meeting Abstract CT 43rd European Mathematical Genetics Meeting (EMGM) CY APR 16-17, 2015 CL Brest, FRANCE C1 [Boehringer, S.] Leiden Univ, Med Ctr, Med Stat & Bioinformat, Leiden, Netherlands. [Hilbers, F. S.; Devilee, P.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Pfeiffer, R.] NCI, Biostat Branch, Dept Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2015 VL 79 IS 1 MA A6 BP 31 EP 31 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA CE5NB UT WOS:000351881300011 ER PT J AU Conlon, KC Lugli, E Welles, HC Rosenberg, SA Fojo, AT Morris, JC Fleisher, TA Dubois, SP Perera, LP Stewart, DM Goldman, CK Bryant, BR Decker, JM Chen, J Worthy, TA Figg, WD Peer, CJ Sneller, MC Lane, HC Yovandich, JL Creekmore, SP Roederer, M Waldmann, TA AF Conlon, Kevin C. Lugli, Enrico Welles, Hugh C. Rosenberg, Steven A. Fojo, Antonio Tito Morris, John C. Fleisher, Thomas A. Dubois, Sigrid P. Perera, Liyanage P. Stewart, Donn M. Goldman, Carolyn K. Bryant, Bonita R. Decker, Jean M. Chen, Jing Worthy, Tat'Yana A. Figg, William D., Sr. Peer, Cody J. Sneller, Michael C. Lane, H. Clifford Yovandich, Jason L. Creekmore, Stephen P. Roederer, Mario Waldmann, Thomas A. TI Redistribution, Hyperproliferation, Activation of Natural Killer Cells and CD8 T Cells, and Cytokine Production During First-in-Human Clinical Trial of Recombinant Human Interleukin-15 in Patients With Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTITUMOR-ACTIVITY; METASTATIC MELANOMA; GROWTH-FACTOR; GAMMA-CHAIN; BETA-CHAIN; IL-15; RECEPTOR; MICE; EXPRESSION; THERAPY AB Purpose Interleukin-15 (IL-15) has significant potential in cancer immunotherapy as an activator of antitumor CD8 T and natural killer (NK) cells. The primary objectives of this trial were to determine safety, adverse event profile, dose-limiting toxicity, and maximum-tolerated dose of recombinant human IL-15 (rhIL-15) administered as a daily intravenous bolus infusion for 12 consecutive days in patients with metastatic malignancy. Patients and Methods We performed a first in-human trial of Escherichia coli-produced rhIL-15. Bolus infusions of 3.0, 1.0, and 0.3 mu g/kg per day of IL-15 were administered for 12 consecutive days to patients with metastatic malignant melanoma or metastatic renal cell cancer. Results Flow cytometry of peripheral blood lymphocytes revealed dramatic efflux of NK and memory CD8 T cells from the circulating blood within minutes of IL-15 administration, followed by influx and hyperproliferation yielding 10-fold expansions of NK cells that ultimately returned to baseline. Up to 50-fold increases of serum levels of multiple inflammatory cytokines were observed. Dose-limiting toxicities observed in patients receiving 3.0 and 1.0 mu g/kg per day were grade 3 hypotension, thrombocytopenia, and elevations of ALT and AST, resulting in 0.3 mu g/kg per day being determined the maximum-tolerated dose. Indications of activity included clearance of lung lesions in two patients. Conclusion IL-15 could be safely administered to patients with metastatic malignancy. IL-15 administration markedly altered homeostasis of lymphocyte subsets in blood, with NK cells and gamma delta cells most dramatically affected, followed by CD8 memory T cells. To reduce toxicity and increase efficacy, alternative dosing strategies have been initiated, including continuous intravenous infusions and subcutaneous IL-15 administration. C1 [Conlon, Kevin C.; Rosenberg, Steven A.; Fojo, Antonio Tito; Morris, John C.; Fleisher, Thomas A.; Dubois, Sigrid P.; Perera, Liyanage P.; Stewart, Donn M.; Goldman, Carolyn K.; Bryant, Bonita R.; Decker, Jean M.; Chen, Jing; Worthy, Tat'Yana A.; Figg, William D., Sr.; Peer, Cody J.; Waldmann, Thomas A.] NIH, Bethesda, MD 20892 USA. [Lugli, Enrico; Welles, Hugh C.; Sneller, Michael C.; Lane, H. Clifford; Roederer, Mario] NIAID, Bethesda, MD 20892 USA. [Yovandich, Jason L.; Creekmore, Stephen P.] NIH, Frederick, MD USA. [Welles, Hugh C.] George Washington Univ, Columbian Coll Arts & Sci, Washington, DC USA. RP Waldmann, TA (reprint author), NIH, Lymphoid Malignancies Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 40 TC 67 Z9 69 U1 5 U2 19 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 74 EP U123 DI 10.1200/JCO.2014.57.3329 PG 17 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300014 PM 25403209 ER PT J AU Wentzensen, N Walker, JL Gold, MA Smith, KM Zuna, RE Mathews, C Dunn, ST Zhang, R Moxley, K Bishop, E Tenney, M Nugent, E Graubard, BI Wacholder, S Schiffman, M AF Wentzensen, Nicolas Walker, Joan L. Gold, Michael A. Smith, Katie M. Zuna, Rosemary E. Mathews, Cara Dunn, S. Terence Zhang, Roy Moxley, Katherine Bishop, Erin Tenney, Meaghan Nugent, Elizabeth Graubard, Barry I. Wacholder, Sholom Schiffman, Mark TI Multiple Biopsies and Detection of Cervical Cancer Precursors at Colposcopy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; INTRAEPITHELIAL NEOPLASIA; CONSENSUS GUIDELINES; SCREENING-TESTS; CYTOLOGICAL ABNORMALITIES; INTEROBSERVER AGREEMENT; ENDOCERVICAL CURETTAGE; WOMEN; MANAGEMENT; PARTICIPANTS AB Purpose Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. Methods The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. Results In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% (95% CI, 80.3% to 90.2%) after two biopsies and to 95.6% (95% CI, 91.3% to 99.2%) after three biopsies. A significant increase in sensitivity of multiple biopsies was observed in all subgroups. The highest increase in yield of HSIL was observed for women with a high-grade colposcopic impression, HSIL cytology, and human papillomavirus (HPV) type 16 positivity. Only 2% of all HSILs diagnosed in the participants were detected by biopsies of normal-appearing transformation zone. Conclusion Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy. C1 [Wentzensen, Nicolas; Graubard, Barry I.; Wacholder, Sholom; Schiffman, Mark] NCI, Bethesda, MD 20892 USA. [Walker, Joan L.; Smith, Katie M.; Zuna, Rosemary E.; Mathews, Cara; Dunn, S. Terence; Zhang, Roy; Moxley, Katherine; Bishop, Erin; Tenney, Meaghan; Nugent, Elizabeth] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Gold, Michael A.] Tulsa Canc Inst, Tulsa, OK USA. [Gold, Michael A.] Univ Oklahoma, Sch Community Med, Tulsa, OK USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA. EM wentzenn@mail.nih.gov RI Schiffman, Mark/B-9766-2015 FU Intramural Research Program of the National Cancer Institute, Bethesda, MD FX Supported by the Intramural Research Program of the National Cancer Institute, Bethesda, MD. NR 25 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 83 EP U135 DI 10.1200/JCO.2014.55.9948 PG 12 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300015 PM 25422481 ER PT J AU Ahn, IE Mailankody, S Korde, N Landgren, O AF Ahn, Inhye E. Mailankody, Sham Korde, Neha Landgren, Ola TI Dilemmas in Treating Smoldering Multiple Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; UNDETERMINED SIGNIFICANCE MGUS; MULTIPARAMETER FLOW-CYTOMETRY; GENE-EXPRESSION SIGNATURE; MONOCLONAL GAMMOPATHY; HIGH-RISK; PROGNOSTIC-SIGNIFICANCE; MELPHALAN-PREDNISONE; PLUS DEXAMETHASONE AB Novel therapies hold promise for high-risk smoldering multiple myeloma (SMM). Recent studies suggest that modern combination approaches can be options for high-risk SMM to obtain deep molecular responses with favorable toxicity profiles. Although pioneering treatment trials based on small numbers of patients suggest progression-free and overall survival benefits, application of the data to real-life practice remains to be validated. Therapeutic modulation of disease tempo, disease burden, clonal evolution, and tumor microenvironment in SMM remains to be understood and calls for reliable biomarkers reflective of disease biology. Here, we review studies that open a new management platform for SMM, address ongoing dilemmas in practice and under investigation, and highlight emerging scientific questions in the era of SMM treatment. (C) 2014 by American Society of Clinical Oncology C1 [Ahn, Inhye E.; Mailankody, Sham] NCI, NIH, Bethesda, MD 20892 USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA. EM landgrec@mskcc.org FU Intramural Program of the National Cancer Institute, National Institutes of Health FX Supported by the Intramural Program of the National Cancer Institute, National Institutes of Health. NR 75 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 115 EP U178 DI 10.1200/JCO.2014.56.4351 PG 10 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300019 PM 25422486 ER PT J AU Pai, AB AF Pai, Amy Barton TI Keeping kidneys safe: The pharmacist's role in NSAID avoidance in high-risk patients SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE-RENAL-FAILURE; INJURY; OUTCOMES; DISEASE; INTERVENTION; PRESCRIPTION; PROGRAM; NETWORK; AGENTS AB Objective: To provide information on the role of pharmacists in nonsteroidal anti-inflammatory drug (NSAID) avoidance in high-risk patients. Summary: Nonprescription analgesics such as ibuprofen and naproxen are widely used by Americans. These nonsteroidal anti-inflammatory drugs (NSAIDs) are available in large quantities in pharmacies and also in wholesale stores, gas stations, and convenience stores. In addition, more than 111 million people use prescription NSAIDs each year, including many older Americans. NSAIDs may seem innocuous, but they carry a significant risk of disrupting blood flow to the kidneys and thus precipitating acute kidney injury (AKI). Episodes of AKI can lead to costly hospitalizations and long-term consequences such as new-onset chronic kidney disease (CKD) or more rapid progression of existing CKD. Most cases of NSAID-induced AKI can be avoided by recognizing high-risk patients and counseling them on appropriate use of these medications. Community pharmacy-based NSAID counseling and education at the point of prescription dispensing or nonprescription purchase could complement and augment NSAID-induced AKI education provided by other members of the health care team to high-risk patients. Conclusion: NSAID use is widespread and severely compromises effective renal perfusion in high-risk patients. The community pharmacist can play a pivotal role in NSAID avoidance education to prevent potential episodes of AKI that have long-term consequences for patients. C1 [Pai, Amy Barton] Albany Coll Pharm & Hlth Sci, Albany, NY 12208 USA. [Pai, Amy Barton] Natl Kidney Dis Educ Program, Pharm Working Grp, NIH, Bethesda, MD USA. RP Pai, AB (reprint author), Albany Coll Pharm & Hlth Sci, Albany, NY 12208 USA. FU Forest Laboratories FX Amy Barton Pai, PharmD, BCPS, FASN, FCCP has received a research grant from Forest Laboratories. APhA's editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see the APhA Accreditation Information section at www.pharmacist.com/education. NR 52 TC 1 Z9 1 U1 0 U2 12 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 EI 1544-3450 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JAN-FEB PY 2015 VL 55 IS 1 BP E15 EP E25 DI 10.1331/JAPhA.2015.15506 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE7IN UT WOS:000352012700001 PM 25503987 ER PT J AU Frazier, JJ Stein, CD Tseytlin, E Bekhuis, T AF Frazier, John J. Stein, Corey D. Tseytlin, Eugene Bekhuis, Tanja TI Building a gold standard to construct search filters: a case study with biomarkers for oral cancer SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID MEDLINE; MEDICINE AB Objective: To support clinical researchers, librarians and informationists may need search filters for particular tasks. Development of filters typically depends on a "gold standard'' dataset. This paper describes generalizable methods for creating a gold standard to support future filter development and evaluation using oral squamous cell carcinoma (OSCC) as a case study. OSCC is the most common malignancy affecting the oral cavity. Investigation of biomarkers with potential prognostic utility is an active area of research in OSCC. The methods discussed here should be useful for designing quality search filters in similar domains. Methods: The authors searched MEDLINE for prognostic studies of OSCC, developed annotation guidelines for screeners, ran three calibration trials before annotating the remaining body of citations, and measured inter-annotator agreement (IAA). Results: We retrieved 1,818 citations. After calibration, we screened the remaining citations (n=1,767; 97.2%); IAA was substantial (kappa=0.76). The dataset has 497 (27.3%) citations representing OSCC studies of potential prognostic biomarkers. Conclusions: The gold standard dataset is likely to be high quality and useful for future development and evaluation of filters for OSCC studies of potential prognostic biomarkers. C1 [Frazier, John J.] Amer Acad Oral & Maxillofacial Pathol, New York, NY 10016 USA. [Frazier, John J.] Amer Board Oral & Maxillofacial Pathol, New York, NY USA. [Frazier, John J.] Natl Lib Med, Bethesda, MD 20894 USA. [Stein, Corey D.; Tseytlin, Eugene; Bekhuis, Tanja] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15206 USA. [Stein, Corey D.; Tseytlin, Eugene; Bekhuis, Tanja] Univ Pittsburgh, Dept Dent Publ Hlth, Pittsburgh, PA 15206 USA. [Stein, Corey D.; Tseytlin, Eugene; Bekhuis, Tanja] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15206 USA. [Stein, Corey D.; Tseytlin, Eugene; Bekhuis, Tanja] Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15206 USA. RP Frazier, JJ (reprint author), Amer Acad Oral & Maxillofacial Pathol, New York, NY 10016 USA. EM jjf60@pitt.edu; cds51@pitt.edu; tseytlin@pitt.edu; tcb24@pitt.edu OI Bekhuis, Tanja/0000-0002-8537-9077 FU US National Library of Medicine of the National Institutes of Health (NIH) [5T15-LM007059, 5R00LM010943] FX The US National Library of Medicine of the National Institutes of Health (NIH) partially supported this research (grant numbers 5T15-LM007059 and 5R00LM010943). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 29 TC 0 Z9 0 U1 0 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2015 VL 103 IS 1 BP 22 EP 30 DI 10.3163/1536-5050.103.1.005 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA CE3HW UT WOS:000351718300005 PM 25552941 ER PT J AU Tang, YX Hu, H Zhang, MG Song, JB Nie, LM Wang, SJ Niu, G Huang, P Lu, GM Chen, XY AF Tang, Yuxia Hu, Hao Zhang, Molly Gu Song, Jibin Nie, Liming Wang, Shouju Niu, Gang Huang, Peng Lu, Guangming Chen, Xiaoyuan TI An aptamer-targeting photoresponsive drug delivery system using "off-on" graphene oxide wrapped mesoporous silica nanoparticles SO NANOSCALE LA English DT Article ID PHOTODYNAMIC THERAPY; CANCER-CELLS; PHOTOTHERMAL THERAPY; GOLD NANOPARTICLES; IN-VIVO; RELEASE; NANOCARRIERS; THERANOSTICS; NANORODS; ACID AB We have developed a novel aptamer-targeting photoresponsive drug delivery system by non-covalent assembly of a Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The two "off-on" switches of the MSN-Dox@GO-Apt were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting and real-time indicator abilities by "off-on" Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When the GO wrapping falls off upon laser irradiation, the "off-on" photoresponsive drug delivery system is activated, thus inducing chemotherapy. Interestingly, with an increase in laser power, the synergism of chemotherapy and photothermal therapy in a single MSN-Dox@GO-Apt platform led to much more effective cancer cell killing than monotherapies, providing a new approach for treatment against cancer. C1 [Tang, Yuxia; Wang, Shouju; Lu, Guangming] Nanjing Univ, Sch Med, Jinling Hosp, Dept Med Imaging, Nanjing 210002, Jiangsu, Peoples R China. [Tang, Yuxia; Hu, Hao; Zhang, Molly Gu; Song, Jibin; Niu, Gang; Huang, Peng; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Nie, Liming] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen, Peoples R China. [Tang, Yuxia; Lu, Guangming] Nanjing Univ, State Key Lab Analyt Chem Life Sci, Nanjing 210008, Jiangsu, Peoples R China. RP Huang, P (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM peng.huang@nih.gov; cjr.luguangming@vip.163.com; shawn.chen@nih.gov RI Nie, Liming/F-7718-2016; Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Key Basic Research Program of the PRC [2014CB744504, 2014CB744503, 2013CB733802, 2011CB707700]; Major International (Regional) Joint Research Program of China [81120108013]; National Natural Science Foundation of China [81201175, 81371611, 81371596, 81401465]; China Postdoctoral Science Foundation [2014T71012, 2013M542576]; Jiangsu planned Projects for Postdoctoral Research Funds [1301023]; Intramural Research Program (IRP) of the NIBIB, NIH FX This work was supported in part, by the National Key Basic Research Program of the PRC (2014CB744504, 2014CB744503, 2013CB733802 and 2011CB707700), the Major International (Regional) Joint Research Program of China (81120108013), the National Natural Science Foundation of China (81201175, 81371611, 81371596, 81401465), the China Postdoctoral Science Foundation (2014T71012 and 2013M542576) and Jiangsu planned Projects for Postdoctoral Research Funds (1301023) and by the Intramural Research Program (IRP) of the NIBIB, NIH. NR 37 TC 24 Z9 26 U1 16 U2 151 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2015 VL 7 IS 14 BP 6304 EP 6310 DI 10.1039/c4nr07493a PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CE6GL UT WOS:000351934700045 PM 25782595 ER PT J AU Schnermann, MJ Shenvi, RA AF Schnermann, Martin J. Shenvi, Ryan A. TI Syntheses and biological studies of marine terpenoids derived from inorganic cyanide SO NATURAL PRODUCT REPORTS LA English DT Review ID SPONGE HALICHONDRIA SP; PARASITE PLASMODIUM-FALCIPARUM; ANTIMALARIAL-DRUG ARTEMISININ; FORMAL TOTAL-SYNTHESIS; DIELS-ALDER REACTION; ACANTHELLA-CAVERNOSA; CARBONYL-COMPOUNDS; NATURAL-PRODUCTS; ABSOLUTE-CONFIGURATION; CYMBASTELA-HOOPERI AB Isocyanoterpenes (ICTs) are marine natural products biosynthesized through an unusual pathway that adorns terpene scaffolds with nitrogenous functionality derived from cyanide. The appendage of nitrogen functional groups - isonitriles in particular - onto stereochemically-rich carbocyclic ring systems provides enigmatic, bioactive molecules that have required innovative chemical syntheses. This review discusses the challenges inherent to the synthesis of this diverse family and details the development of the field. We also present recent progress in isolation and discuss key aspects of the remarkable biological activity of these compounds. C1 [Schnermann, Martin J.] NCI, Biol Chem Lab, Frederick, MD 21701 USA. [Shenvi, Ryan A.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Frederick, MD 21701 USA. EM martin.schnermann@nih.gov; rshenvi@scripps.edu RI Schnermann, Martin/M-6595-2014; OI Shenvi, Ryan/0000-0001-8353-6449 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institutes of Health [GM105766]; Alfred P. Sloan Foundation; Baxter Foundation; Amgen; Boehringer-Ingelheim; Eli Lilly FX M.J.S. is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. R.A.S. acknowledges the generous support of the National Institutes of Health (GM105766), as well as the Alfred P. Sloan Foundation, Amgen, the Baxter Foundation, Boehringer-Ingelheim, and Eli Lilly. M.J.S. thanks Alexander P. Gorka for helpful suggestions. R.A.S. thanks Ted Molinski (UCSD) for helpful conversations, members of his lab for proofreading (Steven W. M. Crossley, Chris A. Reiher, Jeremy J. Roach, Kanny K. Wan), and Joseph Gassert for help with formatting. NR 177 TC 14 Z9 14 U1 3 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 EI 1460-4752 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2015 VL 32 IS 4 BP 543 EP 577 DI 10.1039/c4np00109e PG 35 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CE3FE UT WOS:000351710900003 PM 25514696 ER PT J AU Qian, WJ Burke, TR AF Qian, Wen-Jian Burke, Terrence R., Jr. TI Mitsunobu mischief: neighbor-directed histidine N(tau)-alkylation provides access to peptides containing selectively functionalized imidazolium heterocycles SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID SPONGE THEONELLA-SWINHOEI; ESTERIFICATION REACTION; ALKYLATION; PHOSPHOPEPTIDES; PEPTIDOMIMETICS; GLYCOPEPTIDE; POTENT AB There are few methodologies that yield peptides containing His residues with selective N(tau), N(pi)-bis-alkylated imidazole rings. We have found that, under certain conditions, on-resin Mitsunobu coupling of alcohols with peptides having a N(pi)-alkylated His residue results in selective and high-yield alkylation of the imidazole N(tau) nitrogen. The reaction requires the presence of a proximal phosphoric, carboxylic or sulfonic acid, and proceeds through an apparent intramolecular mechanism involving Mitsunobu intermediates. These transformations have particular application to phosphopeptides, where "charge masking" of one phosphoryl anionic charge by the cationic histidine imidazolium ion is now possible. This chemistry opens selective access to peptides containing differentially functionalized imidazolium heterocycles, which provide access to new classes of peptides and peptide mimetics. C1 [Qian, Wen-Jian; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Natl Canc Inst Frederick, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Biol Chem Lab, Natl Canc Inst Frederick, Ctr Canc Res,NIH, POB B,Boyles St, Frederick, MD 21702 USA. EM burkete@helix.nih.gov FU Intramural Research Program of the NIH, Center for Cancer Research; National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the NIH, Center for Cancer Research and the National Cancer Institute, National Institutes of Health. NR 17 TC 2 Z9 2 U1 3 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2015 VL 13 IS 14 BP 4221 EP 4225 DI 10.1039/c5ob00171d PG 5 WC Chemistry, Organic SC Chemistry GA CE2BO UT WOS:000351618000014 PM 25739367 ER PT J AU Weinberger, DM Klugman, KP Steiner, CA Simonsen, L Viboud, C AF Weinberger, Daniel M. Klugman, Keith P. Steiner, Claudia A. Simonsen, Lone Viboud, Cecile TI Association between Respiratory Syncytial Virus Activity and Pneumococcal Disease in Infants: A Time Series Analysis of US Hospitalization Data SO PLOS MEDICINE LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINE; BACTERIAL-INFECTION; UNITED-STATES; INFLUENZA; CHILDREN; IMPACT; YOUNGER; SEASON; RISK AB Background: The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV. Methods and Findings: We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and > 16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal peak of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated the association between the incidence of pneumococcal disease in children and the activity of RSV and influenza (where there is a well-established association) using Poisson regression models that controlled for shared seasonal variations. Finally, we estimated changes in the rate of hospitalizations coded as RSV following the introduction of PCV7. RSV and pneumococcal pneumonia shared a distinctive spatiotemporal pattern (correlation of peak timing: p = 0.70, 95% CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]: 20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1-2 y (AP: 10.1%, 95% CI: 7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal pneumonia among children aged 1-2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we observed a significant decline in RSV-coded hospitalizations in children aged,1 y following PCV7 introduction (-18.0%, 95% CI: -22.6%, -13.1%, for 2004/2005-2008/2009 versus 1997/1998-1999/2000). This study used aggregated hospitalization data, and studies with individual-level, laboratory-confirmed data could help to confirm these findings. Conclusions: These analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV. Please see later in the article for the Editors' Summary. C1 [Weinberger, Daniel M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Weinberger, Daniel M.; Simonsen, Lone; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Klugman, Keith P.] Emory Univ, Dept Global Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Steiner, Claudia A.] Agcy Healthcare Res & Qual, Healthcare Cost & Utilizat Project, Rockville, MD USA. [Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC USA. RP Weinberger, DM (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. EM Daniel.weinberger@yale.edu OI Simonsen, Lone/0000-0003-1535-8526; Weinberger, Daniel/0000-0003-1178-8086 FU Division of International Epidemiology and Population Studies, Fogarty International Center, US National Institutes of Health; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine [P30AG021342 NIH/NIA]; Yale Center for Clinical Investigation [UL1 TR000142]; Bill & Melinda Gates Foundation; RAPIDD (Research and Policy for Infectious Disease Dynamics) program of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center FX DMW and CV were supported by the Division of International Epidemiology and Population Studies, Fogarty International Center, US National Institutes of Health. DMW is supported by the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (#P30AG021342 NIH/NIA), the Yale Center for Clinical Investigation (UL1 TR000142), and the Bill & Melinda Gates Foundation. LS acknowledges support from the RAPIDD (Research and Policy for Infectious Disease Dynamics) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 22 Z9 23 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD JAN PY 2015 VL 12 IS 1 AR e1001776 DI 10.1371/journal.pmed.1001776 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CE3GX UT WOS:000351715800002 PM 25562317 ER PT J AU Balageas, DL Roche, JM Leroy, FH Liu, WM Gorbach, AM AF Balageas, Daniel L. Roche, Jean-Michel Leroy, Francois-Henri Liu, Wei-Min Gorbach, Alexander M. TI The thermographic signal reconstruction method: A powerful tool for the enhancement of transient thermographic images SO BIOCYBERNETICS AND BIOMEDICAL ENGINEERING LA English DT Review DE Stimulated thermography; Non-destructive evaluation; Experimental mechanics; Damage detection; Biomedicine; Thermographic signal reconstruction ID PHASE INFRARED THERMOGRAPHY; SEQUENCES; HUMANS; PULSE AB Important progress occurred in pulse-stimulated thermography, in particular thanks to the TSR technique, a technique based on the decomposition of thermograms on a logarithmic polynomial basis and the use of the logarithmic derivatives to enhance the detection of defects in structures. Its fields of application begin to broaden to the characterization of transient internal heat sources in experimental mechanics and biomedicine. The TSR technique is presented, in particular the last developments leading to the production of a unique synthetic image. Two recent examples of applications in experimental mechanics and biomedicine, taken from literature, are described: in situ detection of damages in a composite material during mechanical tests and in vivo visualization of subcutaneous functional angioarchitecture in humans. (C) 2014 Nalecz Institute of Biocybermetics and Biomedical Engineering. Published by Elsevier Urban & Partner Sp. z o.o.. All rights reserved. C1 [Balageas, Daniel L.] Inst Mech & Engn Bordeaux, TREFLE Dept, Bordeaux, France. [Roche, Jean-Michel; Leroy, Francois-Henri] Off Natl Etud & Rech Aerosp, Composite Mat & Struct Dept, Chatillon, France. [Liu, Wei-Min] Natl Chung Cheng Univ, Dept Comp Sci & Informat Engn, Minxiong Township, Chiayi County, Taiwan. [Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, Bethesda, MD USA. RP Balageas, DL (reprint author), Inst Mech & Engn Bordeaux, TREFLE Dept, Bordeaux, France. EM daniel.balageas@wanadoo.fr FU Intramural NIH HHS [ZIC EB000060-06] NR 18 TC 5 Z9 5 U1 3 U2 14 PU PWN-POLISH SCIENTIFIC PUBL PI WARSAW PA UL KS TROJDENA 4, WARSAW, 02-109, POLAND SN 0208-5216 J9 BIOCYBERN BIOMED ENG JI Biocybern. Biomed. Eng. PY 2015 VL 35 IS 1 BP 1 EP 9 DI 10.1016/j.bbe.2014.07.002 PG 9 WC Engineering, Biomedical SC Engineering GA CD8EP UT WOS:000351328300001 PM 25678731 ER PT J AU Kwak, JT Hong, CW Pinto, PA Williams, M Xu, S Kruecker, J Yan, PK Turkbey, B Choyke, PL Wood, BJ AF Kwak, Jin Tae Hong, Cheng William Pinto, Peter A. Williams, Molly Xu, Sheng Kruecker, Jochen Yan, Pingkun Turkbey, Baris Choyke, Peter L. Wood, Bradford J. TI Is Visual Registration Equivalent to Semiautomated Registration in Prostate Biopsy? SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID CANCER-DETECTION; 3 T; SEXTANT; FUSION; LOCALIZATION; STRATEGY; IMPROVES; MRI AB In magnetic resonance iimaging-(MRI-) ultrasound (US) guided biopsy, suspicious lesions are identified on MRI, registered on US, and targeted during biopsy. The registration can be performed either by a human operator (visual registration) or by fusion software. Previous studies showed that software registration is fairly accurate in locating suspicious lesions and helps to improve the cancer detection rate. Here, the performance of visual registration was examined for ability to locate suspicious lesions defined on MRI. This study consists of 45 patients. Two operators with differing levels of experience (<1 and 18 years) performed visual registration. The overall spatial difference by the two operators in 72 measurements was 10.6 +/- 6.0 mm. Each operator showed a spatial difference of 9.4 +/- 5.1 mm (experienced; 39 lesions) and 12.1 +/- 6.6 mm (inexperienced; 33 lesions), respectively. In a head-to-head comparison of the same 16 lesions from 12 patients, the spatial differences were 9.7 mm +/- 4.9 mm (experienced) and 13.4 mm +/- 7.4 mm (inexperienced). There were significant differences between the two operators (unpaired, P value = 0.042; paired, P value = 0.044). The substantial differences by the two operators suggest that visual registration could improperly and inaccurately target many tumors, thereby potentially leading to missed diagnosis or false characterization on pathology. C1 [Kwak, Jin Tae; Hong, Cheng William; Xu, Sheng; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. [Williams, Molly] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA. [Kruecker, Jochen; Yan, Pingkun] Philips Res North Amer, Briarcliff Manor, NY 10510 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. EM bwood@cc.nih.gov FU NIH Center FX This work was supported in part by the Intramural Research Program of the NIH Center for Interventional Oncology. NR 19 TC 1 Z9 1 U1 0 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 394742 DI 10.1155/2015/394742 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CD8WY UT WOS:000351378400001 ER PT J AU Carter, JR Goldstein, DS AF Carter, Jason R. Goldstein, David S. TI Sympathoneural and Adrenomedullary Responses to Mental Stress SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID SYMPATHETIC-NERVE ACTIVITY; POLYMORPHIC-VENTRICULAR-TACHYCARDIA; NEURALLY-MEDIATED SYNCOPE; HEAD-UP TILT; DOPAMINE-BETA-HYDROXYLASE; COLD PRESSOR TEST; CONDITIONED EMOTIONAL DISTURBANCES; SPONTANEOUSLY HYPERTENSIVE-RATS; CARDIAC NORADRENALINE SPILLOVER; CIVILIAN TRAUMA VICTIMS AB This concept-based review provides historical perspectives and updates about sympathetic noradrenergic and sympathetic adrenergic responses to mental stress. The topic of this review has incited perennial debate, because of disagreements over definitions, controversial inferences, and limited availability of relevant measurement tools. The discussion begins appropriately with Cannon's "homeostasis" and his pioneering work in the area. This is followed by mental stress as a scientific idea and the relatively new notions of allostasis and allostatic load. Experimental models of mental stress in rodents and humans are discussed, with particular attention to ethical constraints in humans. Sections follow on sympathoneural responses to mental stress, reactivity of catecholamine systems, clinical pathophysiologic states, and the cardiovascular reactivity hypothesis. Future advancement of the field will require integrative approaches and coordinated efforts between physiologists and psychologists on this interdisciplinary topic. Published 2015. C1 [Carter, Jason R.] Michigan Technol Univ, Dept Kinesiol & Integrat Physiol, Houghton, MI 49931 USA. [Goldstein, David S.] NIH, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res, Bethesda, MD 20892 USA. RP Carter, JR (reprint author), Michigan Technol Univ, Dept Kinesiol & Integrat Physiol, Houghton, MI 49931 USA. EM jcarter@mtu.edu FU Intramural NIH HHS [Z99 NS999999] NR 298 TC 13 Z9 14 U1 6 U2 23 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD JAN PY 2015 VL 5 IS 1 BP 119 EP 146 DI 10.1002/cphy.c140030 PG 28 WC Physiology SC Physiology GA CE0JS UT WOS:000351490900005 PM 25589266 ER PT J AU Kumar, S Malhotra, S Prasad, AK Van der Eycken, EV Bracke, ME Stetler-Stevenson, WG Parmar, VS Ghosh, B AF Kumar, Sarvesh Malhotra, Shashwat Prasad, Ashok K. Van der Eycken, Erik V. Bracke, Marc E. Stetler-Stevenson, William G. Parmar, Virinder S. Ghosh, Balaram TI Anti-Inflammatory and Antioxidant Properties of Piper Species: A Perspective from Screening to Molecular Mechanisms SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Anti-inflammatory; Antioxidant; Cell adhesion molecules (CAMs); Endothelial cells; Piper longum; Piper galeatum ID NF-KAPPA-B; CELL-ADHESION MOLECULES; MICROSOMAL LIPID-PEROXIDATION; ALPHA-INDUCED EXPRESSION; HUMAN ENDOTHELIAL-CELLS; BETA-SITOSTEROL; INFLAMMATORY RESPONSE; OXIDATIVE STRESS; BLACK PEPPER; IN-VITRO AB Identifying novel therapeutic agents from natural sources and their possible intervention studies has been one of the major areas in biomedical research in recent years. Piper species are highly important - commercially, economically and medicinally. Our groups have been working for more than two decades on the identification and characterization of novel therapeutic lead molecules from Piper species. We have extensively studied the biological activities of various extracts of Piper longum and Piper galeatum, and identified and characterized novel molecules from these species. Using synthetic chemistry, various functional groups of the lead molecules were modified and structure activity relationship (SAR) studies identified synthetic molecules with better efficacy and lower IC50 values. Moreover, the mechanisms of actions of some of these molecules were studied at the molecular level. The objective of this review is to summarize experimental data published from our laboratories and others on antioxidant and anti-inflammatory potentials of Piper species and their chemical constituents. C1 [Kumar, Sarvesh; Stetler-Stevenson, William G.] Natl Canc Inst, Radiat Oncol Branch, Ctr Canc Res, NIH, Gaithersburg, MD 20877 USA. [Kumar, Sarvesh; Ghosh, Balaram] CSIR, Inst Genom & Integrat Biol, Immunogenet Mol Lab, Delhi 110007, India. [Malhotra, Shashwat; Prasad, Ashok K.; Parmar, Virinder S.] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India. [Van der Eycken, Erik V.; Parmar, Virinder S.] Univ Leuven KU Leuven, Dept Chem, LOMAC, B-3001 Leuven, Belgium. [Bracke, Marc E.; Parmar, Virinder S.] Univ Ghent, Univ Hosp, Lab Expt Canc Res, B-9000 Ghent, Belgium. RP Parmar, VS (reprint author), CSIR, Inst Genom & Integrat Biol, Immunogenet Mol Lab, Mall Rd, Delhi 110007, India. EM virparmar@gmail.com; bghosh@igib.res.in FU Council of Scientific and Industrial Research, Govt. of India [NWP 0033, BSC 0116]; EU FX BG received grants (NWP 0033 and BSC 0116) from Council of Scientific and Industrial Research, Govt. of India; VSP was supported by a grant from the EU under its Erasmus Mundus EMA-2 Program. NR 59 TC 0 Z9 0 U1 1 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2015 VL 15 IS 9 BP 886 EP 893 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CE5FC UT WOS:000351855200007 PM 25697561 ER PT J AU Forni, PE Wray, S AF Forni, Paolo E. Wray, Susan TI GnRH, anosmia and hypogonadotropic hypogonadism - Where are we? SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE GnRH; Olfactory placode; Neural crest; Kallmann syndrome; Waardenburg syndrome; Olfactory ensheathing cells; Hypogonadotropic hypogonadism; Craniofacial defects; Hypothalamic-pituitary-gonadal (HPG) axis ID GONADOTROPIN-RELEASING-HORMONE; OLFACTORY ENSHEATHING CELLS; TRANSCRIPTION FACTOR SOX10; MULTIPLE MOLECULAR-FORMS; ZEBRAFISH DANIO-RERIO; OF-FUNCTION MUTATIONS; NEURAL CREST CELLS; NERVE-FIBER LAYER; EUROPEAN SEA BASS; KALLMANN-SYNDROME AB Gonadotropin releasing hormone (GnRH) neurons originate the nasal placode and migrate into the brain during prenatal development. Once within the brain, these cells become integral components of the hypothalamic-pituitary-gonadal axis, essential for reproductive function. Disruption of this system causes hypogonadotropic hypogonadism (HH). HH associated with anosmia is clinically defined as Kallman syndrome (KS). Recent work examining the developing nasal region has shed new light on cellular composition, cell interactions and molecular cues responsible for the development of this system in different species. This review discusses some developmental aspects, animal models and current advancements in our understanding of pathologies affecting GnRH. In addition we discuss how development of neural crest derivatives such as the glia of the olfactory system and craniofacial structures control GnRH development and reproductive function. Published by Elsevier Inc. C1 [Forni, Paolo E.] SUNY Albany, Dept Biol Sci, Albany, NY 12222 USA. [Forni, Paolo E.] SUNY Albany, Ctr Neurosci Res, Albany, NY 12222 USA. [Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Forni, PE (reprint author), SUNY Albany, Dept Biol Sci, SUNY 1400 Washington Ave, Albany, NY 12222 USA. EM pforni@albany.edu; wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU Intramural Research Program of the NIH, NINDS; Departmental Startup Grant SUNY, Albany FX This work was supported by the Intramural Research Program of the NIH, NINDS. Paolo E. Forni's research is supported by Departmental Startup Grant SUNY, Albany. NR 194 TC 17 Z9 17 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 EI 1095-6808 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JAN PY 2015 VL 36 BP 165 EP 177 DI 10.1016/j.yfrne.2014.09.004 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CD4CQ UT WOS:000351030600010 PM 25306902 ER PT J AU Alter, BP Giri, N Savage, SA Rosenberg, PS AF Alter, Blanche P. Giri, Neelam Savage, Sharon A. Rosenberg, Philip S. TI Telomere length in inherited bone marrow failure syndromes SO HAEMATOLOGICA LA English DT Article ID SHWACHMAN-DIAMOND-SYNDROME; FANCONI-ANEMIA; DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; CLINICAL PRESENTATION; MUTATIONS; FISH AB Telomeres are long DNA repeats and a protein complex at chromosome ends that are essential for genome integrity. Telomeres are very short in patients with dyskeratosis congenita due to germline mutations in telomere biology genes. We compared telomere length in patients with Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome with telomere length in dyskeratosis congenita. Telomere length was measured in six leukocyte subsets by automated multicolor flow fluorescence in situ hybridization, and age-adjusted using Z-scores (-2.326 = 1st percentile) were created. We examined individual data, and used canonical variate analysis for group comparisons and outlier detection. Most dyskeratosis congenita telomere lengths were below the 1st percentile, while only 2 Fanconi anemia and one each Diamond-Blackfan anemia and Shwachman-Diamond syndrome were that low. However, Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome clustered in the bottom half of the normal range. Canonical variate analysis separated dyskeratosis congenita widely from the other three syndromes by the first canonical variable (89.7% of the variance); the second variable (10.0%) separated Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and Fanconi anemia from each other. Overall, unlike in dyskeratosis congenita, telomere lengths in patients with non-dyskeratosis congenita inherited bone marrow failure syndromes were usually in the normal range, albeit shorter than in unaffected individuals. clinicaltrials.gov identifier: 00027274 C1 [Alter, Blanche P.; Giri, Neelam; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Dept Hlth & Human Serv,NIH, Rockville, MD 20850 USA. [Rosenberg, Philip S.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Dept Hlth & Human Serv,NIH, Rockville, MD USA. RP Alter, BP (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Dept Hlth & Human Serv,NIH, Rockville, MD 20850 USA. EM alterb@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural Research Program of the National Cancer Institute of the National Institutes of Health; Westat [HHSN261201100018C] FX This research was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health, and by contract HHSN261201100018C with Westat. NR 24 TC 10 Z9 10 U1 0 U2 8 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2015 VL 100 IS 1 BP 49 EP 54 DI 10.3324/haematol.2014.114389 PG 6 WC Hematology SC Hematology GA CD7NX UT WOS:000351278500022 PM 25304614 ER PT J AU Andritsos, LA Dunavin, N Lozanski, G Jones, JA Blachly, JS Lucas, DM Byrd, JC Kraut, E Grever, MR AF Andritsos, Leslie A. Dunavin, Neil Lozanski, Gerard Jones, Jeffrey A. Blachly, James S. Lucas, David M. Byrd, John C. Kraut, Eric Grever, Michael R. TI Reduced dose pentostatin for initial management of hairy cell leukemia patients who have active infection or risk of hemorrhage is safe and effective SO HAEMATOLOGICA LA English DT Letter DE hairy cell leukemia; pentostatin ID TERM-FOLLOW-UP; LONG-TERM; CLADRIBINE TREATMENT; TRIAL C1 [Andritsos, Leslie A.; Jones, Jeffrey A.; Blachly, James S.; Lucas, David M.; Byrd, John C.; Kraut, Eric; Grever, Michael R.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Dunavin, Neil] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. [Lozanski, Gerard] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. RP Andritsos, LA (reprint author), Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. EM leslie.andritsos@osumc.edu RI Lucas, David/E-3555-2011; Jones, Jeffrey/E-3321-2011; OI Blachly, James/0000-0002-4275-5562 NR 15 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2015 VL 100 IS 1 BP E18 EP E20 DI 10.3324/haematol.2014.113290 PG 3 WC Hematology SC Hematology GA CD7NX UT WOS:000351278500006 PM 25361945 ER PT J AU Kranick, SM Goncalves, PH Stetler-Stevenson, M Aleman, K Polizzotto, MN Little, RF Yarchoan, R Uldrick, TS AF Kranick, Sarah M. Goncalves, Priscila H. Stetler-Stevenson, Maryalice Aleman, Karen Polizzotto, Mark N. Little, Richard F. Yarchoan, Robert Uldrick, Thomas S. TI Paradoxical central nervous system immune reconstitution syndrome in acquired immunodeficiency syndrome-related primary central nervous system lymphoma SO HAEMATOLOGICA LA English DT Letter DE lymphoproliferative disorders; immunodeficiencies; infectious disorders; primary CNS lymphoma ID PRIMARY CNS LYMPHOMA; ANTIRETROVIRAL THERAPY; INFLAMMATORY SYNDROME; CEREBROSPINAL-FLUID; INFECTION; SURVIVAL; CELLS; AIDS C1 [Kranick, Sarah M.] NINDS, Sect Infect Nervous Syst, Bethesda, MD 20892 USA. [Goncalves, Priscila H.; Aleman, Karen; Polizzotto, Mark N.; Little, Richard F.; Yarchoan, Robert; Uldrick, Thomas S.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Uldrick, TS (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM uldrickts@mail.nih.gov FU Intramural NIH HHS NR 15 TC 1 Z9 1 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2015 VL 100 IS 1 BP E21 EP E24 DI 10.3324/haematol.2014.114736 PG 4 WC Hematology SC Hematology GA CD7NX UT WOS:000351278500007 PM 25304612 ER PT J AU Zein, WM Falsini, B Tsilou, ET Turriff, AE Schultz, JM Friedman, TB Brewer, CC Zalewski, CK King, KA Muskett, JA Rehman, AU Morell, RJ Griffith, AJ Sieving, PA AF Zein, Wadih M. Falsini, Benedetto Tsilou, Ekaterina T. Turriff, Amy E. Schultz, Julie M. Friedman, Thomas B. Brewer, Carmen C. Zalewski, Christopher K. King, Kelly A. Muskett, Julie A. Rehman, Atteeq U. Morell, Robert J. Griffith, Andrew J. Sieving, Paul A. TI Cone Responses in Usher Syndrome Types 1 and 2 by Microvolt Electroretinography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cone function; microvolt electroretinogram; Usher syndrome; Usher genes ID VISUAL-FIELD LOSS; SYNDROME TYPE-II; RETINITIS-PIGMENTOSA; DISEASE COURSE; SYNDROME GENES; MUTATIONS; USH2A; MYO7A; ERG AB PURPOSE. Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. METHODS. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. RESULTS. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P < 0.01) compared with controls. USH1 and USH2 had similar rates of progressive logarithmic ERG amplitude decline with disease duration (-0.012 log mu V/y). Of interest, ERG phase delays did not progress over time. Two USH1C subjects retained normal response timing despite reduced amplitudes. The CxC ERG method provided reliable responses in all subjects, whereas conventional ERG was undetectable in 7 of 42 subjects. CONCLUSIONS. Cycle-by-cycle ERG showed progressive loss of amplitude in both USH1 and USH2 subjects, comparable to that reported with psychophysical measures. Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. C1 [Zein, Wadih M.; Falsini, Benedetto; Tsilou, Ekaterina T.; Turriff, Amy E.; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Schultz, Julie M.; Friedman, Thomas B.; Rehman, Atteeq U.; Morell, Robert J.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Bethesda, MD USA. [Brewer, Carmen C.; Zalewski, Christopher K.; King, Kelly A.; Muskett, Julie A.; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA. RP Sieving, PA (reprint author), NIH, Bldg 31,Room 6A03,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov OI Falsini, Benedetto/0000-0002-1694-1062; Falsini , Benedetto/0000-0002-3569-4968; Morell, Robert/0000-0003-1537-7356 FU National Institutes of Health Intramural Research Programs of the National Eye Institute (Bethesda, MD, USA) [05-EI-0096]; National Institute on Deafness and Other Communication Disorders (Bethesda, MD, USA) [DC000060-12, DC000039-16] FX Supported by grants from the National Institutes of Health Intramural Research Programs of the National Eye Institute (Protocol 05-EI-0096; Bethesda, MD, USA) and National Institute on Deafness and Other Communication Disorders (DC000060-12 [AJG] and DC000039-16 [TBF]; Bethesda, MD, USA). NR 32 TC 0 Z9 0 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2015 VL 56 IS 1 BP 107 EP 114 DI 10.1167/iovs.14-15355 PG 8 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800012 ER PT J AU Petrou, PA Cunningham, D Shimel, K Harrington, M Hammel, K Cukras, CA Ferris, FL Chew, EY Wong, WT AF Petrou, Philip A. Cunningham, Denise Shimel, Katherine Harrington, Molly Hammel, Keri Cukras, Catherine A. Ferris, Frederick L. Chew, Emily Y. Wong, Wai T. TI Intravitreal Sirolimus for the Treatment of Geographic Atrophy: Results of a Phase I/II Clinical Trial SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE age-related macular degeneration; geographic atrophy; sirolimus; clinical trial ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; DIABETIC MACULAR EDEMA; FACTOR-H POLYMORPHISM; BEAVER DAM EYE; SUBCONJUNCTIVAL SIROLIMUS; RETINITIS-PIGMENTOSA; MOUSE MODEL; DEGENERATION; RAPAMYCIN AB PURPOSE. To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). METHODS. The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. RESULTS. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. CONCLUSIONS. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. C1 [Petrou, Philip A.; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. [Cunningham, Denise; Shimel, Katherine] NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Harrington, Molly; Hammel, Keri] EMMES Corp, Rockville, MD USA. [Cukras, Catherine A.; Ferris, Frederick L.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bldg 6,Room 215, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural Research Program of the National Eye Institute, National Institutes of Health; National Institutes of Health (NIH) Medical Research Scholars Program - NIH; Pfizer, Inc.; Doris Duke Charitable Foundation; Alexandria Real Estate Equities, Inc.; Howard Hughes Medical Institute FX Supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health. PAP is supported by the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer, Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. NR 43 TC 6 Z9 6 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2015 VL 56 IS 1 BP 330 EP 338 DI 10.1167/iovs.14-15877 PG 9 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800035 ER PT J AU Chen, P Tucker, W Hannes, S Liu, BY Si, H Gupta, A Lee, RWJ Sen, HN Nussenblatt, RB AF Chen, Ping Tucker, William Hannes, Susan Liu, Baoying Si, Han Gupta, Ankur Lee, Richard W. J. Sen, H. Nida Nussenblatt, Robert B. TI Levels of Blood CD1c(+) mDC1 and CD1c(hi) mDC1 Subpopulation Reflect Disease Activity in Noninfectious Uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CD1c(+) mDC1; CD1c(hi) mDC1 subpopulation; noninfectious uveitis; autoimmune disease ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PULSED DENDRITIC CELLS; PERIPHERAL-BLOOD; T-CELLS; PHENOTYPE; ARTHRITIS; NOMENCLATURE; SUBSETS; DISPLAY AB PURPOSE. Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis. METHODS. Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity. RESULTS. Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive. CONCLUSIONS. Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients. C1 [Chen, Ping; Tucker, William; Hannes, Susan; Liu, Baoying; Si, Han; Gupta, Ankur; Sen, H. Nida; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lee, Richard W. J.] Univ Bristol, Dept Clin Sci, Bristol, Avon, England. RP Nussenblatt, RB (reprint author), NEI, NIH, 9000 Rockville Pike,Bldg 10-10N109, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov FU Intramural Research Program of the National Eye Institute at the National Institutes of Health FX Supported by the Intramural Research Program of the National Eye Institute at the National Institutes of Health. The authors alone are responsible for the content and the writing of the paper. NR 22 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2015 VL 56 IS 1 BP 346 EP 351 DI 10.1167/iovs.14-15416 PG 6 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800037 ER PT J AU Lazar, CH Mutsuddi, M Kimchi, A Zelinger, L Mizrahi-Meissonnier, L Marks-Ohana, D Boleda, A Ratnapriya, R Sharon, D Swaroop, A Banin, E AF Lazar, Csilla H. Mutsuddi, Mousumi Kimchi, Adva Zelinger, Lina Mizrahi-Meissonnier, Liliana Marks-Ohana, Devorah Boleda, Alexis Ratnapriya, Rinki Sharon, Dror Swaroop, Anand Banin, Eyal TI Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE next generation sequencing; photoreceptor degeneration; inherited blindness ID AUTOSOMAL-DOMINANT CONE; RETINAL GUANYLATE-CYCLASE; EARLY MACULAR INVOLVEMENT; RETINITIS-PIGMENTOSA; PROGRESSIVE CONE; CLINICAL CHARACTERISTICS; CONGENITAL AMAUROSIS; MUTATION ANALYSIS; CHINESE FAMILY; DEGENERATION AB PURPOSE. The Israeli population has a unique genetic make-up, with a high prevalence of consanguineous marriages and autosomal recessive diseases. In rod-dominated phenotypes, disease-causing genes and mutations that differ from those identified in other populations often are incurred. We used whole exome sequencing (WES) to identify genetic defects in Israeli families with cone-dominated retinal phenotypes. METHODS. Clinical analysis included family history, detailed ocular examination, visual function testing, and retinal imaging. Whole exome sequencing, followed by segregation analysis, was performed in 6 cone-dominated retinopathy families in which prior mutation analysis did not reveal the causative gene. Based on the WES findings, we screened 106 additional families with cone-dominated phenotypes. RESULTS. The WES analysis revealed mutations in known retinopathy genes in five of the six families: two pathogenic mutations in the GUCY2D gene in three families, and one each in CDHR1 and C8orf37. Targeted screening of additional cone-dominated families led to identification of GUCY2D mutations in four other families, which included two highly probable novel disease-causing variants. CONCLUSIONS. Our study suggested that GUCY2D is a major cause of autosomal dominant cone and cone-rod dystrophies in Israel; this is similar to other Caucasian populations and is in contrast with retinitis pigmentosa (primary rod disease), where the genetic make-up of the Israeli population is distinct from other ethnic groups. We also conclude that WES permits more comprehensive and rapid analyses that can be followed by targeted screens of larger samples to delineate the genetic structure of retinal disease in unique population cohorts. C1 [Lazar, Csilla H.; Mutsuddi, Mousumi; Zelinger, Lina; Boleda, Alexis; Ratnapriya, Rinki; Swaroop, Anand; Banin, Eyal] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Lazar, Csilla H.] Univ Babes Bolyai, Mol Biol Ctr, Interdisciplinary Res Inst Bionano Sci, R-3400 Cluj Napoca, Romania. [Mutsuddi, Mousumi] Banaras Hindu Univ, Dept Mol & Human Genet, Varanasi 221005, Uttar Pradesh, India. [Kimchi, Adva; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Marks-Ohana, Devorah; Sharon, Dror; Banin, Eyal] Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, Israel. RP Swaroop, A (reprint author), NEI, NIH Bldg 6-338,6 Ctr Dr, Bethesda, MD 20892 USA. EM dror.sharon1@gmail.com; swaroopa@nei.nih.gov; banine@mail.huji.ac.il RI Sharon, Dror/P-4539-2015; OI Sharon, Dror/0000-0002-1789-5811; Swaroop, Anand/0000-0002-1975-1141 FU United States-Israel Binational Science Foundation [2011202]; Yedidut Research Grant; Intramural Research Program of the National Eye Institute, National Institutes of Health FX Supported by the United States-Israel Binational Science Foundation (Grant 2011202; DS, AS), the Yedidut Research Grant (EB), and the Intramural Research Program of the National Eye Institute, National Institutes of Health (AS). NR 53 TC 7 Z9 7 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2015 VL 56 IS 1 BP 420 EP 430 DI 10.1167/iovs.14-15647 PG 11 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800046 ER PT J AU Majdi, JA Qian, HH Li, YC Langsner, RJ Shea, KI Agrawal, A Hammer, DX Hanig, JP Cohen, ED AF Majdi, Joseph A. Qian, Haohua Li, Yichao Langsner, Robert J. Shea, Katherine I. Agrawal, Anant Hammer, Daniel X. Hanig, Joseph P. Cohen, Ethan D. TI The Use of Time-Lapse Optical Coherence Tomography to Image the Effects of Microapplied Toxins on the Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE microperfusion; optical coherence tomography; retinotoxins ID ALPHA-AMINOADIPIC ACID; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; SPREADING DEPRESSION; PIGMENT-EPITHELIUM; SCATTERING CHANGES; OCULAR TOXICITY; HYDROXYCHLOROQUINE RETINOPATHY; CHLOROQUINE RETINOPATHY; RABBIT RETINA AB PURPOSE. We developed a novel technique for accelerated drug screening and retinotoxin characterization using time-lapse optical coherence tomography (OCT) and a drug microapplication device. METHODS. Using an ex vivo rabbit eyecup preparation, we studied retinotoxin effects in real-time by microperfusing small retinal areas under a transparent fluoropolymer tube. Known retinotoxic agents were applied to the retina for 5-minute periods, while changes in retinal structure, thickness, and reflectance were monitored with OCT. The OCT images of two agents with dissimilar mechanisms, cyanide and kainic acid, were compared to their structural changes seen histologically. RESULTS. We found the actions of retinotoxic agents tested could be classified broadly into two distinct types: (1) agents that induce neuronal depolarization, such as kainic acid, causing increases in OCT reflectivity or thickness of the inner plexiform and nuclear layers, and decreased reflectivity of the outer retina; and (2) agents that disrupt mitochondrial function, such as cyanide, causing outer retinal structural changes as evidenced by a reduction in the OCT reflectivity of the photoreceptor outer segment and pigment epithelium layers. CONCLUSIONS. Retinotoxin-induced changes in retinal layer reflectivity and thickness under the microperfusion tube in OCT images closely matched the histological evidence of retinal injury. Time-lapse OCT imaging of the microperfused local retina has the potential to accelerate drug retinotoxicological screening and expand the use of OCT as an evaluation tool for preclinical animal testing. C1 [Majdi, Joseph A.; Langsner, Robert J.; Agrawal, Anant; Hammer, Daniel X.; Cohen, Ethan D.] US FDA, Div Biomed Phys, Off Sci & Engn Lab, Ctr Devices & Radiol Hlth,White Oak Fed Res Labs, Silver Spring, MD 20993 USA. [Qian, Haohua; Li, Yichao] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. [Shea, Katherine I.; Hanig, Joseph P.] US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, White Oak Fed Res Labs, Silver Spring, MD 20993 USA. RP Cohen, ED (reprint author), US FDA, Div Biomed Phys, Off Sci & Engn Lab, Ctr Devices & Radiol Hlth,White Oak Fed Res Labs, Room 1204,Bldg 62, Silver Spring, MD 20993 USA. EM ethan.cohen@fda.hhs.gov FU FDA Critical Path Initiative FX Supported by a grant from the FDA Critical Path Initiative. The content of this publication represents solely the authors' views and may not reflect any position of the United States Government or the Food and Drug Administration. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 73 TC 2 Z9 2 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2015 VL 56 IS 1 BP 587 EP 597 DI 10.1167/iovs.14-15594 PG 11 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800066 PM 25525175 ER PT J AU Zhang, C Kuo, CC Moghadam, SH Monte, L Rice, KC Rissman, RA AF Zhang, Cheng Kuo, Ching-Chang Moghadam, Setareh H. Monte, Louise Rice, Kenner C. Rissman, Robert A. TI Corticotropin-Releasing Factor Receptor-1 Antagonism Reduces Oxidative Damage in an Alzheimer's Disease Transgenic Mouse Model SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; corticotropin-releasing factor-1 receptor (CRFR1); glutathione; glutathione peroxide; glutathione reductase; oxidative stress; oxidized glutathione; R121919; S-glutathionylated protein ID MILD COGNITIVE IMPAIRMENT; GLUTATHIONE-PEROXIDASE ACTIVITY; TAU PHOSPHORYLATION; CAPILLARY-ELECTROPHORESIS; PARKINSONS-DISEASE; NITROSATIVE STRESS; COMPONENT ANALYSIS; HYDROGEN-PEROXIDE; BRAIN; PROTEIN AB Reports from Alzheimer's disease (AD) biomarker work have shown a strong link between oxidative stress and AD neuropathology. The nonenzymatic antioxidant, glutathione (GSH), plays a crucial role in defense against reactive oxygen species and maintenance of GSH redox homeostasis. In particular, our previous studies on GSH redox imbalance have implicated oxidative stress induced by excessive reactive oxygen species as a major mediator of AD-like events, with the presence of S-glutathionylated proteins (Pr-SSG) appearing prior to overt AD neuropathology. Furthermore, evidence suggests that oxidative stress may be associated with dysfunction of the hypothalamic-pituitary-adrenal axis, leading to activation of inflammatory pathways and increased production of corticotropin-releasing factor (CRF). Therefore, to investigate whether oxidative insults can be attenuated by reduction of central CRF signaling, we administered the type-1 CRF receptor (CRFR1) selective antagonist, R121919, to AD-transgenic mice beginning in the preclinical/prepathologic period (30-day-old) for 150 days, a timepoint where behavioral impairments and pathologic progression should be measureable. Our results indicate that R121919 treatment can significantly reduce Pr-SSG levels and increase glutathione peroxide activity, suggesting that interference of CRFR1 signaling may be useful as a preventative therapy for combating oxidative stress in AD. C1 [Zhang, Cheng; Moghadam, Setareh H.; Monte, Louise; Rissman, Robert A.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Kuo, Ching-Chang] Univ Oregon, NeuroInformat Ctr, Eugene, OR 97403 USA. [Rice, Kenner C.] Natl Inst Drug Abuse & Alcohol Abuse & Alcoholism, Chem Biol Res Branch, NIH, Bethesda, MD USA. RP Zhang, C (reprint author), UCSD, Sch Med, Dept Neurosci, 9500 Gilman Dr, La Jolla, CA 92037 USA. EM chz002@ucsd.edu; rrissman@ucsd.edu FU National Institutes of Health [AG032755, AG047484, DK026741, AG010483]; Alzheimer's Art Quilt Initiative; Alzheimer's Association; Foundation for Medical Research; NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA); National Institute of Alcohol Abuse and Alcoholism (NIAAA) FX This study was supported by National Institutes of Health Grants AG032755, AG047484, DK026741, and AG010483; the Alzheimer's Art Quilt Initiative; the Alzheimer's Association; the Foundation for Medical Research. The work of the Drug Design and Synthesis Section, CBRB, NIDA, and NIAAA was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism (NIAAA). NR 54 TC 0 Z9 0 U1 3 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 45 IS 2 BP 639 EP 650 DI 10.3233/JAD-141722 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CE1PL UT WOS:000351583900028 PM 25649650 ER PT J AU Su, TP AF Su, Tsung-Ping TI A Perspective on sigma-1 receptor research: Past and future Preface SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Editorial Material C1 NIDA, Cellular Pathobiol Sect, Intramural Res Program, Integrat Neurosci Branch,NIH,Dept Hlth & Human Se, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Sect, Intramural Res Program, Integrat Neurosci Branch,NIH,Dept Hlth & Human Se, 333 Cassell Dr, Baltimore, MD 21224 USA. NR 0 TC 4 Z9 4 U1 0 U2 3 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD JAN PY 2015 VL 127 IS 1 SI SI BP 1 EP 1 DI 10.1016/j.jphs.2014.11.001 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE2MT UT WOS:000351650400001 PM 25704010 ER PT J AU Ajiro, M Zheng, ZM AF Ajiro, Masahiko Zheng, Zhi-Ming TI E6 E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78 SO MBIO LA English DT Article ID CERVICAL-CANCER CELLS; HIGH-RISK; INTRAEPITHELIAL NEOPLASIA; NUCLEAR-LOCALIZATION; GENE-EXPRESSION; MESSENGER-RNA; TYPE-16 E6; PHASE-I; HPV; P53 AB Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role of E6<^>E7, a novel isoform containing the 41 N-terminal amino acid (aa) residues of E6 and the 38 C-terminal aa residues of E7, in the regulation of E6 and E7 stability. Through mass spectrometric analysis, we identified that HSP90 and GRP78, which are frequently upregulated in cervical cancer tissues, are two E6<^>E7-interacting proteins responsible for the stability and function of E6<^>E7, E6, and E7. Although GRP78 and HSP90 do not bind each other, GRP78, but not HSP90, interacts with E6 and E7. E6<^>E7 protein, in addition to self-binding, interacts with E6 and E7 in the presence of GRP78 and HSP90, leading to the stabilization of E6 and E7 by prolonging the half-life of each protein. Knocking down E6<^>E7 expression in HPV16-positive CaSki cells by a splice junction-specific small interfering RNA (siRNA) destabilizes E6 and E7 and prevents cell growth. The same is true for the cells with a GRP78 knockdown or in the presence of an HSP90 inhibitor. Moreover, mapping and alignment analyses for splicing elements in 36 alpha-HPVs (alpha-HPVs) suggest the possible expression of E6<^>E7 mostly by other oncogenic or possibly oncogenic alpha-HPVs (HPV18, -30, -31, -39, -42, -45, -56, -59, -70, and -73). HPV18 E6<^>E7 is detectable in HPV18-positive HeLa cells and HPV18-infected raft tissues. All together, our data indicate that viral E6<^>E7 and cellular GRP78 or HSP90 might be novel targets for cervical cancer therapy. IMPORTANCE HPV16 is the most prevalent HPV genotype, being responsible for 60% of invasive cervical cancer cases worldwide. What makes HPV16 so potent in the development of cervical cancer remains a mystery. We discovered in this study that, besides producing two well-known oncoproteins, E6 and E7, seen in other high-risk HPVs, HPV16 produces E6<^>E7, a novel splice isoform of E6 and E7. E6<^>E7, in addition to self-interacting, binds cellular chaperone proteins, HSP90 and GRP78, and viral E6 and E7 to increase the steady-state levels and half-lives of viral oncoproteins, leading to cell proliferation. The splicing cis elements in the regulation of HPV16 E6<^>E7 production are highly conserved in 11 oncogenic or possibly oncogenic HPVs, and we confirmed the production of HPV18 E6<^>E7 in HPV18-infected cells. This study provides new insight into the mechanism of splicing, the interplay between different products of the polycistronic viral message, and the role of the host chaperones as they function. C1 [Ajiro, Masahiko; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. EM zhengt@exchange.nih.gov NR 79 TC 9 Z9 10 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2015 VL 6 IS 1 AR e02068-14 DI 10.1128/mBio.02068-14 PG 15 WC Microbiology SC Microbiology GA CC8PZ UT WOS:000350631900009 PM 25691589 ER PT J AU Blazejewski, T Nursimulu, N Pszenny, V Dangoudoubiyam, S Namasivayam, S Chiasson, MA Chessman, K Tonkin, M Swapna, LS Hung, SS Bridgers, J Ricklefs, SM Boulanger, MJ Dubey, JP Porcella, SF Kissinger, JC Howe, DK Grigg, ME Parkinson, J AF Blazejewski, Tomasz Nursimulu, Nirvana Pszenny, Viviana Dangoudoubiyam, Sriveny Namasivayam, Sivaranjani Chiasson, Melissa A. Chessman, Kyle Tonkin, Michelle Swapna, Lakshmipuram S. Hung, Stacy S. Bridgers, Joshua Ricklefs, Stacy M. Boulanger, Martin J. Dubey, Jitender P. Porcella, Stephen F. Kissinger, Jessica C. Howe, Daniel K. Grigg, Michael E. Parkinson, John TI Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle SO MBIO LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; OPOSSUMS DIDELPHIS-VIRGINIANA; ENHYDRA-LUTRIS-NEREIS; HOST-CELL INVASION; TOXOPLASMA-GONDII; APICOMPLEXAN PARASITES; SURFACE-ANTIGENS; IMMUNE-RESPONSE; INFECTION; VIRULENCE AB Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts. IMPORTANCE Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals-including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with acute sarcocystosis. Among Sarcocystis species, S. neurona has a wide host range and causes fatal encephalitis in horses, marine mammals, and several other mammals. To provide insights into the transition from a purely enteric parasite (e.g., Eimeria) to one that forms tissue cysts (Toxoplasma), we present the first genome sequence of S. neurona. Comparisons with other coccidian genomes highlight the molecular innovations that drive its distinct life cycle strategies. C1 [Blazejewski, Tomasz; Nursimulu, Nirvana; Chessman, Kyle; Swapna, Lakshmipuram S.; Hung, Stacy S.; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada. [Nursimulu, Nirvana; Chessman, Kyle] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. [Pszenny, Viviana; Chiasson, Melissa A.; Grigg, Michael E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Dangoudoubiyam, Sriveny; Howe, Daniel K.] Univ Kentucky, Gluck Equine Res Ctr, Dept Vet Sci, Lexington, KY USA. [Namasivayam, Sivaranjani; Bridgers, Joshua; Kissinger, Jessica C.] Univ Georgia, Dept Genet, Athens, GA 30602 USA. [Tonkin, Michelle; Boulanger, Martin J.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Hung, Stacy S.; Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Ricklefs, Stacy M.; Dubey, Jitender P.] ARS, USDA, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, Beltsville, MD USA. [Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs, Hamilton, MT USA. [Kissinger, Jessica C.] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA. [Kissinger, Jessica C.] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA. [Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON, Canada. RP Parkinson, J (reprint author), Hosp Sick Children, Program Mol Struct & Funct, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM griggm@niaid.nih.gov; john.parkinson@utoronto.ca FU Canadian Institute for Health Research [CIHR-MOP 84556]; NIH; NIAID; Natural Sciences and Engineering Research Council of Canada (NSERC); USDA NIFA [2009-65109-05918]; Amerman Family Equine Research Fund FX This study was financially supported by the Canadian Institute for Health Research (CIHR-MOP 84556 to J.P. and M.E.G.) and the Intramural Research Program of the NIH and NIAID (M.E.G.). M.J.B. was supported by a discovery grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). M.E.G. is a scholar of the Canadian Institute for Advanced Research (CIFAR) Integrated Microbial Biodiversity Program. D.K.H. and J.C.K. were supported by a grant from the USDA NIFA (2009-65109-05918). D.K.H. was additionally supported by the Amerman Family Equine Research Fund. NR 51 TC 3 Z9 3 U1 5 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2015 VL 6 IS 1 AR e02445-14 DI 10.1128/mBio.02445-14 PG 16 WC Microbiology SC Microbiology GA CC8PZ UT WOS:000350631900012 ER PT J AU Kugelman, JR Sanchez-Lockhart, M Andersen, KG Gire, S Park, DJ Sealfon, R Lin, AE Wohl, S Sabeti, PC Kuhn, JH Palacios, GF AF Kugelman, Jeffrey R. Sanchez-Lockhart, Mariano Andersen, Kristian G. Gire, Stephen Park, Daniel J. Sealfon, Rachel Lin, Aaron E. Wohl, Shirlee Sabeti, Pardis C. Kuhn, Jens H. Palacios, Gustavo F. TI Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics SO MBIO LA English DT Article ID NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; MONOCLONAL-ANTIBODIES; MORPHOLINO OLIGOMERS; RNA INTERFERENCE; ZAIRE-EBOLAVIRUS; INFECTION; VARIANTS; DISEASE; NOMENCLATURE AB Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain. C1 [Kugelman, Jeffrey R.; Sanchez-Lockhart, Mariano; Palacios, Gustavo F.] US Army Med Res Inst Infect Dis, Ctr Genome Sci Div, Frederick, MD 21702 USA. [Andersen, Kristian G.; Gire, Stephen; Park, Daniel J.; Lin, Aaron E.; Wohl, Shirlee; Sabeti, Pardis C.] Harvard Univ, Ctr Syst Biol, Cambridge, MA 02138 USA. [Sealfon, Rachel] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. RP Palacios, GF (reprint author), US Army Med Res Inst Infect Dis, Ctr Genome Sci Div, Frederick, MD 21702 USA. EM gustavo.f.palacios.ctr@us.army.mil RI Palacios, Gustavo/I-7773-2015; OI Palacios, Gustavo/0000-0001-5062-1938; Kuhn, Jens H./0000-0002-7800-6045 FU Defense Threat Reduction Agency; NIAID [HHSN272200700016I]; National Science Foundation Graduate research fellowship [DGE 1144152] FX This work was supported by Defense Threat Reduction Agency. J.H.K. performed this work as an employee of Tunnell Government Services, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under contract no. HHSN272200700016I. This material is based upon work supported by the National Science Foundation Graduate research fellowship under grant no. DGE 1144152. NR 24 TC 22 Z9 23 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2015 VL 6 IS 1 AR e02227-14 DI 10.1128/mBio.02227-14 PG 4 WC Microbiology SC Microbiology GA CC8PZ UT WOS:000350631900039 ER PT J AU Morelli, M Dennis, AF Patton, JT AF Morelli, Marco Dennis, Allison F. Patton, John T. TI Putative E3 Ubiquitin Ligase of Human Rotavirus Inhibits NF-kappa B Activation by Using Molecular Mimicry To Target beta-TrCP SO MBIO LA English DT Article ID INTERFERON-REGULATORY-FACTORS; ANTIVIRAL INNATE IMMUNITY; I INTERFERON; VPU PROTEIN; DEGRADATION; NSP1; EXPRESSION; RECEPTOR; VIRUSES; ALPHA AB NF-kappa B plays a critical role in the induction and maintenance of innate and adaptive immune transcriptional programs. An associated inhibitor of kappa B protein (I kappa B) regulates NF-kappa B activation and contains a degron motif (DSG Phi xS) that undergoes phosphorylation following pathogen recognition or other proinflammatory signals. The E3 ubiquitin ligase SCF beta-TrCP recognizes this phosphodegron through its beta-transducin repeat-containing protein (beta-TrCP) subunit and induces I kappa B degradation, allowing NF-kappa B to translocate to the nucleus and modulate gene expression. Rotavirus (RV), a major cause of pediatric gastroenteritis, can block NF-kappa B activation through the action of its nonstructural protein NSP1, a putative E3 ubiquitin ligase that mediates the degradation of beta-TrCP or other immunomodulatory proteins in a virus strain-specific manner. Here, we show that NSP1 targets beta-TrCP by mimicking the I kappa B phosphodegron. The NSP1 proteins of most human and porcine RV strains conserve a C-terminal phosphodegron-like (PDL) motif, DSG Phi S. Deletion of this motif or mutation of its serine residues disrupts NSP1-mediated degradation of beta-TrCP and inhibition of NF-kappa B activation. Additionally, a point mutation within the phosphodegron-binding pocket protects beta-TrCP from NSP1-mediated turnover. Fusion of the PDL motif to an NSP1 protein known to target other immunomodulatory proteins generates a chimeric NSP1 protein that can induce beta-TrCP degradation and block NF-kappa B activation. Other viral proteins (Epstein-Barr virus LMP1, HIV-1 Vpu, and vaccinia virus A49) also contain a PDL motif and interact with beta-TrCP to inhibit NF-kappa B activation. Taken together, these data suggest that targeting beta-TrCP by molecular mimicry may be a common strategy used by human viruses to evade the host immune response. IMPORTANCE The transcription factor NF-kappa B, a central regulator of the host response to infection, is a frequent target of viral antagonism. Pathogen detection activates NF-kappa B by inducing the phosphorylation of an associated inhibitor protein (I kappa B), which targets I kappa B for degradation by the E3 ubiquitin ligase beta-TrCP. Rotavirus, a significant cause of childhood gastroenteritis, antagonizes NF-kappa B through the activity of its NSP1 protein, a putative E3 ubiquitin ligase that mediates beta-TrCP turnover. Here, we show that NSP1 functions by mimicking the I kappa B phosphodegron recognized by beta-TrCP. Nearly all human rotavirus strains conserve this motif at the NSP1 C terminus, and its removal disrupts NSP1 antagonist activity. This sequence conserves the biochemical properties of the I kappa B phosphodegron and can rescue antagonist activity when fused to an NSP1 protein otherwise inactive against beta-TrCP. Other viral proteins also mimic I kappa B to disrupt NF-kappa B activation, indicating that this is an important immune evasion strategy. C1 [Morelli, Marco; Dennis, Allison F.; Patton, John T.] NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. NR 63 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2015 VL 6 IS 1 AR e02490-14 DI 10.1128/mBio.02490-14 PG 13 WC Microbiology SC Microbiology GA CC8PZ UT WOS:000350631900046 ER PT J AU Orru, CD Groveman, BR Hughson, AG Zanusso, G Coulthart, MB Caughey, B AF Orru, Christina D. Groveman, Bradley R. Hughson, Andrew G. Zanusso, Gianluigi Coulthart, Michael B. Caughey, Byron TI Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid SO MBIO LA English DT Article ID QUAKING-INDUCED CONVERSION; PRION PROTEIN; SCRAPIE PRION; ASSAY AB Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. IMPORTANCE A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer's, Parkinson's, and tauopathies. C1 [Orru, Christina D.; Groveman, Bradley R.; Hughson, Andrew G.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. [Coulthart, Michael B.] Publ Hlth Agcy Canada, Canadian CJD Surveillance Syst, Ottawa, ON, Canada. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bcaughey@nih.gov OI ZANUSSO, Gianluigi/0000-0001-5199-6264 FU Intramural Research Program of the NIAID; Alliance Biosecure Foundation FX This work was supported by the Intramural Research Program of the NIAID and in part by the Alliance Biosecure Foundation. NR 25 TC 23 Z9 23 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2015 VL 6 IS 1 AR e02451-14 DI 10.1128/mBio.02451-14 PG 7 WC Microbiology SC Microbiology GA CC8PZ UT WOS:000350631900047 ER PT J AU Endisha, H Merrill-Schools, J Zhao, M Bristol, M Wang, X Kubben, N Elmore, LW AF Endisha, Helal Merrill-Schools, Jacqueline Zhao, Min Bristol, Molly Wang, Xu Kubben, Nard Elmore, Lynne W. TI Restoring SIRT6 Expression in Hutchinson-Gilford Progeria Syndrome Cells Impedes Premature Senescence and Formation of Dysmorphic Nuclei SO PATHOBIOLOGY LA English DT Article DE Hutchinson-Gilford progeria syndrome; SIRT6; Senescence; Anti-aging; Progerin ID DNA-DAMAGE RESPONSES; GENOMIC INSTABILITY; TELOMERE DYSFUNCTION; REPLICATIVE SENESCENCE; DEFECTIVE MATURATION; CELLULAR SENESCENCE; LAMIN; REPAIR; METABOLISM; CHROMATIN AB Objectives: Mice overexpressing SIRT6 live longer than wildtype mice while SIRT6 knockout mice exhibit similar degenerative phenotypes as individuals with Hutchinson-Gilford progeria syndrome (HGPS). Thus, we sought to test whether levels of SIRT6 are reduced in cells from individuals with HGPS and whether restored SIRT6 expression may impede premature aging phenotypes. Methods: Levels of endogenous SIRT6 and progerin in HGPS and normal fibroblasts were assessed by Western blotting and immunofluorescence. A tetracycline-inducible system was utilized to test whether progerin causes a rapid reduction in SIRT6 protein. SIRT6 was overexpressed in HGPS cells via lentiviral infection with biological endpoints including senescence-associated beta-galactosidase (SA-beta-gal) positivity, frequency of nuclear atypia, the number of 53BP1-positive DNA damage foci and growth rates. Results: Typical HGPS fibroblasts express lower levels of SIRT6 than fibroblasts from normal and atypical HGPS donors. Experimental induction of progerin did not cause a detectable reduction of SIRT6 protein. However, overexpression of SIRT6 in HGPS cells was associated with a reduced frequency of SA-beta-gal positivity, fewer misshapen nuclei, fewer DNA damage foci, and increased growth rates. Conclusions: Typical HGPS fibroblasts exhibit reduced levels of SIRT6 protein via a mechanism that remains to be elucidated. Our findings suggest that restoring SIRT6 expression in HGPS cells may partially impede senescence and the formation of dysmorphic nuclei. (C) 2015 S. Karger AG, Basel C1 [Endisha, Helal; Merrill-Schools, Jacqueline; Zhao, Min; Bristol, Molly; Wang, Xu; Elmore, Lynne W.] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA. [Merrill-Schools, Jacqueline; Elmore, Lynne W.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Kubben, Nard] NCI, NIH, Bethesda, MD 20892 USA. RP Elmore, LW (reprint author), Virginia Commonwealth Univ, Dept Pathol, 1101 East Marshall St, Richmond, VA 23298 USA. EM lelmore@mcvh-vcu.edu FU VCU Massey Cancer Center National Cancer Institute Training Grant in Cancer Biology [T32]; VCU Department of Pathology; NIH-NINDS Center Core Grant [5P3ON-SO47463-02]; NIH-NCI Cancer Center Support Grant [P30 CA016059]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX The author(s) acknowledge receipt of the following financial support for the research, authorship, and/or publication of this article: VCU Massey Cancer Center National Cancer Institute Training Grant (T32) in Cancer Biology (J.M.-S.) and VCU Department of Pathology (L.E.). The microscopy was performed at the Virginia Commonwealth University Department of Anatomy and Neurobiology Microscopy Facility, supported in part with funding from NIH-NINDS Center Core Grant (5P3ON-SO47463-02). Viral services and products in support of this investigation were generated by the VCU Massey Cancer Center Biological Macromolecule Shared Resource, supported in part with funding from NIH-NCI Cancer Center Support Grant (P30 CA016059) and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We are grateful to Dr. Colleen Jackson-Cook for use of the Bioview Duet Scanning Station for obtaining images for the determination of contour ratios. NR 45 TC 5 Z9 5 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 EI 1423-0291 J9 PATHOBIOLOGY JI Pathobiology PY 2015 VL 82 IS 1 BP 9 EP 20 DI 10.1159/000368856 PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CE0WD UT WOS:000351529200002 ER PT J AU Sato, K Nakajima, T Choyke, PL Kobayashi, H AF Sato, Kazuhide Nakajima, Takahito Choyke, Peter L. Kobayashi, Hisataka TI Selective cell elimination in vitro and in vivo from tissues and tumors using antibodies conjugated with a near infrared phthalocyanine SO RSC ADVANCES LA English DT Article ID PLURIPOTENT STEM-CELLS; CLINICAL-APPLICATION; CANCER-IMMUNOTHERAPY; NONHUMAN PRIMATE; PHOTOIMMUNOTHERAPY; THERAPY; MOLECULES; RECEPTOR; SAFETY; AGE AB Cell cultures and tissues often contain cellular subpopulations that potentially interfere with or contaminate other cells of interest. However, it is difficult to eliminate unwanted cells without damaging the very cell population one is seeking to protect, especially established tissue. Here, we report a method of eliminating a specific subpopulation of cells from a mixed 2D or 3D cell culture in vitro and a mixed-population in vivo tumor model by using antibody-photosensitizer conjugates (APC) with a near infrared (NIR) phthalocyanine-derivative (IRdye700DX, IR700) combined with NIR light exposure with minimal damage to non-targeted cells. Thus, APC combined with NIR light exposure holds promise as a method of removing specific cells from mixed cell cultures and tumors. C1 [Sato, Kazuhide; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. K.S. is supported with JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. NR 37 TC 6 Z9 6 U1 1 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2015 VL 5 IS 32 BP 25105 EP 25114 DI 10.1039/c4ra13835j PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA CD8OE UT WOS:000351354000034 PM 25866624 ER PT J AU Ito, S Barrett, AJ Dutra, A Pak, E Miner, S Keyvanfar, K Hensel, NF Rezvani, K Muranski, P Liu, P Melenhorst, JJ Larochelle, A AF Ito, Sawa Barrett, A. John Dutra, Amalia Pak, Evgenia Miner, Samantha Keyvanfar, Keyvan Hensel, Nancy F. Rezvani, Katayoun Muranski, Pawel Liu, Paul Melenhorst, J. Joseph Larochelle, Andre TI Long term maintenance of myeloid leukemic stem cells cultured with unrelated human mesenchymal stromal cells SO STEM CELL RESEARCH LA English DT Article ID COCULTURE; MICE AB Mesenchymal stromal cells (MSCs) support the growth and differentiation of normal hematopoietic stem cells (HSCs). Here we studied the ability of MSCs to support the growth and survival of leukemic stem cells (LSCs) in vitro. Primary leukemic blasts isolated from the peripheral blood of 8 patients with acute myeloid leukemia (AML) were co-cultured with equal numbers of irradiated MSCs derived from unrelated donor bone marrow, with or without cytokines for up to 6 weeks. Four samples showed CD34(+) CD38(-) predominance, and four were predominantly CD34(+) CD38(+). CD34(+) CD38(-) predominant leukemia cells maintained the CD34(+) CD38(-) phenotype and were viable for 6 weeks when co-cultured with MSCs compared to co-cultures with cytokines or medium only, which showed rapid differentiation and loss of the LSC phenotype. In contrast, CD34(+) CD38(+) predominant leukemic cells maintained the CD34(+) CD38(+) phenotype when co-cultured with MSCs alone, but no culture conditions supported survival beyond 4 weeks. Cell cycle analysis showed that MSCs maintained a higher proportion of CD34(+) blasts in G0 than leukemic cells cultured with cytokines. AML blasts maintained in culture with MSCs for up to 6 weeks engrafted NSG mice with the same efficiency as their non-cultured counterparts, and the original karyotype persisted after co-culture. Chemosensitivity and transwell assays suggest that MSCs provide pro-survival benefits to leukemic blasts through cell-cell contact. We conclude that MSCs support long-term maintenance of LSCs in vitro. This simple and inexpensive approach will facilitate basic investigation of LSCs and enable screening of novel therapeutic agents targeting LSCs. Published by Elsevier B.V. C1 [Ito, Sawa; Barrett, A. John; Miner, Samantha; Keyvanfar, Keyvan; Hensel, Nancy F.; Muranski, Pawel; Melenhorst, J. Joseph; Larochelle, Andre] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Dutra, Amalia; Pak, Evgenia] NHGRI, Cytogenet & Microscopy Core, NIH, Bethesda, MD 20892 USA. [Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Liu, Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. RP Ito, S (reprint author), 10 Ctr Dr,Bldg 10 CRC 3E 5288, Bethesda, MD 20892 USA. EM itos2@mail.nih.gov FU Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute, NIH FX This research was supported by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute, NIH. NR 17 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD JAN PY 2015 VL 14 IS 1 BP 95 EP 104 DI 10.1016/j.scr.2014.11.007 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CD4VX UT WOS:000351084600009 PM 25535865 ER PT S AU Mitchell, SJ Scheibye-Knudsen, M Longo, DL de Cabo, R AF Mitchell, Sarah J. Scheibye-Knudsen, Morten Longo, Dan L. de Cabo, Rafael BE Lewin, HA Roberts, RM TI Animal Models of Aging Research: Implications for Human Aging and Age-Related Diseases SO ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 3 SE Annual Review of Animal Biosciences LA English DT Article; Book Chapter DE aging; animal models; rodents; nonhuman primates ID NAKED MOLE-RAT; GILFORD-PROGERIA-SYNDROME; EXTENDS LIFE-SPAN; GENETICALLY HETEROGENEOUS MICE; INSULIN SIGNALING PATHWAY; LEUKOCYTE TELOMERE LENGTH; PIGMENTOSUM GROUP-A; ULTIMATE BODY-SIZE; AMES DWARF MICE; CALORIC RESTRICTION AB Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research. C1 [Mitchell, Sarah J.; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Scheibye-Knudsen, Morten] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Lab Genet, NIH, Baltimore, MD 21224 USA. RP Mitchell, SJ (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. EM sarah.mitchell@nih.gov; scheibyem@mail.nih.gov; longod@grc.nia.nih.gov; decabora@grc.nia.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Scheibye-Knudsen, Morten/0000-0002-6637-1280; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 158 TC 9 Z9 9 U1 4 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2165-8102 BN 978-0-8243-0003-6 J9 ANNU REV ANIM BIOSCI PY 2015 VL 3 BP 283 EP 303 DI 10.1146/annurev-animal-022114-110829 PG 21 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology SC Agriculture; Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology GA BC2JB UT WOS:000350991900012 PM 25689319 ER PT S AU Schnermann, J AF Schnermann, Jurgen BE Julius, D TI Concurrent Activation of Multiple Vasoactive Signaling Pathways in Vasoconstriction Caused by Tubuloglomerular Feedback: A Quantitative Assessment SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 77 SE Annual Review of Physiology LA English DT Review; Book Chapter DE afferent arteriole; vasomotor tone; glomerular filtration rate; glomerular capillary pressure; meta-analysis ID NITRIC-OXIDE SYNTHASE; GLOMERULAR-FILTRATION-RATE; MACULA DENSA CELLS; CONVERTING-ENZYME-INHIBITION; THICK ASCENDING LIMB; SPONTANEOUSLY HYPERTENSIVE-RATS; RECEPTOR-DEFICIENT MICE; ACUTE RENAL DENERVATION; ANGIOTENSIN-II; CONNECTING TUBULE AB Tubuloglomerular feedback (TGF) describes the negative relationship between (a) NaCl concentration at the macula densa and (b) glomerular filtration rate or glomerular capillary pressure. TGF-induced vasoconstriction of the afferent arteriole results from the enhanced effect of several vasoconstrictors with an effect size sequence of adenosine = 20-HETE > angiotensin II > thromboxane = superoxide > renal nerves > ATP. TGF-mediated vasoconstriction is limited by the simultaneous release of several vasodilators with an effect size sequence of nitric oxide > carbon monoxide = kinins > adenosine. The sum of the constrictor effects exceeds that of the dilator effects by the magnitude of the TGF response. The validity of the additive model used in this analysis can be tested by determining the effect of combined inhibition of some or all agents contributing to TGF. Multiple independent contributors to TGF are consistent with the variability of TGF and of the factors contributing to TGF resetting. C1 NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov FU Intramural NIH HHS NR 144 TC 5 Z9 5 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0377-8 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2015 VL 77 BP 301 EP 322 DI 10.1146/annurev-physiol-021014-071829 PG 22 WC Physiology SC Physiology GA BC2JD UT WOS:000350992800015 PM 25668021 ER PT J AU Thorne, JT Segal, TR Chang, S Jorge, S Segars, JH Leppert, PC AF Thorne, Jeffrey T. Segal, Thalia R. Chang, Sydney Jorge, Soledad Segars, James H. Leppert, Phyllis C. TI Dynamic Reciprocity Between Cells and Their Microenvironment in Reproduction SO BIOLOGY OF REPRODUCTION LA English DT Review DE breast; dynamic reciprocity (DR); extracellular matrix (ECM); fibroids; folliculogenesis; mechanotransduction (MT); ovary ovulation; pathogenesis; uterine leiomyoma ID MAMMARY EPITHELIAL-CELLS; PLASMINOGEN-ACTIVATOR EXPRESSION; PERIODONTAL-LIGAMENT FIBROBLASTS; GLAND BRANCHING MORPHOGENESIS; ESTROGEN-RECEPTOR-ALPHA; HUMAN BREAST CELLS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; 3-DIMENSIONAL CULTURE; TISSUE ARCHITECTURE AB Dynamic reciprocity (DR) refers to the ongoing, bidirectional interaction between cells and their microenvironment, specifically the extracellular matrix (ECM). The continuous remodeling of the ECM exerts mechanical force on cells and modifies biochemical mediators near the cell membrane, thereby initiating cell-signaling cascades that produce changes in gene expression and cell behavior. Cellular changes, in turn, affect the composition and organization of ECM components. These continuous interactions are the fundamental principle behind DR, and its critical role throughout development and adult tissue homeostasis has been extensively investigated. While DR in the mammary gland has been well described, we provide direct evidence that similar dynamic interactions occur in other areas of reproductive biology as well. In order to establish the importance of DR in the adaptive functioning of the female reproductive tract, we present our most current understanding of DR in reproductive tissues, exploring the mammary gland, ovary, and uterus. In addition to explaining normal physiological function, investigating DR may shed new light into pathologic processes that occur in these tissues and provide an exciting opportunity for novel therapeutic intervention. C1 [Thorne, Jeffrey T.] Univ Connecticut, Sch Med, Dept Obstet & Gynecol, Farmington, CT USA. [Segal, Thalia R.] Norht Shore Long Isl Jewish Hosp, Dept Obstet & Gynecol, Manhasset, NY USA. [Chang, Sydney; Jorge, Soledad; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Reprod Endocrinol & Infertil, NIH, Bethesda, MD 20892 USA. [Chang, Sydney; Leppert, Phyllis C.] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA. [Jorge, Soledad] Yale Univ, Sch Med, New Haven, CT USA. RP Leppert, PC (reprint author), Duke Univ, Sch Med, 242 Sands Bldg, Durham, NC 27710 USA. EM phyllis.leppert@duke.edu FU CRTP training NIH program; [HD-008737-11] FX Supported by CRTP training NIH program (to S.C. and S.J.) and partial HD-008737-11 (to J.H.S.). NR 154 TC 7 Z9 8 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD JAN 1 PY 2015 VL 92 IS 1 AR 25 DI 10.1095/biolreprod.114.121368 PG 10 WC Reproductive Biology SC Reproductive Biology GA CD1AO UT WOS:000350806200010 PM 25411389 ER PT S AU Verma, M AF Verma, Mukesh BE Verma, M TI Cancer Epigenetics Risk Assessment, Diagnosis, Treatment, and Prognosis Preface SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Verma, Mukesh] NIH, Rockville, MD 20892 USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Verma, M (reprint author), NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP V EP VI D2 10.1007/978-1-4939-1804-1 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200001 PM 25568925 ER PT S AU Satterlee, JS Beckel-Mitchener, A McAllister, K Procaccini, DC Rutter, JL Tyson, FL Chadwick, LH AF Satterlee, John S. Beckel-Mitchener, Andrea McAllister, Kim Procaccini, Dena C. Rutter, Joni L. Tyson, Frederick L. Chadwick, Lisa Helbling BE Verma, M TI Community Resources and Technologies Developed Through the NIH Roadmap Epigenomics Program SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bisulfite; Cell-type; Chemo-epigenetic; ChIP-seq; Chromatin; Immunoprecipitation; CRISPR; Crotonylation; Deacetylase; Hi-C; Ectoderm; ENCODE; Endoderm; Epigenetic; Epigenome; Genome-wide; HDAC; Histone; hmC; IHEC; mC; MeDIP-Seq; Methylation; MethylC-seq; Methylome; MRE-Seq; mRNA; Nucleosomes; Nucleus; Opto-epigenetic; Pluripotent; RNA-seq; Roadmap; RRBS; Transcription ID EMBRYONIC STEM-CELLS; EPIGENETIC REGULATION; POSTTRANSLATIONAL MODIFICATION; SUPER-ENHANCERS; DNA METHYLATION; GENE-EXPRESSION; COMMON DISEASE; CHIP-SEQ; GENOME; IDENTIFICATION AB This chapter describes resources and technologies generated by the NIH Roadmap Epigenomics Program that may be useful to epigenomics researchers investigating a variety of diseases including cancer. Highlights include reference epigenome maps for a wide variety of human cells and tissues, the development of new technologies for epigenetic assays and imaging, the identification of novel epigenetic modifications, and an improved understanding of the role of epigenetic processes in a diversity of human diseases. We also discuss future needs in this area including exploration of epigenomic variation between individuals, single-cell epigenomics, environmental epigenomics, exploration of the use of surrogate tissues, and improved technologies for epigenome manipulation. C1 [Satterlee, John S.; Procaccini, Dena C.; Rutter, Joni L.] NIDA, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. [Beckel-Mitchener, Andrea] NIMH, NIH, Bethesda, MD 20892 USA. [McAllister, Kim; Tyson, Frederick L.; Chadwick, Lisa Helbling] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Satterlee, JS (reprint author), NIDA, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. NR 61 TC 3 Z9 3 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 27 EP 49 DI 10.1007/978-1-4939-1804-1_2 D2 10.1007/978-1-4939-1804-1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200003 PM 25421653 ER PT S AU Banaudha, KK Verma, M AF Banaudha, Krishna K. Verma, Mukesh BE Verma, M TI Epigenetic Biomarkers in Liver Cancer SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biogenesis; Biomarkers; Epigenetics; Epidemiology; Hepatitis; Liver cancer; miRNA; Treatment ID HUMAN HEPATOCELLULAR-CARCINOMA; DNA METHYLATION; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; RISK-ASSESSMENT; MESSENGER-RNA; CIRRHOSIS; HCC; MARKERS; EPIDEMIOLOGY AB Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter. C1 [Banaudha, Krishna K.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Verma, Mukesh] NIH, Rockville, MD USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Banaudha, KK (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NR 70 TC 2 Z9 2 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 65 EP 76 DI 10.1007/978-1-4939-1804-1_4 D2 10.1007/978-1-4939-1804-1 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200005 PM 25421655 ER PT S AU McKee, TC Tricoli, JV AF McKee, Tawnya C. Tricoli, James V. BE Verma, M TI Epigenetics of Prostate Cancer SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Epigenetics; Methylation; -Methylome; MicroRNA; Prostate cancer ID CPG ISLAND HYPERMETHYLATION; GLUTATHIONE-S-TRANSFERASE; WNT/BETA-CATENIN PATHWAY; DNA METHYLATION; ANDROGEN RECEPTOR; INTRAEPITHELIAL NEOPLASIA; MESENCHYMAL TRANSITION; HISTONE DEACETYLASES; CELL-LINES; EXPRESSION AB The introduction of novel technologies that can be applied to the investigation of the molecular underpinnings of human cancer has allowed for new insights into the mechanisms associated with tumor development and progression. They have also advanced the diagnosis, prognosis and treatment of cancer. These technologies include microarray and other analysis methods for the generation of large-scale gene expression data on both mRNA and miRNA, next-generation DNA sequencing technologies utilizing a number of platforms to perform whole genome, whole exome, or targeted DNA sequencing to determine somatic mutational differences and gene rearrangements, and a variety of proteomic analysis platforms including liquid chromatography/mass spectrometry (LC/MS) analysis to survey alterations in protein profiles in tumors. One other important advancement has been our current ability to survey the methylome of human tumors in a comprehensive fashion through the use of sequence-based and array-based methylation analysis (Bock et al., Nat Biotechnol 28: 1106-1114, 2010; Harris et al., Nat Biotechnol 28: 1097-1105, 2010). The focus of this chapter is to present and discuss the evidence for key genes involved in prostate tumor development, progression, or resistance to therapy that are regulated by methylation-induced silencing. C1 [McKee, Tawnya C.; Tricoli, James V.] NCI, Div Canc Treatment & Diag, Canc Diag Program, Diagnost Biomarkers & Technol Branch,NIH, Bethesda, MD 20892 USA. RP McKee, TC (reprint author), NCI, Div Canc Treatment & Diag, Canc Diag Program, Diagnost Biomarkers & Technol Branch,NIH, Bethesda, MD 20892 USA. NR 96 TC 4 Z9 4 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 217 EP 234 DI 10.1007/978-1-4939-1804-1_11 D2 10.1007/978-1-4939-1804-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200012 PM 25421662 ER PT S AU Zhang, XB Tang, NM Rishi, AK Pass, HI Wali, A AF Zhang, Xinbo Tang, Naimei Rishi, Arun K. Pass, Harvey I. Wali, Anil BE Verma, M TI Methylation Profile Landscape in Mesothelioma: Possible Implications in Early Detection, Disease Progression, and Therapeutic Options SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarker; Cancer; Histone inhibitor; Mesothelioma; Methylation ID MALIGNANT PLEURAL MESOTHELIOMA; ABERRANT PROMOTER METHYLATION; DNA METHYLATION; CANCER; EPIGENETICS; HYPERMETHYLATION; ASBESTOS; GENE; RASSF1A; CELLS AB Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy of the pleura associated with asbestos exposure. Incidence of MPM is expected to increase over the course of next decade in both Europe and the developing countries. Although significant progress has been made in terms of etiology and pathogenesis of this disease, currently available therapeutic options have not significantly improved the survival outcome of patients on standard chemotherapeutic regimens. Integrity of the cellular DNA is often altered in many cancers. Understanding of the molecular mechanisms that regulate cellular DNA alterations to facilitate cancer initiation and development has potential to allow better design of cancer cell inhibitory strategies. In this context, there is a need to explore the gamut of "omics" strategies to provide a comprehensive epigenetics profile for MPM. This chapter discusses the functional genomics and epigenetic patterns observed by various investigators studying MPM patient populations on global fronts, and attempts to present a holistic approach in combating this insidious disease. Here we provide investigators in this field with novel insights and methodologies used in other types of cancers that might have profound impact in the early detection, prognosis and potential therapeutic strategies for MPM. C1 [Zhang, Xinbo; Tang, Naimei; Rishi, Arun K.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48202 USA. [Zhang, Xinbo; Tang, Naimei; Rishi, Arun K.] John D Dingell VA Med Ctr, Detroit, MI USA. [Pass, Harvey I.] NYU, Langone Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Wali, Anil] NCI, Ctr Reduce Canc Hlth Dispar, NIH, Bethesda, MD 20892 USA. RP Zhang, XB (reprint author), Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48202 USA. NR 41 TC 2 Z9 2 U1 3 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 235 EP 247 DI 10.1007/978-1-4939-1804-1_12 D2 10.1007/978-1-4939-1804-1 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200013 PM 25421663 ER PT S AU Vedham, V Verma, M AF Vedham, Vidya Verma, Mukesh BE Verma, M TI Cancer-Associated Infectious Agents and Epigenetic Regulation SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarker; Cancer; Epigenetics; Histone; Methylation; Risk assessment; Virus; Early-life exposure; Childhood cancer; Adult cancer; Cofactors; AIDS-related malignancies; Targeted therapy; Vaccines ID EPSTEIN-BARR-VIRUS; HELICOBACTER-PYLORI INFECTION; HEPATITIS-B INFECTION; HUMAN-PAPILLOMAVIRUS VACCINATION; GENE PROMOTER METHYLATION; ABERRANT DNA METHYLATION; GASTRIC EPITHELIAL-CELLS; ACUTE MYELOID-LEUKEMIA; HEPATOCELLULAR-CARCINOMA; NASOPHARYNGEAL CARCINOMA AB Infectious agents are one of the factors which contribute to cancer development. Few examples include human papilloma virus in cervical cancer, hepatitis virus in hepatocellular carcinoma, herpes virus in Kaposi's sarcoma, Epstein-Barr virus in nasopharyngeal carcinoma, human T-cell lymphotropic virus type-1 (HTLV-1) in T-cell leukemia and lymphoma, Helicobacter pylori in gastric cancer. These agents cause genomic instability in the host and most of them affect host immune system. Infectious agents may integrate in the host genome although their sit of integration is not fixed. Expression of some infectious agents involves epigenetic regulation by DNA methylation, histone modification, miRNA level alteration, and chromatin condensation. This chapter provides examples where epigenetic regulation has been reported in cancer-associated infectious agents. Epigenetic inhibitors and their potential in cancer control and treatment are also discussed. C1 [Vedham, Vidya] NCI, Knowledge Management & Special Projects Branch, Ctr Strateg Sci Initiat, Off Director,NIH, Rockville, MD 20892 USA. [Verma, Mukesh] NIH, Rockville, MD USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Vedham, V (reprint author), NCI, Knowledge Management & Special Projects Branch, Ctr Strateg Sci Initiat, Off Director,NIH, Rockville, MD 20892 USA. NR 167 TC 2 Z9 2 U1 1 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 333 EP 354 DI 10.1007/978-1-4939-1804-1_18 D2 10.1007/978-1-4939-1804-1 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200019 PM 25421669 ER PT S AU Verma, M AF Verma, Mukesh BE Verma, M TI Toxicoepigenomics and Cancer: Implications for Screening SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarkers; Epigenetics; Epidemiology; Liver cancer; miRNA; Treatment ID ABERRANT PROMOTER METHYLATION; BLOOD MONONUCLEAR-CELLS; DNA METHYLATION; GENE-EXPRESSION; HISTONE-CODE; TRANSGENERATIONAL INHERITANCE; ARSENIC BIOMETHYLATION; NICKEL-CARCINOGENESIS; CADMIUM EXPOSURE; VALPROIC ACID AB Scientists have long considered genetics to be the key mechanism that alters gene expression because of exposure to the environment and toxic substances (toxicants). Recently, epigenetic mechanisms have emerged as an alternative explanation for alterations in gene expression resulting from such exposure. The fact that certain toxic substances that contribute to tumor development do not induce mutations probably results from underlying epigenetic mechanisms. The field of toxicoepigenomics emerged from the combination of epigenetics and classical toxicology. High-throughput technologies now enable evaluation of altered epigenomic profiling in response to toxins and environmental pollutants. Furthermore, differences in the epigenomic backgrounds of individuals may explain why, although whole populations are exposed to toxicants, only a few people in a population develop cancer. Metals in the environment and toxic substances not only alter DNA methylation patterns and histone modifications but also affect enzymes involved in posttranslational modifications of proteins and epigenetic regulation, and thereby contribute to carcinogenesis. This article describes different toxic substances and environmental pollutants that alter epigenetic profiling and discusses how this information can be used in screening populations at high risk of developing cancer. Research opportunities and challengers in the field also are discussed. C1 [Verma, Mukesh] NIH, Rockville, MD 20892 USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Verma, M (reprint author), NIH, Rockville, MD 20892 USA. NR 78 TC 0 Z9 0 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 355 EP 367 DI 10.1007/978-1-4939-1804-1_19 D2 10.1007/978-1-4939-1804-1 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200020 PM 25421670 ER PT S AU Verma, M AF Verma, Mukesh BE Verma, M TI Epigenetic Regulation of HIV, AIDS, and AIDS-Related Malignancies SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE AIDS; Cancer; Epigenetics; HIV; Methylation; Prevention; Risk assessment treatment ID ANTIRETROVIRAL THERAPY; MICRORNA TARGETS; KAPOSIS-SARCOMA; METHYLATION; LATENCY; CELLS; EXPRESSION; STRATEGIES; COMPLEX; HDAC4 AB Although epigenetics is not a new field, its implications for acquired immunodeficiency syndrome (AIDS) research have not been explored fully. To develop therapeutic and preventive approaches against the human immunodeficiency virus (HIV) and AIDS, it is essential to understand the mechanisms of interaction between the virus and the host, involvement of genetic and epigenetic mechanisms, characterization of viral reservoirs, and factors influencing the latency of the virus. Both methylation of viral genes and histone modifications contribute to initiating and maintaining latency and, depending on the context, triggering viral gene repression or expression. This chapter discusses progress made at the National Institutes of Health (NIH), recommendations from the International AIDS Society Scientific Working Group on HIV Cure, and underlying epigenetic regulation. A number of epigenetic inhibitors have shown potential in treating AIDS-related malignancies. Epigenetic drugs approved by the US Food and Drug Administration and their implications for the eradication of HIV/AIDS and AIDS-related malignancies also are discussed. Past and current progress in developing treatments and understanding the molecular mechanisms of AIDS and HIV infection has greatly improved patient survival. However, increased survival has been coupled with the development of cancer at higher rates than those observed among the HIV/AIDS-negative population. During the early days of the AIDS epidemic, the most frequent AIDS-defining malignancies were Kaposi's sarcoma and non-Hodgkin lymphoma (NHL). Now, with increased survival as the result of widespread use in the developed world of highly active antiretroviral therapy (HAART), non-AIDS defining cancers (i.e., anal, skin, and lung cancers, and Hodgkin disease) are on the increase in HIV-infected populations. The current status of AIDS-related malignancies also is discussed. C1 [Verma, Mukesh] NIH, Rockville, MD 20892 USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Verma, M (reprint author), NIH, Rockville, MD 20892 USA. NR 33 TC 2 Z9 2 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 381 EP 403 DI 10.1007/978-1-4939-1804-1_21 D2 10.1007/978-1-4939-1804-1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200022 PM 25421672 ER PT S AU Verma, M Banerjee, HN AF Verma, Mukesh Banerjee, Hirendra Nath BE Verma, M TI Epigenetic Inhibitors SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cancer; Chromatin; Epigenetics; Histone deacetylase; Histone inhibitors; Methylation; Methyltransferase; microRNAs ID HISTONE-DEACETYLASE INHIBITORS; ACUTE MYELOID-LEUKEMIA; SUBEROYLANILIDE HYDROXAMIC ACID; NUCLEOSOME CORE PARTICLE; DNA METHYLATION PATTERNS; CPG ISLAND METHYLATION; TUMOR-SUPPRESSOR GENE; CELLS IN-VITRO; CANCER-CELLS; MYELODYSPLASTIC SYNDROMES AB Traditional treatments for cancer include chemotherapy, radiation therapy, and surgery. Recently, epigenetic inhibitors have been found to be very effective in cancer treatment. Epigenetic changes such as DNA methylation, histone deacetylation, and microRNA (miRNA) expression are capable of silencing the expression of tumor suppressor genes and inducing oncogenes, leading to clonal proliferation of tumor cells. Methyltransferase inhibitors and histone deacetylase inhibitors have attracted the attention of researchers and clinicians because they provide an alternative therapeutic regime in some diseases, including cancer. Epigenetic changes are characterized by altered gene expression without any changes in the nucleotide sequences of DNA. In addition, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, several epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. Their mechanisms of action and potential in treating cancer are described in this article. C1 [Verma, Mukesh] NIH, Rockville, MD 20892 USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. [Banerjee, Hirendra Nath] Univ N Carolina, Elizabeth City State Univ, Dept Biol & Pharmaceut Sci, Elizabeth City, NC USA. RP Verma, M (reprint author), NIH, Rockville, MD 20892 USA. NR 192 TC 4 Z9 4 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 469 EP 485 DI 10.1007/978-1-4939-1804-1_24 D2 10.1007/978-1-4939-1804-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200025 PM 25421675 ER PT S AU Hyman, G Manglik, V Rousch, JM Verma, M Kinkebiel, D Banerjee, HN AF Hyman, Gwyneth Manglik, Vinod Rousch, Jeffrey M. Verma, Mukesh Kinkebiel, David Banerjee, Hirendra Nath BE Verma, M TI Epigenetic Approaches in Glioblastoma Multiforme and Their Implication in Screening and Diagnosis SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarker; Epigenetics; Glioblastoma multiforme; Histone; Methyl transferase; Methylation ID DNA METHYLATION ANALYSIS; CANCER EPIGENETICS; PROSTATE-CANCER; HISTONE MODIFICATIONS; PROMOTER METHYLATION; CPG-ISLANDS; HUMAN BRAIN; CELLS; GENETICS; HYPOMETHYLATION AB Epigenetic modifications have been reported in a number of non-germ-line tumor types. Epigenetic modifications to the genome, especially DNA methylation and histone modifications, affect gene expression causing increased risk for cancers and other diseases. We have summarized information about DNA methylation percentages in Glioblastoma multiforme (GBM) line HTB-12, alveolar cell carcinoma, and acute lymphocytic leukemia samples and determined H3 (K27) methyltransferase activity in GBM and leukemia cells and made comparisons to H3 (K27) methyltransferase activity in normal astrocyte, lung, and lymphocyte cells. GBM and alveolar cell carcinoma gDNA possessed lower gDNA methylation percentages compared to normal cells. Methyl-sensitive cut counting analysis (MSCC) showed fold decreases in GBM CpG methylation sites for genes PBK, KIF23, COL6A3, and LOX. There was no significant difference in CpG DNA methylation, but less histone methyltransferase activity in acute lymphocytic leukemia compared to normal cells. GBM possessed increased histone methyltransferase activity compared to normal samples. Challenges in the field in diagnosis and prognosis for cancer risk especially with regard to the results of this work are discussed. C1 [Hyman, Gwyneth] Univ N Carolina, Elizabeth City State Univ, Dept Biol Sci & Pharmaceut Sci, Elizabeth City, NC 27909 USA. [Verma, Mukesh] NIH, Rockville, MD USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. [Kinkebiel, David] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. [Manglik, Vinod; Rousch, Jeffrey M.; Banerjee, Hirendra Nath] Univ N Carolina, Elizabeth City State Univ, Dept Biol & Pharmaceut Sci, Elizabeth City, NC USA. RP Hyman, G (reprint author), Univ N Carolina, Elizabeth City State Univ, Dept Biol Sci & Pharmaceut Sci, Elizabeth City, NC 27909 USA. NR 70 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 511 EP 521 DI 10.1007/978-1-4939-1804-1_26 D2 10.1007/978-1-4939-1804-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200027 PM 25421677 ER PT S AU Litzelman, K Verma, M AF Litzelman, Kristin Verma, Mukesh BE Verma, M TI Epigenetic Regulation in Biopsychosocial Pathways SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Psychological stress; Psychosocial factors; Epigenetics; Cancer ID PITUITARY-ADRENAL AXIS; STRUCTURED PSYCHIATRIC INTERVENTION; BETA-ADRENERGIC RECEPTORS; PROSTATE-CANCER CELLS; DNA METHYLATION; BREAST-CANCER; OVARIAN-CANCER; CHRONIC STRESS; PSYCHOSOCIAL STRESS; BEHAVIORAL STRESS AB Theory and empirical evidence suggest that psychological stress and other adverse psychosocial experiences can contribute to cancer progression. Research has begun to explore the potential role of epigenetic changes in these pathways. In basic, animal and human models, exposure to stressors or to the products of the physiological stress response (e.g., cortisol) has been associated with epigenetic changes, such as DNA methylation and microRNA (miR) expression, which may influence tumor growth, progression, metastasis, or chemoresistance. However, the specific biological pathways linking stress, epigenetic changes, and cancer outcomes remain unclear. Numerous opportunities exist to extend the preliminary evidence for the role of epigenetic mechanisms in the biopsychosocial pathways contributing to cancer progression. Such work will improve our understanding of how the psychosocial environment influences cancer risk and survival, potentially leading to improved prevention and treatment strategies. C1 [Litzelman, Kristin] NCI, Behav Res Program, Div Canc Control & Populat Sci, Basic Biobehav & Psychol Sci Branch,NIH, Bethesda, MD 20892 USA. [Verma, Mukesh] NIH, Rockville, MD USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Litzelman, K (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Basic Biobehav & Psychol Sci Branch,NIH, Bethesda, MD 20892 USA. NR 135 TC 1 Z9 1 U1 3 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 549 EP 567 DI 10.1007/978-1-4939-1804-1_29 D2 10.1007/978-1-4939-1804-1 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200030 PM 25421680 ER PT S AU Mishra, A Brat, DJ Verma, M AF Mishra, Alok Brat, Daniel J. Verma, Mukesh BE Verma, M TI P53 Tumor Suppression Network in Cancer Epigenetics SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE p53; Acetylation; Cancer; Chromatin; Epigenetic; ChIP; Histones; Methylation; Micro RNA ID EPITHELIAL-MESENCHYMAL TRANSITION; EMBRYONIC STEM-CELLS; DNA-DAMAGE; METHYLATION ANALYSIS; GENE-EXPRESSION; PROMOTER; MICRORNAS; PATHWAY; COMPLEX; TRANSCRIPTION AB The tumor suppressor p53 is one of the most complex and widely studied genes in cancer biology. In spite of the vast on literature the transcriptional regulation of p53, aspects of its especially epigenetic regulation are not completely understood. This chapter presents a concise overview of p53-related epigenetic events involved in oncogenesis and tumor suppression. We limit the scope to epigenetic modifications of the p53 promoter per se as well as its well-established downstream targets. The indirect role of p53 affecting the epigenetic machinery of cancer cells via specific proteins and transcription factors is discussed. Current concepts of p53-related cancer epigenetics offer myriad avenues for cancer therapies. Challenges in the field are also discussed. C1 [Mishra, Alok] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Brat, Daniel J.] Emory Univ, Dept Pathol & Lab Med, Emory Univ Hosp, Sch Med, Atlanta, GA 30322 USA. [Verma, Mukesh] NIH, Rockville, MD USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Mishra, A (reprint author), Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 49 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 597 EP 605 DI 10.1007/978-1-4939-1804-1_31 D2 10.1007/978-1-4939-1804-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200032 PM 25421682 ER PT S AU Vaish, V Khare, T Verma, M Khare, S AF Vaish, Vivek Khare, Tripti Verma, Mukesh Khare, Sharad BE Verma, M TI Epigenetic Therapy for Colorectal Cancer SO CANCER EPIGENETICS: RISK ASSESSMENT, DIAGNOSIS, TREATMENT, AND PROGNOSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Colon cancer; Epigenetic therapy; Methylation; Acetylation ID HISTONE-DEACETYLASE INHIBITORS; DNA METHYLTRANSFERASE 1; ANTISENSE OLIGONUCLEOTIDE MG98; CHROMATIN-MODIFYING DRUGS; TUMOR-SUPPRESSOR GENES; ADVANCED SOLID TUMORS; PHASE-II TRIAL; COLON-CANCER; ANTITUMOR-ACTIVITY; ANTICANCER AGENTS AB Aberrations in epigenome that include alterations in DNA methylation, histone acetylation, and miRNA (microRNA) expression may govern the progression of colorectal cancer (CRC). These epigenetic changes affect every phase of tumor development from initiation to metastasis. Since epigenetic alterations can be reversed by DNA demethylating and histone acetylating agents, current status of the implication of epigenetic therapy in CRC is discussed in this article. Interestingly, DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have shown promising results in controlling cancer progression. The information provided here might be useful in developing personalized medicine approaches. C1 [Vaish, Vivek; Khare, Tripti] Univ Missouri, Dept Internal Med, Sect Gastroenterol & Hepatol, Columbia, MO 65211 USA. [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. [Khare, Sharad] Hines Vet Affairs Med Ctr, Hines, IL USA. RP Vaish, V (reprint author), Univ Missouri, Dept Internal Med, Sect Gastroenterol & Hepatol, Columbia, MO 65211 USA. FU BLRD VA [I01 BX000824]; NCI NIH HHS [R03 CA150081] NR 101 TC 6 Z9 6 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1804-1; 978-1-4939-1803-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1238 BP 771 EP 782 DI 10.1007/978-1-4939-1804-1_40 D2 10.1007/978-1-4939-1804-1 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1TK UT WOS:000350417200041 PM 25421691 ER PT J AU Jacobson, KA AF Jacobson, Kenneth A. TI Meet the Editorial Board SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material C1 [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2015 VL 15 IS 4 BP 279 EP 279 PG 1 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CD3WA UT WOS:000351013200001 ER PT J AU Collins, PY Musisi, S Frehywot, S Patel, V AF Collins, Pamela Y. Musisi, Seggane Frehywot, Seble Patel, Vikram TI The core competencies for mental, neurological, and substance use disorder care in sub-Saharan Africa SO GLOBAL HEALTH ACTION LA English DT Article DE mental health care; neurology; core competencies; human resources; task sharing; capacity-building; Africa ID SYSTEMATIC ANALYSIS; HEALTH-PROFESSIONS; GLOBAL BURDEN; EDUCATION; COUNTRIES; INJURIES; DISEASES AB The 2010 Global Burden of Disease Study points to a changing landscape in which non-communicable diseases, such as mental, neurological, and substance use (MNS) disorders, account for an increasing proportion of premature mortality and disability globally. Despite evidence of the need for care, a remarkable deficit of providers for MNS disorder service delivery persists in sub-Saharan Africa. This critical workforce can be developed from a range of non-specialist and specialist health workers who have access to evidence-based interventions, whose roles, and the associated tasks, are articulated and clearly delineated, and who are equipped to master and maintain the competencies associated with providing MNS disorder care. In 2012, the Neuroscience Forum of the Institute of Medicine convened a meeting of key stakeholders in Kampala, Uganda, to discuss a set of candidate core competencies for the delivery of mental health and neurological care, focusing specifically on depression, psychosis, epilepsy, and alcohol use disorders. This article discusses the candidate core competencies for non-specialist health workers and the complexities of implementing core competencies in low-and middle-income country settings. Sub-Saharan Africa, however, has the potential to implement novel training initiatives through university networks and through structured processes that engage ministries of health. Finally, we outline challenges associated with implementing competencies in order to sustain a workforce capable of delivering quality services for people with MNS disorders. C1 [Collins, Pamela Y.] NIMH, Off Res Dispar & Global Mental Hlth, Bethesda, MD 20892 USA. [Musisi, Seggane] Makerere Univ Coll Hlth Sci, Dept Psychiat, Kampala, Uganda. [Frehywot, Seble] George Washington Univ, Dept Hlth Policy, Washington, DC USA. [Frehywot, Seble] George Washington Univ, Dept Global Hlth, Washington, DC USA. [Patel, Vikram] London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London WC1, England. [Patel, Vikram] Publ Hlth Fdn India, Ctr Chron Condit & Injuries, New Delhi, India. RP Collins, PY (reprint author), NIMH, 6001 Execut Blvd,Suite 6217, Bethesda, MD 20892 USA. EM pamela.collins@nih.gov NR 33 TC 0 Z9 0 U1 2 U2 5 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1654-9880 J9 GLOBAL HEALTH ACTION JI Glob. Health Action PY 2015 VL 8 BP 1 EP 6 DI 10.3402/gha.v8.26682 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CD3SY UT WOS:000351002600001 ER PT J AU Lin, WY Camp, NJ Ghoussaini, M Beesley, J Michailidou, K Hopper, JL Apicella, C Southey, MC Stone, J Schmidt, MK Broeks, A Van't Veer, LJ Rutgers, EJT Muir, K Lophatananon, A Stewart-Brown, S Siriwanarangsan, P Fasching, PA Haeberle, L Ekici, AB Beckmann, MW Peto, J Dos-Santos-Silva, I Fletcher, O Johnson, N Bolla, MK Wang, Q Dennis, J Sawyer, EJ Cheng, T Tomlinson, I Kerin, MJ Miller, N Marme, F Surowy, HM Burwinkel, B Guenel, P Truong, T Menegaux, F Mulot, C Bojesen, SE Nordestgaard, BG Nielsen, SF Flyger, H Benitez, J Zamora, MP Perez, JIA Menendez, P Gonzalez-Neira, A Pita, G Alonso, MR Alvarez, N Herrera, D Anton-Culver, H Brenner, H Dieffenbach, AK Arndt, V Stegmaier, C Meindl, A Lichtner, P Schmutzler, RK Muller-Myhsok, B Brauch, H Bruning, T Ko, YD Tessier, DC Vincent, D Bacot, F Nevanlinna, H Aittomaki, K Blomqvist, C Khan, S Matsuo, K Ito, H Iwata, H Horio, A Bogdanova, NV Antonenkova, NN Dork, T Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Wu, AH Tseng, CC Van den Berg, D Stram, DO Neven, P Wauters, E Wildiers, H Lambrechts, D Chang-Claude, J Rudolph, A Seibold, P Flesch-Janys, D Radice, P Peterlongo, P Manoukian, S Bonanni, B Couch, FJ Wang, XS Vachon, C Purrington, K Giles, GG Milne, RL Mclean, C Haiman, CA Henderson, BE Schumacher, F Le Marchand, L Simard, J Goldberg, MS Labreche, F Dumont, M Teo, SH Yip, CH Hassan, N Vithana, EN Kristensen, V Zheng, W Deming-Halverson, S Shrubsole, MJ Long, JR Winqvist, R Pylkas, K Jukkola-Vuorinen, A Kauppila, S Andrulis, IL Knight, JA Glendon, G Tchatchou, S Devilee, P Tollenaar, RAEM Seynaeve, C Van Asperen, CJ Garcia-Closas, M Figueroa, J Lissowska, J Brinton, L Czene, K Darabi, H Eriksson, M Brand, JS Hooning, MJ Hollestelle, A Van den Ouweland, AMW Jager, A Li, JM Liu, JJ Humphreys, K Shu, XO Lu, W Gao, YT Cai, H Cross, SS Reed, MWR Blot, W Signorello, LB Cai, QY Pharoah, PDP Perkins, B Shah, M Blows, FM Kang, D Yoo, KY Noh, DY Hartman, M Miao, H Chia, KS Putti, TC Hamann, U Luccarini, C Baynes, C Ahmed, S Maranian, M Healey, CS Jakubowska, A Lubinski, J Jaworska-Bieniek, K Durda, K Sangrajrang, S Gaborieau, V Brennan, P Mckay, J Slager, S Toland, AE Yannoukakos, D Shen, CY Hsiung, CN Wu, PE Ding, SL Ashworth, A Jones, M Orr, N Swerdlow, AJ Tsimiklis, H Makalic, E Schmidt, DF Bui, QM Chanock, SJ Hunter, DJ Hein, R Dahmen, N Beckmann, L Aaltonen, K Muranen, TA Heikkinen, T Irwanto, A Rahman, N Turnbull, CA Waisfisz, Q Meijers-Heijboer, HEJ Adank, MA Van der Luijt, RB Hall, P Chenevix-Trench, G Dunning, A Easton, DF Cox, A AF Lin, Wei-Yu Camp, Nicola J. Ghoussaini, Maya Beesley, Jonathan Michailidou, Kyriaki Hopper, John L. Apicella, Carmel Southey, Melissa C. Stone, Jennifer Schmidt, Marjanka K. Broeks, Annegien Van't Veer, Laura J. Rutgers, Emiel J. Th Muir, Kenneth Lophatananon, Artitaya Stewart-Brown, Sarah Siriwanarangsan, Pornthep Fasching, Peter A. Haeberle, Lothar Ekici, Arif B. Beckmann, Matthias W. Peto, Julian Dos-Santos-Silva, Isabel Fletcher, Olivia Johnson, Nichola Bolla, Manjeet K. Wang, Qin Dennis, Joe Sawyer, Elinor J. Cheng, Timothy Tomlinson, Ian Kerin, Michael J. Miller, Nicola Marme, Frederik Surowy, Harald M. Burwinkel, Barbara Guenel, Pascal Truong, Therese Menegaux, Florence Mulot, Claire Bojesen, Stig E. Nordestgaard, Borge G. Nielsen, Sune F. Flyger, Henrik Benitez, Javier Zamora, M. Pilar Arias Perez, Jose Ignacio Menendez, Primitiva Gonzalez-Neira, Anna Pita, Guillermo Rosario Alonso, M. Alvarez, Nuria Herrera, Daniel Anton-Culver, Hoda Brenner, Hermann Dieffenbach, Aida Karina Arndt, Volker Stegmaier, Christa Meindl, Alfons Lichtner, Peter Schmutzler, Rita K. Mueller-Myhsok, Bertram Brauch, Hiltrud Bruening, Thomas Ko, Yon-Dschun Tessier, Daniel C. Vincent, Daniel Bacot, Francois Nevanlinna, Heli Aittomaeki, Kristiina Blomqvist, Carl Khan, Sofia Matsuo, Keitaro Ito, Hidemi Iwata, Hiroji Horio, Akiyo Bogdanova, Natalia V. Antonenkova, Natalia N. Doerk, Thilo Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Wu, Anna H. Tseng, Chiu-Chen Van den Berg, David Stram, Daniel O. Neven, Patrick Wauters, Els Wildiers, Hans Lambrechts, Diether Chang-Claude, Jenny Rudolph, Anja Seibold, Petra Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Bonanni, Bernardo Couch, Fergus J. Wang, Xianshu Vachon, Celine Purrington, Kristen Giles, Graham G. Milne, Roger L. Mclean, Catriona Haiman, Christopher A. Henderson, Brian E. Schumacher, Fredrick Le Marchand, Loic Simard, Jacques Goldberg, Mark S. Labreche, France Dumont, Martine Teo, Soo Hwang Yip, Cheng Har Hassan, Norhashimah Vithana, Eranga Nishanthie Kristensen, Vessela Zheng, Wei Deming-Halverson, Sandra Shrubsole, Martha J. Long, Jirong Winqvist, Robert Pylkaes, Katri Jukkola-Vuorinen, Arja Kauppila, Saila Andrulis, Irene L. Knight, Julia A. Glendon, Gord Tchatchou, Sandrine Devilee, Peter Tollenaar, Robert A. E. M. Seynaeve, Caroline Van Asperen, Christi J. Garcia-Closas, Montserrat Figueroa, Jonine Lissowska, Jolanta Brinton, Louise Czene, Kamila Darabi, Hatef Eriksson, Mikael Brand, Judith S. Hooning, Maartje J. Hollestelle, Antoinette Van den Ouweland, Ans M. W. Jager, Agnes Li, Jingmei Liu, Jianjun Humphreys, Keith Shu, Xiao-Ou Lu, Wei Gao, Yu-Tang Cai, Hui Cross, Simon S. Reed, Malcolm W. R. Blot, William Signorello, Lisa B. Cai, Qiuyin Pharoah, Paul D. P. Perkins, Barbara Shah, Mitul Blows, Fiona M. Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Hartman, Mikael Miao, Hui Chia, Kee Seng Putti, Thomas Choudary Hamann, Ute Luccarini, Craig Baynes, Caroline Ahmed, Shahana Maranian, Mel Healey, Catherine S. Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul Mckay, James Slager, Susan Toland, Amanda E. Yannoukakos, Drakoulis Shen, Chen-Yang Hsiung, Chia-Ni Wu, Pei-Ei Ding, Shian-ling Ashworth, Alan Jones, Michael Orr, Nick Swerdlow, Anthony J. Tsimiklis, Helen Makalic, Enes Schmidt, Daniel F. Bui, Quang M. Chanock, Stephen J. Hunter, David J. Hein, Rebecca Dahmen, Norbert Beckmann, Lars Aaltonen, Kirsimari Muranen, Taru A. Heikkinen, Tuomas Irwanto, Astrid Rahman, Nazneen Turnbull, Clare A. Waisfisz, Quinten Meijers-Heijboer, Hanne E. J. Adank, Muriel A. Van der Luijt, Rob B. Hall, Per Chenevix-Trench, Georgia Dunning, Alison Easton, Douglas F. Cox, Angela CA GENICA Network kConFab Investigators Australian Ovarian Canc Study Grp Breast Ovarian Canc Susceptibility TI Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; CASP8; ENHANCERS; DISEASE; GENE AB Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, Cl)] for the minor allele of 1.05(1.03-1.07), P = 1 x 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 x 10(-6)), yielding a combined OR (95% Cl) of 1.06(1.04-1.08), P = 1 x 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis. C1 [Lin, Wei-Yu; Reed, Malcolm W. R.; Cox, Angela] Univ Sheffield, Sch Med, Dept Oncol, Sheffield S10 2RX, S Yorkshire, England. [Lin, Wei-Yu] Chang Gung Mem Hosp, Dept Neurosurg, Kaohsiung 333, Taoyuan County, Taiwan. [Camp, Nicola J.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA. [Ghoussaini, Maya; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Pharoah, Paul D. P.; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Dunning, Alison; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England. [Beesley, Jonathan; Chenevix-Trench, Georgia] Dept Genet, Brisbane, Qld 4006, Australia. QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Stone, Jennifer] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Tsimiklis, Helen] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia. [Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Rutgers, Emiel J. Th] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9QQ, Lancs, England. [Siriwanarangsan, Pornthep] Minist Publ Hlth, Nonthaburi 11000, Thailand. [Fasching, Peter A.; Haeberle, Lothar; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Peto, Julian; Dos-Santos-Silva, Isabel] Univ London London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1E 7HT, England. [Fletcher, Olivia; Johnson, Nichola; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Garcia-Closas, Montserrat; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Breast Canc Res, London SW3 6JB, England. [Orr, Nick] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Div Canc Studies, London SE1 9RT, England. [Cheng, Timothy; Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Cheng, Timothy; Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England. [Kerin, Michael J.; Miller, Nicola] Natl Univ Ireland, Sch Med, Galway, Ireland. [Marme, Frederik; Surowy, Harald M.; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, D-69117 Heidelberg, Germany. [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, D-69117 Heidelberg, Germany. [Surowy, Harald M.; Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany. 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[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3A 0G4, Canada. [Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Labreche, France] Univ Montreal, Ecole Sante Publ, Dept Sante Environm & Sante Travail, Montreal, PQ H3T 1J4, Canada. [Labreche, France] Univ Montreal, Ecole Sante Publ, Dept Med Sociale & Prevent, Montreal, PQ H3T 1J4, Canada. [Teo, Soo Hwang; Hassan, Norhashimah] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya, Selangor, Malaysia. [Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur 50603, Malaysia. [Vithana, Eranga Nishanthie] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 119077, Singapore. [Kristensen, Vessela] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, N-0372 Oslo, Norway. [Kristensen, Vessela] Univ Oslo UiO, Fac Div Ahus, Fac Med, N-0316 Oslo, Norway. [Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Shu, Xiao-Ou; Cai, Hui; Blot, William; Signorello, Lisa B.; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA. [Winqvist, Robert; Pylkaes, Katri] Ctr Nord Lab, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu 90570, Finland. [Winqvist, Robert; Pylkaes, Katri] Ctr Nord Lab, Bioctr Oulu, Northern Finland Lab, Oulu 90570, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, FIN-90570 Oulu, Finland. [Kauppila, Saila] Univ Oulu, Oulu Univ Hosp, Dept Pathol, FIN-90570 Oulu, Finland. [Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Mt Sinai Hosp, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Mol Genet, Toronto, ON M5S 2J7, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5S 2J7, Canada. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2300 RC Leiden, Netherlands. [Van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands. [Seynaeve, Caroline; Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes] Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, NL-3075 EA Rotterdam, Netherlands. [Garcia-Closas, Montserrat; Jones, Michael; Swerdlow, Anthony J.; Rahman, Nazneen; Turnbull, Clare A.; Breast Ovarian Canc Susceptibility] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London SW7 3RP, England. Inst Canc Res, Div Canc Genet, London SW7 3RP, England. [Figueroa, Jonine; Brinton, Louise; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3075 EA Rotterdam, Netherlands. [Liu, Jianjun; Irwanto, Astrid] Genome Inst Singapore, Human Genet Div, Singapore 138672, Singapore. [Li, Jingmei; Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai 200336, Peoples R China. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai 220025, Peoples R China. [Cross, Simon S.] Univ Sheffield, Royal Hallamshire Hosp, Dept Neurosci, Sheffield S10 2JF, S Yorkshire, England. [Blot, William; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD 20850 USA. [Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea. [Kang, Daehee] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 151742, South Korea. [Hartman, Mikael; Miao, Hui; Chia, Kee Seng] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore. [Hartman, Mikael] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 117597, Singapore. [Putti, Thomas Choudary] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pathol, Singapore 117597, Singapore. [Hartman, Mikael; Miao, Hui; Chia, Kee Seng] Natl Univ Hlth Syst, Singapore 119228, Singapore. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, PL-70204 Szczecin, Poland. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand. [Gaborieau, Valerie; Brennan, Paul; Mckay, James] Int Agcy Res Canc, F-69372 Lyon, France. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Aghia Paraskevi Attikis, Athens 15310, Greece. [Shen, Chen-Yang; Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. [Wu, Pei-Ei] Acad Sinica, Taiwan Biobank, Inst Biomed Sci, Taipei 115, Taiwan. [Shen, Chen-Yang] China Med Univ, Coll Publ Hlth, Taichung 40402, Taiwan. [Ding, Shian-ling] Kang Ning Jr Coll Med Care & Management, Dept Nursing, Taipei 11529, Taiwan. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Hein, Rebecca] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, PMV Res Grp, D-50923 Cologne, Germany. [Dahmen, Norbert] Johannes Gutenberg Univ Mainz, Dept Psychiat, D-55122 Mainz, Germany. [Beckmann, Lars] Inst Qual & Efficiency Hlth Care IQWiG, D-50670 Cologne, Germany. [Waisfisz, Quinten; Meijers-Heijboer, Hanne E. J.; Adank, Muriel A.] Vrije Univ Amsterdam, Med Ctr, Sect Oncogenet, Dept Clin Genet, NL-1081 HZ Amsterdam, Netherlands. [Van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands. RP Cox, A (reprint author), Univ Sheffield, Sch Med, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM a.cox@sheffield.ac.uk RI Knight, Julia/A-6843-2012; Yip, Cheng-Har/B-1909-2010; Teo, Soo-hwang/H-2353-2014; Shrubsole, Martha/K-5052-2015; Hartman, Mikael/B-4324-2011; Lin, Wei-Yu/F-4505-2010; Dork, Thilo/J-8620-2012; U-ID, Kyushu/C-5291-2016; Gonzalez-Neira, Anna/C-5791-2015; Hartikainen, Jaana/E-6256-2015; Li, Jingmei/I-2904-2012; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Andrulis, Irene/E-7267-2013; Brenner, Hermann/B-4627-2017; Cheng, Timothy/D-8747-2017; manoukian, siranoush/E-7132-2017; Rahman, Nazneen/D-2802-2013; OI Shrubsole, Martha/0000-0002-5591-7575; Lin, Wei-Yu/0000-0002-9267-7988; Li, Jingmei/0000-0001-8587-7511; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Yannoukakos, Drakoulis/0000-0001-7509-3510; Giles, Graham/0000-0003-4946-9099; Muranen, Taru/0000-0002-5895-1808; Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754; Rahman, Nazneen/0000-0003-4376-0440; Dunning, Alison Margaret/0000-0001-6651-7166; Khan, Sofia/0000-0003-4185-8882; Cox, Angela/0000-0002-5138-1099 FU European Community [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/ A11174, C1281/Al2014, C5047/A8384, C5047/A15007, C5047/A10692]; National Institutes of Health [CA128978, RO1 CA77398]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1 -0341]; Canadian Institutes of Health Research (CIHR); Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; United States National Cancer Institute; National Institutes of Health (NIH) [RFA-CA-06-503, U01 CA69467, U01 CA69417, U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839, 2009 4363, RUL 1997-1505]; Dutch government [NWO 184.021.007]; Dutch National Genomics Initiative; Breast Cancer Research Trust, UK; ELAN-Fond of the University Hospital of Erlangen; UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); Institut National de Cancer; NIHR Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, UK; Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Fondation de France; Institut National du Cancer (INCa); Ligue Nationale contre le Cancer; Ligue contre le Cancer Grand Ouest; Agence Nationale de Securite Sanitaire (ANSES); Agence Nationale de la Recherche (ANR); Chief Physician Johan Boserup; Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espaliola Contra el Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI081120]; Instituto de Salud Carlos III; California Breast Cancer Act; Lon V Smith Foundation [LV539420]; California Breast Cancer Research Fund [97-10500]; California Department of Public Health [103885]; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe); German Cancer Aid [109076]; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance; Institute of the Ruhr University Bochum (IPA), Bochum, Germany; Department of Internal Medicine; Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Helsinki University Central Hospital Research Fund; Academy of Finland [266528]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Nordic Center of Excellence in Disease Genetics based on samples regionally selected from Finland; Ministry of Education, Science, Sports, Culture and Technology of Japan; Ministry Health, Labour and Welfare of Japan; Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan; National Cancer Center Research and Development Fund; Friends of Hannover Medical School; Rudolf Baffling Foundation; Stockholm County Council; Karolinska Institutet; Swedish Cancer Society; Gustav V Jubilee foundation; special Government Funding (EVO) of Kuopio University Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; strategic funding of the University of Eastern Finland; National Breast Cancer Foundation; NHMRC; Queensland Cancer Fund; Cancer Councils of New South Wales; Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600]; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania and Human Molecular Genetics [I 295]; California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098]; California Department of Health; National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program [N01CN25403]; Stichting tegen Kanker' [232-2008, 196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center; Federal Ministry of Education and Research (BMBF) German [01KH0402, 01KH0408, 01KH0409]; Italian Association for Cancer Research (AIRC); NTH [CA128978]; NTH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; David F. and Margaret T. Grohne Family Foundation; Ting Tsung and Wei Fong Chao Foundation; VicHealth and Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711]; NIH [CA63464, CA54281, CA098758, CA132839, R01CA100374]; Quebec Breast Cancer Foundation; Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program [CRN-87521]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Malaysian Ministry of Science, Technology and Innovation (MOSTI); Malaysian Ministry of Higher Education [UM.C/H1R/MOHE/06]; Cancer Research Initiatives Foundation (CARIF); Biomedical Research Council, Singapore [BMRC08/1/35/19/550]; National medical Research Council, Singapore [NMRC/CG/SERI/2010]; Norwegian Research council [155218/V40, 175240/S10, FUGE-NFR 181600N11, 155218/ V40]; Swizz Bridge Award; Finnish Cancer Foundation; Academy of Finland Centre [251314]; University of Oulu; Oulu University Hospital special Govermental EVO Research Funds; National Cancer Institute [UM1 CA164920]; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA; Writ and Hans Rausings Initiative Against Breast Cancer; Agency for Science, Technology and Research of Singapore (A* STAR); US National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; NIH grants [RO1CA64277, RO1CA148667, R37CA70867, CA 65725, CA87969, CA49449, CA67262, CA50385, 5U01CA098233]; Yorkshire Cancer Research awards [S295, S299, 5305PA]; Sheffield Experimental Cancer Medicine Centre Network; NCI [RO1 CA163353]; Avon Foundation [02-2009-080]; National Institute of Health [R01 CA092447]; National Program of Cancer Registries; Centers for Disease Control and Prevention (CDC); Korea Health 21 RD Project [A030001]; Ministry of Health and Welfare, Republic of Korea; National Medical Research Council; Biomedical Research Council [05/1/21/19/ 425]; DKFZ; National Cancer Institute Thailand; MCBCS (National Institutes of Health) [CA116167, CA176785]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; European Union (European Social Fund ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; Taiwan Biobank project of the Institute of Biomedical Sciences; Academia Sinica, Taiwan; Institute of Cancer Research (ICR); Wellcome Trust; Cancer Research [C8620/A8372]; Netherlands Organisation for Scientific Research (NWO) as part of a ZonMwNIDI grant [91756341]; NWO Groot Investments [175.010.2005.011]; [KULPFV/10/016-SymBioSysII]; [P30 CA68485]; [DDHK 2004-3124]; [DDHK 2009-4318]; [NMRC/CG/NCIS /2010]; [PBZ_KBN_122/P05/2004] FX Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/ A11174, C1281/Al2014, C5047/A8384, C5047/A15007 and C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 the GAME-ON initiative), the Department of Defence (W81XWH-10-1 -0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. The ABCFS, NC-BCFR and OFBCR work was supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417) and University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C.S. is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The ABCS was supported by the Dutch Cancer Society (grants NKI 2007-3839, 2009 4363); BBMRI-NL, which is a Research Infrastructure financed by the Dutch government (NWO 184.021.007); and the Dutch National Genomics Initiative. The ACP study is funded by the Breast Cancer Research Trust, UK. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BBCS GWAS received funding from The Institut National de Cancer. E. S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, UK. I. T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Ligue contre le Cancer Grand Ouest, Agence Nationale de Securite Sanitaire (ANSES) and Agence Nationale de la Recherche (ANR). The was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.; The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espaliola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI081120). The Human GenotypingCEGEN Unit (CNIO) is supported by the Instituto de Salud Carlos III. The CTS was supported by the California Breast Cancer Act of 1993, National Institutes of Health (grants RO1 CA77398 and the Lon V Smith Foundation, LV539420) and the California Breast Cancer Research Fund (contract 97-10500). Collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no. 109076; coordinator: R.K.S.). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The GWS population allele and genotype frequencies were obtained from the data source funded by the Nordic Center of Excellence in Disease Genetics based on samples regionally selected from Finland, Sweden and Denmark. The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by National Cancer Center Research and Development Fund. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Baffling Foundation. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, The Swedish Cancer Society and the Gustav V Jubilee foundation. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704 and 454508).; Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Human Molecular Genetics, 2015, Vol. 24, No. I 295 Cancer Foundation of Western Australia and the NHMRC (199600). G.C.T. and P.W. are supported by the NHMRC. LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018 and 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP), which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII. The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center and the Federal Ministry of Education and Research (BMBF) Germany (01KH0402, 01KH0408 and 01KH0409). MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5 x 1000'). The MCBCS was supported by the NTH grant CA128978, an NTH Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCC S cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The MEC was support by NTH grants CA63464, CA54281, CA098758 and CA132839. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/H1R/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and the National medical Research Council, Singapore (NMRC/CG/SERI/2010). The NBCS was supported by grants from the Norwegian Research council, 155218/V40, 175240/S10 to ALBD, FUGE-NFR 181600N11 to VNK and a Swizz Bridge Award to ALBD. The NBCS was supported by grants from the Norwegian Research council, 155218/ V40, 175240/S10 to ALBD, FUGE-NFR 181600N11 to VNK and a Swizz Bridge Award to ALBD. The NBHS was supported by NTH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485.; The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland Centre of Excellence grant 251314, the Sigrid Juselius Foundation, the University of Oulu, and the Oulu University Hospital special Govermental EVO Research Funds. The OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The pKARMA study was supported by Writ and Hans Rausings Initiative Against Breast Cancer. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A* STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants RO1CA64277, RO1CA148667 and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The SBCS was supported by Yorkshire Cancer Research awards S295, S299, 5305PA and by the Sheffield Experimental Cancer Medicine Centre Network. N.J.C. was supported by NCI grant RO1 CA163353 and The Avon Foundation (02-2009-080). The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by programme grants from Cancer Research UK (C490/A10124, C490/A16561) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The SEBCS was supported by the Korea Health 21 R&D Project [A030001], Ministry of Health and Welfare, Republic of Korea. SGBCC is funded by the National Medical Research Council start-up Grant and Centre Grant (NMRC/CG/NCIS /2010).; Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/ 425. SKKDKFZS is supported by the DKFZ. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer Institute Thailand. The TNBCC was supported by: MCBCS (National Institutes of Health Grants CA116167, CA176785 and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. This research has been partly financed by the European Union (European Social Fund ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. Investing in knowledge society through the European Social Fund; and the Stefanie Spielman Breast Fund and the Ohio State University Comprehensive Cancer Center. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the RMH/ICR NIHR Specialist Biomedical Research Centre for Cancer. The Nurses' Health Studies (CGEMS) are supported by NIH grants CA 65725, CA87969, CA49449, CA67262, CA50385 and 5U01CA098233. The UK2 GWAS was funded by Wellcome Trust and Cancer Research UK. It included samples collected through the BOCS study, which is funded by Cancer Research UK [C8620/A8372]. It included control data obtained through the WTCCC which was funded by the Wellcome Trust. The DFBBCS GWAS was funded by The Netherlands Organisation for Scientific Research (NWO) as part of a ZonMwNIDI grant number 91756341. Control GWA genotype data from the Rotterdam Study were funded by NWO Groot Investments (project nr. 175.010.2005.011). NR 20 TC 7 Z9 7 U1 1 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2015 VL 24 IS 1 BP 285 EP 298 DI 10.1093/hmg/ddu431 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CC1WH UT WOS:000350135400023 PM 25168388 ER PT J AU Yamashita, H Pandiri, A Bhusari, S Shockley, K Peddada, S Gerrish, K Rider, C Hoenerhoff, M Sills, R AF Yamashita, H. Pandiri, A. Bhusari, S. Shockley, K. Peddada, S. Gerrish, K. Rider, C. Hoenerhoff, M. Sills, R. TI MicroRNA Profiling of Hepatocellular Carcinomas in B6C3F1 Mice Treated with Ginkgo biloba Extract by Gavage for 2 Years SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the American-College-of-Toxicology (ACT) CY NOV 09-12, 2014 CL Orlando, FL SP Amer Coll Toxicol C1 [Yamashita, H.] Taisho Pharmaceut Co Ltd, Saitama, Japan. [Pandiri, A.] Expt Pathol Labs, Res Triangle Pk, NC USA. [Bhusari, S.; Rider, C.; Hoenerhoff, M.; Sills, R.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Shockley, K.; Peddada, S.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Gerrish, K.] NIEHS, Mol Genom Core Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2015 VL 34 IS 1 MA P313 BP 88 EP 88 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CB9WZ UT WOS:000349986200042 ER PT J AU Richards, JM Patel, N Daniele-Zegarelli, T MacPherson, L Lejuez, CW Ernst, M AF Richards, Jessica M. Patel, Nilam Daniele-Zegarelli, Teresa MacPherson, Laura Lejuez, C. W. Ernst, Monique TI Social anxiety, acute social stress, and reward parameters interact to predict risky decision-making among adolescents SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Gambling; Wheel of fortune; Expected value; Uncertainty; Youths ID THREAT PERCEPTION ABNORMALITIES; BEHAVIORAL-INHIBITION; ATTENTIONAL CONTROL; COLLEGE-STUDENTS; TAKING BEHAVIOR; SUBSTANCE USE; CHILDREN; DISORDER; ALCOHOL; IMPULSIVITY AB Risk-taking behavior increases during adolescence, leading to potentially disastrous consequences. Social anxiety emerges in adolescence and may compound risk-taking propensity, particularly during stress and when reward potential is high. However, the manner in which social anxiety, stress, and reward parameters interact to impact adolescent risk-taking is unclear. To clarify this question, a community sample of 35 adolescents (15-18 yo), characterized as having high or low social anxiety, participated in a study over two separate days, during each of which they were exposed to either a social stress or a control condition, while performing a risky decision-making task. The task manipulated, orthogonally, reward magnitude and probability across trials. Three findings emerged. First, reward magnitude had a greater impact on the rate of risky decisions in high social anxiety (HSA) than low social anxiety (LSA) adolescents.:Second, reaction times (RTs) were similar during the social stress and the control conditions for the HSA:group, whereas the LSA group's RTs differed between conditions. Third, HSA adolescents showed the longest RTs on the most negative trials. These findings suggest that risk-taking in adolescents is modulated by context and reward parameters differentially as a function of social anxiety. Published by Elsevier Ltd. C1 [Richards, Jessica M.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD 21224 USA. [Patel, Nilam; Ernst, Monique] NIMH, Bethesda, MD 20817 USA. [Daniele-Zegarelli, Teresa] Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. [MacPherson, Laura; Lejuez, C. W.] Univ Maryland, Dept Psychol, College Pk, MD 20741 USA. RP Ernst, M (reprint author), NIMH, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 35 TC 5 Z9 6 U1 2 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2015 VL 29 BP 25 EP 34 DI 10.1016/j.janxdis.2014.10.001 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CC3RC UT WOS:000350265700005 PM 25465884 ER PT J AU Milovancev, M Hauck, M Keller, C Stranahan, LW Mansoor, A Malarkey, DE AF Milovancev, M. Hauck, M. Keller, C. Stranahan, L. W. Mansoor, A. Malarkey, D. E. TI Comparative Pathology of Canine Soft Tissue Sarcomas: Possible Models of Human Non-rhabdomyosarcoma Soft Tissue Sarcomas SO JOURNAL OF COMPARATIVE PATHOLOGY LA English DT Article DE comparative pathology; dog; man; soft tissue sarcoma ID DRUG DEVELOPMENT; DOGS; TUMORS; TARGETS; BIOLOGY AB Comparative analyses of canine and human soft tissue sarcomas (STSs) are lacking. This study compared the histological and immunohistochemical (labelling for desmin, smooth muscle actin [SMA], CD31, pancytokeratin, S100 and CD34) appearance of 32 archived, formalin-fixed, paraffin wax-embedded canine STS tumour specimens by board-certified veterinary and medical pathologists, both blinded to the other's interpretations. Comparison between the veterinary and human diagnoses revealed a generally consistent pattern of interpretation with few notable variations. Most tumours (13/32) were judged to display similar histomorphological appearance to human low-grade spindle cell sarcomas, appearing non-distinctive and morphologically of a fibroblastic/myofibroblastic type. Five canine cases resembled human liposarcoma, but with atypical desmin-positive epithelioid cells present. Five canine cases resembled human spindle cell sarcoma with myxoid features and two additional cases resembled human myxofibrosarcoma. Seven canine cases were noted to resemble human undifferentiated sarcoma. Findings in the present study demonstrate that canine STSs display histological and immunohistochemical features similar to their human equivalents. Because of these cross-species similarities, a particular opportunity exists to understand the biology and treatment of human STS by potentially including dogs as clinical models. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Milovancev, M.] Oregon State Univ, Dept Clin Sci, Corvallis, OR 97331 USA. [Hauck, M.; Stranahan, L. W.] N Carolina State Univ, Dept Clin Sci, Raleigh, NC 27695 USA. [Keller, C.] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA. [Mansoor, A.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Malarkey, D. E.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA. [Keller, C.] Childrens Canc Therapy Dev Inst, Ft Collins, CO 80524 USA. RP Milovancev, M (reprint author), Oregon State Univ, Dept Clin Sci, Corvallis, OR 97331 USA. EM milan.milovancev@oregonstate.edu OI Milovancev, Milan/0000-0002-0556-4409 NR 18 TC 3 Z9 3 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9975 EI 1532-3129 J9 J COMP PATHOL JI J. Comp. Pathol. PD JAN PY 2015 VL 152 IS 1 BP 22 EP 27 DI 10.1016/j.jcpa.2014.09.005 PG 6 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA CD2OX UT WOS:000350920000004 PM 25435513 ER PT J AU Johnson, CL Green, DS Zoon, KC AF Johnson, Chase L. Green, Daniel S. Zoon, Kathryn C. TI Human Monocytes in the Presence of Interferons Alpha2a and Gamma Are Potent Killers of Serous Ovarian Cancer Cell Lines in Combination with Paclitaxel and Carboplatin SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MACROPHAGES AB Interferons (IFNs) play an important role in immune surveillance of tumors; however, their efficacy in the treatment of malignancies has been limited. Monocytes are mononuclear phagocytes that are critical to the generation of an innate immune response to tumors. The authors and others have shown that treatment of tumor cell lines in vitro and in vivo with human monocytes primed with type I and type II IFNs results in killing. We now expand on this work, in an extended panel of ovarian cancer cell lines. In this study, we hypothesized that there would be variable sensitivity amongst cell lines to the killing properties of monocytes and IFNs. To this end, we explored the interactions of IFN primed monocytes in conjunction with the standard of therapy for ovarian cancer, taxane, and platinum-based chemotherapeutics. Using 6 ovarian cancer cell lines, we demonstrated that there is variation from cell line to cell line in the ability of IFN-alpha 2a and IFN-gamma primed monocytes to synergistically kill target tumor cells, and further, there is an additive killing effect when target cells are treated with both IFN primed monocytes and chemotherapy. C1 [Johnson, Chase L.; Green, Daniel S.; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. RP Green, DS (reprint author), NIAID, Cytokine Biol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM daniel.green2@nih.gov FU Cytokine Biology Section; Intramural Research Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) FX The authors would like to thank Christina M. Annunziata (NCI) for reagents and discussions, Raj Puri (FDA) for discussions, Joe Bekisz and the Cytokine Biology Section for support and discussions.; This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID). NR 20 TC 2 Z9 2 U1 2 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN 1 PY 2015 VL 35 IS 1 BP 55 EP 62 DI 10.1089/jir.2014.0057 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CD7MT UT WOS:000351275300007 PM 25068849 ER PT J AU Camps, J Erdos, MR Ried, T AF Camps, Jordi Erdos, Michael R. Ried, Thomas TI The role of lamin B1 for the maintenance of nuclear structure and function SO NUCLEUS LA English DT Article DE alternative splicing; B1; chromosome territories; chromatin decondensation; DNA replication; histone modifications; Lamin LMNB1; nuclear organization; S-phase ID HUTCHINSON-GILFORD-PROGERIA; DNA-REPLICATION; MAMMALIAN-CELLS; CHROMOSOME TERRITORIES; GENE-EXPRESSION; ORGANIZATION; CHROMATIN; ARCHITECTURE; SENESCENCE; ENVELOPE AB Lamins constitute an integral structural component of the nuclear lamina. However, their impact on the structure and stability of chromosome territories, and on the regulation of gene expression is explored to a lesser extent. By 3D-FISH, Camps and colleagues showed that lamin B1 (LMNB1) is required for proper chromosome condensation in interphase nuclei, and deficiency of LMNB1 triggers the relocation of the epigenetic mark of facultative heterochromatin, H3K27me3, toward the interior of the nucleus. Additionally, LMNB1 repression slowed cellular growth due to S-phase delays and increased genomic instability. Finally, silencing of LMNB1 resulted in enlarged nuclear speckles and in extensive changes in alternative splicing of multiple genes. Altogether, the data suggest a central role of LMNB1 for the condensation of chromosome territories, for the distribution of heterochromatin, and for the regulation of gene expression and splicing. C1 [Camps, Jordi] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CIBERehd, Lab Gastrointestinal & Pancreat Oncol, Barcelona, Spain. [Erdos, Michael R.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ried, T (reprint author), NCI, Sect Canc Genom, Genet Branch, NIH, Bethesda, MD 20892 USA. EM jcamps@clinic.ub.es; riedt@mail.nih.gov FU NIH, National Cancer Institute; Instituto de Salud Carlos III [CP13/00160] FX This project was supported by the Intramural Research Program of the NIH, National Cancer Institute. JC is supported by Instituto de Salud Carlos III (CP13/00160). NR 37 TC 2 Z9 2 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PD JAN-FEB PY 2015 VL 6 IS 1 BP 8 EP 14 DI 10.1080/19491034.2014.1003510 PG 7 WC Cell Biology SC Cell Biology GA CD1FY UT WOS:000350821400003 PM 25602590 ER PT J AU Chen, HM Comment, N Chen, J Ronquist, S Hero, A Ried, T Rajapakse, I AF Chen, Haiming Comment, Nicholas Chen, Jie Ronquist, Scott Hero, Alfred Ried, Thomas Rajapakse, Indika TI Chromosome Conformation of Human Fibroblasts Grown in 3-Dimensional Spheroids SO NUCLEUS LA English DT Article DE chromatin; chromosome conformation; chromosome territories; interphase nucleus; 3-dimensional spheroids ID GENE DENSITY; CELL-NUCLEI; HI-C; CHROMATIN; ORGANIZATION; CAPTURE; TERRITORIES; MITOSIS; GENOME AB In the study of interphase chromosome organization, genome-wide chromosome conformation capture (Hi-C) maps are often generated using 2-dimensional (2D) monolayer cultures. These 2D cells have morphological deviations from cells that exist in 3-dimensional (3D) tissues in vivo, and may not maintain the same chromosome conformation. We used Hi-C maps to test the extent of differences in chromosome conformation between human fibroblasts grown in 2D cultures and those grown in 3D spheroids. Significant differences in chromosome conformation were found between 2D cells and those grown in spheroids. Intra-chromosomal interactions were generally increased in spheroid cells, with a few exceptions, while inter-chromosomal interactions were generally decreased. Overall, chromosomes located closer to the nuclear periphery had increased intra-chromosomal contacts in spheroid cells, while those located more centrally had decreased interactions. This study highlights the necessity to conduct studies on the topography of the interphase nucleus under conditions that mimic an in vivo environment. C1 [Chen, Haiming; Comment, Nicholas; Chen, Jie; Ronquist, Scott; Hero, Alfred; Rajapakse, Indika] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Chen, Jie; Hero, Alfred] Univ Michigan, Dept Elect Engn & Comp Sci, Coll Engn, Ann Arbor, MI 48109 USA. [Hero, Alfred] Univ Michigan, Dept Stat, Coll Literature Sci & Arts, Ann Arbor, MI 48109 USA. [Hero, Alfred] Univ Michigan, Coll Engn, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Ried, Thomas] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rajapakse, Indika] Univ Michigan, Dept Math, Coll Literature Sci & Arts, Ann Arbor, MI 48109 USA. RP Rajapakse, I (reprint author), Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. EM indikar@umich.edu RI Chen, Jie/G-2080-2015 FU Defense Advanced Research Projects Agency (DARPA) Biochronicity Project; National Institutes of Health (NIH) [K25DK082791-01A109]; Defense Advanced Research Projects Agency (DARPA) under the Predicting Health and Disease (PHD) program FX This work is supported with a grant from Defense Advanced Research Projects Agency (DARPA) Biochronicity Project and National Institutes of Health (NIH; grant K25DK082791-01A109) to IR. The work of J. Chen and A. O. Hero was partially supported by Defense Advanced Research Projects Agency (DARPA), under the Predicting Health and Disease (PHD) program. NR 28 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PD JAN-FEB PY 2015 VL 6 IS 1 BP 55 EP 65 DI 10.1080/19491034.2014.1003745 PG 11 WC Cell Biology SC Cell Biology GA CD1FY UT WOS:000350821400009 PM 25738643 ER PT J AU Courcoutsakis, N Prassopoulos, P Stratakis, C AF Courcoutsakis, Nikos Prassopoulos, Panos Stratakis, Constantine TI Carney Complex: One More Entity with Skin and Bone Manifestations SO RADIOGRAPHICS LA English DT Letter ID DISORDERS; GENETICS C1 [Courcoutsakis, Nikos; Prassopoulos, Panos] Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Radiol & Med Imaging, Alexandroupolis 68100, Greece. [Stratakis, Constantine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Intramural Res, Bethesda, MD USA. RP Courcoutsakis, N (reprint author), Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Radiol & Med Imaging, Alexandroupolis 68100, Greece. EM ncourcou@med.duth.gr NR 6 TC 1 Z9 1 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2015 VL 35 IS 1 BP 296 EP 297 DI 10.1148/rg.351140249 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD0FF UT WOS:000350745300023 PM 25590407 ER PT S AU Subramanian, M Li, XL Hara, T Lal, A AF Subramanian, Murugan Li, Xiao Ling Hara, Toshifumi Lal, Ashish BE Carmichael, GG TI A Biochemical Approach to Identify Direct MicroRNA Targets SO REGULATORY NON-CODING RNAS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE MicroRNA; Pre-miRNA; MicroRNP; RISC; Native agarose gel; Native PAGE; Argonaute; Dicer; Ribonucleoprotein; RNA-protein ID RNA-BINDING PROTEIN; CELL-PROLIFERATION; MESSENGER-RNAS; RECOGNITION; SITES; IDENTIFICATION; EXPRESSION; PATHWAYS; MIR-519; CLIP AB We have recently developed a biochemical approach to isolate miRNA-bound mRNAs and have used this method to identify the genome-wide mRNAs regulated by the tumor suppressor miRNA miR-34a. This method involves transfection of cells with biotinylated miRNA mimics, streptavidin pulldown, RNA isolation, and qRT-PCR. The protocol in this chapter describes these steps and the issues that should be considered while designing such pulldown experiments. C1 [Subramanian, Murugan; Li, Xiao Ling; Hara, Toshifumi; Lal, Ashish] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Subramanian, M (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 24 TC 2 Z9 2 U1 0 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1369-5; 978-1-4939-1368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1206 BP 29 EP 37 DI 10.1007/978-1-4939-1369-5_3 D2 10.1007/978-1-4939-1369-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA BC2DN UT WOS:000350764500004 PM 25240884 ER PT J AU Trabert, B Chen, J Devesa, SS Bray, F McGlynn, KA AF Trabert, B. Chen, J. Devesa, S. S. Bray, F. McGlynn, K. A. TI International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973-2007 SO ANDROLOGY LA English DT Article DE birth cohort; international trends; seminoma; testicular cancer incidence ID TEMPORAL VARIATION; COHORT MODELS; AGE PERIOD; MORTALITY; RATES; IMMIGRANTS; INCREASES; DECLINES; SWEDEN; RISKS AB Incidence rates of testicular cancer in Northern European and North American countries have been widely reported, whereas rates in other populations, such as Eastern Europe, Central/South America, Asia, and Africa, have been less frequently evaluated. We examined testicular cancer incidence rates overall and by histologic type by calendar time and birth cohort for selected global populations 1973-2007. Age-standardized incidence rates over succeeding 5-year periods were calculated from volumes 4-9 of Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume 10) database. Annual percent change over the 35-year period was calculated using weighted least squares regression. Age-period-cohort analyses were performed and observed rates and fitted rate ratios presented by birth cohort. Incidence rates of testicular cancer increased between 1973-1977 and 2003-2007 in most populations evaluated worldwide. Of note, incidence rates in Eastern European countries rose rapidly and approached rates in Northern European countries. Rates in Central and South America also increased and are now intermediate to the high rates among men of European ancestry and low rates among men of Asian or African descent. Some heterogeneity in the trends in seminoma and nonseminoma were observed in Denmark, the United Kingdom, and among US whites, particularly in recent generations, with rapid and uniform increases in the incidence of both histologic types in Slovakia. Reasons for the rising incidence rates among European and American populations remain unexplained; however, changing distributions in the prevalence of risk factors for testicular cancer cannot be ruled out. C1 [Trabert, B.; Chen, J.; Devesa, S. S.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bray, F.] Int Agcy Res Canc, Sect Canc Surveillance, F-69372 Lyon, France. RP Trabert, B (reprint author), 9609 Med Ctr Dr,Room 7E 228, Bethesda, MD 20892 USA. EM trabertbl@mail.nih.gov RI Trabert, Britton/F-8051-2015 FU Intramural NIH HHS [Z01 CP010126-13] NR 20 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JAN PY 2015 VL 3 IS 1 SI SI BP 4 EP 12 DI 10.1111/andr.293 PG 9 WC Andrology SC Endocrinology & Metabolism GA CC3ZA UT WOS:000350288800002 PM 25331326 ER PT J AU Ghazarian, AA Trabert, B Devesa, SS McGlynn, KA AF Ghazarian, A. A. Trabert, B. Devesa, S. S. McGlynn, K. A. TI Recent trends in the incidence of testicular germ cell tumors in the United States SO ANDROLOGY LA English DT Article DE ethnic groups; incidence; testicular cancer; testicular germ cell tumor; trends ID PERINATAL VARIABLES; SUSCEPTIBILITY LOCI; CANCER-EXPERIENCES; RISK; METAANALYSIS; VARIANTS AB Testicular germ cell tumors (TGCT), which comprise 98% of all testicular malignancies, are the most commonly occurring cancers among men between the ages of 15 and 44years in the United States (US). A prior report from our group found that while TGCT incidence among all US men increased between 1973 and 2003, the rate of increase among black men was more pronounced starting in 1989-1993 than was the rate of increase among other men. In addition, TGCT incidence increased among Hispanic white men between 1992 and 2003. To determine whether these patterns have continued, in the current study, we examined temporal trends in incidence through 2011. Between 1992 and 2011, 21271 TGCTs (12419 seminomas; 8715 non-seminomas; 137 spermatocytic seminomas) were diagnosed among residents of the Surveillance, Epidemiology, and End Results 13 registry areas. The incidence of TGCT was highest among non-Hispanic white men (6.97 per 100000 man-years) followed by American Indian/Alaska Native (AI/AN; 4.66), Hispanic white (4.11), Asian/Pacific Islander (A/PI; 1.95), and black (1.20) men. Non-Hispanic white men were more likely to present with smaller tumors (3.5cm) and localized disease (72.6%) than were men of other races/ethnicities. Between 1992 and 2011, TGCT incidence increased significantly among Hispanic white [annual percent change (APC)=2.94, p<0.0001], black (APC=1.67, p=0.03), non-Hispanic white (APC=1.23, p<0.0001), and A/PI (APC=1.04, p=0.05) men. Incidence rates also increased, although not significantly, among AI/AN men (APC=2.96, p=0.06). The increases were greater for non-seminoma than seminoma. In summary, while non-Hispanic white men in the US continue to have the highest incidence of TGCT, they present at more favorable stages of disease and with smaller tumors than do other men. The increasing rates among non-white men, in conjunction with the larger proportion of non-localized stage disease, suggest an area where future research is warranted. C1 [Ghazarian, A. A.; Trabert, B.; Devesa, S. S.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP McGlynn, KA (reprint author), NCI, 9609 Med Ctr Dr,Room 7-E104, Bethesda, MD 20892 USA. EM mcglynnk@mail.nih.gov RI Trabert, Britton/F-8051-2015 FU National Cancer Institute (NCI) FX This work was supported by the intramural research program of the National Cancer Institute (NCI). NR 30 TC 8 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JAN PY 2015 VL 3 IS 1 SI SI BP 13 EP 18 DI 10.1111/andr.288 PG 6 WC Andrology SC Endocrinology & Metabolism GA CC3ZA UT WOS:000350288800003 PM 25331158 ER PT J AU Stang, A Trabert, B Rusner, C Poole, C Almstrup, K Rajpert-De Meyts, E McGlynn, KA AF Stang, A. Trabert, B. Rusner, C. Poole, C. Almstrup, K. Rajpert-De Meyts, E. McGlynn, K. A. TI A survey of etiologic hypotheses among testicular cancer researchers SO ANDROLOGY LA English DT Article DE testicular neoplasms; testis; testis cancer; etiology; survey ID GERM-CELL TUMORS; RISK-FACTORS; CRYPTORCHIDISM; HYPOSPADIAS; EXPOSURE; BOYS; QUESTIONS; NUTRITION; CARCINOMA; TESTIS AB Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term testicular cancer' and published within 10years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer. C1 [Stang, A.] Univ Klinikum Essen, Zentrum Klin Epidemiol, Inst Med Informat Biometrie & Epidemiol, D-45147 Essen, Germany. [Stang, A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Trabert, B.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Rusner, C.] Univ Halle Wittenberg, Fak Med, Inst Klin Epidemiol, D-06108 Halle, Germany. [Poole, C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Almstrup, K.; Rajpert-De Meyts, E.] Rigshosp, Copenhagen Univ Hosp, Univ Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. RP Stang, A (reprint author), Univ Klinikum Essen, Zentrum Klin Epidemiol, Inst Med Informat Biometrie & Epidemiol, Hufelandstr 55, D-45147 Essen, Germany. EM andreas.stang@uk-essen.de RI Trabert, Britton/F-8051-2015; Almstrup, Kristian/C-4668-2008 OI Almstrup, Kristian/0000-0002-1832-0307 FU Intramural NIH HHS [Z01 CP010126-13] NR 34 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JAN PY 2015 VL 3 IS 1 SI SI BP 19 EP 26 DI 10.1111/andr.306 PG 8 WC Andrology SC Endocrinology & Metabolism GA CC3ZA UT WOS:000350288800004 PM 25538016 ER PT J AU Greene, MH Mai, PL Loud, JT Pathak, A Peters, JA Mirabello, L McMaster, ML Rosenberg, P Stewart, DR AF Greene, M. H. Mai, P. L. Loud, J. T. Pathak, A. Peters, J. A. Mirabello, L. McMaster, M. L. Rosenberg, P. Stewart, D. R. TI Familial testicular germ cell tumors (FTGCT) - overview of a multidisciplinary etiologic study SO ANDROLOGY LA English DT Review DE cohort studies; comet assay; cryptorchidism; cytogenetics; DNA methylation; epidemiology; familial cancer; gene polymorphism; genetic disorders; genome wide sequencing; Genome-wide association studies; testis cancer ID COPY-NUMBER VARIATION; SUSCEPTIBILITY LOCI; HEALTH COMMUNICATION; HEREDITARY BREAST; CANCER; RISK; MICROLITHIASIS; MEN; VARIANTS; ASSOCIATION AB This Review summarizes the cumulative results of the National Cancer Institute Clinical Genetics Branch Multidisciplinary Etiologic Study of Familial Testicular Germ Cell Tumors (FTGCT). Initiated 12years ago, this protocol enrolled 724 subjects from 147 unrelated families with either 2 affected men (n=90) with TGCT or a proband with bilateral TGCT and a negative family history for this cancer (n=57). Data were collected directly from 162 subjects evaluated at the NIH Clinical Center, and 562 subjects provided information from their home communities (Field Cohort). The primary study aims included (i) ascertaining, enrolling eligible FTGCT kindred, (ii) characterizing the clinical phenotype of multiple-case families, (iii) identifying the underlying genetic mechanism for TGCT susceptibility in families, (iv) evaluating counseling, psychosocial, and behavioral issues resulting from membership in an FTGCT family, and (v) creating an annotated biospecimen repository to permit subsequent translational research studies. Noteworthy findings include (i) documenting the epidemiologic similarities between familial and sporadic TGCT, (ii) demonstrating significantly younger age-at-diagnosis for familial vs. sporadic TGCT, (iii) absence of a dysmorphic phenotype in affected family members, (iv) shifting the focus of gene discovery from a search for rare, highly penetrant susceptibility variants to the hypothesis that multiple, more common, lower penetrance genes underlie TGCT genetic risk, (v) implicating testicular microlithiasis in FTGCT risk, and (vi) observing that aberrant methylation may contribute to FTGCT risk. A clinically based, biospecimen-intensive, multidisciplinary research strategy has provided novel, valuable insights into the etiology of FTGCT, and created a research resource which will support FTGCT clinical and laboratory studies for years to come. C1 [Greene, M. H.; Mai, P. L.; Loud, J. T.; Pathak, A.; Peters, J. A.; Stewart, D. R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Mirabello, L.; McMaster, M. L.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Rosenberg, P.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, 9606 Med Ctr Dr,Room 6E 454, Rockville, MD 20850 USA. EM greenem@mail.nih.gov FU U.S. National Cancer Institute, National Institutes of Health; Westat Inc., Rockville, Maryland, USA; [00261200109D261011019]; [HHSN261200655004C]; [HHSN261201300003C] FX We acknowledge the absolutely essential contributions made by our study participants, who selflessly donated their time, bio-specimens, life experiences and support to this project. Without them, this work would have been impossible. We also express special appreciation to the ongoing support of Mr. Doug Bank, President of the Testicular Cancer Resource Center patient advocacy group, for his patient accrual contributions to this study. He assisted above and beyond the call of duty. We also thank the numerous members of the contract support staff from We stat (including Ron Kase, Rissah Watkins, Janet Bracci, and Kathy Nichols), who provided the clinical research infrastructure for our program, as well as investigators from the Indiana University Testicular Cancer Research Program and to Dr. Katherine McGlynn of NCI's Hormone and Reproductive Epidemiology Branch for family referrals. Finally, multiple clinical investigators who served within the Clinical Genetics Branch played an important role in the conduct of this study in earlier years. These include Drs. Joan Kramer, Larissa Korde, and Christian Kratz. The research conducted by Drs. Greene, Mai, Loud, Pathak, Peters, McMaster, Mirabello, Rosenberg, and Stewart was supported the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health. The research was supported by support services contracts 00261200109D261011019, HHSN261200655004C, and HHSN261201300003C with Westat Inc., Rockville, Maryland, USA. NR 72 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JAN PY 2015 VL 3 IS 1 SI SI BP 47 EP 58 DI 10.1111/andr.294 PG 12 WC Andrology SC Endocrinology & Metabolism GA CC3ZA UT WOS:000350288800007 PM 25303766 ER PT S AU Murray, GJ AF Murray, Gary J. BE Vasiliou, V Zakhari, S Seitz, HK Hoek, JB TI Biological Basis of Alcohol-Induced Cancer Introduction SO BIOLOGICAL BASIS OF ALCOHOL-INDUCED CANCER SE Advances in Experimental Medicine and Biology LA English DT Editorial Material; Book Chapter ID DNA METHYLATION; POOLED ANALYSIS; NECK CANCERS; DISEASE; RISK; HEAD; EPIDEMIOLOGY; CONSUMPTION; ESOPHAGEAL; WOMEN C1 NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. RP Murray, GJ (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. EM gary.murray@nih.gov NR 20 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-09614-8; 978-3-319-09613-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 815 BP 1 EP 6 DI 10.1007/978-3-319-09614-8_1 D2 10.1007/978-3-319-09614-8 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1UK UT WOS:000350426600002 PM 25427898 ER PT S AU Vasiliou, V Zakhari, S Seitz, HK Hoek, JB AF Vasiliou, Vasilis Zakhari, Samir Seitz, Helmut K. Hoek, Jan B. BE Vasiliou, V Zakhari, S Seitz, HK Hoek, JB TI Biological Basis of Alcohol-Induced Cancer Preface SO BIOLOGICAL BASIS OF ALCOHOL-INDUCED CANCER SE Advances in Experimental Medicine and Biology LA English DT Editorial Material; Book Chapter C1 [Vasiliou, Vasilis] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA. [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. [Zakhari, Samir] DISCUS, SVP, Sci, Washington, DC USA. [Seitz, Helmut K.] Heidelberg Univ, Alcohol Res Ctr, D-69115 Heidelberg, Germany. [Seitz, Helmut K.] Salem Med Ctr, Heidelberg, Germany. [Hoek, Jan B.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Vasiliou, V (reprint author), Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-09614-8; 978-3-319-09613-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 815 BP V EP VI D2 10.1007/978-3-319-09614-8 PG 2 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1UK UT WOS:000350426600001 ER PT S AU Zakhari, S Hoek, JB AF Zakhari, Samir Hoek, Jan B. BE Vasiliou, V Zakhari, S Seitz, HK Hoek, JB TI Alcohol and Breast Cancer: Reconciling Epidemiological and Molecular Data SO BIOLOGICAL BASIS OF ALCOHOL-INDUCED CANCER SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Breast cancer; Epidemiology; Alcohol; Acetaldehyde; Reactive oxygen species; Estrogen; Folate; Metabolism; Epigenetics; Alcohol dehydrogenase; Aldehyde dehydrogenase; BRCA1; BRCA2 ID PROGESTERONE-RECEPTOR STATUS; RAT MAMMARY TISSUE; DIETARY-FOLATE INTAKE; ESTROGEN-RECEPTOR; POSTMENOPAUSAL WOMEN; HORMONE-THERAPY; GENE-EXPRESSION; RISK-FACTORS; ACETALDEHYDE ACCUMULATION; PROSPECTIVE COHORT AB Breast cancer is the most diagnosed cancer in women worldwide. Epidemiological studies have suggested a possible causative role of alcohol consumption as a risk factor for breast cancer. However, such conclusions should be interpreted with considerable caution for several reasons. While epidemiological studies can help identify the roots of health problems and disease incidence in a community, they are by necessity associative and cannot determine cause and effect relationships. In addition, all these studies rely on self-reporting to determine the amount and type of alcoholic beverage consumed, which introduces recall bias. This is documented in a recent study which stated that the apparent increased risk of cancer among light-moderate drinkers may be "substantially due to underreporting of intake." Another meta-analysis about alcohol and breast cancer declared "the modest size of the association and variation in results across studies leave the causal role of alcohol in question." Furthermore, breast cancer develops over decades; thus, correlations between alcohol consumption and breast cancer cannot be determined in epidemiological studies with windows of alcohol exposure that captures current or recent alcohol intake, after clinical diagnosis. Numerous risk factors are involved in breast carcinogenesis; some are genetic and beyond the control of a woman; others are influenced by lifestyle factors. Breast cancer is a heterogeneous and polygenic disease which is further influenced by epigenetic mechanisms that affect the transciptomes, proteomes and metabolomes, and ultimately breast cancer evolution. Environmental factors add another layer of complexity by their interactions with the susceptibility genes for breast cancer and metabolic diseases. The current state-of-knowledge about alcohol and breast cancer association is ambiguous and confusing to both a woman and her physician. Confronting the huge global breast cancer issue should be addressed by sound science. It is advised that women with or without a high risk for breast cancer should avoid overconsumption of alcohol and should consult with their physician about risk factors involved in breast cancer. Since studies associating moderate alcohol consumption and breast cancer are contradictory, a woman and her physician should weigh the risks and benefits of moderate alcohol consumption. C1 [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20852 USA. [Zakhari, Samir] DISCUS, SVP, Sci, Washington, DC 20005 USA. [Hoek, Jan B.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Zakhari, S (reprint author), DISCUS, SVP, Sci, Washington, DC 20005 USA. EM szakhari@discus.org OI Hoek, Jan/0000-0001-7127-4218 NR 125 TC 4 Z9 4 U1 1 U2 18 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-09614-8; 978-3-319-09613-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 815 BP 7 EP 39 DI 10.1007/978-3-319-09614-8_2 D2 10.1007/978-3-319-09614-8 PG 33 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1UK UT WOS:000350426600003 PM 25427899 ER PT S AU Balbo, S Brooks, PJ AF Balbo, Silvia Brooks, Philip J. BE Vasiliou, V Zakhari, S Seitz, HK Hoek, JB TI Implications of Acetaldehyde-Derived DNA Adducts for Understanding Alcohol-Related Carcinogenesis SO BIOLOGICAL BASIS OF ALCOHOL-INDUCED CANCER SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Acetaldehyde; DNA adducts; N-2-ethyldeoxyguanosine; Upper aerodigestive tract cancers ID ORAL-CAVITY; ALDEHYDE DEHYDROGENASE-2; ESOPHAGEAL EPITHELIUM; SALIVARY ACETALDEHYDE; ETHANOL-METABOLISM; POSSIBLE MECHANISM; CELL REGENERATION; DRINKING ALCOHOL; POLYMERASE ETA; HUMAN STOMACH AB Among various potential mechanisms that could explain alcohol carcinogenicity, the metabolism of ethanol to acetaldehyde represents an obvious possible mechanism, at least in some tissues. The fundamental principle of genotoxic carcinogenesis is the formation of mutagenic DNA adducts in proliferating cells. If not repaired, these adducts can result in mutations during DNA replication, which are passed on to cells during mitosis. Consistent with a genotoxic mechanism, acetaldehyde does react with DNA to form a variety of different types of DNA adducts. In this chapter we will focus more specifically on N-2-ethylidene-deoxyguanosine (N-2-ethylidene-dG), the major DNA adduct formed from the reaction of acetaldehyde with DNA and specifically highlight recent data on the measurement of this DNA adduct in the human body after alcohol exposure. Because results are of particular biological relevance for alcohol-related cancer of the upper aerodigestive tract (UADT), we will also discuss the histology and cytology of the UADT, with the goal of placing the adduct data in the relevant cellular context for mechanistic interpretation. Furthermore, we will discuss the sources and concentrations of acetaldehyde and ethanol in different cell types during alcohol consumption in humans. Finally, in the last part of the chapter, we will critically evaluate the concept of carcinogenic levels of acetaldehyde, which has been raised in the literature, and discuss how data from acetaldehyde genotoxicity are and can be utilized in physiologically based models to evaluate exposure risk. C1 [Balbo, Silvia] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. [Brooks, Philip J.] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Brooks, Philip J.] NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Balbo, S (reprint author), Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. EM balbo006@umn.edu; pjbrooks@mail.nih.gov FU NIEHS NIH HHS [ES-11297] NR 60 TC 7 Z9 8 U1 1 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-09614-8; 978-3-319-09613-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 815 BP 71 EP 88 DI 10.1007/978-3-319-09614-8_5 D2 10.1007/978-3-319-09614-8 PG 18 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1UK UT WOS:000350426600006 PM 25427902 ER PT S AU Manna, SK Thompson, MD Gonzalez, FJ AF Manna, Soumen K. Thompson, Matthew D. Gonzalez, Frank J. BE Vasiliou, V Zakhari, S Seitz, HK Hoek, JB TI Application of Mass Spectrometry-Based Metabolomics in Identification of Early Noninvasive Biomarkers of Alcohol-Induced Liver Disease Using Mouse Model SO BIOLOGICAL BASIS OF ALCOHOL-INDUCED CANCER SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Alcohol-induced liver disease; PPAR alpha; Ppara-null mouse; Steatosis; Metabolomics; UPLC-ESI-QTOFMS; Multivariate data analysis; Biomarker; Genetic background; Indole-3-lactic acid; Phenyllactic acid ID ACTIVATED-RECEPTOR-ALPHA; PPARA-NULL MOUSE; FATTY LIVER; ASPARTATE-AMINOTRANSFERASE; HEPATOCELLULAR-CARCINOMA; LIPID-METABOLISM; GENE; DEHYDROGENASE; MICE; POLYMORPHISMS AB A rapid, non-invasive urine test for early stage alcohol-induced liver disease (ALD) would permit risk stratification and treatment of high-risk individuals before ALD leads to irreversible liver damage and death. Urinary metabolomic studies were carried out to identify ALD-associated metabolic biomarkers using Ppara-null mouse model that is susceptible to ALD development on chronic alcohol consumption. Two successive studies were conducted to evaluate the applicability of mass spectrometry-based metabolomics in identification of ALD-specific signatures and to examine the robustness of these biomarkers against genetic background. Principal components analysis of ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-generated urinary metabolic fingerprints showed that alcoholtreated wild-type and Ppara-null mice could be distinguished from control animals. It also showed that a combined endogenous biomarker panel helps to identify subjects with ALD as well as those at risk of developing ALD even without any information on alcohol intake or genetics. Quantitative analysis showed that increased excretion of indole-3-lactic acid and phenyllactic acid was a genetic background-independent signature exclusively associated with ALD pathogenesis in Ppara-null mice that showed liver pathologies similar to those observed in early stages of human ALD. These findings demonstrated that mass spectrometry-based metabolomic analysis could help in the identification of ALD-specific signatures, and that metabolites such as indole-3-lactic acid and phenyllactic acid, may serve as robust noninvasive biomarkers for early stages of ALD. C1 [Manna, Soumen K.; Thompson, Matthew D.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM soumenmanna@gmail.com; matthew.thompson2@nih.gov; gonzalef@mail.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [U01ES016013] NR 60 TC 7 Z9 7 U1 5 U2 31 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-09614-8; 978-3-319-09613-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 815 BP 217 EP 238 DI 10.1007/978-3-319-09614-8_13 D2 10.1007/978-3-319-09614-8 PG 22 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC1UK UT WOS:000350426600014 PM 25427910 ER PT J AU Ito, S Barrett, AJ AF Ito, Sawa Barrett, A. John TI ST2: the biomarker at the heart of GVHD severity SO BLOOD LA English DT Editorial Material ID VERSUS-HOST-DISEASE; HEMATOPOIETIC-CELL TRANSPLANTATION; THERAPY C1 [Ito, Sawa; Barrett, A. John] NHLBI, Bethesda, MD 20892 USA. RP Ito, S (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 1 PY 2015 VL 125 IS 1 BP 10 EP 11 PG 4 WC Hematology SC Hematology GA CD1BT UT WOS:000350809500007 PM 25554746 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, Kieron Wilson, Wyndham H. TI Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach? SO BLOOD LA English DT Review ID NON-HODGKINS-LYMPHOMA; REED-STERNBERG CELLS; DOSE-ADJUSTED EPOCH; CD23 EXPRESSION; CHEMOTHERAPY; RITUXIMAB; CHOP; FEATURES; JAK2; AMPLIFICATION AB Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is putatively derived from a thymic B cell. Accounting for up to 10% of cases of DLBCL, this subtype predominantly affects women in the third and fourth decades of life. Its clinical and molecular characteristics are distinct from other subtypes of DLBCL and, in fact, closely resemble those of nodular sclerosing Hodgkin lymphoma (NSHL). Recently, mediastinal lymphomas with features intermediate between PMBL and NSHL, called mediastinal gray-zone lymphomas, have been described. The optimal management of PMBL is controversial, and most standard approaches include a combination of immunochemotherapy and mediastinal radiation. Recently, the recognition that mediastinal radiation is associated with significant long-term toxicities has led to the development of novel approaches for PMBL that have shown excellent efficacy and challenge the need for routine mediastinal radiation. C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov FU National Cancer Institute FX The authors receive funding from the Intramural Program of the National Cancer Institute. NR 52 TC 24 Z9 24 U1 3 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 1 PY 2015 VL 125 IS 1 BP 33 EP 39 DI 10.1182/blood-2014-05-575092 PG 7 WC Hematology SC Hematology GA CD1BT UT WOS:000350809500010 PM 25499450 ER PT J AU Ganapathi, KA Townsley, DM Hsu, AP Arthur, DC Zerbe, CS Cuellar-Rodriguez, J Hickstein, DD Rosenzweig, SD Braylan, RC Young, NS Holland, SM Calvo, KR AF Ganapathi, Karthik A. Townsley, Danielle M. Hsu, Amy P. Arthur, Diane C. Zerbe, Christa S. Cuellar-Rodriguez, Jennifer Hickstein, Dennis D. Rosenzweig, Sergio D. Braylan, Raul C. Young, Neal S. Holland, Steven M. Calvo, Katherine R. TI GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HYPOPLASTIC MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTOR GATA-2; FLOW-CYTOMETRIC ANALYSIS; MONOMAC SYNDROME; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; HEMATOPOIETIC-CELLS; MUTATIONS; DIFFERENTIATION AB Germ-line GATA2 gene mutations, leading to haploinsufficiency, have been identified in patients with familial myelodysplastic syndrome/acute myeloid leukemia, monocytopenia and mycobacterial infections, Emberger syndrome, and dendritic cell, monocyte, B-, and NK-cell deficiency. GATA2 mutations have also been reported in aminority of patients with congenital neutropenia and aplastic anemia (AA). The bone marrow (BM) from patients with GATA2 deficiency is typically hypocellular, with varying degrees of dysplasia. Distinguishing GATA2 patients from those with AA is critical for selecting appropriate therapy. We compared the BM flow cytometric, morphologic, and cytogenetic features of 28 GATA2 patients with those of 32 patients being evaluated for idiopathic AA. The marrow of GATA2 patients had severely reduced monocytes, B cells, and NK cells; absent hematogones; and inverted CD4: CD8 ratios. Atypical megakaryocytes and abnormal cytogenetics were more common in GATA2 marrows. CD34(+) cells were comparably reduced in GATA2 and AA. Using these criteria, we prospectively identified 4 of 32 patients with suspected AA who had features suspicious for GATA2 mutations, later confirmed by DNA sequencing. Our results show that routine BM flow cytometry, morphology, and cytogenetics in patients who present with cytopenia(s) can identify patients for whom GATA2 sequencing is indicated. C1 [Ganapathi, Karthik A.; Arthur, Diane C.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Townsley, Danielle M.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hsu, Amy P.; Zerbe, Christa S.; Cuellar-Rodriguez, Jennifer; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol, Bethesda, MD 20892 USA. [Rosenzweig, Sergio D.] NIH, Immunol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Braylan, Raul C.; Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Calvo, KR (reprint author), NIH, Hematol Sect, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2C390, Bethesda, MD 20892 USA. EM calvok@mail.nih.gov OI Calvo, Katherine/0000-0002-0771-4191 FU National Institutes of Health Division of Intramural Research; National Institutes of Health, Clinical Center; National Institutes of Health, National Institute of Allergy and Infectious Diseases; National Institutes of Health, National Heart, Lung, and Blood Institute; National Institutes of Health, National Cancer Institute FX This work was supported by the National Institutes of Health Division of Intramural Research, Clinical Center, National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, and National Cancer Institute. NR 52 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 1 PY 2015 VL 125 IS 1 BP 56 EP 70 DI 10.1182/blood-2014-06-580340 PG 15 WC Hematology SC Hematology GA CD1BT UT WOS:000350809500013 PM 25359990 ER PT J AU Ley, AM Chau, CH Figg, WD AF Ley, Ariel M. Chau, Cindy H. Figg, William D. TI Structural studies reveal thalidomide's mechanism of action and clinical effects: crystal clear or clearly complexed? SO CANCER BIOLOGY & THERAPY LA English DT Article DE angiogenesis; cereblon; IMiDs; immunomodulation; lenalidomide; pomalido- mide; teratogenesis; Thalidomide; ubiquitin ligase AB Another piece of the thalidomide puzzle is unraveled through structural studies of thalidomide and its derivatives bound to its protein target cereblon. Two recent studies published in Nature (Fischer etal.) and Nature Structural & Molecular Biology (Chamberlain etal.) have shed light on the drug's mechanisms of action and its complex biological effects. C1 [Ley, Ariel M.; Chau, Cindy H.; Figg, William D.] NIH, Natl Canc Inst, Ctr Canc Res, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NIH, Natl Canc Inst, Ctr Canc Res, Genitourinary Malignancies Branch, Bldg 10, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 5 TC 0 Z9 0 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2015 VL 16 IS 1 BP 19 EP 20 DI 10.4161/15384047.2014.972828 PG 2 WC Oncology SC Oncology GA CC0AJ UT WOS:000349996700004 PM 25692618 ER PT J AU Witkin, KL Hanlon, SE Strasburger, JA Coffin, JM Jaffrey, SR Howcroft, TK Dedon, PC Steitz, JA Daschner, PJ Read-Connole, E AF Witkin, Keren L. Hanlon, Sean E. Strasburger, Jennifer A. Coffin, John M. Jaffrey, Samie R. Howcroft, T. Kevin Dedon, Peter C. Steitz, Joan A. Daschner, Phil J. Read-Connole, Elizabeth TI RNA editing, epitranscriptomics, and processing in cancer progression SO CANCER BIOLOGY & THERAPY LA English DT Article DE ADAR; APOBEC; editing; epitranscriptomic; DNA mutations; methylation; RNA modification; tRNA ID SACCHAROMYCES-CEREVISIAE; N-6-METHYLADENOSINE; TRANSLATION; LEVEL; MASS; FTO AB The transcriptome is extensively and dynamically regulated by a network of RNA modifying factors. RNA editing enzymes APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and ADAR (adenosine deaminase, RNA-specific) irreversibly recode primary RNA sequences, whereas newly described methylases (writers) and de-methylases (erasers) dynamically alter RNA molecules in response to environmental conditions. RNA modifications can affect RNA splicing, nuclear-cytoplasmic transport, translation, and regulation of gene expression by RNA interference. In addition, tRNA base modifications, processing, and regulated cleavage have been shown to alter global patterns of mRNA translation in response to cellular stress pathways. Recent studies, some of which were discussed at this workshop, have rekindled interest in the emerging roles of RNA modifications in health and disease. On September 10th, 2014, the Division of Cancer Biology, NCI sponsored a workshop to explore the role of epitranscriptomic RNA modifications and tRNA processing in cancer progression. The workshop attendees spanned a scientific range including chemists, virologists, and RNA and cancer biologists. The goal of the workshop was to explore the interrelationships between RNA editing, epitranscriptomics, and RNA processing and the enzymatic pathways that regulate these activities in cancer initiation and progression. At the conclusion of the workshop, a general discussion focused on defining the major challenges and opportunities in this field, as well as identifying the tools, technologies, resources and community efforts required to accelerate research in this emerging area. C1 [Witkin, Keren L.; Hanlon, Sean E.; Strasburger, Jennifer A.; Howcroft, T. Kevin; Daschner, Phil J.; Read-Connole, Elizabeth] NCI, Div Canc Biol, Bethesda, MD 20892 USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Jaffrey, Samie R.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Dedon, Peter C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Steitz, Joan A.] Yale Univ, Boyer Ctr Mol Med, New Haven, CT USA. RP Howcroft, TK (reprint author), NCI, Div Canc Biol, Bethesda, MD 20892 USA. EM Howcrofk@mail.nih.gov FU NCI NIH HHS [R37 CA089441] NR 23 TC 2 Z9 2 U1 2 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2015 VL 16 IS 1 BP 21 EP 27 DI 10.4161/15384047.2014.987555 PG 7 WC Oncology SC Oncology GA CC0AJ UT WOS:000349996700005 PM 25455629 ER PT J AU Weimer, K Colloca, L Enck, P AF Weimer, Katja Colloca, Luana Enck, Paul TI Age and Sex as Moderators of the Placebo Response - An Evaluation of Systematic Reviews and Meta-Analyses across Medicine SO GERONTOLOGY LA English DT Review DE Placebo response; Age; Sex; Randomized controlled trials; Meta-analyses ID RANDOMIZED CONTROLLED-TRIALS; IRRITABLE-BOWEL-SYNDROME; MAJOR DEPRESSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RESTLESS LEGS SYNDROME; CLINICAL-TRIALS; PARKINSONS-DISEASE; META-REGRESSION; ANTIDEPRESSANT TREATMENT; SPONTANEOUS IMPROVEMENT AB Predictors of the placebo response (PR) in randomized controlled trials (RCT) have been searched for ever since RCT have become the standard for testing novel therapies and age and gender are routinely documented data in all trials irrespective of the drug tested, its indication, and the primary and secondary end points chosen. To evaluate whether age and gender have been found to be reliable predictors of the PR across medical subspecialties, we extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine) known for high PR rates. The literature database used contains approximately 2,500 papers on various aspects of the genuine PR. These 'meta-analyses' were screened for statistical predictors of the PR across multiple RCT, including age and gender, but also other patient-based and design-based predictors of higher PR rates. Retrieved papers were sorted for areas and disease categories. Only 15 of the 75 analyses noted an effect of younger age to be associated with higher PR, and this was predominantly in psychiatric conditions but not in depression, and internal medicine but not in gastroenterology. Female gender was associated with higher PR in only 3 analyses. Among the patient-based predictors, the most frequently noted factor was lower symptom severity at baseline, and among the design-based factors, it was a randomization ratio that selected more patients to drugs than to placebo, more frequent study visits, and more recent trials that were associated with higher PR rates. While younger age may contribute to the PR in some conditions, sex does not. There is currently no evidence that the PR is different in the elderly. PR are, however, markedly influenced by the symptom severity at baseline, and by the likelihood of receiving active treatment in placebo-controlled trials. (C) 2014 S. Karger AG, Basel C1 [Weimer, Katja; Enck, Paul] Univ Tubingen Hosp, Dept Internal Med 6, Psychosomat Med & Psychotherapy, DE-72076 Tubingen, Germany. [Colloca, Luana] NIH, Bethesda, MD 20892 USA. RP Enck, P (reprint author), Univ Tubingen Hosp, Dept Internal Med 6, Psychosomat Med & Psychotherapy, Frondsbergstr 23, DE-72076 Tubingen, Germany. EM paul.enck@umi-tuebingen.de OI Colloca, Luana/0000-0002-6503-4709 FU Deutsche Forschungsgemeinschaft FX This study was supported by a grant from Deutsche Forschungsgemeinschaft. NR 110 TC 9 Z9 9 U1 2 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X EI 1423-0003 J9 GERONTOLOGY JI Gerontology PY 2015 VL 61 IS 2 BP 97 EP 108 DI 10.1159/000365248 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CC5IY UT WOS:000350393500002 PM 25427869 ER PT J AU Faucette, AN Unger, BL Gonik, B Chen, K AF Faucette, Azure N. Unger, Benjamin L. Gonik, Bernard Chen, Kang TI Maternal vaccination: moving the science forward SO HUMAN REPRODUCTION UPDATE LA English DT Review DE pregnancy; vaccine; immunology; antibody; animal model ID B STREPTOCOCCAL INFECTION; INFLUENZAE TYPE-B; ACELLULAR PERTUSSIS-VACCINE; RESPIRATORY SYNCYTIAL VIRUS; TETANUS TOXOID CONJUGATE; GUINEA-PIG MODEL; LOW-BIRTH-WEIGHT; PERIPHERAL-BLOOD LYMPHOCYTES; RECURRENT PREGNANCY LOSSES; NEONATAL RESEARCH NETWORK AB BACKGROUND: Infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. In the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. Despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hampered by the lack of thorough understanding of the efficacy and safety in the pregnant women and the offspring. METHODS: An outline was synthesized based on the current status and major gaps in the knowledge of maternal vaccination. A systematic literature search in PUBMED was undertaken using the key words in each section title of the outline to retrieve articles relevant to pregnancy. Articles cited were selected based on relevance and quality. On the basis of the reviewed information, a perspective on the future directions of maternal vaccination research was formulated. RESULTS: Maternal vaccination can generate active immune protection in the mother and elicit systemic immunoglobulinG(IgG) and mucosal IgG, IgA and IgM responses to confer neonatal protection. The maternal immune system undergoes significant modulation during pregnancy, which influences responsiveness to vaccines. Significant gaps exist in our knowledge of the efficacy and safety of maternal vaccines, and no maternal vaccines against a large number of old and emerging pathogens are available. Public acceptance of maternal vaccination has been low. CONCLUSIONS: To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be coupled with human studies in an iterative manner for maternal vaccine experimentation, evaluation and optimization. Systems biology approaches should be adopted to improve the speed, accuracy and safety of maternal vaccine targeting. C1 [Faucette, Azure N.; Unger, Benjamin L.; Gonik, Bernard; Chen, Kang] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Faucette, Azure N.; Unger, Benjamin L.; Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. [Chen, Kang] Barbara Ann Karmanos Canc Inst, Tumor Biol & Microenvironm Program, Detroit, MI 48201 USA. [Chen, Kang] Wayne State Univ, Dept Immunol & Microbiol, Detroit, MI 48201 USA. [Chen, Kang] Wayne State Univ, Dept Oncol, Detroit, MI 48201 USA. [Chen, Kang] NIAID, Mucosal Immunol Studies Team, NIH, Bethesda, MD 20892 USA. RP Chen, K (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. EM kchen@med.wayne.edu FU US National Institutes of Health [U01 AI95776]; American Congress of Obstetricians and Gynecologists; Burroughs Wellcome Fund; Wayne State University Perinatal Initiative [176512]; Wayne State University Office of the Vice President for Research; Barbara Ann Karmanos Cancer Institute FX The authors' research is supported by the US National Institutes of Health (U01 AI95776 Young Investigator Award), American Congress of Obstetricians and Gynecologists (Merck Industrial Research Award), Burroughs Wellcome Fund (Preterm Birth Research Award), Wayne State University Perinatal Initiative (176512), Wayne State University Office of the Vice President for Research and Barbara Ann Karmanos Cancer Institute to K.C. NR 253 TC 10 Z9 10 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 EI 1460-2369 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD JAN-FEB PY 2015 VL 21 IS 1 BP 119 EP 135 DI 10.1093/humupd/dmu041 PG 17 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CC2BQ UT WOS:000350150100007 PM 25015234 ER PT J AU Yang, YB Staudt, LM AF Yang, Yibin Staudt, Louis M. TI Protein ubiquitination in lymphoid malignancies SO IMMUNOLOGICAL REVIEWS LA English DT Review DE ubiquitination; E3 ligase; lymphoma; multiple myeloma; ABC DLBCL ID NF-KAPPA-B; CHAIN ASSEMBLY COMPLEX; F-BOX PROTEINS; LINEAR POLYUBIQUITIN CHAINS; T-CELL-ACTIVATION; ZINC-FINGER 7; MULTIPLE-MYELOMA; TUMOR-SUPPRESSOR; LIGASE COMPLEX; MENTAL-RETARDATION AB Human lymphoid malignancies inherit gene expression networks from their normal B-cell counterpart and co-opt them for their own oncogenic purpose, which is usually governed by transcription factors and signaling pathways. These transcription factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. Protein ubiqutination plays a role in almost all cellular events and in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here, we discuss our current understanding of both proteolytic and non-proteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid-restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers. C1 [Yang, Yibin; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors have no conflicts of interest to declare. NR 140 TC 5 Z9 5 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2015 VL 263 IS 1 SI SI BP 240 EP 256 DI 10.1111/imr.12247 PG 17 WC Immunology SC Immunology GA CC2HN UT WOS:000350166200016 PM 25510281 ER PT J AU Wang, Q Guo, TQ Portas, J McPherron, AC AF Wang, Qian Guo, Tingqing Portas, Jennifer McPherron, Alexandra C. TI A Soluble Activin Receptor Type IIB Does Not Improve Blood Glucose in Streptozotocin-Treated Mice SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE activin receptor; glucocorticoid; myostatin; muscle hypertrophy; type 1 diabetes ID MYOSTATIN GENE-EXPRESSION; SKELETAL-MUSCLE MASS; INSULIN SENSITIVITY; DIABETES-MELLITUS; METABOLIC SYNDROME; PANCREATIC-ISLETS; LATENT MYOSTATIN; TRANSGENIC MICE; UP-REGULATION; MOUSE MODEL AB Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of MSTN signaling has been shown to increase muscle mass and prevent the development of obesity, insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also elevated serum levels of the glucocorticoid corticosterone. These results suggest that although MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving health in patients with T1DM. C1 [Portas, Jennifer] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Guo, Tingqing] Novo Nordisk Res Ctr China, Beijing, Peoples R China. [McPherron, Alexandra C.] Myotherapeutics, Silver Spring, MD 20903 USA. RP McPherron, AC (reprint author), Myotherapeutics, 10169 New Hampshire Ave 149, Silver Spring, MD 20903 USA. EM amcpherron@myotherapeutics.com FU Intramural Research Program of the NIDDK, NIH FX We thank Se-Jin Lee for the ACVR2B:Fc cell line, Obiageri Okafor for technical assistance and Oksana Gavrilova for advice about animal procedures. This work was supported by the Intramural Research Program of the NIDDK, NIH. NR 84 TC 7 Z9 7 U1 0 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2015 VL 11 IS 2 BP 199 EP 208 DI 10.7150/ijbs.10430 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CC5OP UT WOS:000350408200008 PM 25561902 ER PT J AU Bian, YS Han, JW Kannabiran, V Mohan, S Cheng, H Friedman, J Zhang, L VanWaes, C Chen, Z AF Bian, Yansong Han, Jiawei Kannabiran, Vishnu Mohan, Suresh Cheng, Hui Friedman, Jay Zhang, Luo VanWaes, Carter Chen, Zhong TI MEK Inhibitor PD-0325901 Overcomes Resistance to CK2 Inhibitor CX-4945 and Exhibits Anti-Tumor Activity in Head and Neck Cancer SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE CX-4945; CK2 inhibitor; PD-0325901; MEK inhibitor; head and neck cancer ID SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; PROTEIN-KINASE CK2; GROWTH-FACTOR-RECEPTOR; SIGNAL PATHWAYS; IN-VITRO; ACTIVATION; LINES; EXPRESSION; PI3K/MTOR AB The serine-threonine kinase CK2 exhibits genomic alterations and aberrant overexpression in human head and neck squamous cell carcinomas (HNSCC). Here, we investigated the effects of CK2 inhibitor CX-4945 in human HNSCC cell lines and xenograft models. The IC50's of CX-4945 for 9 UM-SCC cell lines measured by MTT assay ranged from 3.4-11.9 mu M. CX-4945 induced cell cycle arrest and cell death measured by DNA flow cytometry, and inhibited prosurvival mediators phospho-AKT and p-S6 in UM-SCC1 and UM-SCC46 cells. CX-4945 decreased NF-kappa B and Bcl-XL reporter gene activities in both cell lines, but upregulated proapoptotic TP53 and p21 reporter activities, and induced phospho-ERK, AP-1, and IL-8 activity in UM-SCC1 cells. CX-4945 exhibited modest anti-tumor activity in UM-SCC1 xenografts. Tumor immunostaining revealed significant inhibition of PI3K-Akt-mTOR pathway and increased apoptosis marker TUNEL, but also induced p-ERK, c-JUN, JUNB, FOSL1 and proliferation (Ki67) markers, as a possible resistance mechanism. To overcome the drug resistance, we tested MEK inhibitor PD-0325901 (PD-901), which inhibited ERK-AP-1 activation alone and in combination with CX-4945. PD-901 alone displayed significant anti-tumor effects in vivo, and the combination of PD-901 and CX-4945 slightly enhanced anti- tumor activity when compared with PD-901 alone. Immunostaining of tumor specimens after treatment revealed inhibition of p-AKT S129 and p-AKT T308 by CX-4945, and inhibition of p-ERK T202/204 and AP-1 family member FOSL-1 by PD-901. Our study reveals a drug resistance mechanism mediated by the MEK-ERK-AP-1 pathway in HNSCC. MEK inhibitor PD-0325901 is active in HNSCC resistant to CX-4945, meriting further clinical investigation. C1 [Bian, Yansong; Han, Jiawei; Kannabiran, Vishnu; Mohan, Suresh; Cheng, Hui; Friedman, Jay; VanWaes, Carter; Chen, Zhong] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Han, Jiawei; Zhang, Luo] Capital Med Univ, Dept Otolaryngol Head & Neck Surg, Key Lab Otolaryngol Head & Neck Surg, Natl Key Discipline,Minist Educ,Beijing Tongren H, Beijing, Peoples R China. [Kannabiran, Vishnu; Mohan, Suresh] NIH Clin Res Training Program, NIH Med Res Scholars Program, Bethesda, MD USA. RP Chen, Z (reprint author), NIDCD, NIH, Bldg 10-5D55,10 Ctr Dr, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov; chenz@nidcd.nih.gov OI Mohan, Suresh/0000-0002-4797-9565 FU NIDCD intramural projects [ZIA-DC-000073, ZIA-DC-000074] FX Supported by NIDCD intramural projects ZIA-DC-000073 and ZIA-DC-000074 (YB, JH, VK, SM, JF, ZC, CVW). NR 40 TC 7 Z9 7 U1 2 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2015 VL 11 IS 4 BP 411 EP 422 DI 10.7150/ijbs.10745 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CC5OS UT WOS:000350408500006 PM 25798061 ER PT J AU Hoover, RN Chanock, SJ AF Hoover, Robert N. Chanock, Stephen J. TI Opportunities-And Hard Work-Ahead SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENOME C1 [Hoover, Robert N.; Chanock, Stephen J.] NCI, NCI Shady Grove, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20890 USA. RP Hoover, RN (reprint author), NCI, NCI Shady Grove, Div Canc Epidemiol & Genet, NIH, Room 7E412,9609m Med Ctr Dr, Bethesda, MD 20890 USA. EM hooverr@mail.nih.gov; chanocks@mail.nih.gov NR 8 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju398 DI 10.1093/jnci/dju398 PG 2 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800034 ER PT J AU Madan, RA Gulley, JL AF Madan, Ravi A. Gulley, James L. TI (R)Evolutionary Therapy: The Potential of Immunotherapy to Fulfill the Promise of Personalized Cancer Treatment SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RESISTANT PROSTATE-CANCER; T-CELLS; METASTATIC MELANOMA; PANCREATIC-CANCER; ANTIGEN; SURVIVAL; VACCINE; MICROENVIRONMENT; VEMURAFENIB; LYMPHOCYTES AB Since the millennium, personalized medicine has been at the forefront of therapeutic endeavors in medical oncology. The latest technology has given researchers the ability to define cancer at its molecular core. This has led to the development of "targeted therapies," designed to eliminate driver mutations while leaving healthy cells unscathed. Unfortunately, more than 10 years into the targeted molecular therapy era, successes have been infrequent, and toxicity remains largely unchanged compared with relatively indiscriminant, traditional chemotherapy. Emerging data suggests that the malignant clonal heterogeneity within solid tumors is so diverse that targeting one or even several mutations is likely to have minimal, transient impact. In recent years, new therapies have emerged that can effectively stimulate the immune system and improve survival in patients with metastatic disease. Through immune activation, there is the potential to target the cancer with a biologic diversity that can potentially rival the multiplicity of malignant mutations within tumors. Stimulating the immune system to become an evolving adversary against malignant cells may revolutionize cancer therapy in the years to come. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Madan, RA (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,12N226, Bethesda, MD 20892 USA. EM madanr@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 27 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju347 DI 10.1093/jnci/dju347 PG 4 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800005 ER PT J AU Nichols, HB DeRoo, LA Scharf, DR Sandler, DP AF Nichols, Hazel B. DeRoo, Lisa A. Scharf, Daniel R. Sandler, Dale P. TI Risk-Benefit Profiles of Women Using Tamoxifen for Chemoprevention SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER CHEMOPREVENTION; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; PREVENTION TRIAL; POSTMENOPAUSAL WOMEN; AMERICAN WOMEN; ADHERENCE; METAANALYSIS; RALOXIFENE; REDUCTION AB Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer. This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided. Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen. While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention. C1 [Nichols, Hazel B.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [DeRoo, Lisa A.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Scharf, Daniel R.] Westat Corp, Durham, NC USA. [Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Nichols, HB (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2102A McGavran Greenberg Hall,135 Dauer Dr, Chapel Hill, NC 27599 USA. EM hazel.nichols@unc.edu OI Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES044005]; National Center for Advancing Translational Sciences [KL2-TR001109] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES044005), and the National Center for Advancing Translational Sciences (KL2-TR001109). NR 40 TC 1 Z9 2 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju354 DI 10.1093/jnci/dju354 PG 8 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800007 ER PT J AU Porras, C Hildesheim, A Gonzalez, P Schiffman, M Rodriguez, AC Wacholder, S Jimenez, S Quint, W Guillen, D Kreimer, AR Herrero, R AF Porras, Carolina Hildesheim, Allan Gonzalez, Paula Schiffman, Mark Cecilia Rodriguez, Ana Wacholder, Sholom Jimenez, Silvia Quint, Wim Guillen, Diego Kreimer, Aimee R. Herrero, Rolando CA CVT Vaccine Grp TI Performance of Self-Collected Cervical Samples in Screening for Future Precancer Using Human Papillomavirus DNA Testing SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTRAEPITHELIAL NEOPLASIA; VACCINATION PROGRAM; AMERICAN SOCIETY; FOLLOW-UP; CANCER; WOMEN; ABNORMALITIES; PREVENTION; SPECIMENS AB Self-collected human papillomavirus (HPV) testing could reduce barriers to cervical cancer screening, with performance comparable to clinician-collected specimens. The ability of self-collected specimens to cross-sectionally and prospectively detect precursor lesions was investigated in an HPV vaccine randomized trial in Costa Rica. In the trial, 7466 women age 18 to 25 years received an HPV16/18 or control vaccine and were followed at least annually for four years. In this secondary analysis, we included all women who provided a self-collected cervicovaginal specimen six months after enrollment (5109 women = full analytical cohort). A subset (615 women = restricted cohort) also had clinician-collected specimens at the six-month postenrollment visit. High-grade squamous intraepithelial lesion or repeat low-grade squamous intraepithelial lesion prompted colposcopic referral throughout the study. HPV testing was performed with SPF10PCR/DEIA/LiPA(25). Cross-sectional and prospective sensitivity, specificity, and predictive values were estimated. In the full cohort, one-time HPV testing on self-collected samples detected prevalent CIN2+ with a sensitivity of 88.7% (95% confidence interval [CI] =77.0% to 95.7%) and a specificity of 68.9% (95% CI = 67.6% to 70.1%). For predicting incident CIN2+ in the subsequent four years, sensitivity was 73.9% (95% CI = 65.8% to 81.0%) and specificity 69.4% (95% CI = 68.1% to 70.7%). In the restricted cohort, for incident CIN2+, self-collected HPV was much more sensitive than cytology (80.0% vs 10.0%); relative sensitivity was 0.1 (95% CI = 0.03% to 0.5%). Furthermore, three times more women with normal baseline cytology developed incident CIN2+ than those with negative self-collected HPV. Self-collected and clinician-collected HPV testing had comparable performance. Agreement between self- and clinician-collected samples was 89.7% (kappa = 0.78, McNemar chi 2 = 0.62) for carcinogenic HPV types. Self-collected specimens can be used for HPV-based screening, providing sensitivity and specificity comparable with clinician-collected specimens and detecting disease earlier than cytology. C1 [Porras, Carolina; Gonzalez, Paula; Cecilia Rodriguez, Ana; Jimenez, Silvia; Guillen, Diego] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Hildesheim, Allan; Schiffman, Mark; Wacholder, Sholom; Kreimer, Aimee R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Quint, Wim] DDL Diagnost Lab, Rijswijk, Netherlands. [Gonzalez, Paula; Herrero, Rolando] WHO, Prevent & Implementat Grp, Int Agcy Res Canc, Lyon, France. RP Porras, C (reprint author), Fdn INCIENSA, Proyecto Epidemiol Guanacaste, 300 Mts Oeste ICE,Planta Baja, San Jose, Costa Rica. EM cporras@proyectoguanacaste.org RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015 OI Hildesheim, Allan/0000-0003-0257-2363; FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on Women's Health FX The Costa Rica Human Papillomavirus (HPV) Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the National Cancer Institute (NCI). The trial is sponsored and funded by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health. GlaxoSmithKline Biologicals (GSK) provided vaccine and support for aspects of the trial associated with regulatory submission needs of the company under a Clinical Trials Agreement (FDA BB-IND 7920) during the four-year, randomized blinded phase of our study. NR 37 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju400 DI 10.1093/jnci/dju400 PG 9 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800036 ER PT J AU Wild, CP Bucher, JR de Jong, BWD Dillner, J von Gertten, C Groopman, JD Herceg, Z Holmes, E Holmila, R Olsen, JH Ringborg, U Scalbert, A Shibata, T Smith, MT Ulrich, C Vineis, P McLaughlin, J AF Wild, Christopher P. Bucher, John R. de Jong, Bas W. D. Dillner, Joakim von Gertten, Christina Groopman, John D. Herceg, Zdenko Holmes, Elaine Holmila, Reetta Olsen, Jorgen H. Ringborg, Ulrik Scalbert, Augustin Shibata, Tatsuhiro Smith, Martyn T. Ulrich, Cornelia Vineis, Paolo McLaughlin, John TI Translational Cancer Research: Balancing Prevention and Treatment to Combat Cancer Globally SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COLORECTAL-CANCER; MOLECULAR EPIDEMIOLOGY; ENVIRONMENTAL-FACTORS; RISK; GENOME; HETEROGENEITY; DISCOVERY; CARCINOMA; SMOKING; SCIENCE AB Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population. C1 [Wild, Christopher P.; Herceg, Zdenko; Holmila, Reetta; Scalbert, Augustin] Int Agcy Res Canc, Directors Off, Sect Mech Carcinogenesis, F-69372 Lyon 08, France. [Wild, Christopher P.; Herceg, Zdenko; Holmila, Reetta; Scalbert, Augustin] Int Agcy Res Canc, Directors Off, Sect Nutr & Metab, F-69372 Lyon 08, France. [Bucher, John R.] NIEHS, Res Triangle Pk, NC 27709 USA. [de Jong, Bas W. D.] Erasmus MC, Dept Pathol, Rotterdam, Netherlands. [Dillner, Joakim] Karolinska Inst, Dept Med Epidemiol & Biostat, BioBanking & Mol Resource Infrastruct, Stockholm, Sweden. [von Gertten, Christina] Karolinska Inst, Radiat Med Ctr, Stockholm, Sweden. [Groopman, John D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Holmes, Elaine] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Olsen, Jorgen H.] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Ringborg, Ulrik] Karolinska Univ Hosp Solna, Canc Ctr Karolinska, Stockholm, Sweden. [Shibata, Tatsuhiro] Natl Canc Ctr, Res Inst, Div Canc Genom, Tokyo 104, Japan. [Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Ulrich, Cornelia] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Ulrich, Cornelia] German Canc Res Ctr, Heidelberg, Germany. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [McLaughlin, John] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Wild, CP (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM director@iarc.fr OI Olsen, Jorgen Helge/0000-0001-9633-5662 NR 53 TC 2 Z9 2 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju353 DI 10.1093/jnci/dju353 PG 5 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800006 ER PT J AU Gupta, S Pegu, P Venzon, DJ Gach, JS Ma, ZM Landucci, G Miller, CJ Franchini, G Forthal, DN AF Gupta, Sandeep Pegu, Poonam Venzon, David J. Gach, Johannes S. Ma, Zhong-Min Landucci, Gary Miller, Christopher J. Franchini, Genoveffa Forthal, Donald N. TI Enhanced In Vitro Transcytosis of Simian Immunodeficiency Virus Mediated by Vaccine-Induced Antibody Predicts Transmitted/Founder Strain Number After Rectal Challenge SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE SIV; transcytosis; antibody; Fc neonatal receptor; vaccine ID PREVENT HIV-1 INFECTION; NEONATAL FC-RECEPTOR; 1-INFECTED INDIVIDUALS; IGG; TRIAL; PROTECTION; SECRETIONS; MACAQUES; THAILAND; EFFICACY AB Background. The time to acquisition of simian immunodeficiency virus (SIV) infection following low-dose repeated rectal challenge correlated inversely with the number of transmitted/founder strains among macaques vaccinated with ALVAC-SIV/gp120 or gp120 alone. We determined if the ability of postvaccination, prechallenge sera to enhance SIVmac251 transcytosis across epithelial cells was associated with transmitted/founder strain number. Methods. Transcytosis was carried out by exposing sera and SIVmac251 to the apical surface of human endometrial carcinoma (HEC-1A) cells at pH 6.0 and 12 hours later quantifying virus in fluid bathing the basolateral cell surface (maintained at pH 7.4). These conditions allow Fc neonatal receptor (FcRn)-dependent shuttling of virus across cells. Results. There was a strong correlation between the amount of virus transcytosed and number of transmitted variants (R = 0.86, P < .0001). We also found that 4 animals who remained uninfected after repeated rectal challenges had lower serum transcytosis activity than did 19 animals who subsequently became infected (P = .003). Using immunohistochemistry, we demonstrated FcRn on columnar epithelial cells facing the lumen of the macaque rectum. Conclusions. Vaccine-induced antibody capable of enhancing transcytosis in vitro via FcRn may play a role in determining transmitted/founder strain number and infection outcomes following in vivo challenge. C1 [Gupta, Sandeep; Gach, Johannes S.; Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Div Infect Dis, Dept Med, Irvine, CA 92617 USA. [Pegu, Poonam; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Ma, Zhong-Min; Landucci, Gary] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Miller, Christopher J.] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA 95616 USA. RP Forthal, DN (reprint author), Univ Calif Irvine, Sch Med, Div Infect Dis, Dept Med, 3044 Hewitt Hall, Irvine, CA 92617 USA. EM dnfortha@uci.edu OI Gach, Johannes/0000-0002-5043-5710 FU US Public Health Service grant from the National Institutes of Health (NIH) [AI102715]; Intramural Research Program of the NIH under NCI [HHSN2662004000088C] FX This work was supported by US Public Health Service grant AI102715 from the National Institutes of Health (NIH) and by the Intramural Research Program of the NIH under NCI contract HHSN2662004000088C. NR 21 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2015 VL 211 IS 1 BP 45 EP 52 DI 10.1093/infdis/jiu300 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CC3BY UT WOS:000350220600008 PM 24850790 ER PT J AU Barros, RRM Straimer, J Sa, JM Salzman, RE Melendez-Muniz, VA Mu, JB Fidock, DA Wellems, TE AF Barros, Roberto R. Moraes Straimer, Judith Sa, Juliana M. Salzman, Rebecca E. Melendez-Muniz, Viviana A. Mu, Jianbing Fidock, David A. Wellems, Thomas E. TI Editing the Plasmodium vivax Genome, Using Zinc-Finger Nucleases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE malaria; transfection; allelic modification; dihydrofolate reductase-thymidylate synthase; pyrimethamine; Saimiri boliviensis ID FALCIPARUM; PYRIMETHAMINE; CHLOROQUINE; PARASITES AB Plasmodium vivax is a major cause of malaria morbidity worldwide yet has remained genetically intractable. To stably modify this organism, we used zinc-finger nucleases (ZFNs), which take advantage of homology-directed DNA repair mechanisms at the site of nuclease action. Using ZFNs specific to the gene encoding P. vivax dihydrofolate reductase (pvdhfr), we transfected blood specimens from Saimiri boliviensis monkeys infected with the pyrimethamine (Pyr)-susceptible Chesson strain with a ZFN plasmid carrying a Pyr-resistant mutant pvdhfr sequence. We obtained Pyr-resistant parasites in vivo that carried mutant pvdhfr and additional silent mutations designed to confirm editing. These results herald the era of stable P. vivax genetic modifications. C1 [Barros, Roberto R. Moraes; Sa, Juliana M.; Salzman, Rebecca E.; Melendez-Muniz, Viviana A.; Mu, Jianbing; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Straimer, Judith; Fidock, David A.] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. [Fidock, David A.] Columbia Univ Coll Phys & Surg, Dept Med, Div Infect Dis, New York, NY 10032 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; Brazilian National Council for the Development of Science and Technology, Science Without Frontiers Program [237256/2012-6]; National Institutes of Health [AI50234, AI109023] FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. R. R. M. B. received partial funding from the Brazilian National Council for the Development of Science and Technology, Science Without Frontiers Program (237256/2012-6). D. A. F. gratefully acknowledges extramural funding support from the National Institutes of Health (AI50234 and AI109023). NR 15 TC 3 Z9 3 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2015 VL 211 IS 1 BP 125 EP 129 DI 10.1093/infdis/jiu423 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CC3BY UT WOS:000350220600017 ER PT J AU Fabbri, E An, Y Zoli, M Simonsick, EM Guralnik, JM Bandinelli, S Boyd, CM Ferrucci, L AF Fabbri, Elisa An, Yang Zoli, Marco Simonsick, Eleanor M. Guralnik, Jack M. Bandinelli, Stefania Boyd, Cynthia M. Ferrucci, Luigi TI Aging and the Burden of Multimorbidity: Associations With Inflammatory and Anabolic Hormonal Biomarkers SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Multimorbidity; Inflammation; Interleukin-6; Aging; Chronic diseases ID ALL-CAUSE MORTALITY; OLDER-ADULTS; CHRONIC DISEASES; WOMENS HEALTH; SYSTEMIC INFLAMMATION; GENERAL-PRACTICE; UNITED-STATES; PREVALENCE; COMORBIDITY; CARE AB Background. Multimorbidity increases with aging, but risk factors beyond age are unknown. Objective. To investigate the association of inflammatory and anabolic hormonal biomarkers with presence and prospective development of multimorbidity. Methods. Nine-year longitudinal study of 1018 participants aged 60 years or older (InCHIANTI Study). Multimorbidity was evaluated at baseline and follow-up visits as number of diagnosed diseases from a predefined list of 15 candidate chronic conditions, defined according to standard clinical criteria. Linear mixed models were used to test cross-sectional and longitudinal associations between candidate biomarkers and multimorbidity. Results. At baseline, multimorbidity was significantly higher in older participants (p < .001) and higher IL-6, IL-1ra, TNF-alpha receptor II (TNFAR2), and lower dehydroepiandrosterone sulfate were associated with higher number of diseases, independent of age, sex, body mass index, and education. The rate of longitudinal increase in number of chronic diseases was significantly steeper in participants who were older at baseline (p < .001). In addition, higher baseline IL-6 and steeper increase of IL-6 levels were significantly and independently associated with a steeper increase in multimorbidity over time (p < .001 and p = .003, respectively). Sensitivity analyses, performed using 15 different models obtained by removing each of 15 conditions included in the original list of candidate diseases, confirmed that results were not driven by any specific condition. Conclusions. Accumulation of chronic diseases accelerates at older ages and in persons with higher baseline levels and steeper increase over time of IL-6. High IL-6 and increase in IL-6 may serve as early warning sign to better target interventions aimed at reducing the burden of multimorbidity. C1 [Fabbri, Elisa; An, Yang; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Fabbri, Elisa; Zoli, Marco] Univ Bologna, Dept Med & Surg Sci, I-40126 Bologna, Italy. [Guralnik, Jack M.] Univ Maryland, Sch Med, Div Gerontol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Bandinelli, Stefania] ASF Firenze, Dept Geriatr Med, Florence, Italy. [Boyd, Cynthia M.] Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD USA. RP Fabbri, E (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM elisa.fabbri@nih.gov FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland; Paul Beeson Career Development Award Program [NIA K23 AG032910] FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (contract: N01-AG-5-0002); supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. Dr. C.M.B. was supported by the Paul Beeson Career Development Award Program (NIA K23 AG032910, AFAR, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation, and an anonymous donor). NR 42 TC 19 Z9 19 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 63 EP 70 DI 10.1093/gerona/glu127 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900008 PM 25104822 ER PT J AU Genther, DJ Betz, J Pratt, S Kritchevsky, SB Martin, KR Harris, TB Helzner, E Satterfield, S Xue, QL Yaffe, K Simonsick, EM Lin, FR AF Genther, Dane J. Betz, Joshua Pratt, Sheila Kritchevsky, Steven B. Martin, Kathryn R. Harris, Tamara B. Helzner, Elizabeth Satterfield, Suzanne Xue, Qian-Li Yaffe, Kristine Simonsick, Eleanor M. Lin, Frank R. CA Hlth ABC Study TI Association of Hearing Impairment and Mortality in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Epidemiology; Longevity; Outcomes; Public health; Successful aging ID BLUE-MOUNTAINS HEARING; HEALTH INTERVIEW SURVEY; UNITED-STATES; LONGITUDINAL ANALYSIS; GAIT SPEED; SURVIVAL; RISK; PREDICTORS; DISEASE; DEPRESSION AB Background. Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. Methods. Prospective observational data from 1,958 adults >= 70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4 kHz. HI was defined as pure-tone average >25 dB HL in the better ear. Results. Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). Conclusions. HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation. C1 [Genther, Dane J.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Genther, Dane J.; Betz, Joshua; Xue, Qian-Li; Lin, Frank R.] Johns Hopkins Ctr Aging & Hlth, Baltimore, MD USA. [Betz, Joshua] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Kritchevsky, Steven B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Kritchevsky, Steven B.] J Paul Sticht Ctr Aging, Winston Salem, NC USA. [Martin, Kathryn R.] Univ Aberdeen, Dept Epidemiol, Aberdeen AB9 1FX, Scotland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Xue, Qian-Li; Simonsick, Eleanor M.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21287 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Genther, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,JHOC 6210, Baltimore, MD 21287 USA. EM dgenthe2@jhmi.edu OI Genther, Dane/0000-0002-7925-012X; Betz, Joshua/0000-0003-4488-9799 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute of Nursing Research (NINR) [R01-NR012459]; National Institutes of Health (NIH) [T32DC000027]; National Institute on Deafness and Other Communication Disorders (NIDCD) [K23DC011279]; Intramural Research Program of the National Institute on Aging; Triological Society; American College of Surgeons through the Clinician Scientist Award; Eleanor Schwartz Charitable Foundation FX This research was supported by National Institute on Aging (NIA) (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106); NIA grant (R01-AG028050); and National Institute of Nursing Research (NINR) grant (R01-NR012459). This study was further supported in part by National Institutes of Health (NIH) grant (T32DC000027), NIA grant (K24AG031155), National Institute on Deafness and Other Communication Disorders (NIDCD) grant (K23DC011279), Intramural Research Program of the National Institute on Aging, Triological Society and American College of Surgeons through the Clinician Scientist Award, and Eleanor Schwartz Charitable Foundation. S.P. was supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Pittsburgh, PA; however, the contents do not represent the views of the Department of Veterans Affairs or the United States Government. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation of the manuscript. NR 41 TC 14 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 85 EP 90 DI 10.1093/gerona/glu094 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900011 PM 25024235 ER PT J AU Broer, L Buchman, AS Deelen, J Evans, DS Faul, JD Lunetta, KL Sebastiani, P Smith, JA Smith, AV Tanaka, T Yu, L Arnold, AM Aspelund, T Benjamin, EJ De Jager, PL Eirkisdottir, G Evans, DA Garcia, ME Hofman, A Kaplan, RC Kardia, SLR Kiel, DP Oostra, BA Orwoll, ES Parimi, N Psaty, BM Rivadeneira, F Rotter, JI Seshadri, S Singleton, A Tiemeier, H Uitterlinden, AG Zhao, W Bandinelli, S Bennett, DA Ferrucci, L Gudnason, V Harris, TB Karasik, D Launer, LJ Perls, TT Slagboom, PE Tranah, GJ Weir, DR Newman, AB van Duijn, CM Murabito, JM AF Broer, Linda Buchman, Aron S. Deelen, Joris Evans, Daniel S. Faul, Jessica D. Lunetta, Kathryn L. Sebastiani, Paola Smith, Jennifer A. Smith, Albert V. Tanaka, Toshiko Yu, Lei Arnold, Alice M. Aspelund, Thor Benjamin, Emelia J. De Jager, Philip L. Eirkisdottir, Gudny Evans, Denis A. Garcia, Melissa E. Hofman, Albert Kaplan, Robert C. Kardia, Sharon L. R. Kiel, Douglas P. Oostra, Ben A. Orwoll, Eric S. Parimi, Neeta Psaty, Bruce M. Rivadeneira, Fernando Rotter, Jerome I. Seshadri, Sudha Singleton, Andrew Tiemeier, Henning Uitterlinden, Andre G. Zhao, Wei Bandinelli, Stefania Bennett, David A. Ferrucci, Luigi Gudnason, Vilmundur Harris, Tamara B. Karasik, David Launer, Lenore J. Perls, Thomas T. Slagboom, P. Eline Tranah, Gregory J. Weir, David R. Newman, Anne B. van Duijn, Cornelia M. Murabito, Joanne M. TI GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Longevity; GWAS; FOXO3; APOE ID GENOME-WIDE ASSOCIATION; LONG-LIVED INDIVIDUALS; LIFE-SPAN; GENETIC-DETERMINANTS; AGING RESEARCH; SURVIVAL; MORTALITY; AGE; METAANALYSIS; VARIANTS AB Background. The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. Methods. We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age >= 90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. Results. In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 x 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 x 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85 x 10(-10)). Conclusions. We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages >= 90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants. C1 [Broer, Linda; Hofman, Albert; Oostra, Ben A.; Rivadeneira, Fernando; Tiemeier, Henning; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Broer, Linda; Deelen, Joris; Hofman, Albert; Oostra, Ben A.; Rivadeneira, Fernando; Tiemeier, Henning; Uitterlinden, Andre G.; Slagboom, P. Eline; van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Netherlands Consortium Hlth Ageing, NL-2300 RA Leiden, Netherlands. [Broer, Linda; Rivadeneira, Fernando; Rotter, Jerome I.; Seshadri, Sudha; Singleton, Andrew; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Buchman, Aron S.; Yu, Lei] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Deelen, Joris; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RA Leiden, Netherlands. [Evans, Daniel S.; Parimi, Neeta; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA. [Lunetta, Kathryn L.; Sebastiani, Paola; Seshadri, Sudha] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham, MA 01701 USA. [Lunetta, Kathryn L.; Benjamin, Emelia J.; Murabito, Joanne M.] NHLBIs, Boston, MA USA. [Lunetta, Kathryn L.; Benjamin, Emelia J.; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA 01701 USA. [Smith, Jennifer A.; Kardia, Sharon L. R.; Zhao, Wei] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Smith, Albert V.; Aspelund, Thor; Eirkisdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Benjamin, Emelia J.] Sect Prevent Med, Dept Med, Boston, MA USA. [Benjamin, Emelia J.] Cardiol Sect, Dept Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Framingham, MA 01701 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Psychiat, Boston, MA 02115 USA. [De Jager, Philip L.; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Kaplan, Robert C.] Albert Einstein Coll, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Kiel, Douglas P.; Karasik, David] Harvard Univ, Sch Med, Dept Med, Hebrew SeniorLife,Inst Aging Res, Boston, MA USA. [Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, School Med, Portland, OR 97201 USA. [Psaty, Bruce M.; Karasik, David] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Washington, DC USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rotter, Jerome I.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Framingham, MA 01701 USA. [Singleton, Andrew] NIA, Lab Neurogenet, Bethesda, MD USA. [Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Tiemeier, Henning] Sophia Childrens Univ Hosp, Rotterdam, Netherlands. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Karasik, David] Bar Ilan Univ, Fac Med Galilee, Safed, Israel. [Perls, Thomas T.] Boston Univ, Sch Med, Sect Geriatr, Framingham, MA 01701 USA. [Perls, Thomas T.] Boston Univ, Med Ctr, Framingham, MA 01701 USA. [Tranah, Gregory J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Framingham, MA 01701 USA. RP Murabito, JM (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte,Suite 2, Framingham, MA 01701 USA. EM murabito@bu.edu RI Newman, Anne B./C-6408-2013; Singleton, Andrew/C-3010-2009; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Slagboom, P. Eline/R-4790-2016; OI Newman, Anne B./0000-0002-0106-1150; Tiemeier, Henning/0000-0002-4395-1397; Benjamin, Emelia/0000-0003-4076-2336; Karasik, David/0000-0002-8826-0530; Smith, Jennifer/0000-0002-3575-5468; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Kiel, Douglas/0000-0001-8474-0310; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Slagboom, P. Eline/0000-0002-2875-4723; Seshadri, Sudha/0000-0001-6135-2622; Deelen, Joris/0000-0003-4483-3701 FU Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, AG023629, R01AG29451, U01AG009740, RC2 AG036495, RC4 AG039029, P30AG10161, R01AG17917, R01AG15819, R01AG30146, U01-AG023755, U19-AG023122]; NHLBI [HHSN 268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC 85086, HL080295, HL087652, HL105756]; National Institute of Neurological Disorders and Stroke (NINDS); National Center for Advancing Translational Sciences, CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; NIAMS [R01-AR051124, RC2ARO58973]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Arthritis, Musculoskeletal and Skin Diseases; NIA [R01 AR/AG 41398]; NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Illinois Department of Public Health; Translational Genomics Research Institute; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]; Intramural Research Program of the NIH, National Institute on Aging; [1R01AG028321]; [1R01HL092577] FX The Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810, Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.; SOF is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576.; This CHS research was supported by NHLBI contracts HHSN 268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC 85086; and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; MrOS is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. NIAMS provides funding for the MrOS ancillary study 'Replication of candidate gene associations and bone strength phenotype in MrOS' under the grant number R01-AR051124. NIAMS provides funding for the MrOS ancillary study 'GWAS in MrOS and SOF' under the grant number RC2ARO58973.; The Framingham Heart Study genetic association analyses for this project were supported by the National Institute of Aging (R01AG29451, J.M. M., K.L.L.). "This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center." E.J.B. and KLL were funded by 1R01AG028321 and 1R01HL092577. D.P.K.'s effort was supported by a grant from the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the NIA (R01 AR/AG 41398).; HRS is supported by the National Institute on Aging (NIA U01AG009740). The genotyping was funded separately by the National Institute on Aging (RC2 AG036495, RC4 AG039029). Our genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington.; AGES is funded by NIH contract number N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). Genotyping was conducted at the NIA Intramural Research Program Laboratory of Neurogenetics.; The MAP and ROS data used in this analysis was supported by National Institute on Aging grants P30AG10161, R01AG17917, R01AG15819, R01AG30146, the Illinois Department of Public Health, and the Translational Genomics Research Institute.; The InCHIANTI study baseline (1998 -2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336).; The BLSA was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.; The analysis of LLFS and NECS data were supported by the National Institute on Aging (NIA cooperative agreements U01-AG023755 and U19-AG023122 to T.P.) NR 51 TC 32 Z9 32 U1 3 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 110 EP 118 DI 10.1093/gerona/glu166 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900015 PM 25199915 ER PT J AU Armstrong, JJ Mitnitski, A Launer, LJ White, LR Rockwood, K AF Armstrong, Joshua J. Mitnitski, Arnold Launer, Lenore J. White, Lon R. Rockwood, Kenneth TI Frailty in the Honolulu-Asia Aging Study: Deficit Accumulation in a Male Cohort Followed to 90% Mortality SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Frailty; Epidemiology; Deficit accumulation; Frailty index; Mortality ID COMPREHENSIVE GERIATRIC ASSESSMENT; RELATIVE FITNESS; CUMULATIVE DEFICITS; ELDERLY-PEOPLE; HEALTH-STATUS; OLDER-PEOPLE; INDEX; AGE; TRANSITIONS; LONGEVITY AB Background. A frailty index (FI) based on the accumulation of deficits typically has a submaximal limit at about 0.70. The objectives of this study were to examine how population characteristics of the FI change in the Honolulu-Asia Aging Study cohort, which has been followed to near-complete mortality. In particular, we were interested to see if the limit was exceeded. Methods. Secondary analysis of six waves of the Honolulu-Asia Aging Study. Men (n = 3,801) aged 71-93 years at baseline (1991) were followed until death (N = 3,455; 90.9%) or July 2012. FIs were calculated across six waves and the distribution at each wave was evaluated. Kaplan-Meier analyses and Cox proportional hazard models were performed to examine the relationship of frailty with mortality. Results. At each wave, frailty was nonlinearly associated with age, with acceleration in later years. The distributions of the FIs were skewed with long right tails. Despite the increasing mortality in each successive wave, the 99% submaximal limit never exceeded 0.65. The risk of death increased with increasing values of the FI (eg, the hazard rate increased by 1.44 [95% CI = 1.39-1.49] with each increment in the baseline FI grouping). Depending on the wave, the median survival of people with FI more than 0.5 ranged 0.84-2.04 years. Conclusions. Even in a study population followed to almost complete mortality, the limit to deficit accumulation did not exceed 0.65, confirming a quantifiable, maximum number of health deficits that older men can tolerate. C1 [Armstrong, Joshua J.; Mitnitski, Arnold; Rockwood, Kenneth] Dalhousie Univ, Dept Med, Halifax, NS B3H 2E1, Canada. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [White, Lon R.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA. RP Rockwood, K (reprint author), Dalhousie Univ, Ctr Hlth Care Elderly, QEII Hlth Sci Ctr, Capital Dist Hlth Author, Suite 1421,Vet Mem Bldg,5955 Vet Mem Lane, Halifax, NS B3H 2E1, Canada. EM kenneth.rockwood@dal.ca FU Dalhousie Medical Research Foundation; Canadian Institutes of Health Research [MOP-102544, MOP-115006]; Alzheimer Society of Canada [1207] FX This work was supported by the Dalhousie Medical Research Foundation, which provides Kenneth Rockwood with career funding as the Kathryn Allen Weldon Professor of Alzheimer Research; Kenneth Rockwood and Arnold Mitnitski are supported by operating grants from the Canadian Institutes of Health Research (MOP-102544; MOP-115006); and Joshua Armstrong is supported by a postdoctoral fellowship award from the Alzheimer Society of Canada (#1207). NR 41 TC 14 Z9 14 U1 4 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 125 EP 131 DI 10.1093/gerona/glu089 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900017 PM 24973228 ER PT J AU Li, WW Chen, XY AF Li, Wanwan Chen, Xiaoyuan TI Gold nanoparticles for photoacoustic imaging SO NANOMEDICINE LA English DT Review DE atherosclerosis; brain function; cancer; gold nanoparticle; photoacoustic imaging; therapy guidance ID MULTISPECTRAL OPTOACOUSTIC TOMOGRAPHY; PHOTOTHERMAL ABLATION THERAPY; OPTICAL CONTRAST AGENT; MESENCHYMAL STEM-CELLS; SENTINEL LYMPH-NODES; NEAR-INFRARED LIGHT; IN-VIVO; CARBON NANOTUBES; DRUG-DELIVERY; LIVING MICE AB Photoacoustic (PA) imaging is a biomedical imaging modality that provides functional information regarding the cellular and molecular signatures of tissue by using endogenous and exogenous contrast agents. There has been tremendous effort devoted to the development of PA imaging agents, and gold nanoparticles as exogenous contrast agents have great potential for PA imaging due to their inherent and geometrically induced optical properties. The gold-based nanoparticles that are most commonly employed for PA imaging include spheres, rods, shells, prisms, cages, stars and vesicles. This article provides an overview of the current state of research in utilizing these gold nanomaterials for PA imaging of cancer, atherosclerotic plaques, brain function and image-guided therapy. C1 [Li, Wanwan] Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, Shanghai 200240, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU National Basic Research Program of China (973 program) [2013CB733802, 2014CB744503]; National Natural Science Foundation of China [50902093, 81371596, 81371645]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH FX This work was supported in part by the National Basic Research Program of China (973 program, 2013CB733802, 2014CB744503), the National Natural Science Foundation of China (project no. 50902093, 81371596 and 81371645) and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 138 TC 49 Z9 50 U1 33 U2 146 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 2 BP 299 EP 320 DI 10.2217/NNM.14.169 PG 22 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CC3KG UT WOS:000350246300010 PM 25600972 ER PT J AU Huang, D Ovcharenko, I AF Huang, Di Ovcharenko, Ivan TI Identifying causal regulatory SNPs in ChIP-seq enhancers SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ASSOCIATION; COMMON HUMAN DISORDERS; LONG-RANGE ENHANCERS; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; ALPHA-FETOPROTEIN; PROSTATE-CANCER; CELL-TYPES; VARIANTS AB Thousands of non-coding SNPs have been linked to human diseases in the past. The identification of causal alleles within this pool of disease-associated non-coding SNPs is largely impossible due to the inability to accurately quantify the impact of non-coding variation. To overcome this challenge, we developed a computational model that uses ChIP-seq intensity variation in response to non-coding allelic change as a proxy to the quantification of the biological role of non-coding SNPs. We applied this model to HepG2 enhancers and detected 4796 enhancer SNPs capable of disrupting enhancer activity upon allelic change. These SNPs are significantly over-represented in the binding sites of HNF4 and FOXA families of liver transcription factors and liver eQTLs. In addition, these SNPs are strongly associated with liver GWAS traits, including type I diabetes, and are linked to the abnormal levels of HDL and LDL cholesterol. Our model is directly applicable to any enhancer set for mapping causal regulatory SNPs. C1 [Huang, Di; Ovcharenko, Ivan] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Ovcharenko, I (reprint author), Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. EM ovcharen@nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 63 TC 9 Z9 9 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2015 VL 43 IS 1 BP 225 EP 236 DI 10.1093/nar/gku1318 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2XA UT WOS:000350207100025 PM 25520196 ER PT J AU Iyama, T Lee, SY Berquist, BR Gileadi, O Bohr, VA Seidman, MM McHugh, PJ Wilson, DM AF Iyama, Teruaki Lee, Sook Y. Berquist, Brian R. Gileadi, Opher Bohr, Vilhelm A. Seidman, Michael M. McHugh, Peter J. Wilson, David M., III TI CSB interacts with SNM1A and promotes DNA interstrand crosslink processing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION-COUPLED REPAIR; NUCLEOTIDE EXCISION-REPAIR; SYNDROME B PROTEIN; COCKAYNE-SYNDROME; ICL REPAIR; PSORALEN; CELLS; NUCLEASES; PATHWAYS; SPECTRUM AB Cockayne syndrome (CS) is a premature aging disorder characterized by photosensitivity, impaired development and multisystem progressive degeneration, and consists of two strict complementation groups, A and B. Using a yeast two-hybrid approach, we identified the 5'-3' exonuclease SNM1A as one of four strong interacting partners of CSB. This direct interaction was confirmed using purified recombinant proteins-with CSB able to modulate the exonuclease activity of SNM1A on oligonucleotide substrates in vitro-and the two proteins were shown to exist in a common complex in human cell extracts. CSB and SNM1A were also found, using fluorescently tagged proteins in combination with confocal microscopy and laser microirradiation, to be recruited to localized trioxsalen-induced ICL damage in human cells, with accumulation being suppressed by transcription inhibition. Moreover, SNM1A recruitment was significantly reduced in CSB-deficient cells, suggesting coordination between the two proteins in vivo. CSB-deficient neural cells exhibited increased sensitivity to DNA crosslinking agents, particularly, in a non-cycling, differentiated state, as well as delayed ICL processing as revealed by a modified Comet assay and gamma-H2AX foci persistence. The results indicate that CSB coordinates the resolution of ICLs, possibly in a transcription-associated repair mechanism involving SNM1A, and that defects in the process could contribute to the post-mitotic degenerative pathologies associated with CS. C1 [Iyama, Teruaki; Bohr, Vilhelm A.; Seidman, Michael M.; Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lee, Sook Y.; McHugh, Peter J.] Univ Oxford, John Radcliffe Hosp, Dept Oncol, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Berquist, Brian R.] Caliber Biotherapeut, Bryan, TX 77807 USA. [Gileadi, Opher] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov OI Gileadi, Opher/0000-0001-6886-898X FU Intramural Research Program at the NIH, National Institute on Aging; Luke O'Brien Foundation (DMWIII); MRC; Cancer Research UK; National Science Scholarship from the Singaporean Agency for Science, Technology, and Research (A*STAR) FX Intramural Research Program at the NIH, National Institute on Aging; Luke O'Brien Foundation (DMWIII); MRC [to P.J.M. and O.G.]; Cancer Research UK [to P.J.M.]; National Science Scholarship from the Singaporean Agency for Science, Technology, and Research (A*STAR) [to S.Y.L.]. Funding for open access charge: Intramural Research Program at the NIH, National Institute on Aging. NR 41 TC 8 Z9 8 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2015 VL 43 IS 1 BP 247 EP 258 DI 10.1093/nar/gku1279 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2XA UT WOS:000350207100027 PM 25505141 ER PT J AU Taber, JM Chang, CQ Lam, TK Gillanders, EM Hamilton, JG Schully, SD AF Taber, Jennifer M. Chang, Christine Q. Lam, Tram K. Gillanders, Elizabeth M. Hamilton, Jada G. Schully, Sheri D. TI Prevalence and Correlates of Receiving and Sharing High-Penetrance Cancer Genetic Test Results: Findings from the Health Information National Trends Survey SO PUBLIC HEALTH GENOMICS LA English DT Article DE BRCA1/2; Communication of test results; Genetic testing; Health Information National Trends Survey; Hereditary cancer; Hereditary nonpolyposis colorectal cancer; Lynch syndrome ID FAMILY COMMUNICATION; COLORECTAL-CANCER; LYNCH-SYNDROME; DISTANT RELATIVES; RISK-ASSESSMENT; NUMERACY; CARE; BREAST; INDIVIDUALS; AWARENESS AB Background/Aims: The aim of this study was to explore the prevalence and correlates of receiving and sharing high-penetrance cancer genetic test results. Methods: Participants completed the population-based, cross-sectional 2013 Health Information National Trends Survey. We examined sociodemographic characteristics of participants reporting having had BRCA1/2 or Lynch syndrome genetic testing, and sociodemographic and psychosocial correlates of sharing test results with health professionals and family members. Results: Participants who underwent BRCA1/2 or Lynch syndrome genetic testing (n = 77; 2.42% of respondents) were more likely to be female and to have a family or personal history of cancer than those not undergoing testing. Approximately three-quarters of participants shared results with health professionals and three-quarters with their family; only 4% did not share results with anyone. Participants who shared results with health professionals reported greater optimism, self-efficacy for health management, and trust in information from their doctors. Participants who shared results with their family were more likely to be female and to have a personal history of cancer, and had greater self-efficacy for health management, perceived less ambiguity in cancer prevention recommendations, and lower cancer prevention fatalism. Conclusions: We identified several novel psychosocial correlates of sharing genetic information. Health professionals may use this information to identify patients less likely to share information with at-risk family members. (C) 2014 S. Karger AG, Basel C1 [Taber, Jennifer M.; Chang, Christine Q.; Lam, Tram K.; Gillanders, Elizabeth M.; Schully, Sheri D.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hamilton, Jada G.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Taber, JM (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 9609 Med Ctr Dr,Room 3E642, Bethesda, MD 20892 USA. EM Jennifer.taber@nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA008748] NR 48 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2015 VL 18 IS 2 BP 67 EP 77 DI 10.1159/000368745 PG 11 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA CC8BV UT WOS:000350594000001 PM 25427996 ER PT J AU O'Neill, SC Tercyak, KP Baytop, C Alford, SH McBride, CM AF O'Neill, Suzanne C. Tercyak, Kenneth P. Baytop, Chanza Alford, Sharon Hensley McBride, Colleen M. TI A New Approach to Assessing Affect and the Emotional Implications of Personal Genomic Testing for Common Disease Risk SO PUBLIC HEALTH GENOMICS LA English DT Article DE Genetic testing; Health psychology; Psychological impact ID INCIDENTAL FINDINGS; AFFECTIVE ASSOCIATIONS; I FEEL; CANCER; IMPACT; EXOME; INDIVIDUALS; RESPONSES; PATIENT; HEMOCHROMATOSIS AB Aims: Personal genomic testing (PGT) for common disease risk is becoming increasingly frequent, but little is known about people's array of emotional reactions to learning their genomic risk profiles and the psychological harms/benefits of PGT. We conducted a study of post-PGT affect, including positive, neutral, and negative states that may arise after testing. Methods: A total of 228 healthy adults received PGT for common disease variants and completed a semistructured research interview within 2 weeks of disclosure. The study participants reported how the PGT results made them feel in their own words. Using an iterative coding process, the responses were organized into three broad affective categories: negative, neutral, and positive affect. Results: Neutral affect was the most prevalent response (53.9%), followed by positive affect (26.9%) and negative affect (19.2%). We found no differences by gender, race, or education. Conclusions: While <20% of participants reported negative affect in response to learning their genomic risk profile for common diseases, a majority experienced either neutral or positive emotions. These findings contribute to the growing evidence that PGT does not impose significant psychological harms. Moreover, they point to a need to better link theories and assessments in both emotional and cognitive processing to capitalize on PGT information for healthy behavior change. (C) 2015 S. Karger AG, Basel C1 [O'Neill, Suzanne C.; Tercyak, Kenneth P.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Baytop, Chanza] ABT Associates Inc, Bethesda, MD USA. [McBride, Colleen M.] NHGRI, Bethesda, MD 20892 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Detroit, MI USA. RP O'Neill, SC (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM sco4@georgetown.edu FU NHGRI; National Cancer Institute [CA079689, P30051008]; National Institutes of Health [HHSN268200782096C]; American Cancer Society [10-110-01-CPPB]; Office of the Director, National Institutes of Health [HG006754] FX This work was supported by the Intramural Research Program of the NHGRI. However, the proposed research was made possible by collaboration with the Cancer Research Network funded by the National Cancer Institute (CA079689). Additional resources were provided by the Group Health Research Institute and Henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (HHSN268200782096C). We thank the non-author members of the NHGRI Multiplex Initiative Steering Committee (Drs. Lawrence Brody, Robert Reid, Eric Larson, Andreas Baxevanis, and Sharon Kardia) who provided critical review of this report. Our thanks also go to the study participants who were all members of the Henry Ford Health System. The manuscript preparation was supported, in part, by grants from the American Cancer Society (10-110-01-CPPB; to S.C.O.), the Office of the Director, National Institutes of Health (HG006754; to K.P.T.), and the National Cancer Institute (P30051008). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Colleen M. McBride is now Professor and Chair, Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University. NR 53 TC 0 Z9 0 U1 4 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2015 VL 18 IS 2 BP 104 EP 112 DI 10.1159/000370101 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA CC8BV UT WOS:000350594000005 PM 25612474 ER PT J AU Heinssen, RK Insel, TR AF Heinssen, Robert K. Insel, Thomas R. TI Preventing the Onset of Psychosis: Not Quite There Yet SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material ID INTERVENTIONS; METAANALYSIS C1 [Heinssen, Robert K.; Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. RP Heinssen, RK (reprint author), NIMH, Room 7141,Mail Stop 9629 6001 Execut Blvd, Bethesda, MD 20892 USA. EM rheinsse@mail.nih.gov NR 6 TC 3 Z9 3 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 28 EP 29 DI 10.1093/schbul/sbu161 PG 2 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900011 PM 25392518 ER PT J AU Moran, ME Luscher, ZI McAdams, H Hsu, JT Greenstein, D Clasen, L Ludovici, K Lloyd, J Rapoport, J Mori, S Gogtay, N AF Moran, Marcel E. Luscher, Zoe I. McAdams, Harrison Hsu, John T. Greenstein, Deanna Clasen, Liv Ludovici, Katharine Lloyd, Jonae Rapoport, Judith Mori, Susumu Gogtay, Nitin TI Comparing Fractional Anisotropy in Patients With Childhood-Onset Schizophrenia, Their Healthy Siblings, and Normal Volunteers Through DTI SO SCHIZOPHRENIA BULLETIN LA English DT Article DE DTI; COS; siblings; cuneus; FA ID WHITE-MATTER ABNORMALITIES; CORTICAL BRAIN-DEVELOPMENT; PERSONALITY-DISORDERS; NONPSYCHOTIC SIBLINGS; COGNITIVE IMPAIRMENT; ADOLESCENCE; CHILDREN; HALLUCINATIONS; INTEGRITY; INTERVIEW AB Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls. To evaluate WM integrity in this population 39 patients diagnosed with COS, 39 of their healthy (nonpsychotic) siblings, and 50 unrelated healthy volunteers were scanned using a diffusion tensor imaging (DTI) sequence during a 1.5 T MRI acquisition. Each DTI scan was processed via atlas-based analysis using a WM parcellation map, and diffeomorphic mapping that shapes a template atlas to each individual subject space. Fractional anisotropy (FA), a measure of WM integrity was averaged over each of the 46 regions of the atlas. Eleven WM regions were examined based on previous reports of WM growth abnormalities in COS. Of those regions, patients with COS, and their healthy siblings had significantly lower mean FA in the left and right cuneus as compared to the healthy volunteers (P < .005). Together, these findings represent the largest DTI study in COS to date, and provide evidence that WM integrity is significantly impaired in COS. Shared deficits in their healthy siblings might result from increased genetic risk. C1 [Moran, Marcel E.; Luscher, Zoe I.; McAdams, Harrison; Greenstein, Deanna; Clasen, Liv; Ludovici, Katharine; Lloyd, Jonae; Rapoport, Judith; Gogtay, Nitin] NIMH, NIH, Bethesda, MD 20892 USA. [Hsu, John T.; Mori, Susumu] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Gogtay, N (reprint author), NIMH, NIH, Room 3B19 10 Ctr Dr, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov FU intramural research program at the National Institute of Mental Health FX The funding was provided by the intramural research program at the National Institute of Mental Health. NR 47 TC 7 Z9 7 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 66 EP 73 DI 10.1093/schbul/sbu123 PG 8 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900015 PM 25217482 ER PT J AU Chereji, RV Morozov, AV AF Chereji, Razvan V. Morozov, Alexandre V. TI Functional roles of nucleosome stability and dynamics SO BRIEFINGS IN FUNCTIONAL GENOMICS LA English DT Article DE chromatin; nucleosome; DNA; transcription factor; gene regulation; stress response ID BASE-PAIR RESOLUTION; SACCHAROMYCES-CEREVISIAE; COLLABORATIVE COMPETITION; POSITIONED NUCLEOSOMES; ANGSTROM RESOLUTION; HISTONE OCTAMER; GENE ACTIVATION; CORE PARTICLE; DNA; CHROMATIN AB Nucleosome is a histone-DNA complex known as the fundamental repeating unit of chromatin. Up to 90% of eukaryotic DNA is wrapped around consecutive octamers made of the core histones H2A, H2B, H3 and H4. Nucleosome positioning affects numerous cellular processes that require robust and timely access to genomic DNA, which is packaged into the tight confines of the cell nucleus. In living cells, nucleosome positions are determined by intrinsic histone-DNA sequence preferences, competition between histones and other DNA-binding proteins for genomic sequence, and ATP-dependent chromatin remodelers. We discuss the major energetic contributions to nucleosome formation and remodeling, focusing especially on partial DNA unwrapping off the histone octamer surface. DNA unwrapping enables efficient access to nucleosome-buried binding sites and mediates rapid nucleosome removal through concerted action of two or more DNA-binding factors. High-resolution, genomescale maps of distances between neighboring nucleosomes have shown that DNA unwrapping and nucleosome crowding (mutual invasion of nucleosome territories) are much more common than previously thought. Ultimately, constraints imposed by nucleosome energetics on the rates of ATP-dependent and spontaneous chromatin remodeling determine nucleosome occupancy genome-wide, and shape pathways of cellular response to environmental stresses. C1 [Chereji, Razvan V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Morozov, Alexandre V.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA. RP Morozov, AV (reprint author), Rutgers State Univ, Dept Phys & Astron, 136 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM morozov@physics.rutgers.edu RI Morozov, Alexandre/E-1984-2016; OI Morozov, Alexandre/0000-0003-2598-7000; Chereji, Razvan/0000-0002-0572-6412 FU National Institutes of Health [R01 HG004708]; Alfred P. Sloan Research Fellowship FX A.V.M. was supported by National Institutes of Health (R01 HG004708) and an Alfred P. Sloan Research Fellowship. NR 62 TC 10 Z9 10 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2041-2649 EI 2041-2657 J9 BRIEF FUNCT GENOMICS JI Brief. Funct. Genomics PD JAN PY 2015 VL 14 IS 1 SI SI BP 50 EP 60 DI 10.1093/bfgp/elu038 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CC0VP UT WOS:000350056300006 PM 25275099 ER PT J AU Berger, VW AF Berger, Vance W. TI A note on response-adaptive randomization SO CONTEMPORARY CLINICAL TRIALS LA English DT Letter DE Big stick; Maximal procedure; Medical ethics; Time horizons C1 [Berger, Vance W.] NCI, Rockville, MD 20850 USA. [Berger, Vance W.] Univ Maryland Baltimore Cty, Biometry Res Grp, NCI, Rockville, MD 20850 USA. RP Berger, VW (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM vb78@nih.gov NR 4 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2015 VL 40 BP 240 EP 240 DI 10.1016/j.cct.2014.12.013 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CB6IZ UT WOS:000349732000027 PM 25545024 ER PT J AU Gupta, A Thiruvengadam, G Desai, SA AF Gupta, Ankit Thiruvengadam, Girija Desai, Sanjay A. TI The conserved clag multigene family of malaria parasites: Essential roles in host-pathogen interaction SO DRUG RESISTANCE UPDATES LA English DT Review DE malaria parasites; host-pathogen interactions; clag multigene family; cytoadherence; merozoite invasion; nutrient channels; epigenetics; gene regulation; antimalarial drug development ID SURFACE ANION CHANNEL; FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; PARASITOPHOROUS VACUOLE MEMBRANE; RHOPTRY PROTEIN COMPLEX; PLASMODIUM-FALCIPARUM; NUTRIENT-UPTAKE; ENDOPLASMIC-RETICULUM; COMPARATIVE GENOMICS; FUNCTIONAL-ANALYSIS AB The clag multigene family is strictly conserved in malaria parasites, but absent from neighboring genera of protozoan parasites. Early research pointed to roles in merozoite invasion and infected cell cytoadherence, but more recent studies have implicated channel-mediated uptake of ions and nutrients from host plasma. Here, we review the current understanding of this gene family, which appears to be central to host-parasite interactions and an important therapeutic target. Published by Elsevier Ltd. C1 [Gupta, Ankit; Thiruvengadam, Girija; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We thank Ryan Kissinger and Anita Mora for help with manuscript figures. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 96 TC 8 Z9 8 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 EI 1532-2084 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD JAN PY 2015 VL 18 BP 47 EP 54 DI 10.1016/j.drup.2014.10.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CB8KH UT WOS:000349878000004 PM 25467627 ER PT J AU Li, CL Yang, XK Feng, J Lei, P Wang, YB AF Li, Caili Yang, Xiaokun Feng, Jing Lei, Ping Wang, Yubao TI Proinflammatory and prothrombotic status in emphysematous rats exposed to intermittent hypoxia SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Overlap syndrome; intermittent hypoxia; emphysema; inflammation; coagulant factors ID OBSTRUCTIVE SLEEP-APNEA; PULMONARY-DISEASE; OXIDATIVE STRESS; OVERLAP SYNDROME; STEM-CELLS; COPD; APOPTOSIS; BLOOD; INFLAMMATION; ATHEROSCLEROSIS AB Objectives: To develop an "overlap syndrome (OS)" rat model by intermittent hypoxia (IH) exposure on the base of pre-existing emphysema, and to explore whether "OS" exposure results in more severe systemic inflammation, and whether the inflammation changes levels of coagulant/anticoagulant factors and oxidative stress status. Methods: Sixty Wistar rats were put into 4 groups: Control group; IH group, IH exposure; Emphysema group, smoke exposure; Overlap group, smoke exposure and IH exposure. We obtained peripheral blood for apoptosis of CD3(+) CD4(+), CD3(+) CD8(+) T lymphocytes and neutrophils, and for endothelial progenitor cell (EPC) counts. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and coagulant/anticoagulant factors [antithrombin (AT), fibrinogen (FIB), Factor VIII (FVIII) and von Willebrand factor (vWF)] were evaluated. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress [superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration]. Results: The levels of TNF-alpha and IL-6, CD3(+) CD4(+) T lymphocyte apoptosis, EPC counts, coagulant factors and MDA are the highest in Overlap group, the lowest in Control group, when the levels of neutrophil apoptosis, CD3(+) CD8(+) T lymphocyte apoptosis, AT, SOD and CAT are the lowest in Overlap group, the highest in Control group (all P values < 0.05). Conclusion: In model animals, when IH is combined with emphysema, there will be a more severe or an "overlapped" systemic/multiple organic inflammation, oxidative stress and hyper-coagulability. And the pro-inflammatory and pro-thrombotic status resulted from "OS" exposure may elicit a robust EPC mobilization, which needs further investigation. C1 [Li, Caili; Yang, Xiaokun; Feng, Jing] Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. [Feng, Jing] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Lei, Ping] Tianjin Med Univ, Gen Hosp, Departmen Geriatr, Tianjin 300052, Peoples R China. [Wang, Yubao] Tianjin Med Univ, Affiliated Hosp 2, Infect Dis Inst, Tianjin 300211, Peoples R China. RP Feng, J (reprint author), Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. EM zyyhxkfj@126.com; tjzyyleiping@126.com FU National Natural Science Foundation of China [81270144, 30800507, 81170071] FX We are grateful to the information and correction from Danielle Speer and Ambrose Chiang of Division of Pulmonary and Critical Care Medicine in Duke University Medical Center, Durham, North Carolina, USA. This study was supported by grants from the National Natural Science Foundation of China (81270144, 30800507, and 81170071). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 1 Z9 1 U1 3 U2 3 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2015 VL 8 IS 1 BP 374 EP U1097 PG 13 WC Oncology; Pathology SC Oncology; Pathology GA CB7WG UT WOS:000349838700038 PM 25755725 ER PT J AU Zuo, RC Naik, HB Steinberg, SM Baird, K Mitchell, SA Kuzmina, Z Pavletic, SZ Cowen, EW AF Zuo, Rena C. Naik, Haley B. Steinberg, Seth M. Baird, Kristin Mitchell, Sandra A. Kuzmina, Zoya Pavletic, Steven Z. Cowen, Edward W. TI Risk Factors and Characterization of Vitiligo and Alopecia Areata in Patients With Chronic Graft-vs-Host Disease SO JAMA DERMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; OF-THE-LITERATURE; CLASS-II ALLELES; GENERALIZED VITILIGO; ADOPTIVE TRANSFER; LICHEN-SCLEROSUS; TOTAL LEUKODERMA; RECIPIENT SEX; T-CELLS AB IMPORTANCE Cutaneous manifestations of chronic graft-vs-host disease (GvHD) are highly variable and may recapitulate well-characterized autoimmune diseases, including systemic sclerosis and Sjogren syndrome. However, vitiligo and alopecia areata (AA) have not been well characterized in the chronic GvHD setting. OBJECTIVE To determine laboratory markers, transplant-related factors, and other systemic manifestations associated with vitiligo and/or AA in patients with chronic GvHD. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional, retrospective study conducted by the National Institutes of Health (NIH) of 282 adult and pediatric patients with chronic GvHD seen under the NIH natural history protocol between 2004 and 2013. MAIN OUTCOMES AND MEASURES Demographic, clinical, and laboratory data, including measures of 11 antibodies, were included in the analysis. Patients with vitiligo and/or AA were identified from dermatologist documentation and photographic evidence. Univariate and multivariable logistic regression analyses were used to determine risk factors for vitiligo and AA development. RESULTS Fifteen (5.3%) of 282 patients demonstrated vitiligo (14 of 282; 4.9%) and/or AA (2 of 282; 0.7%) (1 patient had both vitiligo and AA). Univariate analysis identified female donor to male recipient sex mismatch (P = .003), positive test results for anticardiolipin (ACA) IgG (P = .03) or antiparietal antibody (P = .049), elevated CD19 level (P = .045), and normal or elevated IgG level (P = .02) as risk factors for vitiligo or AA. Female donor to male recipient sex mismatch (P = .003) and positive findings for ACA-IgG (P = .01) retained significance in the multivariable analysis. CONCLUSIONS AND RELEVANCE Female donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or AA. Further studies are needed to explore transplant-related risk factors that may lead to better understanding of the pathomechanisms of chronic GvHD. C1 [Zuo, Rena C.; Naik, Haley B.; Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Baird, Kristin] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Kuzmina, Zoya; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute; NIH Medical Research Scholars Program; Pfizer Inc; Doris Duke Charitable Foundation; Alexandria Real Estate Equities Inc; Howard Hughes Medical Institute FX This study was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), the National Cancer Institute, and the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities Inc, Mr and Mrs Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. NR 59 TC 3 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD JAN PY 2015 VL 151 IS 1 BP 23 EP 32 DI 10.1001/jamadermatol.2014.1550 PG 10 WC Dermatology SC Dermatology GA CB6RI UT WOS:000349753900004 PM 25207994 ER PT J AU Brown, GT Cowen, EW Lee, CCR AF Brown, G. Thomas Cowen, Edward W. Lee, Chyi-chia Richard TI Malignant Melanoma Masquerading as an Angiofibroma in a Patient With MEN-1 SO JAMA DERMATOLOGY LA English DT Letter ID ENDOCRINE NEOPLASIA TYPE-1; GENE C1 [Brown, G. Thomas; Lee, Chyi-chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Brown, GT (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 2B50, Bethesda, MD 20892 USA. EM gtom.brown@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD JAN PY 2015 VL 151 IS 1 BP 105 EP 106 DI 10.1001/jamadermatol.2014.2186 PG 3 WC Dermatology SC Dermatology GA CB6RI UT WOS:000349753900027 PM 25317507 ER PT J AU Littlejohns, TJ Kos, K Henley, WE Cherubini, A Ferrucci, L Lang, IA Langa, KM Melzer, D Llewellyn, DJ AF Littlejohns, Thomas J. Kos, Katarina Henley, William E. Cherubini, Antonio Ferrucci, Luigi Lang, Iain A. Langa, Kenneth M. Melzer, David Llewellyn, David J. TI Serum Leptin and Risk of Cognitive Decline in Elderly Italians SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Adipokines; cognitive decline; cohort analysis; epidemiology; leptin ID BLOOD-BRAIN-BARRIER; TAU PHOSPHORYLATION; PLASMA LEPTIN; NEURONAL CELLS; OLDER WOMEN; BODY-WEIGHT; A-BETA; OBESITY; DEMENTIA; ASSOCIATION AB Background: US studies suggest that leptin, a fat- derived hormone, may be protective against the development of dementia. Objective: To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. Methods: We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population- based InCHIANTI study between 1998 and 2009 (mean follow- up of 8.0 years). Global cognitive decline was defined as a reduction of >= 5 points on the Mini- Mental State Examination (MMSE). Trail- Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. Results: The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73- 0.97) in relation to baseline sex- standardized log- leptin levels. High leptin levels showed a non- significant trend toward a reduced risk of decline on the Trail- Making Tests A (RR = 0.85, 95% CI 0.71- 1.02) and B (RR = 0.90, 0.79- 1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. Conclusions: High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians. C1 [Littlejohns, Thomas J.; Kos, Katarina; Henley, William E.; Lang, Iain A.; Melzer, David; Llewellyn, David J.] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England. [Cherubini, Antonio] IRCCS, INRCA, Geriatr, Ancona, AC, Italy. [Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. [Langa, Kenneth M.] Vet Affairs Ann Arbor Ctr Clin Management Res, Div Gen Med, Ann Arbor, MI USA. [Langa, Kenneth M.] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. [Langa, Kenneth M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. RP Llewellyn, DJ (reprint author), Univ Exeter, Sch Med, Coll House,Heavitree Rd, Exeter EX1 2LU, Devon, England. EM david.llewellyn@exeter.ac.uk RI Kos, Katarina/G-6772-2014; OI Melzer, David/0000-0002-0170-3838; Lang, Iain/0000-0002-8473-2350; Cherubini, Antonio/0000-0003-0261-9897 FU Italian Ministry of Health, U.S. National Institute on Aging [ICS110.1/RF97.71, 263 MD 9164, 263 MD 821336]; U.S. National Institute on Aging [N.1-AG-1-1, N.1-AG-12111, N01-AG-5-0002]; Intramural research program of the National Institute on Aging; National Institutes of Health, Baltimore, Maryland; Alzheimer's Association [NIRG-11-200737]; Mary Kinross Charitable Trust; James Tudor Foundation; Halpin Trust; Sir Halley Stewart Trust; Age Related Diseases and Health Trust; National Institute for Health Research (NIHR) FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health, and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336). The follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-12111); the follow-up 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002). Supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. Additional support was also provided by NIRG-11-200737 from the Alzheimer's Association, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, the Sir Halley Stewart Trust, the Age Related Diseases and Health Trust, and the Norman Family Charitable Trust (to D.J.L.). This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care SouthWest Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. None of the funding sources had any role in the design of the study; in the analysis and interpretation of the data; or in the preparation of the manuscript. NR 34 TC 2 Z9 2 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 44 IS 4 BP 1231 EP 1239 DI 10.3233/JAD-141836 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CC0BW UT WOS:000350001000017 PM 25502764 ER PT J AU Cornwell, B Marcum, C Silverstein, M AF Cornwell, Benjamin Marcum, Christopher Silverstein, Merril TI The Social Network Approach in Gerontological Research SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Editorial Material ID PERSONAL NETWORKS; LIFE C1 [Cornwell, Benjamin] Cornell Univ, Dept Sociol, Ithaca, NY 14853 USA. [Marcum, Christopher] NHGRI, NIH, Bethesda, MD 20892 USA. [Silverstein, Merril] Syracuse Univ, Maxwell Sch, Dept Sociol, New York, NY USA. [Silverstein, Merril] Syracuse Univ, Falk Coll, Sch Social Work, New York, NY USA. RP Cornwell, B (reprint author), Cornell Univ, Dept Sociol, 342 Uris Hall, Ithaca, NY 14853 USA. EM btc49@cornell.edu OI Marcum, Christopher/0000-0002-0899-6143 NR 17 TC 1 Z9 1 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2015 VL 70 IS 1 BP 87 EP 90 DI 10.1093/geronb/gbu157 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CC0QA UT WOS:000350039400011 PM 25399011 ER PT J AU Smith, EJ Marcum, CS Boessen, A Almquist, ZW Hipp, JR Nagle, NN Butts, CT AF Smith, Emily J. Marcum, Christopher S. Boessen, Adam Almquist, Zack W. Hipp, John R. Nagle, Nicholas N. Butts, Carter T. TI The Relationship of Age to Personal Network Size, Relational Multiplexity, and Proximity to Alters in the Western United States SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Multiplexity; Social networks; Support relations ID AGING IN-PLACE; SOCIAL SUPPORT; OLDER-ADULTS; RESPONSE RATES; CONTACT; LIFE; MODEL; NEED AB Objectives. This study examines the association of age and other sociodemographic variables with properties of personal networks; using samples of individuals residing in the rural western United States and the City of Los Angeles, we evaluate the degree to which these associations vary with geographical context. For both samples, we test the hypothesis that age is negatively associated with network size (i.e., degree) and positively associated with network multiplexity (the extent of overlap) on 6 different relations: core discussion members, social activity participants, emergency contacts, neighborhood safety contacts, job informants, and kin. We also examine the relationship between age and spatial proximity to alters. Method. Our data consist of a large-scale, spatially stratified egocentric network survey containing information about respondents and those to whom they are tied. We use Poisson regression to test our hypothesis regarding degree while adjusting for covariates, including education, gender, race, and self-reported sense of neighborhood belonging. We use multiple linear regression to test our hypotheses on multiplexity and distance to alters. Results. For both rural and urban populations, we find a nonmonotone association between age and numbers of core discussants and emergency contacts, with rural populations also showing nonmonotone associations for social activity partners and kin. These nonmonotone relationships show a peak in expected degree at midlife, followed by an eventual decline. We find a decline in degree among the elderly for all relations in both populations. Age is positively associated with distance to nonhousehold alters for the rural population, although residential tenure is associated with shorter egoalter distances in both rural and urban settings. Additionally, age is negatively associated with network multiplexity for both populations. Discussion. Although personal network size ultimately declines with age, we find that increases for some relations extend well into late-midlife and most elders still maintain numerous contacts across diverse relations. The evidence we present suggests that older people tap into an wider variety of different network members for different types of relations than do younger people. This is true even for populations in rural settings, for whom immediate access to potential alters is more limited. C1 [Smith, Emily J.; Butts, Carter T.] Univ Calif Irvine, Dept Sociol, Irvine, CA 92697 USA. [Marcum, Christopher S.] NIH, Bethesda, MD 20892 USA. [Boessen, Adam] Univ Missouri, Dept Criminol & Criminal Justice, St Louis, MO USA. [Almquist, Zack W.] Univ Minnesota, Sch Stat, Minnesota Populat Ctr, Dept Sociol, Minneapolis, MN 55455 USA. [Hipp, John R.] Univ Calif Irvine, Dept Criminol Law & Soc, Irvine, CA 92697 USA. [Nagle, Nicholas N.] Univ Tennessee, Dept Geog, Knoxville, TN 37996 USA. [Butts, Carter T.] Univ Calif Irvine, Dept Stat, Irvine, CA 92697 USA. [Butts, Carter T.] Univ Calif Irvine, Dept EECS, Irvine, CA 92697 USA. [Butts, Carter T.] Univ Calif Irvine, Inst Math & Behav Sci, Irvine, CA 92697 USA. RP Butts, CT (reprint author), Univ Calif Irvine, Dept Sociol, 3151 Social Sci Plaza, Irvine, CA 92697 USA. EM buttsc@uci.edu OI Marcum, Christopher/0000-0002-0899-6143; Almquist, Zack/0000-0002-1967-123X FU National Science Foundation [BCS-0927027, OIA-1028394]; Office of Naval Research [N00014-08-1-1015]; NIH Intramural Research Program [Z01HG200335] FX National Science Foundation (BCS-0927027, OIA-1028394); Office of Naval Research (N00014-08-1-1015); NIH Intramural Research Program (Z01HG200335). NR 43 TC 1 Z9 1 U1 4 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2015 VL 70 IS 1 BP 91 EP 99 DI 10.1093/geronb/gbu142 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CC0QA UT WOS:000350039400012 PM 25324292 ER PT J AU Koehly, LM Ashida, S Schafer, EJ Ludden, A AF Koehly, Laura M. Ashida, Sato Schafer, Ellen J. Ludden, Amanda TI Caregiving Networks-Using a Network Approach to Identify Missed Opportunities SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Alzheimer's disease; Caregiving; Dementia; Family structure; Social networks ID FAMILY CAREGIVERS; ALZHEIMERS-DISEASE; SOCIAL NETWORK; PHYSICAL HEALTH; FRAIL SENIORS; CARE NETWORKS; SUPPORT; DEMENTIA; PERSPECTIVE; BURDEN AB Objectives. This study demonstrates the added value to caregiving research by using a multi-informant social network approach within the context of Alzheimer's disease and related dementia. Method. Sixty-six informants from 24 families enumerated caregiving network members in 2012. Comparisons were made between networks based on a single informant versus multiple informants in terms of network composition and caregiving roles, core-periphery structure, and identification of "missed opportunities" in recruitment. Results. On average, each informant beyond the index enumerated 6.2 new members, resulting in about 10 new members per family network when the multiple-informant approach is used. Compared with index informants' networks, multi-informant networks showed an 85% increase in identification of direct care providers (1.71 compared with 3.42) and a 48% increase in identification of those involved in care decision making (3.33 compared with 4.92). Informants from the same network generally showed agreement in reported participation in caregiving activities. However, the reports of non-participation in these roles were less consistent among the informants. Resulting structure indicated a core caregiving network (M = 6.12 members), with semi-peripheral and peripheral members (M = 5.19 and M = 14.83 members, respectively). Discussion. Results suggest that an iterative, targeted sampling approach with at least three informants allows for a more comprehensive assessment of caregiving processes. Applying this approach in future research will greatly enhance our knowledge and better inform future interventions to facilitate family adaptation. C1 [Koehly, Laura M.; Ludden, Amanda] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Ashida, Sato; Schafer, Ellen J.] Univ Iowa, Coll Publ Hlth, Aging Mind & Brain Initiat, Dept Community & Behav Hlth, Iowa City, IA 52242 USA. RP Koehly, LM (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Room B1B37D, Bethesda, MD 20892 USA. EM koehlyl@mail.nih.gov FU National Human Genome Research Institute at the National Institutes of Health [Z01HG200335] FX This work was supported by the National Human Genome Research Institute at the National Institutes of Health (Z01HG200335 to L. M. Koehly). NR 55 TC 2 Z9 2 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2015 VL 70 IS 1 BP 143 EP 154 DI 10.1093/geronb/gbu111 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CC0QA UT WOS:000350039400017 PM 25224254 ER PT J AU Song, HJ Rosano, JM Wang, Y Garson, CJ Prabhakarpandian, B Pant, K Klarmann, GJ Perantoni, A Alvarez, LM Lai, E AF Song, Hongjun Rosano, Jenna M. Wang, Yi Garson, Charles J. Prabhakarpandian, Balabhaskar Pant, Kapil Klarmann, George J. Perantoni, Alan Alvarez, Luis M. Lai, Eva TI Continuous-flow sorting of stem cells and differentiation products based on dielectrophoresis SO LAB ON A CHIP LA English DT Article ID DIELECTRIC-PROPERTIES; CANCER-CELLS; BONE-MARROW; SEPARATION; BLOOD; FRACTIONATION; ENRICHMENT; MICROELECTRODES; REMOVAL; THERAPY AB This paper presents a continuous-flow microfluidic device for sorting stem cells and their differentiation progenies. The principle of the device is based on the accumulation of multiple dielectrophoresis (DEP) forces to deflect cells laterally in conjunction with the alternating on/off electric field to manipulate the cell trajectories. The microfluidic device containing a large array of oblique interdigitated electrodes was fabricated using a combination of standard and soft lithography techniques to generate a PDMS-gold electrode construct. Experimental testing with human mesenchymal stem cells (hMSC) and their differentiation progenies (osteoblasts) was carried out at different flow rates, and clear separation of the two populations was achieved. Most of the osteoblasts experiencing stronger DEP forces were deflected laterally and continuously, following zig-zag trajectories, and moved towards the desired collection outlet, whereas most of the hMSCs remained on the original trajectory due to weaker DEP forces. The experimental measurements were characterized and evaluated quantitatively, and consistent performance was demonstrated. Collection efficiency up to 92% and 67% for hMSCs and osteoblasts, respectively, along with purity up to 84% and 87% was obtained. The experimental results established the feasibility of our microfluidic DEP sorting device for continuous, label-free sorting of stem cells and their differentiation progenies. C1 [Song, Hongjun; Rosano, Jenna M.; Wang, Yi; Garson, Charles J.; Prabhakarpandian, Balabhaskar; Pant, Kapil] CFD Res Corp, Huntsville, AL 35806 USA. [Klarmann, George J.; Perantoni, Alan; Alvarez, Luis M.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. [Alvarez, Luis M.] US Mil Acad, Dept Chem & Life Sci, West Point, NY 10996 USA. [Lai, Eva] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Lai, Eva] US Army Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Ft Detrick, MD 21702 USA. RP Wang, Y (reprint author), CFD Res Corp, 701 McMillian Way NW, Huntsville, AL 35806 USA. EM yxw@cfdrc.com FU U.S. Army Medical Research and Materiel Command (USAMRMC) under SBIR contract [W81XWH-12-C-0069] FX This research was sponsored by the U.S. Army Medical Research and Materiel Command (USAMRMC) under SBIR contract no. W81XWH-12-C-0069. GJK and LMA acknowledge Dr. Alan Perantoni and Ms. Nirmala Sharma of the Cancer and Developmental Biology Laboratory for providing access to specialized tissue culture facilities and for discussions regarding analysis of differentiation and development markers. NR 50 TC 23 Z9 24 U1 9 U2 60 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2015 VL 15 IS 5 BP 1320 EP 1328 DI 10.1039/c4lc01253d PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CB7WC UT WOS:000349838200012 PM 25589423 ER PT J AU Dudas, G Bedford, T Lycett, S Rambaut, A AF Dudas, Gytis Bedford, Trevor Lycett, Samantha Rambaut, Andrew TI Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1-PB2-HA Gene Complex SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE influenza; reassortment; evolution; phylogenetics; speciation ID HOMOLOGOUS RECOMBINATION; COCIRCULATING LINEAGES; EPIDEMIC SEASON; PB1 GENE; VIRUS; HEMAGGLUTININ; POPULATION; EVOLUTION; DYNAMICS; VACCINE AB Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1-PB2-HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation. C1 [Dudas, Gytis; Lycett, Samantha; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. [Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Lycett, Samantha] Univ Glasgow, Inst Biodivers Anim Hlth & Comparat Med, Glasgow, Lanark, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh, Midlothian, Scotland. RP Dudas, G (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. EM g.dudas@sms.ed.ac.uk OI Bedford, Trevor/0000-0002-4039-5794; Rambaut, Andrew/0000-0003-4337-3707; Dudas, Gytis/0000-0002-0227-4158; Lycett, Samantha/0000-0003-3159-596X FU Natural Environment Research Council studentship [D76739X]; Newton International Fellowship from the Royal Society; European Research Council under the European Community [278433-PREDEMICS]; ERC [260864]; Wellcome Trust [092807] FX The authors thank Darren Obbard and Paul Wikramaratna for helpful discussions and anonymous reviewers for comments and suggestions. This study was supported by a Natural Environment Research Council studentship D76739X to G.D. and a Newton International Fellowship from the Royal Society to T.B. The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 278433-PREDEMICS and ERC Grant Agreement No. 260864. A.R. and S.L. acknowledge the support of the Wellcome Trust (Grant No. 092807). NR 49 TC 16 Z9 16 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JAN PY 2015 VL 32 IS 1 BP 162 EP 172 DI 10.1093/molbev/msu287 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA CC0TR UT WOS:000350050200015 PM 25323575 ER PT B AU Renvoise, B Blackstone, C AF Renvoise, Benoit Blackstone, Craig BE LeDoux, MS TI Hereditary Spastic Paraplegias: Genetics and Clinical Features SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID BRAIN IRON ACCUMULATION; AUTOSOMAL-DOMINANT; MUTATION; NEURODEGENERATION; PREVALENCE; C19ORF12; FREQUENT; ATAXIA; FORM C1 [Renvoise, Benoit; Blackstone, Craig] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Renvoise, B (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 29 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 1063 EP 1071 DI 10.1016/B978-0-12-405195-9.00069-X PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700071 ER PT B AU Blackstone, C AF Blackstone, Craig BE LeDoux, MS TI Murine Models of Autosomal Recessive Hereditary Spastic Paraplegia SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID COMPLEX GANGLIOSIDES; TROYER-SYNDROME; DEFICIENT MICE; PROTEIN; SPARTIN; KIF1A; ACCUMULATION; DEGENERATION; TRAFFICKING; MAINTENANCE C1 NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 1087 EP 1093 DI 10.1016/B978-0-12-405195-9.00071-8 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700073 ER PT J AU Martinez, K Battaglia, R Start, R Mastal, MF Matlock, AM AF Martinez, Kathleen Battaglia, Rosemarie Start, Rachel Mastal, Margaret F. Matlock, Ann Marie TI Nursing-Sensitive Indicators in Ambulatory Care SO NURSING ECONOMICS LA English DT Article ID QUALITY AB Ambulatory nursing care can be difficult to comprehend in all its complexity. In August 2013, the American Academy of Ambulatory Care Nursing commissioned a task force to identify nursing-sensitive indicators specific to ambulatory care settings. Given the great variation in settings, staff mix, patient populations, role dimensions, skill sets, documentation systems, and resources, determining metrics that apply across the entire continuum of care is a daunting task. However, it is incumbent upon nurse leaders to define the metrics that will promote the value of the registered nurse in ambulatory practice and care coordination. Once initial measures are identified, piloted, and validated, the infrastructure can be created for ongoing benchmarking and collaboration. The long-term goal is to leverage professional nursing practice, based in the ambulatory care setting, to improve quality, safety, and cost in health care. C1 [Martinez, Kathleen] Childrens Hosp Colorado, Aurora, CO 80045 USA. [Battaglia, Rosemarie] MUSC Childrens Hosp, Charleston, SC USA. [Start, Rachel] Rush Oak Pk Hosp, Magnet Program, Oak Pk, IL USA. [Mastal, Margaret F.] Amer Acad Ambulatory Care Nursing, Pitman, NJ USA. [Matlock, Ann Marie] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Martinez, K (reprint author), Childrens Hosp Colorado, Aurora, CO 80045 USA. NR 10 TC 1 Z9 1 U1 7 U2 10 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JAN-FEB PY 2015 VL 33 IS 1 BP 59 EP + PG 6 WC Nursing SC Nursing GA CB9FL UT WOS:000349937300009 PM 26214940 ER PT J AU Wade, KL Ito, Y Ramarathnam, A Holtzclaw, WD Fahey, JW AF Wade, Kristina L. Ito, Yoichiro Ramarathnam, Aarthi Holtzclaw, W. David Fahey, Jed W. TI Purification of Active Myrosinase from Plants by Aqueous Two-Phase Counter-Current Chromatography SO PHYTOCHEMICAL ANALYSIS LA English DT Article DE Counter-current chromatography; broccoli; daikon; glucosinolate; isothiocyanate; moringa; mustard ID ONE-STEP PURIFICATION; SCALE-UP; CELL-LYSATE; SYSTEM; ISOTHIOCYANATES; GLUCORAPHANIN; TECHNOLOGY; CENTRIFUGE; EXTRACTION; PROTECTION AB Introduction - Myrosinase (thioglucoside glucohydrolase; E.C. 3.2.1.147), is a plant enzyme of increasing interest and importance to the biomedical community. Myrosinase catalyses the formation of isothiocyanates such as sulforaphane (from broccoli) and 4( alpha-L-rhamnopyranosyloxy) benzyl isothiocyanate (from moringa), which are potent inducers of the cytoprotective phase-2 response in humans, by hydrolysis of their abundant glucosinolate (beta-thioglucoside N-hydroxysulphate) precursors. Objective - To develop an aqueous two-phase counter-current chromatography (CCC) system for the rapid, three-step purification of catalytically active myrosinase. Methods - A high-concentration potassium phosphate and polyethylene glycol biphasic aqueous two-phase system (ATPS) is used with a newly developed CCC configuration that utilises spiral-wound, flat-twisted tubing (with an ovoid cross-section). Results - Making the initial crude plant extract directly in the ATPS and injecting only the lower phase permitted highly selective partitioning of the myrosinase complex before a short chromatography on a spiral disk CCC. Optimum phase retention and separation of myrosinase from other plant proteins afforded a 60-fold purification. Conclusion - Catalytically active myrosinase is purified from 3-day broccoli sprouts, 7-day daikon sprouts, mustard seeds and the leaves of field-grown moringa trees, in a CCC system that is predictably scalable. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Wade, Kristina L.; Ramarathnam, Aarthi; Holtzclaw, W. David; Fahey, Jed W.] Johns Hopkins Univ, Sch Med, Lewis B & Dorothy Cullman Chemoprotect Ctr, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Fahey, Jed W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD 21205 USA. RP Fahey, JW (reprint author), Johns Hopkins Univ, Sch Med, Cullman Chemoprotect Ctr, Suite 625,John G Rangos Bldg,855 N Wolfe St, Baltimore, MD 21205 USA. EM jfahey@jhmi.edu FU Lewis and Dorothy Cullman Foundation; American Institute for Cancer Research; NIH [CA 093780] FX This work was supported by the Lewis and Dorothy Cullman Foundation, the American Institute for Cancer Research, and the NIH (CA 093780). We are most grateful to: Paul Talalay (Baltimore, MD, USA) for discussions; Janet Gutierrez (Monterrey, MX) for preliminary evaluation of alternative CCC configurations; Rodney Perdew (Sherman Oaks, CA) for providing fresh moringa leaves; and Katherine Stephenson (Baltimore, MD, USA) for technical assistance. NR 37 TC 5 Z9 5 U1 4 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0958-0344 EI 1099-1565 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD JAN-FEB PY 2015 VL 26 IS 1 BP 47 EP 53 DI 10.1002/pca.2535 PG 7 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA CB9PC UT WOS:000349963000007 PM 25130502 ER PT J AU Roll-Mecak, A AF Roll-Mecak, Antonina TI Intrinsically disordered tubulin tails: complex tuners of microtubule functions? SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Microtubule; Post-translational modification; Tubulin tyrosine ligase; Molecular motors; Brush polymer; Intrinsically disordered proteins ID HEREDITARY SPASTIC PARAPLEGIA; CARBOXY-TERMINAL TAILS; MAJOR ALPHA-TUBULIN; BETA-TUBULIN; POSTTRANSLATIONAL MODIFICATIONS; IN-VITRO; RAT-BRAIN; FLEXURAL RIGIDITY; MESSENGER-RNAS; KINESIN MOTOR AB Microtubules are essential cellular polymers assembled from tubulin heterodimers. The tubulin dimer consists of a compact folded globular core and intrinsically disordered C-terminal tails. The tubulin tails form a lawn of densely grafted, negatively charged, flexible peptides on the exterior of the microtubule, potentially akin to brush polymers in the field of synthetic materials. These tails are hotspots for conserved, chemically complex posttranslational modifications that have the potential to act in a combinatorial fashion to regulate microtubule polymer dynamics and interactions with microtubule effectors, giving rise to a "tubulin code". In this review, I summarize our current knowledge of the enzymes that generate the astonishing tubulin chemical diversity observed in cells and describe recent advances in deciphering the roles of tubulin C-terminal tails and their posttranslational modifications in regulating the activity of molecular motors and microtubule associated proteins. Lastly, I outline the promises, challenges and potential pitfalls of deciphering the tubulin code. (C) 2014 Published by Elsevier Ltd. C1 [Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA. [Roll-Mecak, Antonina] NHLBI, Ctr Biophys, Bethesda, MD 20892 USA. RP Roll-Mecak, A (reprint author), NIH, Porter Neurosci Res Ctr, Cell Biol & Biophys Unit, Bldg 35,Room 3B-203,35 Convent Dr,MSC 3700, Bethesda, MD 20892 USA. EM Antonina@gmail.nih.gov FU intramural program of the National Institute of Neurological Disorders and Stroke (NINDS); intramural program of the National Heart, Lung and Blood Institute (NHLBI) FX I apologize to the many colleagues whose work I was unable to cover because of space limitations. I also thank the anonymous reviewers for their insights and suggestions. A.R.-M. is a Searle Scholar and is supported by the intramural programs of the National Institute of Neurological Disorders and Stroke (NINDS) and the National Heart, Lung and Blood Institute (NHLBI). NR 130 TC 18 Z9 18 U1 4 U2 25 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JAN PY 2015 VL 37 BP 11 EP 19 DI 10.1016/j.semcdb.2014.09.026 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CC2ES UT WOS:000350158600003 PM 25307498 ER PT J AU Jiang, YM Fan, XM Wang, Y Chen, P Zeng, H Tan, HS Gonzalez, FJ Huang, M Bi, HC AF Jiang, Yiming Fan, Xiaomei Wang, Ying Chen, Pan Zeng, Hang Tan, Huasen Gonzalez, Frank J. Huang, Min Bi, Huichang TI Schisandrol B Protects Against Acetaminophen-Induced Hepatotoxicity by Inhibition of CYP-Mediated Bioactivation and Regulation of Liver Regeneration SO TOXICOLOGICAL SCIENCES LA English DT Article DE acetaminophen; schisandrol B; liver injury; bioactivation; liver regeneration ID MOLECULAR-MECHANISMS; DRUG-INTERACTIONS; MICE; INJURY; INVOLVEMENT; EXPRESSION; INDUCTION; CHINENSIS; TOXICITY; PRODUCTS AB Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. Schisandra sphenanthera is a traditional hepato-protective Chinese medicine and Schisandrol B (SolB) is one of its major active constituents. In this study, the protective effect of SolB against APAP-induced acute hepatotoxicity in mice and the involved mechanisms were investigated. Morphological and biochemical assessments clearly demonstrated a protective effect of SolB against APAP-induced liver injury. SolB pretreatment significantly attenuated the increases in alanine aminotransferase and aspartate aminotransferase activity, and prevented elevated hepatic malondialdehyde formation and the depletion of mitochondrial glutathione (GSH) in a dose-dependent manner. SolB also dramatically altered APAP metabolic activation by inhibiting the activities of CYP2E1 and CYP3A11, which was evidenced by significant inhibition of the formation of the oxidized APAP metabolite NAPQI-GSH. A molecular docking model also predicted that SolB had potential to interact with the CYP2E1 and CYP3A4 active sites. In addition, SolB abrogated APAP-induced activation of p53 and p21, and increased expression of liver regeneration and antiapoptotic-related proteins such as cyclin D1 (CCND1), PCNA, and BCL-2. This study demonstrated that SolB exhibited a significant protective effect toward APAP-induced liver injury, potentially through inhibition of CYP-mediated APAP bioactivation and regulation of the p53, p21, CCND1, PCNA, and BCL-2 to promote liver regeneration. C1 [Jiang, Yiming; Fan, Xiaomei; Wang, Ying; Chen, Pan; Zeng, Hang; Tan, Huasen; Huang, Min; Bi, Huichang] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bi, HC (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, 132 Waihuandong Rd, Guangzhou 510006, Guangdong, Peoples R China. EM bihchang@mail.sysu.edu.cn OI chen, pan/0000-0003-0271-2725 FU Natural Science Foundation of China [81373470, 81320108027]; Science and Technology Ministry of China [2012ZX09506001-004]; Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation [2011A060901014]; Fundamental Research Funds for the Central Universities [13ykpy08] FX Natural Science Foundation of China (Grant 81373470, 81320108027), the Science and Technology Ministry of China (Grant 2012ZX09506001-004), the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation (Grant 2011A060901014), and the Fundamental Research Funds for the Central Universities (No. 13ykpy08). The authors have declared that there is no conflict of interest. NR 38 TC 6 Z9 8 U1 3 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2015 VL 143 IS 1 BP 107 EP 115 DI 10.1093/toxsci/kfu216 PG 9 WC Toxicology SC Toxicology GA CC1LH UT WOS:000350101700012 PM 25319358 ER PT J AU Subramanian, N Torabi-Parizi, P Gottschalk, RA Germain, RN Dutta, B AF Subramanian, Naeha Torabi-Parizi, Parizad Gottschalk, Rachel A. Germain, Ronald N. Dutta, Bhaskar TI Network representations of immune system complexity SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Article ID PROTEIN-PROTEIN INTERACTION; TOLL-LIKE RECEPTORS; NF-KAPPA-B; TRANSCRIPTION FACTOR DATABASE; HOST-PATHOGEN INTERACTIONS; SINGLE-CELL ANALYSIS; HEPATITIS-C VIRUS; INNATE IMMUNITY; LYMPH-NODES; ESCHERICHIA-COLI AB The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction, positioning, and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels, while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating 'omics' and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular-and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. C1 [Subramanian, Naeha] Inst Syst Biol, Seattle, WA USA. [Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A.; Germain, Ronald N.; Dutta, Bhaskar] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Torabi-Parizi, Parizad] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Dutta, B (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM naeha.subramanian@systemsbiology.org; bhaskar.dutta@nih.gov FU National Institute of Allergy and Infectious Diseases; Institute for Systems Biology FX This work was generously supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, and institutional support funds from the Institute for Systems Biology to NS. NR 174 TC 7 Z9 7 U1 5 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 EI 1939-005X J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD JAN-FEB PY 2015 VL 7 IS 1 BP 13 EP 38 DI 10.1002/wsbm.1288 PG 26 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CC2BF UT WOS:000350148900002 PM 25625853 ER PT J AU Menezes, LF Germino, GG AF Menezes, Luis Fernando Germino, Gregory G. TI Systems biology of polycystic kidney disease: a critical review SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Article ID CYST FLUID; REGULATORY NETWORKS; RAT MODEL; GENES; CILIA; IDENTIFICATION; EXPRESSION; PATHWAYS; CELLS; PKD2 AB The proliferation and diminishing costs of 'omics' approaches have finally opened the doors for small and medium laboratories to enter the 'systems biology era'. This is a welcome evolution that requires a new framework to design, interpret, and validate studies. Here, we highlight some of the challenges, contributions, and prospects of the 'cyst-ems biology' of polycystic kidney disease. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. C1 [Menezes, Luis Fernando; Germino, Gregory G.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. [Germino, Gregory G.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Menezes, LF (reprint author), NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. EM luis.menezes@nih.gov RI Menezes, Luis Fernando/C-7286-2015 FU NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1ZIADK075042-05] FX This research was supported by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), grant 1ZIADK075042-05. NR 59 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 EI 1939-005X J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD JAN-FEB PY 2015 VL 7 IS 1 BP 39 EP 52 DI 10.1002/wsbm.1289 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CC2BF UT WOS:000350148900003 PM 25641951 ER PT S AU Cameron, HA Glover, LR AF Cameron, Heather A. Glover, Lucas R. BE Fiske, ST TI Adult Neurogenesis: Beyond Learning and Memory SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 66 SE Annual Review of Psychology LA English DT Review; Book Chapter DE hippocampus; granule cells; behavior; emotion; stress ID NEUROENDOCRINE STRESS RESPONSES; VENTRAL HIPPOCAMPUS CONTRIBUTE; ANXIETY-RELATED BEHAVIOR; NMDA RECEPTOR BLOCKADE; LONG-TERM-MEMORY; DENTATE GYRUS; PATTERN SEPARATION; VICARIOUS TRIAL; GRANULE CELLS; RAT-BRAIN AB New neurons continue to be generated in the dentate gyrus throughout life, providing this region of the hippocampus with exceptional structural plasticity, but the function of this ongoing neurogenesis is unknown. Inhibition of adult neurogenesis produces some behavioral impairments that suggest a role for new neurons in learning and memory; however, other behavioral changes appear inconsistent with this function. A review of studies investigating the function of the hippocampus going back several decades reveals many ideas that seem to converge on a critical role for the hippocampus in stress response and emotion. These potential hippocampal functions provide new avenues for investigating the behavioral functions of adult neurogenesis. And, conversely, studies in animals lacking adult neurogenesis, which are likely to have more limited and more specific impairments than are seen with lesions, may provide valuable new insights into the function of the hippocampus. A complete understanding of the function of the hippocampus must explain its role in emotion and the relationship between its emotional and memory functions. C1 [Cameron, Heather A.; Glover, Lucas R.] NIMH, Sect Neuroplast, NIH, Bethesda, MD 20892 USA. [Glover, Lucas R.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Cameron, HA (reprint author), NIMH, Sect Neuroplast, NIH, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 FU Intramural NIH HHS; PHS HHS [1ZIAMH002784] NR 171 TC 33 Z9 33 U1 7 U2 43 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0266-5 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2015 VL 66 BP 53 EP 81 DI 10.1146/annurev-psych-010814-015006 PG 29 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BB9PZ UT WOS:000348560800004 PM 25251485 ER PT S AU Pine, DS Fox, NA AF Pine, Daniel S. Fox, Nathan A. BE Fiske, ST TI Childhood Antecedents and Risk for Adult Mental Disorders SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 66 SE Annual Review of Psychology LA English DT Review; Book Chapter DE developmental psychopathology; amygdala; prefrontal cortex; anxiety ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BIAS MODIFICATION TREATMENT; BEHAVIORAL-INHIBITION; ANXIETY DISORDERS; INDIVIDUAL-DIFFERENCES; DEPRESSIVE-DISORDERS; IMAGING BIOMARKERS; DELETION SYNDROME; PANIC DISORDER AB Progress in treating and preventing mental disorders may follow from research that integrates development, genetics, and neuroscience. This review first delineates how longitudinal research has identified three particular groups of disorders shown to differ on the basis of symptom trajectories and risk-factor profiles. In the next section, the review describes how research on genetic contributions to psychopathology has elucidated the nature of risk for two groups of disorders, the neurodevelopmental and psychotic disorders. In the third section, the review describes how research on environmental contributions to psychopathology has targeted early temperament, its associated perturbations in information-processing functions, and its relations to a third group of disorders, the emotional disorders. For all three groups of disorders, such integrative research has generated ideas about novel interventions. The hope is that over the coming decade such ideas will lead to novel treatments that alter the trajectory of risk in developmental psychopathology. C1 [Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Bethesda, MD 20892 USA. EM daniel.pine@nih.gov FU Intramural NIH HHS; NICHD NIH HHS [R37HD17899]; NIMH NIH HHS [MH074454] NR 94 TC 14 Z9 14 U1 3 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0266-5 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2015 VL 66 BP 459 EP 485 DI 10.1146/annurev-psych-010814-015038 PG 27 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BB9PZ UT WOS:000348560800019 PM 25559116 ER PT J AU Herrick, JA Metenou, S Makiya, MA Taylar-Williams, CA Law, MA Klion, AD Nutman, TB AF Herrick, Jesica A. Metenou, Simon Makiya, Michelle A. Taylar-Williams, Cheryl A. Law, Melissa A. Klion, Amy D. Nutman, Thomas B. TI Eosinophil-Associated Processes Underlie Differences in Clinical Presentation of Loiasis Between Temporary Residents and Those Indigenous to Loa-Endemic Areas SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Loa loa; eosinophil; loiasis ID HYPERRESPONSIVE SYNDROME; EXPERIMENTAL-INFECTION; HUMAN FILARIASIS; T-CELLS; ENCEPHALITIS; POPULATIONS; ANTIGEN; IGG4 AB Background. Loa loa has emerged as an important public health problem due to the occurrence of immune-mediated severe posttreatment reactions following ivermectin distribution. Also thought to be immune-mediated are the dramatic differences seen in clinical presentation between infected temporary residents (TR) and individuals native to endemic regions (END). Methods. All patients diagnosed with loiasis at the National Institutes of Health between 1976 and 2012 were included. Patients enrolled in the study underwent a baseline clinical and laboratory evaluation and had serum collected and stored. Stored pretreatment serum was used to measure filaria-specific antibody responses, eosinophil-related cytokines, and eosinophil granule proteins. Results. Loa loa infection in TR was characterized by the presence of Calabar swelling (in 82% of subjects), markedly elevated eosinophil counts, and increased filaria-specific immunoglobulin G (IgG) levels; these findings were thought to reflect an unmodulated immune response. In contrast, END showed strong evidence for immune tolerance to the parasite, with high levels of circulating microfilariae, few clinical symptoms, and diminished filaria-specific IgG. The striking elevation in eosinophil counts among the TR group was accompanied by increased eosinophil granule protein levels (associated with eosinophil activation and degranulation) as well as elevated levels of eosinophil-associated cytokines. Conclusions. These data support the hypothesis that differing eosinophil-associated responses to the parasite may be responsible for the marked differences in clinical presentations between TR and END populations with loiasis. C1 [Herrick, Jesica A.; Metenou, Simon; Makiya, Michelle A.; Taylar-Williams, Cheryl A.; Law, Melissa A.; Klion, Amy D.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Herrick, JA (reprint author), Univ Illinois, Div Infect Dis Immunol & Int Med, 808 S Wood St,MC 735, Chicago, IL 60612 USA. EM christe5@uic.edu NR 32 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 55 EP 63 DI 10.1093/cid/ciu723 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300011 PM 25234520 ER PT J AU Kadri, SS Hohmann, SF Orav, EJ Bonne, SL Moffa, MA Timpone, JG Strich, JR Palmore, T Christopher, KB Varughese, C Hooper, DC Danner, RL AF Kadri, Sameer S. Hohmann, Samuel F. Orav, E. John Bonne, Stephanie L. Moffa, Matthew A. Timpone, Joseph G. Strich, Jeffrey R. Palmore, Tara Christopher, Kenneth B. Varughese, Christy Hooper, David C. Danner, Robert L. TI Tracking Colistin-Treated Patients to Monitor the Incidence and Outcome of Carbapenem-Resistant Gram-Negative Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE colistin; carbapenem resistance; gram-negative infection; extensively drug resistant; surveillance ID BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS; PSEUDOMONAS-AERUGINOSA COLONIZATION; CYSTIC-FIBROSIS; ANTIMICROBIAL THERAPY; BACTERIAL-INFECTIONS; SEVERE SEPSIS; EPIDEMIOLOGY; MORTALITY; ENTEROBACTERIACEAE AB Background. Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown. Methods. A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100 000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay. Results. From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100 000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria. Conclusions. Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home. C1 [Kadri, Sameer S.; Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Palmore, Tara] NIH, Hosp Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Kadri, Sameer S.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Varughese, Christy] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Orav, E. John] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Hohmann, Samuel F.] Rush Univ, Univ HealthSyst Consortium, Chicago, IL 60612 USA. [Hohmann, Samuel F.] Rush Univ, Dept Hlth Syst Management, Chicago, IL 60612 USA. [Bonne, Stephanie L.] Barnes Jewish Hosp, Dept Gen Surg, St Louis, MO 63110 USA. [Moffa, Matthew A.; Timpone, Joseph G.] Georgetown Univ Hosp, Div Infect Dis & Travel Med, Washington, DC 20007 USA. [Strich, Jeffrey R.] Georgetown Univ Hosp, Dept Med, Washington, DC 20007 USA. RP Kadri, SS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. EM sameer.kadri@nih.gov FU intramural National Institutes of Health funds FX This work was supported by intramural National Institutes of Health funds. NR 38 TC 6 Z9 7 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 79 EP 87 DI 10.1093/cid/ciu741 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300014 PM 25246597 ER PT J AU Strykowski, JL Schech, JM AF Strykowski, Jennifer L. Schech, Joseph M. TI Effectiveness of Recommended Euthanasia Methods in Larval Zebrafish (Danio rerio) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID TRICAINE METHANESULFONATE; EFFICACY; MS222 AB The popularity of zebrafish and its use as a model organism in biomedical research including genetics, development, and toxicology, has increased over the past 20 y and continues to grow. However, guidelines for euthanasia remain vague, and the responsibility of creating appropriate euthanasia protocols essentially falls on individual facilities. To reduce variation in experimental results among labs, a standard method of euthanasia for zebrafish would be useful. Although various euthanasia methods have been compared, few studies focus on the effectiveness of euthanasia methods for larval zebrafish. In this study, we exposed larval zebrafish to each of 3 euthanasia agents (MS222, eugenol, and hypothermic shock) and assessed the recovery rate. Hypothermic shock appeared to be the most effective method for euthanizing zebrafish at 14 d after fertilization; however, this method may not be considered an efficient method for large numbers of larval zebrafish. Exposure to chemicals, such as MS222 and eugenol, were ineffective methods for euthanasia at this stage of development. When these agents are used, secondary measures should be taken to ensure death. Choosing a euthanasia method that is effective, efficient, and humane can be challenging. Determining a method of euthanasia that is suitable for fish of all stages will bring the zebrafish community closer to meeting this challenge. C1 [Strykowski, Jennifer L.] NIH, Charles River Labs, Bethesda, MD 20892 USA. [Strykowski, Jennifer L.; Schech, Joseph M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Schech, JM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM schechj@dir6.nichd.nih.gov NR 12 TC 3 Z9 3 U1 2 U2 19 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JAN PY 2015 VL 54 IS 1 BP 81 EP 84 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CB4DF UT WOS:000349577700014 PM 25651096 ER PT J AU Chini, MG Ferroni, C Cantone, V Dambruoso, P Varchi, G Pepe, A Fischer, K Pergola, C Werz, O Bruno, I Riccio, R Bifulco, G AF Chini, Maria Giovanna Ferroni, Claudia Cantone, Vincenza Dambruoso, Paolo Varchi, Greta Pepe, Antonella Fischer, Katrin Pergola, Carlo Werz, Oliver Bruno, Ines Riccio, Raffaele Bifulco, Giuseppe TI Elucidating new structural features of the triazole scaffold for the development of mPGES-1 inhibitors SO MEDCHEMCOMM LA English DT Article ID PROSTAGLANDIN-E SYNTHASE-1; E-2 SYNTHASE-1; IN-VIVO; CANCER; 5-LIPOXYGENASE; CHONDROCYTES; CARTILAGE; DOCKING; BIOLOGY; TARGET AB We report a new potent revisited version of a triazole-based inhibitor obtained by structure-based drug design on the human mPGES-1 crystal structure. Moreover, we disclosed the substitution with a halogen atom at position 5 as a new key factor influencing the biological activity on the mPGES-1 enzyme. C1 [Chini, Maria Giovanna; Cantone, Vincenza; Bruno, Ines; Riccio, Raffaele; Bifulco, Giuseppe] Dept Pharm, I-84084 Fisciano, SA, Italy. [Ferroni, Claudia; Dambruoso, Paolo; Varchi, Greta] ISOF CNR Area Ric Bologna, Inst Organ Synth & Photoreact, I-40129 Bologna, Italy. [Pepe, Antonella] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Synthet Chem, Frederick, MD 21702 USA. [Fischer, Katrin; Pergola, Carlo; Werz, Oliver] Univ Jena, Inst Pharm, Dept Pharmaceut Med Chem, D-07743 Jena, Germany. RP Bifulco, G (reprint author), Dept Pharm, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy. EM bifulco@unisa.it RI Bifulco, Giuseppe/A-5413-2011; Riccio, Raffaele/A-3405-2008; Dambruoso, Paolo/A-3778-2014; OI Bifulco, Giuseppe/0000-0002-1788-5170; Riccio, Raffaele/0000-0001-5073-5513; Dambruoso, Paolo/0000-0003-3937-9671; Varchi, Greta/0000-0002-8358-3437 FU University of Salerno; Associazione Italiana Ricerca sulCancro (AIRC) [IG 2012 - IG_12777] FX Financial support by the University of Salerno, and by Associazione Italiana Ricerca sulCancro (AIRC) Grant IG 2012 - IG_12777 - Bifulco Giuseppe is gratefully acknowledged. We thank Dr Massimo Capobianco (ISOF-CNR) for MS measurements. NR 29 TC 4 Z9 4 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2015 VL 6 IS 1 BP 75 EP 79 DI 10.1039/c4md00319e PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CB5XD UT WOS:000349700400006 ER PT J AU Yan, XF Hu, H Lin, J Jin, AJ Niu, G Zhang, SL Huang, P Shen, BZ Chen, XY AF Yan, Xuefeng Hu, Hao Lin, Jing Jin, Albert J. Niu, Gang Zhang, Shaoliang Huang, Peng Shen, Baozhong Chen, Xiaoyuan TI Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies SO NANOSCALE LA English DT Article ID PHOTOTHERMAL/PHOTODYNAMIC CANCER-THERAPY; TARGETED PHOTODYNAMIC THERAPY; CONTINUOUS-WAVE LASER; GRAPHENE OXIDE; PHOTOTHERMAL THERAPY; ENHANCED-FLUORESCENCE; NANO-GRAPHENE; GOLD NANORODS; PHOTOSENSITIZER; THERANOSTICS AB Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT. C1 [Yan, Xuefeng; Shen, Baozhong] Harbin Med Univ, Hosp 4, Dept Radiol, Harbin, Heilongjiang, Peoples R China. [Yan, Xuefeng; Hu, Hao; Lin, Jing; Niu, Gang; Huang, Peng; Chen, Xiaoyuan] NIBIB, NIH, Bethesda, MD 20892 USA. [Yan, Xuefeng; Shen, Baozhong] Harbin Med Univ, Mol Imaging Ctr, Harbin, Heilongjiang, Peoples R China. [Jin, Albert J.] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Zhang, Shaoliang] Jiangxi Qinglong Grp Co Ltd, Yichun 336000, Jiangxi, Peoples R China. RP Huang, P (reprint author), NIBIB, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM peng.huang@nih.gov; shenbzh@vip.sina.com; shawn.chen@nih.gov RI Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU National Basic Research Program of China [2013CB733802, 2014CB744503, 2015CB931800, 2015CB931803]; National Natural Science Foundation of China [81371596, 81401465, 81130028, 31210103913]; Key Grant Project of Heilongjiang Province [GA12C302]; Ph.D. Programs Foundation of Ministry of Education of China [201123071100203]; Key Laboratory of Molecular Imaging Foundation(College of Heilongjiang Province); National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported, in part, by the National Basic Research Program of China (2013CB733802, 2014CB744503, 2015CB931800 and 2015CB931803), National Natural Science Foundation of China (81371596, 81401465, 81130028, 31210103913), the Key Grant Project of Heilongjiang Province (GA12C302), the Ph.D. Programs Foundation of Ministry of Education of China (201123071100203), the Key Laboratory of Molecular Imaging Foundation(College of Heilongjiang Province) and by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 36 TC 18 Z9 19 U1 16 U2 123 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2015 VL 7 IS 6 BP 2520 EP 2526 DI 10.1039/c4nr06868h PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CB2QH UT WOS:000349472300043 PM 25573051 ER PT J AU Rao, J Chiappelli, J Kochunov, P Regenold, WT Rapoport, SI Hong, LE AF Rao, Jagadeesh Chiappelli, Joshua Kochunov, Peter Regenold, William T. Rapoport, Stanley I. Hong, L. Elliot TI Is Schizophrenia a Neurodegenerative Disease? Evidence from Age-Related Decline of Brain-Derived Neurotrophic Factor in the Brains of Schizophrenia Patients and Matched Nonpsychiatric Controls SO NEURODEGENERATIVE DISEASES LA English DT Article DE Aging; Brain; Prefrontal cortex; White matter; Schizophrenia; Postmortem; Brain-derived neurotrophic factor ID ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; MAJOR DEPRESSION; EXCESS MORTALITY; GENE-EXPRESSION; BDNF; RATS; PSYCHOSES AB Background: Brain-derived neurotrophic factor (BDNF) protein levels decline in the brain during senescence and are also shown to be reduced in schizophrenia patients. BDNF is present in both the gray and white matters of the brain. It is unclear whether BDNF abnormalities in schizophrenia are specific to gray and/or white matter. Objective: We hypothesized that the age-related BDNF decline is abnormal and contributes to the reduced BDNF in schizophrenia. Methods: We tested this hypothesis by measuring BDNF protein levels in postmortem gray and white matter, using the prefrontal cortex (PFC) and the genu of the corpus callosum as regions of interests, from 20 schizophrenia patients and 20 matched nonpsychiatric controls. Samples were selected across the adult lifespan from 20 to 80 years of age. Results: PFC gray matter BDNF protein levels were significantly lower in older age in both nonpsychiatric comparisons and patients, while BDNF in white matter did not decrease significantly with age in either group. PFC BDNF was linearly lower from 20 to 80 years of age in nonpsychiatric comparisons. In schizophrenia, the age effect was similarly linear in younger patients but a decline did not occur in older patients. Conclusion: PFC BDNF does not follow a normative linear age effect in schizophrenia patients as they grow older, which may represent a 'floor effect' due to earlier decline or a survivor cohort of older patient donors who are less susceptible to a schizophrenia-related pathological aging process. (C) 2014 S. Karger AG, Basel C1 [Rao, Jagadeesh; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. [Chiappelli, Joshua; Kochunov, Peter; Hong, L. Elliot] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Regenold, William T.] Univ Maryland, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Baltimore, MD 21201 USA. RP Hong, LE (reprint author), Maryland Psychiat Res Ctr, 55 Wade Ave, Baltimore, MD 21201 USA. EM ehong@mprc.umaryland.edu FU National Institutes of Health [R01MH085646, P50MH10322, R21MH079172]; Intramural Program of the National Institute on Aging FX We thank Dr. Robert P. McMahon for statistical consultation on this paper. This research was supported by National Institutes of Health grants R01MH085646, P50MH10322, and R21MH079172 and by the Intramural Program of the National Institute on Aging. NR 39 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2015 VL 15 IS 1 BP 38 EP 44 DI 10.1159/000369214 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB5IB UT WOS:000349659600004 PM 25531449 ER PT J AU Meilleur, KG Jain, MS Hynan, LS Shieh, CY Kim, E Waite, M McGuire, M Fiorini, C Glanzman, AM Main, M Rose, K Duong, T Bendixen, R Linton, MM Arveson, IC Nichols, C Yang, K Fischbeck, KH Wagner, KR North, K Mankodi, A Grunseich, C Hartnett, EJ Smith, M Donkervoort, S Schindler, A Kokkinis, A Leach, M Foley, AR Collins, J Muntoni, F Rutkowski, A Bonnemann, CG AF Meilleur, Katherine G. Jain, Minal S. Hynan, Linda S. Shieh, Ching-Yi Kim, Eunice Waite, Melissa McGuire, Michelle Fiorini, Courtney Glanzman, Allan M. Main, Marion Rose, Kristy Duong, Tina Bendixen, Roxanna Linton, Melody M. Arveson, Irene C. Nichols, Carmel Yang, Kelly Fischbeck, Kenneth H. Wagner, Kathryn R. North, Kathryn Mankodi, Ami Grunseich, Christopher Hartnett, Elizabeth J. Smith, Michaele Donkervoort, Sandra Schindler, Alice Kokkinis, Angela Leach, Meganne Foley, A. Reghan Collins, James Muntoni, Francesco Rutkowski, Anne Boennemann, Carsten G. TI Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies SO NEUROMUSCULAR DISORDERS LA English DT Article DE Clinical outcome measures; Neuromuscular disease; Collagen VI related muscular dystrophy; Laminin alpha 2 related dystrophy; Motor function scales ID MOTOR FUNCTION MEASURE; QUALITY-OF-LIFE; NEUROMUSCULAR DISORDERS; ACTIVITY LIMITATIONS; NATURAL-HISTORY; CHILDREN; RELIABILITY; ATROPHY; MUSCLE; RESPONSIVENESS AB Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL(TM) Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL(TM) scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable, and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes. Published by Elsevier B.V. C1 [Meilleur, Katherine G.; Linton, Melody M.; Arveson, Irene C.] NINR, NIH, Bethesda, MD 20814 USA. [Jain, Minal S.; Waite, Melissa; Nichols, Carmel; Smith, Michaele] NIH, Mark O Haeld Clin Res Ctr, Bethesda, MD 20892 USA. [Hynan, Linda S.] Univ Texas Southwestern, Dept Clin Sci Biostat, Dallas, TX USA. [Hynan, Linda S.] Univ Texas Southwestern, Dept Psychiat, Dallas, TX USA. [Shieh, Ching-Yi] NIH, Bethesda, MD 20892 USA. [Kim, Eunice; Rutkowski, Anne] CureCMD, Los Angeles, CA USA. [McGuire, Michelle; Collins, James] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Fiorini, Courtney; Wagner, Kathryn R.] Johns Hopkins Sch Med, Kennedy Krieger Inst, Baltimore, MD USA. [Fiorini, Courtney; Wagner, Kathryn R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Fiorini, Courtney; Wagner, Kathryn R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA. [Glanzman, Allan M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Main, Marion; Foley, A. Reghan; Muntoni, Francesco] UCL, Inst Child Hlth, MRC Ctr Neuromuscular Dis, Dubowitz Neuromuscular Ctr, London, England. [Main, Marion; Foley, A. Reghan; Muntoni, Francesco] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Rose, Kristy; North, Kathryn] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW, Australia. [Duong, Tina; Leach, Meganne] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Bendixen, Roxanna] Univ Pittsburgh, Pittsburgh, PA USA. [Yang, Kelly; Fischbeck, Kenneth H.; Mankodi, Ami; Grunseich, Christopher; Hartnett, Elizabeth J.; Donkervoort, Sandra; Schindler, Alice; Kokkinis, Angela; Leach, Meganne; Boennemann, Carsten G.] NINDS, NIH, Bethesda, MD 20892 USA. [Rutkowski, Anne] Kaiser SCPMG, Los Angeles, CA USA. RP Meilleur, KG (reprint author), NINR, NIH, 1 Cloister Ct,Bldg 60,Rm 252, Bethesda, MD 20814 USA. EM meilleurk@mail.nih.gov; carsten.bonnemann@nih.gov RI North, Kathryn/K-6476-2012; OI North, Kathryn/0000-0003-0841-8009; Hynan, Linda/0000-0002-4642-7769 FU Cure CMD; NIH intramural fund of the NINDS; NIH intramural fund of the NINR; NIH intramural fund of Mark O. Hatfield Clinical Research Center FX We would like to thank the following people without which this study would not have been possible: the participants and their families for their time, flexibility, and commitment during the two years of this study; the nurses and staff of the NIH Clinical Center's outpatient neurology clinic (year 1) and pediatric outpatient clinic (year 2); the National Heart Lung and Blood Institute's Pulmonary Function Lab physicians, therapists, and staff; Mrs. Livija Medne for her assistance with the study in year 2; Dr. Carole Vuillerot and Dr. Joan Austin for their critical feedback on the manuscript. This work was supported by Cure CMD and the NIH intramural funds of the NINDS, NINR, and Mark O. Hatfield Clinical Research Center. NR 39 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JAN PY 2015 VL 25 IS 1 BP 43 EP 54 DI 10.1016/j.nmd.2014.09.010 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB4AR UT WOS:000349571100007 PM 25307854 ER PT J AU Cedarbaum, JM Stephenson, D Rudick, R Carrillo, MC Stebbins, G Kerr, D Heemskerk, J Galpern, WR Kaufmann, P Cella, D Isaac, M Walton, MK AF Cedarbaum, Jesse M. Stephenson, Diane Rudick, Richard Carrillo, Maria C. Stebbins, Glenn Kerr, Douglas Heemskerk, Jill Galpern, Wendy R. Kaufmann, Petra Cella, David Isaac, Maria Walton, Marc K. TI Commonalities and Challenges in the Development of Clinical Trial Measures in Neurology SO NEUROTHERAPEUTICS LA English DT Article DE Clinical trials; Clinical outcome assessments ID DISEASE RATING-SCALE; ALZHEIMERS ASSOCIATION WORKGROUPS; AMYOTROPHIC-LATERAL-SCLEROSIS; SOCIETY-SPONSORED REVISION; PARKINSONS-DISEASE; MDS-UPDRS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS; DEXPRAMIPEXOLE AB As neurologists and neuroscientists, we are trained to evaluate disorders of the nervous system by thinking systematically. Clinically, we think in terms of cognition, behavior, motor function, sensation, balance and co-ordination, and autonomic system function. But when we assess symptoms of neurological disorders for the purpose of drug development, we tend to create disease-specific outcome measures, often using a variety of methods to assess the same types of dysfunction in overlapping, related disorders. To begin to explore the potential to simplify and harmonize the assessment of dysfunction across neurological disorders, a symposium, entitled, "Commonalities in the Development of Outcome Measures in Neurology" was held at the 16th annual meeting of the American Society for Experimental NeuroTherapeutics (ASENT), in February 2014. This paper summarizes the presentations at the symposium. The authors hope that readers will begin to view Clinical Outcome Assessment (COA) development in a new light. We hope that in presenting this material, we will stimulate discussions and collaborations across disease areas to develop common concepts of neurological COA development and construction. C1 [Cedarbaum, Jesse M.] Biogen Idec Inc, Neurol Early Clin Dev, Cambridge, MA 02142 USA. [Stephenson, Diane] Crit Path Inst, Tucson, AZ USA. [Rudick, Richard] Biogen Idec Inc, Value Based Med, Cambridge, MA 02142 USA. [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Stebbins, Glenn] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Kerr, Douglas] Biogen Idec Inc, Clin & Safety Sci, Cambridge, MA 02142 USA. [Heemskerk, Jill] NIMH, Div Adult Translat Res, NIH, Bethesda, MD 20892 USA. [Galpern, Wendy R.] NINDS, Off Clin Res, Bethesda, MD 20892 USA. [Kaufmann, Petra] NIH, Div Clin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Isaac, Maria] European Med Agcy, London, England. [Walton, Marc K.] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Cedarbaum, JM (reprint author), Biogen Idec Inc, Neurol Early Clin Dev, 14 Cambridge Ctr, Cambridge, MA 02142 USA. EM jesse.cedarbaum@biogenidec.com NR 26 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2015 VL 12 IS 1 BP 151 EP 169 DI 10.1007/s13311-014-0310-1 PG 19 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CB3PX UT WOS:000349541800017 PM 25384682 ER PT J AU Steiner, JP Bachani, M Wolfson-Stofko, B Lee, MH Wang, TG Li, GH Li, WX Strayer, D Haughey, NJ Nath, A AF Steiner, Joseph P. Bachani, Muznabanu Wolfson-Stofko, Brett Lee, Myoung-Hwa Wang, Tonguang Li, Guanhan Li, Wenxue Strayer, David Haughey, Norman J. Nath, Avindra TI Interaction of Paroxetine with Mitochondrial Proteins Mediates Neuroprotection SO NEUROTHERAPEUTICS LA English DT Article DE Paroxetine; SSRI; HAND; Neuroprotective; Mitochondria ID MAGNETIC-RESONANCE-SPECTROSCOPY; SEROTONIN REUPTAKE INHIBITORS; REGULATED ANION CHANNELS; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; HIV DEMENTIA; CELL-DEATH; PERMEABILITY TRANSITION; HIPPOCAMPAL NEUROGENESIS; ANTIDEPRESSANT DRUG AB There are severe neurological complications that arise from HIV infection, ranging from peripheral sensory neuropathy to cognitive decline and dementia for which no specific treatments are available. The HIV proteins secreted from infected macrophages, gp120 and Tat, are neurotoxic. The goal of this study was to screen, identify and develop neuroprotective compounds relevant to HIV-associated neurocognitive disorders (HAND). We screened more than 2000 compounds that included FDA approved drugs for protective efficacy against oxidative stress-mediated neurodegeneration and identified selective serotonin reuptake inhibitors (SSRIs) as potential neuroprotectants. Numerous SSRIs were then extensively evaluated as protectants against neurotoxicity as measured by changes in neuronal cell death, mitochondrial potential, and axodendritic degeneration elicited by HIV Tat and gp120 and other mitochondrial toxins. While many SSRIs demonstrated neuroprotective actions, paroxetine was potently neuroprotective (100 nM potency) against these toxins in vitro and in vivo following systemic administration in a gp120 neurotoxicity model. Interestingly, the inhibition of serotonin reuptake by paroxetine was not required for neuroprotection, since depletion of the serotonin transporter had no effect on its neuroprotective properties. We determined that paroxetine interacts selectively and preferentially with brain mitochondrial proteins and blocks calcium-dependent swelling but had less effect on liver mitochondria. Additionally, paroxetine induced proliferation of neural progenitor cells in vitro and in vivo in gp120 transgenic animals. Therefore, SSRIs such as paroxetine may provide a novel adjunctive neuroprotective and neuroregenerative therapy to treat HIV-infected individuals. C1 [Steiner, Joseph P.; Wolfson-Stofko, Brett; Haughey, Norman J.; Nath, Avindra] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. [Steiner, Joseph P.; Bachani, Muznabanu; Wang, Tonguang; Nath, Avindra] NINDS, Translat Neurosci Ctr, Bethesda, MD 20892 USA. [Lee, Myoung-Hwa; Li, Guanhan; Li, Wenxue; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Strayer, David] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Steiner, JP (reprint author), NINDS, Translat Neurosci Ctr, Natl Bldg 10,Room 7C-105,10 Ctr Dr, Bethesda, MD 20892 USA. EM steinerjp@ninds.nih.gov; natha@ninds.nih.gov FU NIH [P30MH075673, R01DA024593] FX We thank Dr. L. Mucke for kindly providing the gp120 transgenic mice and John Pontolillo, Tanya Malpic-Llanos and Daniella Asch for technical assistance. We thank Dr. Carlos Pardo-Villamizar and Jackie Mann for their expert technical assistance with the Luminex multiplex analysis of cytokines and chemokines. We also thank Drs. Robert Cole and Raghothama Chaerkady of the Johns Hopkins Mass Spectrometry and Proteomics Facility for their identification of paroxetine binding proteins. These studies were supported by NIH grants P30MH075673, R01DA024593 and NIH intramural funds NR 64 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2015 VL 12 IS 1 BP 200 EP 216 DI 10.1007/s13311-014-0315-9 PG 17 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CB3PX UT WOS:000349541800020 PM 25404050 ER PT J AU Cedarbaum, JM Stephenson, D Rudick, R Carrillo, MC Stebbins, G Kerr, D Heemskerk, J Galpern, WR Kaufmann, P Cella, D Isaac, M Walton, MK AF Cedarbaum, Jesse M. Stephenson, Diane Rudick, Richard Carrillo, Maria C. Stebbins, Glenn Kerr, Douglas Heemskerk, Jill Galpern, Wendy R. Kaufmann, Petra Cella, David Isaac, Maria Walton, Marc K. TI Commonalities and Challenges in the Development of Clinical Trial Measures in Neurology (vol 12, pg 151, 2015) SO NEUROTHERAPEUTICS LA English DT Correction C1 [Cedarbaum, Jesse M.] Biogen Idec Inc, CambridgeCtr 14, Neurol Early Clin Dev, Cambridge, MA 02142 USA. [Stephenson, Diane] Crit Path Inst, Tucson, AZ USA. [Rudick, Richard] Biogen Idec Inc, Value Based Med, Cambridge, MA USA. [Carrillo, Maria C.] Alzheimers Assoc, Med & Sci Relat, Chicago, IL USA. [Stebbins, Glenn] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Kerr, Douglas] Biogen Idec Inc, Clin & Safety Sci, Cambridge, MA USA. [Heemskerk, Jill] NIMH, Div Adult Translat Res, NIH, Bethesda, MD 20892 USA. [Galpern, Wendy R.] NINDS, Off Clin Res, Bethesda, MD 20892 USA. [Kaufmann, Petra] NIH, Div Clin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Isaac, Maria] European Med Agcy, London, England. [Walton, Marc K.] Ctr Drug Evaluat & Res Food & Drug Adm, Off Translat Sci, Silver Spring, MD USA. RP Cedarbaum, JM (reprint author), Biogen Idec Inc, CambridgeCtr 14, Neurol Early Clin Dev, Cambridge, MA 02142 USA. EM jesse.cedarbaum@biogenidec.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2015 VL 12 IS 1 BP 285 EP 285 DI 10.1007/s13311-014-0323-9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CB3PX UT WOS:000349541800074 PM 25608934 ER PT B AU Raskolnikov, D Turkbey, B Lindenberg, L Choyke, PL Pinto, PA AF Raskolnikov, Dima Turkbey, Baris Lindenberg, Liza Choyke, Peter L. Pinto, Peter A. BE Dicker, AP Kelly, WK Zaorsky, NG Trabulsi, EJ TI Evaluation of Distant Disease: The Utility of Nuclear Imaging SO PROSTATE CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT SE Current Multidisciplinary Oncology LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; METASTATIC PROSTATE-CANCER; MEMBRANE ANTIGEN; PET-CT; C-11-CHOLINE PET/CT; C-11-ACETATE PET/CT; HER2 EXPRESSION; F-18-FDG PET/CT; BONE METASTASES; BREAST-CANCER C1 [Raskolnikov, Dima; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Turkbey, Baris; Lindenberg, Liza; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Raskolnikov, D (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 52 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-59-8 J9 CURR MULTIDISC ONCOL PY 2015 BP 59 EP 65 PG 7 WC Oncology SC Oncology GA BB8YU UT WOS:000347857300009 ER PT J AU Zhang, XX Li, J Ito, Y Sun, WJ AF Zhang, Xinxin Li, Jing Ito, Yoichiro Sun, Wenji TI Simultaneous quantification of five steroid saponins from Dioscorea zingiberensis CH Wright in rat plasma by HPLC-MS/MS and its application to the pharmacokinetic studies SO STEROIDS LA English DT Article DE HPLC-MS/MS; Total steroid saponins; Dioscorea zingiberensis CH Wright; MRM; Pharmacokinetic parameters ID TANDEM MASS-SPECTROMETRY; TIME-OF-FLIGHT; PARIS-POLYPHYLLA; CELL-LINES; IN-VITRO; DIOSCIN; EXTRACTS AB A simple, reliable and sensitive high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was established for simultaneous analyses of the following 5 steroid saponins in rat plasma after the single dose administration of total steroid saponins extracted from the rhizome of Dioscorea zingiberensis C.H. Wright for the first time. Protodioscin, huangjiangsu A, zingiberensis new saponin, dioscin, and gracillin were quantified using ginsenoside Rb-1 as the internal standard (IS). The plasma samples were pretreated by a single step acetonitrile-mediated protein precipitation. The chromatographic separation was performed on an Inersil ODS-3 C-18 column (250 mm x 4.6 mm, 5 mu m) with the mobile phase composed of acetonitrile and water containing 0.1% formic acid under a gradient elution mode at 0.2 mL min(-1) using a microsplit after the eluent from the HPLC apparatus. The quantification was accomplished on a triple quadrupole tandem mass spectrometer using the multiple reaction monitoring (MRM) in the positive ionization mode. The above five analytes were stable under sample storage and preparation conditions applied in the present study. The linearity, precision, accuracy, and recoveries of the analysis confirmed the requirements for quality-control purposes. After validation, this proposed method was successfully adopted to investigate the pharmacokinetic parameters of these five analytes. Published by Elsevier Inc. C1 [Zhang, Xinxin; Li, Jing; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, Lab Bioseparat Technol, NIH, Bethesda, MD 20892 USA. RP Sun, WJ (reprint author), NW Univ Xian, Biomed Key Lab Shaanxi Prov, 229 Taibai North Rd, Xian 710069, Peoples R China. EM itoy@nhlbi.nih.gov; guoxiaolizhang@163.com FU Intramural NIH HHS [Z99 HL999999] NR 29 TC 4 Z9 4 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X EI 1878-5867 J9 STEROIDS JI Steroids PD JAN PY 2015 VL 93 BP 16 EP 24 DI 10.1016/j.steroids.2014.08.023 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CB4EM UT WOS:000349581000003 PM 25201262 ER PT J AU Min, KH Min, HS Lee, HJ Park, DJ Yhee, JY Kim, K Kwon, IC Jeong, SY Silvestre, OF Chen, XY Hwang, YS Kim, EC Lee, SC AF Min, Kyung Hyun Min, Hyun Su Lee, Hong Jae Park, Dong Jin Yhee, Ji Young Kim, Kwangmeyung Kwon, Ick Chan Jeong, Seo Young Silvestre, Oscar F. Chen, Xiaoyuan Hwang, Yu-Shik Kim, Eun-Cheol Lee, Sang Cheon TI pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers SO ACS NANO LA English DT Article DE theranostics; carbon dioxide; mineralization; nanobubble; ultrasound; drug delivery ID MICROBUBBLE CONTRAST AGENTS; DRUG-DELIVERY; TUMOR ANGIOGENESIS; DOXORUBICIN; MICELLES; DIRECTIONS; COPOLYMER; PLATFORM; GENE; US AB We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers. C1 [Min, Kyung Hyun; Min, Hyun Su; Yhee, Ji Young; Kim, Kwangmeyung; Kwon, Ick Chan] Korea Inst Sci & Technol, Biomed Res Inst, Ctr Theragnosis, Seoul 136791, South Korea. [Min, Kyung Hyun; Silvestre, Oscar F.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Lee, Hong Jae; Hwang, Yu-Shik; Lee, Sang Cheon] Kyung Hee Univ, Sch Dent, Dept Maxillofacial Biomed Engn, Seoul 130701, South Korea. [Lee, Hong Jae; Hwang, Yu-Shik; Lee, Sang Cheon] Kyung Hee Univ, Sch Dent, Inst Oral Biol, Seoul 130701, South Korea. [Park, Dong Jin; Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Coll Pharm, Seoul 130701, South Korea. [Kim, Eun-Cheol] Kyung Hee Univ, Sch Dent, Dept Maxillofacial Tissue Regenerat, Seoul 130701, South Korea. [Kim, Eun-Cheol] Kyung Hee Univ, Sch Dent, Res Ctr Tooth & Periodontal Regenerat MRC, Seoul 130701, South Korea. RP Kwon, IC (reprint author), Korea Inst Sci & Technol, Biomed Res Inst, Ctr Theragnosis, Seoul 136791, South Korea. EM ikwon@kist.re.kr; schlee@khu.ac.kr OI Silvestre, Oscar/0000-0002-3750-4187 FU National Research Foundation of Korea (NRF) grant - Korea government (MSIP) [2013R1A2A2A01009239, 2012R1A5A2051388] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Nos. 2013R1A2A2A01009239 and 2012R1A5A2051388). NR 42 TC 32 Z9 32 U1 32 U2 133 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2015 VL 9 IS 1 BP 134 EP 145 DI 10.1021/nn506210a PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CA0PJ UT WOS:000348619000016 PM 25559896 ER PT J AU Afonin, KA Viard, M Kagiampakis, I Case, CL Dobrovolskaia, MA Hofmann, J Vrzak, A Kireeva, M Kasprzak, WK KewalRamani, VN Shapiro, BA AF Afonin, Kirill A. Viard, Mathias Kagiampakis, Ioannis Case, Christopher L. Dobrovolskaia, Marina A. Hofmann, Jen Vrzak, Ashlee Kireeva, Maria Kasprzak, Wojciech K. KewalRamani, Vineet N. Shapiro, Bruce A. TI Triggering of RNA Interference with RNA-RNA, RNA-DNA, and DNA-RNA Nanoparticles SO ACS NANO LA English DT Article DE RNA and DNA nanotechnology; RNA and DNA nanoparticles; RNAi; FRET; RNA-DNA hybrids reassociation ID IN-VITRO; SPLIT FUNCTIONALITIES; EMERGING FIELD; NUCLEIC-ACIDS; PRNA 3WJ; CANCER; NANOSTRUCTURES; NANOTECHNOLOGY; VIVO; DELIVERY AB Control over cellular delivery of different functionalities and their synchronized activation is a challenging task. We report several RNA and RNA/DNA-based nanoparticles designed to conditionally activate the RNA interference in various human cells. These nanoparticles allow precise control over their formulation, stability in blood serum, and activation of multiple functionalities. Importantly, interferon and pro-inflammatory cytokine activation assays indicate the significantly lower responses for DNA nanoparticles compared to the RNA counterparts, suggesting greater potential of these molecules for therapeutic use. C1 [Afonin, Kirill A.; Viard, Mathias; Hofmann, Jen; Vrzak, Ashlee; Shapiro, Bruce A.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Viard, Mathias; Kasprzak, Wojciech K.] NCI, Basic Sci Program, Leidos Biomed Res Inc, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Kagiampakis, Ioannis; Case, Christopher L.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Dobrovolskaia, Marina A.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Kireeva, Maria] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM shapirbr@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the National Institutes of Health, Center for Cancer Research FX We thank Eckert Bindewald for helpful discussion. This publication was funded in part with federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E. This research was additionally supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government NR 68 TC 17 Z9 17 U1 4 U2 37 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2015 VL 9 IS 1 BP 251 EP 259 DI 10.1021/nn504508s PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CA0PJ UT WOS:000348619000026 PM 25521794 ER PT J AU Guo, WS Sun, XL Jacobson, O Yan, XF Min, K Srivatsan, A Niu, G Kiesewetter, DO Chang, J Chen, XY AF Guo, Weisheng Sun, Xiaolian Jacobson, Orit Yan, Xuefeng Min, Kyunghyun Srivatsan, Avinash Niu, Gang Kiesewetter, Dale O. Chang, Jin Chen, Xiaoyuan TI Intrinsically Radioactive [Cu-64]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence SO ACS NANO LA English DT Article DE quantum dots; CRET; CuInS/ZnS; PET imaging; dual-modality imaging ID NANOPARTICLES; FLUORESCENCE; NANOCAGES; CU-64; MODEL AB Functionalized quantum dots (QDs) have been widely explored for multimodality bioimaging and proven to be versatile agents. Attaching positron-emitting radioisotopes onto QDs not only endows their positron emission tomography (PET) functionality, but also results in self-illuminating QDs, with no need for an external light source, by Cerenkov resonance energy transfer (CRET). Traditional chelation methods have been used to incorporate the radionuclide, but these methods are compromised by the potential for loss of radionuclide due to cleavage of the linker between particle and chelator, decomplexation of the metal, and possible altered pharmacokinetics of nanomaterials. Herein, we described a straightforward synthesis of intrinsically radioactive [Cu-64]CuInS/ZnS QDs by directly incorporating Cu-64 into CuInS/ZnS nanostructure with (CuCl2)-Cu-64 as synthesis precursor. The [Cu-64]CuInS/ZnS QDs demonstrated excellent radiochemical stability with less than 3% free Cu-64 detected even after exposure to serum containing EDTA (5 mM) for 24 h. PEGylation can be achieved in situ during synthesis, and the PEGylated radioactive QDs showed high tumor uptake (10.8% ID/g) in a U87MG mouse xenograft model. CRET efficiency was studied as a function of concentration and Cu-64 radioactivity concentration. These [Cu-64]CuInS/ZnS QDs were successfully applied as an efficient PET/self-illuminating luminescence in vivo imaging agents. C1 [Guo, Weisheng; Chang, Jin] Tianjin Univ, Sch Life Sci, Sch Mat Sci & Engn, Tianjin 300072, Peoples R China. [Guo, Weisheng; Sun, Xiaolian; Jacobson, Orit; Yan, Xuefeng; Min, Kyunghyun; Srivatsan, Avinash; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Sun, XL (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM xiaolian.sun@nih.gov; jinchang@tju.edu.cn; shawn.chen@nih.gov FU National High Technology Program of China [2012AA022603]; National Natural Science Foundation of China [51373117, 81171372]; Tianjin Nature Science Foundation [13JCZDJC33200]; Ministry of Education of China [20120032110027]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health; China Scholarship Council (CSC) FX The authors gratefully acknowledge the National High Technology Program of China (2012AA022603), the National Natural Science Foundation of China (51373117 and 81171372), The Key Project of Tianjin Nature Science Foundation (13JCZDJC33200), Doctoral Fund of Ministry of Education of China (20120032110027), and the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, W. Guo was funded in part by the China Scholarship Council (CSC). NR 37 TC 35 Z9 36 U1 10 U2 98 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2015 VL 9 IS 1 BP 488 EP 495 DI 10.1021/nn505660r PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CA0PJ UT WOS:000348619000051 PM 25549258 ER PT J AU Hannoush, H Sachdev, V Brofferio, A Arai, AE LaRocca, G Sapp, J Sidenko, S Brenneman, C Biesecker, LG Keppler-Noreuil, KM AF Hannoush, H. Sachdev, V. Brofferio, A. Arai, A. E. LaRocca, G. Sapp, J. Sidenko, S. Brenneman, C. Biesecker, L. G. Keppler-Noreuil, K. M. TI Myocardial Fat Overgrowth in Proteus Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE proteus syndrome; cardiac; myocardial fatty infiltration; interventricular septum ID LIPOMATOUS HYPERTROPHY; TUBEROUS SCLEROSIS; INTERATRIAL SEPTUM; ACTIVATING MUTATIONS; DIAGNOSTIC-CRITERIA; COSTELLO-SYNDROME; ADIPOSE-TISSUE; PIK3CA CAUSE; TASK-FORCE; CARDIOMYOPATHY AB Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Hannoush, H.; Sachdev, V.; Brofferio, A.; Arai, A. E.; LaRocca, G.; Sidenko, S.; Brenneman, C.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Sapp, J.; Biesecker, L. G.; Keppler-Noreuil, K. M.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Hannoush, H (reprint author), 10 Ctr Dr,CRC,5NE Room 1436, Bethesda, MD 20892 USA. EM hannoushh@mail.nih.gov FU National Heart Lung and Blood Institute; National Human Genome Research Institute, NIH, DHHS FX Grant sponsor: Intramural Research Program of the National Heart Lung and Blood Institute; Grant sponsor: National Human Genome Research Institute, NIH, DHHS. NR 54 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2015 VL 167 IS 1 BP 103 EP 110 DI 10.1002/ajmg.a.36773 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CA3ZD UT WOS:000348843000014 PM 25377688 ER PT J AU Geoghegan, EM Zhang, H Desai, PJ Biragyn, A Markham, RB AF Geoghegan, Eileen M. Zhang, Hong Desai, Prashant J. Biragyn, Arya Markham, Richard B. TI Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HEAVY-CHAIN ANTIBODIES; B-CELL EPITOPES; RECOMBINANT IMMUNOTOXIN; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; GENITAL HERPES; INFECTED-CELLS; PSEUDOMONAS EXOTOXIN; LOW IMMUNOGENICITY; TYPE-2 INFECTION AB Despite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activity in vitro, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells. C1 [Geoghegan, Eileen M.; Zhang, Hong; Markham, Richard B.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. [Desai, Prashant J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Viral Oncol Program, Baltimore, MD 21218 USA. [Biragyn, Arya] NIA, Immunoregulat Sect, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. RP Markham, RB (reprint author), Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. EM rmarkha1@jhu.edu FU Johns Hop kilts Bloomberg School of Public Health; NIH [AI079794]; NIH, National Institute on Aging FX E.M.G. was supported by a Sommer Scholarship from the Johns Hop kilts Bloomberg School of Public Health, and the research was funded by NIH grant AI079794. This research was also supported in part by the intramural Research Program of the NIH, National Institute on Aging. NR 69 TC 1 Z9 1 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2015 VL 59 IS 1 BP 527 EP 535 DI 10.1128/AAC.03818-14 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CA0LO UT WOS:000348609500065 PM 25385102 ER PT J AU Jacobson, O Kiesewetter, DO Chen, XY AF Jacobson, Orit Kiesewetter, Dale O. Chen, Xiaoyuan TI Fluorine-18 Radiochemistry, Labeling Strategies and Synthetic Routes SO BIOCONJUGATE CHEMISTRY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; TRACELESS STAUDINGER LIGATION; FREE CLICK CHEMISTRY; COPPER-FREE CLICK; ALKYNE 1,3-DIPOLAR CYCLOADDITION; FLUORINE BOND FORMATION; IN-VIVO; BREAST-CANCER; NUCLEOPHILIC FLUORINATION; DIARYLIODONIUM-SALTS AB Fluorine-18 is the most frequently used radioisotope in positron emission tomography (PET) radiopharmaceuticals in both clinical and preclinical research. Its physical and nuclear characteristics (97% beta(+) decay, 109.7 min half-life, 635 keV positron energy), along with high specific activity and ease of large scale production, make it an attractive nuclide for radiochemical labeling and molecular imaging. Versatile chemistry including nucleophilic and electrophilic substitutions allows direct or indirect introduction of F-18 into molecules of interest. The significant increase in F-18 radiotracers for PET imaging accentuates the need for simple and efficient F-18-labeling procedures. In this review, we will describe the current radiosynthesis routes and strategies for F-18 labeling of small molecules and biomolecules. C1 [Jacobson, Orit; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 140 TC 36 Z9 36 U1 9 U2 90 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2015 VL 26 IS 1 BP 1 EP 18 DI 10.1021/bc500475e PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA AZ8RU UT WOS:000348483200001 PM 25473848 ER PT J AU Quick, V Corda, KW Martin-Biggers, J Chamberlin, B Schaffner, DW Byrd-Bredbenner, C AF Quick, Virginia Corda, Kirsten W. Martin-Biggers, Jennifer Chamberlin, Barbara Schaffner, Donald W. Byrd-Bredbenner, Carol TI Short food safety videos promote peer networking and behavior change SO BRITISH FOOD JOURNAL LA English DT Article DE Food safety; Youth ID MIDDLE SCHOOL STUDENTS; PLANNED BEHAVIOR; YOUNG-ADULTS; PHYSICAL-ACTIVITY; SOCIAL INFLUENCES; PUBLIC-HEALTH; ADOLESCENTS; INTERVENTIONS; PERCEPTIONS; EDUCATION AB Purpose - The purpose of this paper is to create a series of 30-60-second short videos to promote improved food safety behaviors of middle school youth, determine the feasibility of disseminating the videos through peer networks, and measure their effects on food safety attitudes, perceived social norms, and behaviors of youth. Design/methodology/approach - Food safety content specialists, learning experts, programmers, illustrators, project managers, instructional designers, scriptwriters, and stakeholders were involved in creation of the Don't Be Gross short videos before evaluation by middle school youth (sixth to eighth grades). The experimental group (n = 220) completed the following activities at about one-week intervals: pre-test, viewed videos, post-test, and follow-up test. The control group (n = 112) completed the same activities at similar intervals but did not have access to the videos until after the follow-up test. Findings - Controlling for grade and gender, linear mixed-effects models revealed significant time by group effects for participants' perceived susceptibility to foodborne illness; intentions to perform recommended food safety behaviors approached significance. Additionally, compared to the pre-test, the experimental group perceived their friends as being significantly more confident in performing food safety behaviors at post-and follow-up tests. Google Analytics data revealed that the bounce rate from the home page of the videos was low (38 percent) suggesting that the videos were engaging. Originality/value - The Don't Be Gross videos were liked by youth and shared among their peers and may have the potential to promote positive food safety behaviors and intentions among youth. C1 [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Corda, Kirsten W.] Texas A&M AgrilLife Extens Serv, Rockport, TX USA. [Martin-Biggers, Jennifer; Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Chamberlin, Barbara] New Mexico State Univ, Dept Media Prod, Las Cruces, NM 88003 USA. [Schaffner, Donald W.] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08903 USA. RP Quick, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. EM gingermquick@gmail.com RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 NR 55 TC 0 Z9 0 U1 2 U2 10 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 0007-070X EI 1758-4108 J9 BRIT FOOD J JI Br. Food J. PY 2015 VL 117 IS 1 BP 78 EP 93 DI 10.1108/BFJ-09-2013-0270 PG 16 WC Food Science & Technology SC Food Science & Technology GA CB5AX UT WOS:000349641000007 ER PT B AU Pan, S Kim, JB Mehta, NN Knowles, JW AF Pan, Stephen Kim, Juyong Brian Mehta, Nehal N. Knowles, Joshua W. BE Shah, SJ Arnett, DK TI Genetic Applications in Coronary Artery Disease SO CARDIOVASCULAR GENETICS AND GENOMICS IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID FAMILIAL DEFECTIVE APOLIPOPROTEIN-B-100; SINGLE NUCLEOTIDE POLYMORPHISMS; ASSOCIATION EXPERT PANEL; CHROMOSOME 9P21; HEART-DISEASE; ATHEROSCLEROSIS RISK; INCIDENTAL FINDINGS; PERSONAL GENOMICS; INDUCED MYOPATHY; LDL CHOLESTEROL C1 [Pan, Stephen] Columbia Presbyterian Med Ctr, Ctr Adv Cardiac Care, New York, NY 10032 USA. [Kim, Juyong Brian; Knowles, Joshua W.] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. [Knowles, Joshua W.] FH Fdn, South Pasadena, CA USA. RP Pan, S (reprint author), Columbia Presbyterian Med Ctr, Ctr Adv Cardiac Care, New York, NY 10032 USA. OI Pan, Stephen/0000-0002-1189-4199 NR 74 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-014-3 PY 2015 BP 253 EP 264 PG 12 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BB8EI UT WOS:000346457500021 ER PT B AU Mauer, AC Owens, DS O'Donnell, CJ Post, WS Thanassoulis, G AF Mauer, Andreas C. Owens, David S. O'Donnell, Christopher J. Post, Wendy S. Thanassoulis, George BE Shah, SJ Arnett, DK TI Genetics of Valvular Heart Disease SO CARDIOVASCULAR GENETICS AND GENOMICS IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID MITRAL-VALVE-PROLAPSE; BICUSPID AORTIC-VALVE; LATE SYSTOLIC-MURMUR; CORONARY-ARTERY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; OUTFLOW TRACT OBSTRUCTION; WILLIAMS-BEUREN-SYNDROME; GENOME-WIDE ASSOCIATION; ALL-CAUSE MORTALITY; ANNULAR CALCIFICATION C1 [Mauer, Andreas C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02138 USA. [Owens, David S.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NHLBIs Framingham Heart Study,Cardiol Div, Boston, MA USA. [Post, Wendy S.] Johns Hopkins Sch Med, Baltimore, MD USA. [Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Thanassoulis, George] McGill Univ, Dept Med, Montreal, PQ, Canada. RP Mauer, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02138 USA. NR 183 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-014-3 PY 2015 BP 265 EP 286 PG 22 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BB8EI UT WOS:000346457500022 ER PT J AU Atz, AM Zak, V Mahony, L Uzark, K Shrader, P Gallagher, D Paridon, SM Williams, RV Breitbart, RE Colan, SD Kaltman, JR Margossian, R Pasquali, SK Allen, K Lai, WW Korsin, R Marino, BS Mirarchi, N McCrindle, BW AF Atz, Andrew M. Zak, Victor Mahony, Lynn Uzark, Karen Shrader, Peter Gallagher, Dianne Paridon, Stephen M. Williams, Richard V. Breitbart, Roger E. Colan, Steven D. Kaltman, Jonathan R. Margossian, Renee Pasquali, Sara K. Allen, Kerstin Lai, Wyman W. Korsin, Rosalind Marino, Bradley S. Mirarchi, Nicole McCrindle, Brian W. CA Pediat Heart Network Investigators TI Survival Data and Predictors of Functional Outcome an Average of 15 Years after the Fontan Procedure: The Pediatric Heart Network Fontan Cohort SO CONGENITAL HEART DISEASE LA English DT Article DE Fontan Procedure; Heart Defects; Congenital; Pediatrics; Functional Health Status ID QUALITY-OF-LIFE; GENERIC CORE SCALES; ADULT HEALTH-CARE; EXERCISE PERFORMANCE; YOUNG-ADULTS; DISEASE; OPERATION; MULTICENTER; ADOLESCENTS; PEDSQL(TM) AB ObjectiveMulticenter longitudinal outcome data for Fontan patients surviving into adulthood are lacking. The aim of this study was to better understand contemporary outcomes in Fontan survivors by collecting follow-up data in a previously well-characterized cohort. DesignBaseline data from the Fontan Cross-Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged 11.9 3.4years. We assessed current transplant-free survival status in all subjects 6.8 0.4years after the Fontan 1 study. Anatomic, clinical, and surgical data were collected along with socioeconomic status and access to health care. ResultsThirty subjects (5%) died or underwent transplantation since Fontan 1. Subjects with both an elevated (>21pg/mL) brain natriuretic peptide and a low Child Health Questionnaire physical summary score (<44) measured at Fontan 1 were significantly more likely to die or undergo transplant than the remainder, with a hazard ratio of 6.2 (2.9-13.5). Among 516 Fontan survivors, 427 (83%) enrolled in this follow-up study (Fontan 2) at 18.4 +/- 3.4years of age. Although mean scores on functional health status questionnaires were lower than the general population, individual scores were within the normal range in 78% and 88% of subjects for the Child Health Questionnaire physical and psychosocial summary score, and 97% and 91% for the SF-36 physical and mental aggregate score, respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55% of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1. Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58% of these (n = 68) since Fontan 1. ConclusionsWe found 95% interim transplant-free survival for Fontan survivors over an average of 7years of follow-up. Continued longitudinal investigation into adulthood is necessary to better understand the determinants of long-term outcomes and to improve functional health status. C1 [Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Zak, Victor; Shrader, Peter; Gallagher, Dianne; Allen, Kerstin] New England Res Inst, Watertown, MA 02172 USA. [Breitbart, Roger E.; Colan, Steven D.; Margossian, Renee] Boston Childrens Hosp, Boston, MA USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Uzark, Karen] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Paridon, Stephen M.; Mirarchi, Nicole] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Williams, Richard V.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Kaltman, Jonathan R.] NHLBI, Bethesda, MD 20892 USA. [Pasquali, Sara K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Lai, Wyman W.; Korsin, Rosalind] Cornell Univ, Med Ctr, Dept Pediat, New York, NY 10021 USA. [Marino, Bradley S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [McCrindle, Brian W.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Atz, AM (reprint author), Med Univ S Carolina, Dept Pediat, Div Cardiol, MSC 915,Room 601 Childrens Hosp, Charleston, SC 29425 USA. EM atzam@musc.edu FU U01 grants from the National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288] FX Supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288). This work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health/National Heart, Lung, and Blood Institute. NR 28 TC 9 Z9 9 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-079X EI 1747-0803 J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD JAN-FEB PY 2015 VL 10 IS 1 BP E30 EP E42 DI 10.1111/chd.12193 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB2MU UT WOS:000349462600006 PM 24934522 ER PT J AU Horinouchi, Y Summers, FA Ehrenshaft, M Mason, RP AF Horinouchi, Yuya Summers, Fiona A. Ehrenshaft, Marilyn Mason, Ronald P. TI Free radical generation from an aniline derivative in HepG2 cells: A possible captodative effect SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Cytotoxicity; Environmental chemicals; Captodative effect; Immuno-spin trapping; In-cell western; Confocal microscopy ID ELEMENT SIGNALING PATHWAY; OXIDATIVE STRESS; DNA; IDENTIFICATION; ACTIVATION; DAMAGE AB Xenobiotic metabolism can induce the generation of protein radicals, which are believed to play an important role in the toxicity of chemicals and drugs. It is therefore important to identify chemical structures capable of inducing macromolecular free radical formation in living cells. In this study, we evaluated the ability of four structurally related environmental chemicals, aniline, nitrosobenzene, N, N-dimethylaniline, and N,N-dimethy1-4-nitrosoaniline (DMNA), to induce free radicals and cellular damage in the hepatoma cell line HepG2. Cytotoxicity was assessed using lactate dehydrogenase assays, and morphological changes were observed using phase contrast microscopy. Protein free radicals were detected by immuno-spin trapping using in-cell western experiments and confocal microscopy to determine the subcellular locale of free radical generation. DMNA induced free radical generation, lactate dehydrogenase release, and morphological changes in HepG2 cells, whereas aniline, nitrosobenzene, N, N-dimethylaniline did not. Confocal microscopy showed that DMNA induced free radical generation mainly in the cytosol. Preincubation of HepG2 cells with N-acetylcysteine and 2,2'-dipyridyl significantly prevented free radical generation on subsequent incubation with DMNA, whereas preincubation with apocynin and dimethyl sulfoxide had no effect. These results suggest that DMNA is metabolized to reactive free radicals capable of generating protein radicals which may play a critical role in DMNA toxicity. We propose that the captodative effect, the combined action of the electron-releasing dimethylamine substituent, and the electron-withdrawing nitroso substituent, leads to a thermodynamically stabilized radical, facilitating enhanced protein radical formation by DMNA. (C) 2014 Elsevier Inc. All rights reserved. C1 [Horinouchi, Yuya; Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Free Rad Metab Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Horinouchi, Y (reprint author), Tokushima Univ Hosp, Dept Pharm, 2-50-1 Kuramoto, Tokushima 7708503, Japan. EM yuya.h@basic.med.tokushima-u.ac.jp; summersfa@niehs.nih.gov; ehrensh1@niehs.nih.gov; mason4@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences [Z01 ES050139-13]; Japan Society for the Promotion of Science (JSPS) FX We are very thankful to Dr. Agnes Janoshazi and Jeff Tucker for their expert help and advice with microscopy experiments. We thank Dr. Fabian Leinisch for help with drawing structures. We also sincerely thank Dr. Ann Motten, Mary Mason, and Jean Corbett for help in the careful editing of this manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences (Z01 ES050139-13), and a grant from the Japan Society for the Promotion of Science (JSPS). NR 28 TC 0 Z9 0 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN PY 2015 VL 78 BP 111 EP 117 DI 10.1016/j.freeradbiomed.2014.10.577 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AZ4GB UT WOS:000348178700011 PM 25450331 ER PT S AU Suzuki, R Scheffel, J Rivera, J AF Suzuki, Ryo Scheffel, Joerg Rivera, Juan BE Lafaille, JJ DeLafaille, MAC TI New Insights on the Signaling and Function of the High-Affinity Receptor for IgE SO IGE ANTIBODIES: GENERATION AND FUNCTION SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID FC-EPSILON-RI; MAST-CELL ACTIVATION; BRUTONS TYROSINE KINASE; BASOPHILIC LEUKEMIA-CELLS; IMMEDIATE HYPERSENSITIVITY REACTIONS; DEPENDENT MEDIATOR RELEASE; TOLL-LIKE RECEPTOR-4; IMMUNOGLOBULIN-E; MONOMERIC IGE; HISTAMINE-RELEASE AB Clustering of the high-affinity receptor for immunoglobulin E (FceRI) through the interaction of receptor-bound immunoglobulin E (IgE) antibodies with their cognate antigen is required to couple IgE antibody production to cellular responses and physiological consequences. IgE-induced responses through FceRI are well known to defend the host against certain infectious agents and to lead to unwanted allergic responses to normally innocuous substances. However, the cellular and/or physiological response of individuals that produce IgE antibodies may be markedly different and such antibodies (even to the same antigenic epitope) can differ in their antigen-binding affinity. How affinity variation in the interaction of Fc epsilon RI-bound IgE antibodies with antigen is interpreted into cellular responses and how the local environment may influence these responses is of interest. In this chapter, we focus on recent advances that begin to unravel how FceRI distinguishes differences in the affinity of IgE-antigen interactions and how such discrimination along with surrounding environmental stimuli can shape the (patho) physiological response. C1 [Suzuki, Ryo; Scheffel, Joerg; Rivera, Juan] NIAMSD, Mol Immunol Sect, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. [Rivera, Juan] NIAMS, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Rm 13C103, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 147 TC 2 Z9 2 U1 2 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-319-13725-4; 978-3-319-13724-7 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 388 BP 63 EP 90 DI 10.1007/978-3-319-13725-4_4 D2 10.1007/978-3-319-13725-4 PG 28 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EI UT WOS:000348987100005 PM 25553795 ER PT S AU Jin, H Subbarao, K AF Jin, Hong Subbarao, Kanta BE Oldstone, MBA Compans, RW TI Live Attenuated Influenza Vaccine SO INFLUENZA PATHOGENESIS AND CONTROL - VOL II SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID ANN-ARBOR STRAIN; RANDOMIZED CONTROLLED-TRIAL; CELLULAR IMMUNE-RESPONSES; CULTURE-CONFIRMED INFLUENZA; MASTER DONOR VIRUS; PANDEMIC INFLUENZA; YOUNG-CHILDREN; ANTIBODY-RESPONSE; HEALTHY-ADULTS; POSTMARKETING EVALUATION AB Cold-adapted Ann Arbor based live attenuated influenza vaccine (LAIV) has been available in the USA since 2003. The vaccine is efficacious against influenza infection. Features of LAIV include: easy administration suitable for mass immunization, cross-reactivity to drifted strains for broader coverage, and establishment of herd immunity for control of influenza spread. Annual seasonal LAIV now contains four strains against influenza A H1N1, H3N2, influenza B-Victoria, and B-Yamagata lineages that are co-circulating in humans. LAIV played a significant role in protecting the public from the 2009 H1N1 pandemic and has been evaluated for pandemic preparedness. Pandemic vaccines including influenza H2, H5, H6, H7, and H9 subtypes have been produced and evaluated in preclinical and small-scale phase I clinical studies. This review summarizes the current status and perspectives of seasonal and pandemic LAIV. C1 [Jin, Hong] MedImmune LLC, Mountain View, CA 94043 USA. [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jinh@medimmune.com; ksubbarao@niaid.nih.gov NR 68 TC 17 Z9 18 U1 2 U2 12 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-319-11158-2; 978-3-319-11157-5 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 386 BP 181 EP 204 DI 10.1007/82_2014_410 D2 10.1007/978-3-319-11158-2 PG 24 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EE UT WOS:000348984400008 PM 25059893 ER PT J AU Lai, SH Gerstenblith, G Li, J Zhu, H Bluemke, DA Liu, CY Zimmerman, SL Chen, SG Lai, H Treisman, G AF Lai, Shenghan Gerstenblith, Gary Li, Ji Zhu, Hong Bluemke, David A. Liu, Chia-Ying Zimmerman, Stefan L. Chen, Shaoguang Lai, Hong Treisman, Glenn TI Chronic Cocaine Use and Its Association With Myocardial Steatosis Evaluated by H-1 Magnetic Resonance Spectroscopy in African Americans SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE African Americans; cardiac steatosis; cocaine use; MR spectroscopy; obesity ID SYMPATHETIC-NERVOUS-SYSTEM; LIPOTOXIC DISEASES; LEPTIN PRODUCTION; HEART-DISEASE; WEIGHT; HUMANS; OBESITY; TRIGLYCERIDE; SENSITIVITY; MECHANISMS AB Objectives: Cardiac steatosis is a manifestation of ectopic fat deposition and is associated with obesity. The impact of chronic cocaine use on obesity measures and on the relationship between obesity measures and cardiac steatosis is not well-characterized. The objectives of this study were to compare obesity measures in chronic cocaine users and nonusers, and to explore which factors, in addition to obesity measures, are associated with myocardial triglyceride in African Americans, using noninvasive magnetic resonance spectroscopy. Methods: Between June 2004 and January 2014, 180 healthy African American adults without HIV infection, hypertension, and diabetes were enrolled in an observational proton magnetic resonance spectroscopy and imaging study investigating factors associated with cardiac steatosis. Results: Among these 180 participants, 80 were chronic cocaine users and 100 were nonusers. The median age was 42 (interquartile range, 34-47) years. Obesity measures trended higher in cocaine users than in nonusers. The median myocardial triglyceride was 0.6% (interquartile range, 0.4%-1.1%). Among the factors investigated, years of cocaine use, leptin, and visceral fat were independently associated with myocardial triglyceride. Body mass index and visceral fat, which were significantly associated with myocardial triglyceride in noncocaine users, were not associated with myocardial triglyceride content in cocaine users. Conclusions: This study shows (1) cocaine users may have more fat than nonusers and (2) myocardial triglyceride is independently associated with duration of cocaine use, leptin, and visceral fat in all subjects, whereas leptin and high-density lipoprotein cholesterol, but not visceral fat or body mass index, in cocaine users, suggesting that chronic cocaine use may modify the relationships between obesity measures and myocardial triglyceride. C1 [Lai, Shenghan; Li, Ji; Zhu, Hong; Chen, Shaoguang] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Lai, Shenghan; Gerstenblith, Gary] Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21287 USA. [Lai, Shenghan; Liu, Chia-Ying; Zimmerman, Stefan L.; Lai, Hong] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21287 USA. [Treisman, Glenn] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. [Zhu, Hong] Tianjin Med Univ, Dept Epidemiol & Biostat, Tianjin, Peoples R China. [Bluemke, David A.; Liu, Chia-Ying] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lai, SH (reprint author), Johns Hopkins Sch Med, 600 N Wolfe Str, Baltimore, MD 21287 USA. EM slai@jhmi.edu FU National Institute on Drug Abuse, National Institutes of Health [NIH R01-DA 12777, DA25524, DA15020] FX Supported by grants from the National Institute on Drug Abuse, National Institutes of Health (NIH R01-DA 12777, DA25524, and DA15020). NR 29 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2015 VL 9 IS 1 BP 31 EP 39 DI 10.1097/ADM.0000000000000078 PG 9 WC Substance Abuse SC Substance Abuse GA CB0TP UT WOS:000349340500004 PM 25325298 ER PT J AU Chowell, G Nishiura, H AF Chowell, Gerardo Nishiura, Hiroshi TI Characterizing the Transmission Dynamics and Control of Ebola Virus Disease SO PLOS BIOLOGY LA English DT Editorial Material ID ACUTE RESPIRATORY SYNDROME; HEMORRHAGIC-FEVER; WEST-AFRICA; CONGO; EPIDEMIC; KIKWIT; EVD AB Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates. C1 [Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. [Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA. [Nishiura, Hiroshi] Univ Tokyo, Grad Sch Med, Dept Global Hlth Policy, Tokyo, Japan. [Nishiura, Hiroshi] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan. RP Chowell, G (reprint author), Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. EM gchowell@gsu.edu OI Nishiura, Hiroshi/0000-0003-0941-8537 FU NSF [1414374, 1318788 III]; NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program; UK Biotechnology and Biological Sciences Research Council [BB/M008894/1]; NSF-IIS RAPID [1518939]; Fogarty International Center, US National Institutes of Health; Japan Science and Technology Agency CREST project; Japanese Society for the Promotion of Science (JSPS) KAKENHI [26700028]; St Luke';s Life Science Institute Research Grant for Clinical Epidemiology Research; Commissioned Research program of the Ministry of Health, Labour and Welfare, Japan [H26-ShinkoJitsuyoka-General-016] FX GC acknowledges financial support from the NSF grant 1414374 as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program; UK Biotechnology and Biological Sciences Research Council grant BB/M008894/1, NSF-IIS RAPID award #1518939, and NSF grant 1318788 III: Small: Data Management for Real-Time Data Driven Epidemic simulation, and the Division of International Epidemiology and Population Studies, The Fogarty International Center, US National Institutes of Health. HN received funding support from Japan Science and Technology Agency CREST project; the Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant Number 26700028; St Luke';s Life Science Institute Research Grant for Clinical Epidemiology Research 2014; and the Commissioned Research program of the Ministry of Health, Labour and Welfare, Japan (H26-ShinkoJitsuyoka-General-016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 11 Z9 12 U1 2 U2 40 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2015 VL 13 IS 1 AR e1002057 DI 10.1371/journal.pbio.1002057 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CA8KV UT WOS:000349169900019 PM 25607595 ER PT J AU Deans, AR Lewis, SE Huala, E Anzaldo, SS Ashburner, M Balhoff, JP Blackburn, DC Blake, JA Burleigh, JG Chanet, B Cooper, LD Courtot, M Csosz, S Cui, H Dahdul, W Das, S Dececchi, TA Dettai, A Diogo, R Druzinsky, RE Dumontier, M Franz, NM Friedrich, F Gkoutos, GV Haendel, M Harmon, LJ Hayamizu, TF He, YQ Hines, HM Ibrahim, N Jackson, LM Jaiswal, P James-Zorn, C Kohler, S Lecointre, G Lapp, H Lawrence, CJ Le Novere, N Lundberg, JG Macklin, J Mast, AR Midford, PE Miko, I Mungall, CJ Oellrich, A Osumi-Sutherland, D Parkinson, H Ramirez, MJ Richter, S Robinson, PN Ruttenberg, A Schulz, KS Segerdell, E Seltmann, KC Sharkey, MJ Smith, AD Smith, B Specht, CD Squires, RB Thacker, RW Thessen, A Fernandez-Triana, J Vihinen, M Vize, PD Vogt, L Wall, CE Walls, RL Westerfeld, M Wharton, RA Wirkner, CS Woolley, JB Yoder, MJ Zorn, AM Mabee, PM AF Deans, Andrew R. Lewis, Suzanna E. Huala, Eva Anzaldo, Salvatore S. Ashburner, Michael Balhoff, James P. Blackburn, David C. Blake, Judith A. Burleigh, J. Gordon Chanet, Bruno Cooper, Laurel D. Courtot, Melanie Csoesz, Sandor Cui, Hong Dahdul, Wasila Das, Sandip Dececchi, T. Alexander Dettai, Agnes Diogo, Rui Druzinsky, Robert E. Dumontier, Michel Franz, Nico M. Friedrich, Frank Gkouto, George V. Haendel, Melissa Harmon, Luke J. Hayamizu, Terry F. He, Yongqun Hines, Heather M. Ibrahim, Nizar Jackson, Laura M. Jaiswal, Pankaj James-Zorn, Christina Koehler, Sebastian Lecointre, Guillaume Lapp, Hilmar Lawrence, Carolyn J. Le Novere, Nicolas Lundberg, John G. Macklin, James Mast, Austin R. Midford, Peter E. Miko, Istvan Mungall, Christopher J. Oellrich, Anika Osumi-Sutherland, David Parkinson, Helen Ramirez, Martin J. Richter, Stefan Robinson, Peter N. Ruttenberg, Alan Schulz, Katja S. Segerdell, Erik Seltmann, Katja C. Sharkey, Michael J. Smith, Aaron D. Smith, Barry Specht, Chelsea D. Squires, R. Burke Thacker, Robert W. Thessen, Anne Fernandez-Triana, Jose Vihinen, Mauno Vize, Peter D. Vogt, Lars Wall, Christine E. Walls, Ramona L. Westerfeld, Monte Wharton, Robert A. Wirkner, Christian S. Woolley, James B. Yoder, Matthew J. Zorn, Aaron M. Mabee, Paula M. TI Finding Our Way through Phenotypes SO PLOS BIOLOGY LA English DT Article ID SEMANTIC-WEB; ONTOLOGY; DISEASE; ANATOMY; SEMAPHORINS; BIOLOGY; EVOLUTIONARY; TECHNOLOGIES; ASSOCIATION; CHALLENGE AB Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human-and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. C1 [Deans, Andrew R.; Hines, Heather M.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Lewis, Suzanna E.; Mungall, Christopher J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genome Div, Berkeley, CA 94720 USA. [Huala, Eva] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA. [Huala, Eva] Phoenix Bioinformat, Palo Alto, CA USA. [Anzaldo, Salvatore S.; Franz, Nico M.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. [Ashburner, Michael] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Balhoff, James P.; Lapp, Hilmar] Natl Evolutionary Synth Ctr, Durham, NC USA. [Blackburn, David C.] Calif Acad Sci, Dept Vertebrate Zool & Anthropol, San Francisco, CA 94118 USA. [Blake, Judith A.; Hayamizu, Terry F.] Jackson Lab, Bar Harbor, ME 04609 USA. [Burleigh, J. Gordon] Univ Florida, Dept Biol, Gainesville, FL USA. [Chanet, Bruno; Dettai, Agnes; Lecointre, Guillaume] Museum Natl Hist Nat, Dept Systemat & Evolut, F-75231 Paris, France. [Cooper, Laurel D.; Jaiswal, Pankaj] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Courtot, Melanie] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Csoesz, Sandor] Ecol Res Grp, MTA ELTE MTM, Budapest, Hungary. [Cui, Hong] Univ Arizona, Sch Informat Resources & Lib Sci, Tucson, AZ USA. [Dahdul, Wasila; Dececchi, T. Alexander; Jackson, Laura M.; Mabee, Paula M.] Univ S Dakota, Dept Biol, Vermillion, SD 57069 USA. [Das, Sandip] Univ Delhi, Dept Bot, Delhi 110007, India. [Diogo, Rui] Howard Univ, Coll Med, Dept Anat, Washington, DC USA. [Druzinsky, Robert E.] Univ Illinois, Coll Dent, Dept Oral Biol, Chicago, IL USA. [Dumontier, Michel] Stanford Ctr Biomed Informat Res, Stanford, CA USA. [Friedrich, Frank] Univ Hamburg, Bioctr Grindel & Zool Museum, Hamburg, Germany. [Gkouto, George V.] Aberystwyth Univ, Dept Comp Sci, Aberystwyth, Ceredigion, Wales. [Haendel, Melissa] Oregon Hlth & Sci Univ, Dept Med Informat & Epidemiol, Portland, OR 97201 USA. [Harmon, Luke J.] Univ Idaho, Dept Biol Sci, Moscow, ID 83843 USA. [He, Yongqun] Univ Michigan, Sch Med, Unit Lab Anim Med, Dept Microbiol & Immunol,Ctr Computat Med & Bioin, Ann Arbor, MI USA. [He, Yongqun] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA. [Ibrahim, Nizar] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA. [James-Zorn, Christina; Zorn, Aaron M.] Cincinnati Childrens Hosp, Div Dev Biol, Cincinnati, OH USA. [Koehler, Sebastian] Charite, Inst Med Genet & Human Genet, D-13353 Berlin, Germany. [Lawrence, Carolyn J.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [Lawrence, Carolyn J.] Iowa State Univ, Dept Agron, Ames, IA USA. [Le Novere, Nicolas] Babraham Inst, Babraham, Cambs, England. [Lundberg, John G.] Acad Nat Sci, Dept Ichthyol, Philadelphia, PA USA. [Macklin, James] Eastern Cereal & Oilseed Res Ctr, Ottawa, ON, Canada. [Mast, Austin R.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen] European Mol Biol Lab, European Bioinformat Inst, Hinxton, Cambs, England. [Ramirez, Martin J.] Consejo Nacl Invest Cient & Tecn, Museo Argentino Ciencias Nat, Div Arachnol, RA-1033 Buenos Aires, DF, Argentina. [Richter, Stefan; Wirkner, Christian S.] Univ Rostock, Inst Biowissensch, D-18055 Rostock, Germany. [Robinson, Peter N.] Charite, Inst Med Genet & Humangenet, D-13353 Berlin, Germany. [Ruttenberg, Alan] SUNY Buffalo, Sch Dent Med, Buffalo, NY 14260 USA. [Schulz, Katja S.] Smithsonian Inst, Natl Museum Amer Hist, Washington, DC 20560 USA. [Segerdell, Erik] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Seltmann, Katja C.] Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA. [Sharkey, Michael J.] Univ Kentucky, Dept Entomol, Lexington, KY 40546 USA. [Smith, Aaron D.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA. [Smith, Barry] SUNY Buffalo, Dept Philosophy, Buffalo, NY 14260 USA. [Specht, Chelsea D.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Specht, Chelsea D.] Univ Calif Berkeley, Univ & Jepson Herbaria, Berkeley, CA 94720 USA. [Squires, R. Burke] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. [Thacker, Robert W.] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA. [Thessen, Anne] Data Detektiv, Waltham, MA USA. [Fernandez-Triana, Jose] Canadian Natl Collect Insects, Ottawa, ON, Canada. [Vihinen, Mauno] Lund Univ, Dept Expt Med Sci, Lund, Sweden. [Vize, Peter D.] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. [Vogt, Lars] Univ Bonn, Inst Evolut Biol & Okol, Bonn, Germany. [Wall, Christine E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC USA. [Walls, Ramona L.] iPlant Collaborat Univ Arizona, Tucson, AZ USA. [Westerfeld, Monte] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. [Wharton, Robert A.; Woolley, James B.] Texas A&M Univ, Dept Entomol, College Stn, TX 77843 USA. [Yoder, Matthew J.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL 61820 USA. RP Deans, AR (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. EM adeans@psu.edu RI Richter, Stefan/E-6256-2012; Friedrich, Frank/A-8309-2015; Jaiswal, Pankaj/H-7599-2016; OI Le Novere, Nicolas/0000-0002-6309-7327; Osumi-Sutherland, David/0000-0002-7073-9172; Lewis, Suzanna/0000-0002-8343-612X; Dahdul, Wasila/0000-0003-3162-7490; Balhoff, James/0000-0002-8688-6599; Squires, R Burke/0000-0001-9666-6285; Jaiswal, Pankaj/0000-0002-1005-8383; Deans, Andrew/0000-0002-2119-4663; Diogo, Rui/0000-0002-9008-1910; Segerdell, Erik/0000-0002-9611-1279; Schulz, Katja/0000-0001-7134-3324; He, Yongqun/0000-0001-9189-9661; Thessen, Anne/0000-0002-2908-3327; Blackburn, David/0000-0002-1810-9886; Vihinen, Mauno/0000-0002-9614-7976; Parkinson, Helen/0000-0003-3035-4195; Kohler, Sebastian/0000-0002-5316-1399; Courtot, Melanie/0000-0002-9551-6370 FU US National Science Foundation [DEB-0956049] FX This effort was funded by the US National Science Foundation, grant number DEB-0956049. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 50 Z9 51 U1 16 U2 73 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2015 VL 13 IS 1 AR e1002033 DI 10.1371/journal.pbio.1002033 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CA8KV UT WOS:000349169900001 PM 25562316 ER PT J AU Waldor, MK Tyson, G Borenstein, E Ochman, H Moeller, A Finlay, BB Kong, HH Gordon, JI Nelson, KE Dabbagh, K Smith, H AF Waldor, Matthew K. Tyson, Gene Borenstein, Elhanan Ochman, Howard Moeller, Andrew Finlay, B. Brett Kong, Heidi H. Gordon, Jeffrey I. Nelson, Karen E. Dabbagh, Karim Smith, Hamilton TI Where Next for Microbiome Research? SO PLOS BIOLOGY LA English DT Article ID GUT MICROBIOME; HUMAN SKIN; COMMUNITY; DIVERSITY; BIOLOGY AB The development of high-throughput sequencing technologies has transformed our capacity to investigate the composition and dynamics of the microbial communities that populate diverse habitats. Over the past decade, these advances have yielded an avalanche of metagenomic data. The current stage of " van Leeuwenhoek"-like cataloguing, as well as functional analyses, will likely accelerate as DNA and RNA sequencing, plus protein and metabolic profiling capacities and computational tools, continue to improve. However, it is time to consider: what's next for microbiome research? The short pieces included here briefly consider the challenges and opportunities awaiting microbiome research. C1 [Waldor, Matthew K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis,Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Waldor, Matthew K.] HHMI, Boston, MA USA. [Tyson, Gene] Univ Queensland, Australian Ctr Ecogen, Brisbane, Qld, Australia. [Tyson, Gene] Univ Queensland, Adv Water Management Ctr, Brisbane, Qld, Australia. [Borenstein, Elhanan] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Borenstein, Elhanan] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Borenstein, Elhanan] Santa Fe Inst, Santa Fe, NM 87501 USA. [Ochman, Howard] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA. [Moeller, Andrew] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA. [Finlay, B. Brett] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. [Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA. [Nelson, Karen E.] J Craig Venter Inst, Rockville, MD USA. [Dabbagh, Karim] Second Genome Inc, San Francisco, CA USA. [Smith, Hamilton] J Craig Venter Inst, La Jolla, CA USA. RP Waldor, MK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis,Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM mwaldor@research.bwh.harvard.edu RI Tyson, Gene/C-6558-2013; OI Kong, Heidi/0000-0003-4424-064X FU NCCIH NIH HHS [DP2 AT007802]; NIAID NIH HHS [R37 AI042347] NR 20 TC 29 Z9 31 U1 9 U2 56 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2015 VL 13 IS 1 AR UNSP e1002050 DI 10.1371/journal.pbio.1002050 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CA8KV UT WOS:000349169900016 PM 25602283 ER PT J AU de Araujo, FF Nagarkatti, R Gupta, C Marino, AP Debrabant, A AF de Araujo, Fernanda Fortes Nagarkatti, Rana Gupta, Charu Marino, Ana Paula Debrabant, Alain TI Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID TRYPANOSOMA-CRUZI; AMERICAN TRYPANOSOMIASIS; MURINE HOSTS; VACCINE; MICE; INFECTION; STRAINS; HEART; PCR AB Drug discovery initiatives, aimed at Chagas treatment, have been hampered by the lack of standardized drug screening protocols and the absence of simple pre-clinical assays to evaluate treatment efficacy in animal models. In this study, we used a simple Enzyme Linked Aptamer (ELA) assay to detect T. cruzi biomarker in blood and validate murine drug discovery models of Chagas disease. In two mice models, Apt-29 ELA assay demonstrated that biomarker levels were significantly higher in the infected group compared to the control group, and upon Benznidazole treatment, their levels reduced. However, biomarker levels in the infected treated group did not reduce to those seen in the non-infected treated group, with 100% of the mice above the assay cutoff, suggesting that parasitemia was reduced but cure was not achieved. The ELA assay was capable of detecting circulating biomarkers in mice infected with various strains of T. cruzi parasites. Our results showed that the ELA assay could detect residual parasitemia in treated mice by providing an overall picture of the infection in the host. They suggest that the ELA assay can be used in drug discovery applications to assess treatment efficacy in-vivo. C1 [de Araujo, Fernanda Fortes; Nagarkatti, Rana; Gupta, Charu; Debrabant, Alain] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. [Marino, Ana Paula] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP de Araujo, FF (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. EM alain.debrabant@fda.hhs.gov OI Gupta, Charu/0000-0002-7437-6559 FU US Food and Drug Administration FX Research was supported by intramural grants from the US Food and Drug Administration to AD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 6 Z9 6 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2015 VL 9 IS 1 AR e3451 DI 10.1371/journal.pntd.0003451 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CB0LR UT WOS:000349318100048 PM 25569299 ER PT J AU Chatterjee, S Nutman, TB AF Chatterjee, Soumya Nutman, Thomas B. TI Helminth-Induced Immune Regulation: Implications for Immune Responses to Tuberculosis SO PLOS PATHOGENS LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; HUMAN DENDRITIC CELLS; MYCOBACTERIUM-TUBERCULOSIS; IN-UTERO; LATENT TUBERCULOSIS; CYTOKINE RESPONSES; BCG VACCINATION; T-CELLS; INFECTION; ANTIGENS C1 [Chatterjee, Soumya; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chatterjee, S (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM chatterjees3@mail.nih.gov FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 6 Z9 6 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2015 VL 11 IS 1 AR UNSP e1004582 DI 10.1371/journal.ppat.1004582 PG 6 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CA7OF UT WOS:000349106100019 PM 25632943 ER PT J AU Darby, M Schnoeller, C Vira, A Culley, F Bobat, S Logan, E Kirstein, F Wess, J Cunningham, AF Brombacher, F Selkirk, ME Horsnell, WGC AF Darby, Matthew Schnoeller, Corinna Vira, Alykhan Culley, Fiona Bobat, Saeeda Logan, Erin Kirstein, Frank Wess, Juergen Cunningham, Adam F. Brombacher, Frank Selkirk, Murray E. Horsnell, William G. C. TI The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection SO PLOS PATHOGENS LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; ENTERICA SEROVAR TYPHIMURIUM; T-CELLS; SALMONELLA-TYPHIMURIUM; MICE; M-3; HYPERCONTRACTILITY; DIFFERENTIATION; PHARMACOLOGY; ACTIVATION AB Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R(-/-) mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R(-/-) mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R(-/-) mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-gamma respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection. C1 [Darby, Matthew; Vira, Alykhan; Logan, Erin; Kirstein, Frank; Brombacher, Frank; Horsnell, William G. C.] Univ Cape Town, Int Ctr Genet Engn & Biotechnol, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Darby, Matthew; Vira, Alykhan; Logan, Erin; Kirstein, Frank; Brombacher, Frank; Horsnell, William G. C.] Univ Cape Town, Div Immunol, ZA-7925 Cape Town, South Africa. [Schnoeller, Corinna; Selkirk, Murray E.] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London, England. [Culley, Fiona] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Bobat, Saeeda; Cunningham, Adam F.] Univ Birmingham, Sch Immun & Infect, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Darby, M (reprint author), Univ Cape Town, Int Ctr Genet Engn & Biotechnol, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. EM m.selkirk@imperial.ac.uk; wghorsnell@gmail.com OI Selkirk, Murray/0000-0002-6274-6014 FU South African National Research Foundation [91555]; International Centre for Genetic Engineering and Biotechnology; National Research Foundation; World University Network; Wellcome Trust [059532] FX The project was funded by a South African National Research Foundation Grant (Grant #: 91555) awarded to WH and the International Centre for Genetic Engineering and Biotechnology, the National Research Foundation, the World University Network and the Wellcome Trust (Ref 059532). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 5 Z9 5 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2015 VL 11 IS 1 AR UNSP e1004636 DI 10.1371/journal.ppat.1004636 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CA7OF UT WOS:000349106100046 PM 25629518 ER EF