FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Dix, DB Gratias, E Seibel, NL Chi, YY Tian, J Mullen, E Geller, J Khanna, G Kalapurakal, J Perlman, EJ Ehrlich, P Malogolowkin, M Grundy, P Dome, JS AF Dix, D. B. Gratias, E. Seibel, N. L. Chi, Y. Y. Tian, J. Mullen, E. Geller, J. Khanna, G. Kalapurakal, J. Perlman, E. J. Ehrlich, P. Malogolowkin, M. Grundy, P. Dome, J. S. TI Treatment of Stage IV Favorable Histology Wilms Tumour with Extra-Pulmonary Metastases: A Report from Children's Oncology Group Study AREN0533 SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Dix, D. B.] British Columbia Childrens Hosp, Haematol Oncol, Vancouver, BC, Canada. [Gratias, E.] Evicore Healthcare, Med Oncol, Bluffton, SC USA. [Seibel, N. L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Chi, Y. Y.; Tian, J.] COG Data Ctr, Childrens Oncol Grp, Gainesville, FL USA. [Mullen, E.] Dana Farber Harvard Canc Ctr, Paediat Haematol Oncol, Boston, MA USA. [Geller, J.] Cincinnati Childrens Hosp Med Ctr, Haematol Oncol, Cincinnati, OH 45229 USA. [Khanna, G.] Washington Univ, Sch Med, Paediat Radiol, St Louis, MO USA. [Kalapurakal, J.] Ann & Robert H Lurie Childrens Hosp Chicago, Radiat Oncol, Chicago, IL 60611 USA. [Perlman, E. J.] Ann & Robert H Lurie Childrens Hosp Chicago, Pathol, Chicago, IL 60611 USA. [Ehrlich, P.] CS Mott Childrens Hosp, Pediatrc Surg, Ann Arbor, MI USA. [Malogolowkin, M.] Univ Calif Davis, Ctr Comprehens Canc, Paediat Haematol Oncol, Sacramento, CA 95817 USA. [Grundy, P.] Univ Alberta Hosp, Paediat Haematol Oncol, Edmonton, AB, Canada. [Dome, J. S.] Childrens Natl Med Ctr, Div Oncol, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 3 MA PD-139 BP S93 EP S94 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DY0XF UT WOS:000384818800026 ER PT J AU Liu, Y Easton, J Shao, Y Wilkinson, M Edmonson, M Ma, X Auvil, JG Gerhard, D Winick, N Raetz, E Willman, C Carroll, W Dunsmore, K Winter, S Wood, B Downing, J Loh, M Hunger, S Zhang, J Mullighan, C AF Liu, Y. Easton, J. Shao, Y. Wilkinson, M. Edmonson, M. Ma, X. Auvil, J. Guidry Gerhard, D. Winick, N. Raetz, E. Willman, C. Carroll, W. Dunsmore, K. Winter, S. Wood, B. Downing, J. Loh, M. Hunger, S. Zhang, J. Mullighan, C. TI The Genomic Landscape of T-Lineage Acute Lymphoblastic Leukemia SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Liu, Y.; Easton, J.; Shao, Y.; Edmonson, M.; Ma, X.; Zhang, J.] St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Wilkinson, M.; Downing, J.; Mullighan, C.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Auvil, J. Guidry; Gerhard, D.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Winick, N.] UT Southwestern, Simmons Canc Ctr Dallas, Paediat Haematol & Oncol, Dallas, TX USA. [Raetz, E.] Univ Utak, Huntsman Canc Inst, Salt Lake City, UT USA. [Raetz, E.] Univ Utak, Primary Childrens Hosp, Salt Lake City, UT USA. [Willman, C.; Winter, S.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Carroll, W.] NYU, Med Ctr, Dept Paediat, New York, NY 10016 USA. [Dunsmore, K.] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. [Wood, B.] Seattle Canc Care Alliance, Haematol, Seattle, WA USA. [Loh, M.] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Hunger, S.] Childrens Hosp Philadelphia, Perelman Dept Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 3 MA O-035 BP S15 EP S15 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DY0XF UT WOS:000384818800370 ER PT J AU Ooms, AHAG Gadd, S Gerhard, DS Smith, MA Auvil, JMG Meerzaman, D Ma, Y Marra, MA Huff, V Dome, JS Chi, YY Geller, JI Mullighan, CG Wheeler, DA Hampton, OA Van den Heuvel-Eibrink, MM De Krijger, RR Ross, N Gastier-Foster, JM Perlman, EJ AF Ooms, A. H. A. G. Gadd, S. Gerhard, D. S. Smith, M. A. Auvil, J. M. Gaidry Meerzaman, D. Ma, Y. Marra, M. A. Huff, V. Dome, J. S. Chi, Y. Y. Geller, J. I. Mullighan, C. G. Wheeler, D. A. Hampton, O. A. Van den Heuvel-Eibrink, M. M. De Krijger, R. R. Ross, N. Gastier-Foster, J. M. Perlman, E. J. TI Prognostic Impact of TP53 Mutation Status in Wilms Tumors with Diffuse Anaplasia SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Ooms, A. H. A. G.] Pathan BV, Dept Pathol, Rotterdam, Netherlands. [Ooms, A. H. A. G.; De Krijger, R. R.] Princess Maxima Ctr, Dept Pathol, Utrecht, Netherlands. [Ooms, A. H. A. G.; Gadd, S.; Perlman, E. J.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pathol & Lab Med, Chicago, IL 60611 USA. [Gerhard, D. S.; Auvil, J. M. Gaidry] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Smith, M. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Meerzaman, D.] NCI, Ctr Bioinformat & Informat Technol, Bethesda, MD 20892 USA. [Ma, Y.; Marra, M. A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Marra, M. A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Huff, V.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Dome, J. S.] Childrens Natl Med Ctr, Div Paediat Haematol Oncol, Washington, DC 20010 USA. [Chi, Y. Y.] Univ Florida, Dept Biostat, Gainesville, FL USA. [Geller, J. I.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Paediat Oncol, Cincinnati, OH USA. [Mullighan, C. G.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Wheeler, D. A.; Hampton, O. A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Van den Heuvel-Eibrink, M. M.] Princess Maxima Ctr, Dept Paediat Oncol, Utrecht, Netherlands. [De Krijger, R. R.] Reinier de Graaf Hosp, Dept Pathol, Delft, Netherlands. [Ross, N.; Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Dept Pathol & Lab Med, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. [Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Dept Paediat, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 3 MA O-117 BP S34 EP S35 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DY0XF UT WOS:000384818800452 ER PT J AU Wiener, L Zadeh, S Battles, H Pelletier, W Muriel, A AF Wiener, L. Zadeh, S. Battles, H. Pelletier, W. Muriel, A. TI Understanding the Perceived Influence of Childhood Cancer on the Parents' Relationship SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Wiener, L.; Zadeh, S.; Battles, H.] NCI, Paediat Oncol Branch, Bethesda, MD 20892 USA. [Pelletier, W.] Alberta Childrens Prov Gen Hosp, Paediat Oncol, Calgary, AB, Canada. [Muriel, A.] Dana Farber Canc Inst, Paediat Psychosocial Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 3 MA O-231 BP S59 EP S59 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DY0XF UT WOS:000384818800565 ER PT J AU Withycombe, J Reeve, B McFatrich, M Mack, J Weaver, M Jacobs, S Sung, L Baker, J Pinheiro, L Mowbray, C Palma, D Freyer, D Gibson, D Tomlinson, D Lukshis, J Levine, A Jackson, K Waldon, M Lollar, S Hinds, PS AF Withycombe, J. Reeve, B. McFatrich, M. Mack, J. Weaver, M. Jacobs, S. Sung, L. Baker, J. Pinheiro, L. Mowbray, C. Palma, D. Freyer, D. Gibson, D. Tomlinson, D. Lukshis, J. Levine, A. Jackson, K. Waldon, M. Lollar, S. Hinds, P. S. TI Evaluation of Reading Level and Children's Ability to Complete the Paediatric Patient-Reported Outcome Common Terminology Criteria for Adverse Events (Paediatric PRO-CTCAE) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Withycombe, J.] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. [Reeve, B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [McFatrich, M.; Pinheiro, L.; Jackson, K.] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Mack, J.; Levine, A.] Dana Farber Canc Inst, Paediat Oncol, Boston, MA USA. [Weaver, M.] NIH, Palliat Care, Bldg 10, Bethesda, MD 20892 USA. [Jacobs, S.] Childrens Natl, Oncol, Washington, DC USA. [Sung, L.] Hosp Sick Children, Haematol Oncol, Toronto, ON, Canada. [Baker, J.] St Jude Childrens Res Hosp, Oncol & Paediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA. [Mowbray, C.; Waldon, M.; Hinds, P. S.] Childrens Natl, Nursing Res, Washington, DC USA. [Palma, D.] Univ Southern Calif, Res, Los Angeles, CA USA. [Freyer, D.] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA USA. [Gibson, D.] St Jude Childrens Res Hosp, Nursing, Memphis, TN USA. [Tomlinson, D.] Hosp Sick Children, Clin Res, Toronto, ON, Canada. [Lukshis, J.] Childrens Hosp, Palmetto Hlth, Columbia, SC USA. [Lollar, S.] Palmetto Hlth, Clin Trials, Columbia, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 3 MA PD-156 BP S97 EP S98 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DY0XF UT WOS:000384818800043 ER PT J AU Dumond, JF Zhang, X Izumi, Y Ramkissoon, K Wang, GH Gucek, M Wang, XJ Burg, MB Ferraris, JD AF Dumond, Jenna F. Zhang, Xue Izumi, Yuichiro Ramkissoon, Kevin Wang, Guanghui Gucek, Marjan Wang, Xujing Burg, Maurice B. Ferraris, Joan D. TI Peptide affinity analysis of proteins that bind to an unstructured region containing the transactivating domain of the osmoprotective transcription factor NFAT5 SO PHYSIOLOGICAL GENOMICS LA English DT Article DE NFAT5; hypertonicity; peptide affinity; proteomics; disorder ID INTRINSICALLY DISORDERED PROTEIN; DAMAGE-INDUCIBLE KINASE; LARGE GENE LISTS; HIGH-NACL; FACTOR TONEBP/OREBP; INTERACTION NETWORKS; HYPERTONIC STRESS; OSMOTIC-STRESS; ACTIVATION; CELLS AB NFAT5 is a transcription factor originally identified because it is activated by hypertonicity and that activation increases expression of genes that protect against the adverse effects of the hypertonicity. However, its targets also include genes not obviously related to tonicity. The transactivating domain of NFAT5 is contained in its COOH-terminal region, which is predicted to be unstructured. Unstructured regions are common in transcription factors particularly in transactivating domains where they can bind co-regulatory proteins essential to their function. To identify potential binding partners of NFAT5 from either cytoplasmic or nuclear HEK293 cell extracts, we used peptide affinity chromatography followed by mass spectrometry. Peptide aptamerbaits consisted of overlapping 20 amino acid peptides within the predicted COOH-terminal unstructured region of NFAT5. We identify a total of 351 unique protein preys that associate with at least one COOH-terminal peptide bait from NFAT5 in either cytoplasmic or nuclear extracts from cells incubated at various tonicities (NaCl varied). In addition to finding many proteins already known to associate with NFAT5, we found many new ones whose function suggest novel aspects of NFAT5 regulation, interaction, and function. Relatively few of the proteins pulled down by peptide baits from NFAT5 are generally involved in transcription, and most, therefore, are likely to be specifically related to the regulation of NFAT5 or its function. The novel associated proteins are involved with cancer, effects of hypertonicity on chromatin, development, splicing of mRNA, transcription, and vesicle trafficking. C1 [Dumond, Jenna F.; Zhang, Xue; Izumi, Yuichiro; Ramkissoon, Kevin; Wang, Guanghui; Gucek, Marjan; Wang, Xujing; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. [Izumi, Yuichiro] Kumamoto Univ, Grad Sch Med Sci, Dept Nephrol, Kumamoto, Japan. RP Burg, MB (reprint author), Bldg 10,Rm 6N307,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maurice_burg@nih.gov FU Division of Intramural Research of the National Heart, and Lung Institute FX Funded by the Division of Intramural Research of the National Heart, and Lung Institute. NR 50 TC 0 Z9 0 U1 5 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV 1 PY 2016 VL 48 IS 11 BP 835 EP 849 DI 10.1152/physiolgenomics.00100.2016 PG 15 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA EE5ID UT WOS:000389638800008 ER PT J AU Schneper, LM Brooks-Gunn, J Notterman, DA Suomi, SJ AF Schneper, Lisa M. Brooks-Gunn, Jeanne Notterman, Daniel A. Suomi, Stephen J. TI Early-Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE rhesus monkeys; early social rearing; adult telomere length ID STRESS; ASSOCIATION; EXPOSURE; GENETICS; CORTISOL; PRIMATES; BEHAVIOR; DISEASE; MODELS; DIET AB Objective: Child-rearing environments have been associated with morbidity in adult rhesus monkeys. We examine whether such links are also seen with leukocyte telomere length. Methods: To determine telomere length in leukocytes, blood was collected from 11 adult female monkeys aged 7 to 10 years who had been exposed to different rearing environments between birth and 7 months. Four had been reared with their mothers in typical social groups composed of other female monkeys, their offspring, and 1 to 2 adult male monkeys. The other 7 had been reared in either small groups of peers or individual cages with extensive peer interaction daily. After 7 months, all shared a common environment. Results: Telomere lengths were longer for those adults who had been reared with their mothers in social groups (median = 16.0 kb, interquartile range = 16.5-15.4) than for those who were reared without their mothers (median = 14.0 kb, interquartile range = 14.3-12.7; 2.2 kb/telomere difference, p < .027). Conclusions: This observation adds to emerging knowledge about early adverse child-rearing conditions and their potential for influencing later morbidity. Because newborns were randomly assigned to the mother or other rearing conditions, the findings are not confounded by other conditions that co-occur with adverse child-rearing environments in humans (e.g., prenatal stress, nutrition and health as well as postnatal nutrition and negative life experiences over and above rearing conditions). C1 [Schneper, Lisa M.; Notterman, Daniel A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Brooks-Gunn, Jeanne] Columbia Univ, Teachers Coll, Dept Human Dev, New York, NY 10027 USA. [Suomi, Stephen J.] NICHHD, Bethesda, MD 20892 USA. RP Notterman, DA (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. EM dan1@princeton.edu FU Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development [5R91HD076592] FX The authors thank Michelle Miller and Kristen L. Byers for overseeing the collection and transport of blood samples, Elizabeth Conroy and Iulia Kotenko for aid in measuring telomere length, and Sarah Lazzeroni for assistance with the preparation of this article. This study was supported by the Division of Intramural Research (S.J.S.) and extramural grant #5R91HD076592 (D.A.N.) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 44 TC 2 Z9 2 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2016 VL 78 IS 9 BP 1066 EP 1071 DI 10.1097/PSY.0000000000000402 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA EE5LR UT WOS:000389649600010 PM 27763985 ER PT J AU Thompson, KL Boitier, E Chen, T Couttet, P Ellinger-Ziegelbauer, H Goetschy, M Guillemain, G Kanki, M Kelsall, J Mariet, C de La Moureyre-Spire, C Mouritzen, P Nassirpour, R O'Lone, R Pine, PS Rosenzweig, BA Sharapova, T Smith, A Uchiyama, H Yan, J Yuen, PS Wolfinger, R AF Thompson, Karol L. Boitier, Eric Chen, Tao Couttet, Philippe Ellinger-Ziegelbauer, Heidrun Goetschy, Manuela Guillemain, Gregory Kanki, Masayuki Kelsall, Janet Mariet, Claire de La Moureyre-Spire, Catherine Mouritzen, Peter Nassirpour, Rounak O'Lone, Raegan Pine, P. Scott Rosenzweig, Barry A. Sharapova, Tatiana Smith, Aaron Uchiyama, Hidefumi Yan, Jian Yuen, Peter S. Wolfinger, Russ TI Absolute Measurement of Cardiac Injury-Induced microRNAs in Biofluids across Multiple Test Sites SO TOXICOLOGICAL SCIENCES LA English DT Article DE interlaboratory; microRNA; variance; biomarker ID ACUTE MYOCARDIAL-INFARCTION; REAL-TIME PCR; CIRCULATING MICRORNAS; HEART-FAILURE; BIOMARKERS; PLASMA; RAT; QUANTIFICATION; HEPATOTOXICITY; IDENTIFICATION AB Extracellular microRNAs (miRNAs) represent a promising new source of toxicity biomarkers that are sensitive indicators of site of tissue injury. In order to establish reliable approaches for use in biomarker validation studies, the HESI technical committee on genomics initiated a multi-site study to assess sources of variance associated with quantitating levels of cardiac injury induced miRNAs in biofluids using RT-qPCR. Samples were generated at a central site using a model of acute cardiac injury induced in male Wistar rats by 0.5 mg/kg isoproterenol. Biofluid samples were sent to 11 sites for measurement of 3 cardiac enriched miRNAs (miR-1-3p, miR-208a-3p, and miR-499-5p) and 1 miRNA abundant in blood (miR-16-5p) or urine (miR-192-5p) by absolute quantification using calibration curves of synthetic miRNAs. The samples included serum and plasma prepared from blood collected at 4 h, urine collected from 6 to 24 h, and plasma prepared from blood collected at 24 h post subcutaneous injection. A 3 parameter logistic model was utilized to fit the calibration curve data and estimate levels of miRNAs in biofluid samples by inverse prediction. Most sites observed increased circulating levels of miR-1-3p and miR-208a-3p at 4 and 24 h after isoproterenol treatment, with no difference seen between serum and plasma. The biological differences in miRNA levels and sample type dominated as sources of variance, along with outlying performance by a few sites. The standard protocol established in this study was successfully implemented across multiple sites and provides a benchmark method for further improvements in quantitative assays for circulating miRNAs. C1 [Thompson, Karol L.; Rosenzweig, Barry A.] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Boitier, Eric; Mariet, Claire] Sanofi R&D, Disposit Safety & Anim Res, Vitry Sur Seine, France. [Chen, Tao; Yan, Jian] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Couttet, Philippe; Goetschy, Manuela; Guillemain, Gregory] Novartis Pharma AG, CH-4057 Basel, Switzerland. [Ellinger-Ziegelbauer, Heidrun] Bayer Pharma, Toxicol, D-42096 Wuppertal, AG, Germany. [Kanki, Masayuki] Astellas Pharma Inc, Osaka 5328514, Japan. [Kelsall, Janet] AstraZeneca Ltd, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England. [de La Moureyre-Spire, Catherine] Inst Rech Servier, F-78290 Croissy Sur Seine, France. [Mouritzen, Peter] Exiqon, DK-2950 Vedbaek, Denmark. [Nassirpour, Rounak] Pfizer, Andover, MA 01810 USA. [O'Lone, Raegan] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. [Pine, P. Scott] Natl Inst Stand & Technol, Stanford, CA 94305 USA. [Sharapova, Tatiana] AbbVie, Abbott Pk, N Chicago, IL 60064 USA. [Smith, Aaron] Eli Lilly, Indianapolis, IN 46285 USA. [Uchiyama, Hidefumi] Takeda Pharmaceut Co Ltd, Fujisawa, Kanagawa 2518555, Japan. [Yuen, Peter S.] NIH NIDDK, Bethesda, MD 20892 USA. [Wolfinger, Russ] SAS Inst Inc Cary, Cary, NC 27513 USA. [Nassirpour, Rounak; Pine, P. Scott] Momenta Pharmaceut Inc, Cambridge, MA 02142 USA. RP O'Lone, R (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. EM Rolone@hesiglobal.org FU HESI FX This HESI scientific initiative is primarily supported by in-kind contributions (from public and private sector participants) of time, expertise, and experimental effort. These contributions are supplemented by direct funding (that largely supports program infrastructure and management) that was provided by HESI's corporate sponsors. A list of supporting organizations (public and private) is available at http://hesiglobal.org/application-of-genomics-to-mechanism-based-risk-as sessment-technical-committee/3311. NR 40 TC 0 Z9 0 U1 2 U2 2 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 NOV PY 2016 VL 154 IS 1 BP 115 EP 125 DI 10.1093/toxsci/kfw143 PG 11 WC Toxicology SC Toxicology GA ED6CA UT WOS:000388940900012 PM 27605421 ER PT J AU Ward, DC Beaulieu, GP Leitman, SF Flegel, WA AF Ward, Dawn C. Beaulieu, Gregory P. Leitman, Susan F. Flegel, Willy A. TI Transfused neutrophils home to a joint with fungal infection SO TRANSFUSION LA English DT Editorial Material ID GRANULOCYTE TRANSFUSION; THERAPY C1 [Ward, Dawn C.; Beaulieu, Gregory P.; Leitman, Susan F.; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Flegel, WA (reprint author), NIH, Dept Transfus, Ctr Clin, Med Bldg 10,Room 1C733c MSC-1184,10 Ctr Dr, Bethesda, MD 20892 USA. EM waf@nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD NOV PY 2016 VL 56 IS 11 BP 2655 EP 2656 DI 10.1111/trf.13743 PG 2 WC Hematology SC Hematology GA EE1LV UT WOS:000389344100002 PM 28211956 ER PT J AU Riddell, IA Agama, K Park, GY Pommier, Y Lippard, SJ AF Riddell, Imogen A. Agama, Keli Park, Ga Young Pommier, Yves Lippard, Stephen J. TI Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes SO ACS CHEMICAL BIOLOGY LA English DT Article ID DNA TOPOISOMERASES; STRAND BREAKS; STRUCTURAL BASIS; ANTICANCER; CANCER; CELLS; MECHANISM; INHIBITION; SEQUENCE; DAMAGE AB Drugs capable of trapping topoisomerase II (Top2), an essential enzyme that cleaves DNA to remove naturally occurring knots and tangles, can serve as potent anticancer agents. The monofunctional platinum agent phenanthriplatin, cis-[Pt(NH3)(2)(phenanthridine)Cl] (NO3), is shown here to trap Top2 in addition to its known modes of inhibition of DNA and RNA polymerases. Its potency therefore combines diverse modes of action by which phenanthriplatin kills cancer cells. The observation that phenanthriplatin can act as a Top2 poison highlights opportunities to design nonclassical platinum anticancer agents with this novel mechanism of action. Such complexes have the potential to overcome current limitations with chemotherapy, such as resistance, and to provide treatment options for cancers that do not respond well to classical agents. Covalent DNA-platinum lesions implicated in Top2 poisoning are distinctive from those generated by known therapeutic topoisomerase poisons, which typically exert their action by reversible binding at the interface of Top2-DNA cleavage complexes. C1 [Riddell, Imogen A.; Park, Ga Young; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Agama, Keli; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Agama, Keli; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lippard, SJ (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA.; Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov; lippard@mit.edu RI Riddell, Imogen/B-1078-2017 OI Riddell, Imogen/0000-0002-6801-0198 FU NCI [CA034992]; Misrock Fellowship; Intramural Program of the National Cancer Institute, Center for Cancer Research [Z01-BC006161] FX This work is supported by the NCI under grant CA034992 (S.J.L). G.Y.P. received support from a Misrock Fellowship. K.A. and Y.P. are supported by the Intramural Program of the National Cancer Institute, Center for Cancer Research (Z01-BC006161). NR 42 TC 0 Z9 0 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD NOV PY 2016 VL 11 IS 11 BP 2996 EP 3001 DI 10.1021/acschembio.6b00565 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EC8YX UT WOS:000388430100006 PM 27648475 ER PT J AU Singh, A Venkannagari, S Oh, KH Zhang, YQ Rohde, JM Liu, L Nimmagadda, S Sudini, K Brimacombe, KR Gajghate, S Ma, JF Wang, A Xu, X Shahane, SA Xia, MG Woo, JY Mensah, GA Wang, ZB Ferrer, M Gabrielson, E Li, ZY Rastinejad, F Shen, M Boxer, MB Biswal, S AF Singh, Anju Venkannagari, Sreedhar Oh, Kyu H. Zhang, Ya-Qin Rohde, Jason M. Liu, Li Nimmagadda, Sridhar Sudini, Kuladeep Brimacombe, Kyle R. Gajghate, Sachin Ma, Jinfang Wang, Amy Xu, Xin Shahane, Sampada A. Xia, Menghang Woo, Juhyung Mensah, Geore A. Wang, Zhibin Ferrer, Marc Gabrielson, Edward Li, Zhuyin Rastinejad, Fraydoon Shen, Min Boxer, Matthew B. Biswal, Shyam TI Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors SO ACS CHEMICAL BIOLOGY LA English DT Article ID CELL LUNG-CANCER; TRANSCRIPTION FACTOR NRF2; EXPRESSION; CHEMORESISTANCE; CHEMOTHERAPY; ACTIVATION; GROWTH; RADIORESISTANCE; TUMORIGENESIS; ASSOCIATION AB Loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1), or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2), are common in non-small cell lung cancer (NSCLC) and associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of 400 000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to Nehl, the Cap 'N' Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homologue G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs, doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells, as compared to single agents. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation, leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant antitumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC. C1 [Singh, Anju; Venkannagari, Sreedhar; Oh, Kyu H.; Sudini, Kuladeep; Gajghate, Sachin; Ma, Jinfang; Wang, Zhibin; Biswal, Shyam] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Zhang, Ya-Qin; Rohde, Jason M.; Liu, Li; Brimacombe, Kyle R.; Wang, Amy; Xu, Xin; Shahane, Sampada A.; Xia, Menghang; Ferrer, Marc; Li, Zhuyin; Shen, Min; Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Nimmagadda, Sridhar] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Nimmagadda, Sridhar; Woo, Juhyung; Gabrielson, Edward; Biswal, Shyam] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Mensah, Geore A.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Worcester, MA 01608 USA. [Rastinejad, Fraydoon] Sanford Burnham Med Res Inst, Metab Signaling & Dis Program, Orlando, FL 32827 USA. RP Singh, A; Biswal, S (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.; Biswal, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. EM asingh12@jhu.edu; sbiswal@jhu.edu FU National Institutes of Health (NIH) [R03 MH092170, R01 CA140492, R01 CA206155]; Johns Hopkins Institute for Clinical and Translational Research (ICTR) [UL1 TR 001079]; National Cancer Institute SPORE grants [P50 CA058184]; Flight Attendant Medical Research Institute; National Center for Advancing Translational Sciences and the Molecular Libraries Initiative of the NIH Roadmap for Medical Research [U54MH084681] FX This work was supported by National Institutes of Health (NIH) grants R03 MH092170 and R01 CA140492 (S.B.), R01 CA206155 (S.B.), Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079, National Cancer Institute SPORE grants P50 CA058184 (S.B.), and Flight Attendant Medical Research Institute (A.S.). We thank Dr. Kensler for providing the NRF2-promoter construct, Chris McNees for help with immunoblotting experiments, and Ellen Tully for performing immunohistochemistry experiments. We thank S. Michael and R. Jones for automation support; P. Shinn, M. Itkin, and D. Van Leer for assistance with compound management; and W. Leister, H. Baker, C. LeClair, and E. Fernandez for analytical chemistry and compound purification support. Y-Q.Z., J.M.R, L.L., K.R.B., A.W., X.X., SAS., M.X., M.F., Z.L., M.S., and M.B.B. were supported by the intramural research program of the National Center for Advancing Translational Sciences and the Molecular Libraries Initiative of the NIH Roadmap for Medical Research (U54MH084681). NR 36 TC 0 Z9 0 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD NOV PY 2016 VL 11 IS 11 BP 3214 EP 3225 DI 10.1021/acschembio.6b00651 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EC8YX UT WOS:000388430100030 PM 27552339 ER PT J AU Cuthbert, B AF Cuthbert, B. TI Klein critique SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Letter C1 [Cuthbert, B.] NIMH, Bethesda, MD 20892 USA. RP Cuthbert, B (reprint author), NIMH, Bethesda, MD 20892 USA. EM bcuthber@mail.nih.gov NR 3 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD NOV PY 2016 VL 134 IS 5 BP 454 EP 455 DI 10.1111/acps.12636 PG 3 WC Psychiatry SC Psychiatry GA EC1GB UT WOS:000387851800011 PM 27604587 ER PT J AU Boutin, RD Kaptuch, JM Bateni, CP Chalfant, JS Yao, L AF Boutin, Robert D. Kaptuch, Justin M. Bateni, Cyrus P. Chalfant, James S. Yao, Lawrence TI Influence of IV Contrast Administration on CT Measures of Muscle and Bone Attenuation: Implications for Sarcopenia and Osteoporosis Evaluation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast media; CT; osteoporosis; sarcopenia; skeletal muscle ID COMPUTED-TOMOGRAPHY SCANS; FATTY LIVER-DISEASE; SKELETAL-MUSCLE; PROGNOSTIC-FACTOR; OBESITY; AGE; CARCINOMA; OUTCOMES; COLONOGRAPHY; MORTALITY AB OBJECTIVE. The objective of our study was to characterize enhancement of muscle and bone that occurs on standardized four-phase contrast-enhanced CT. MATERIALS AND METHODS. Two musculoskeletal radiologists reviewed standardized four-phase abdominal CT scans obtained with IV contrast material. The psoas area was measured, and the mean attenuation (in Hounsfield units) was recorded for the aorta, psoas muscles, posterior paraspinal muscles, and L4 vertebral body. CT attenuation measures were compared between anatomic regions and imaging phases with the paired t test; associations between measures were examined with the Pearson correlation coefficient (R). RESULTS. The study included 201 patients (97 men, 104 women; mean age, 57.7 +/- 12.5 [SD] years). Subject age was inversely correlated with unenhanced attenuation in the psoas muscles, posterior paraspinal muscles, and L4 (p < 0.001). The psoas muscles, posterior paraspinal muscles, and L4 enhanced significantly (p < 0.001) at all three contrast-enhanced phases. The greatest muscle enhancement was observed on delayed phase scans, whereas the greatest enhancement in L4 was seen on portal phase imaging. The unenhanced attenuation of the psoas muscles was significantly and negatively correlated with enhancement of the psoas muscles at the portal and delayed phases (p < 0.05 and p < 0.01, respectively), but these correlations were not seen for the posterior paraspinal muscles. Age was positively correlated with posterior paraspinal muscle enhancement at the portal and delayed phases in men (p < 0.05 and p < 0.01, respectively) but not in women. CONCLUSION. Contrast enhancement of commonly measured muscle and bone regions is routinely observed and should be considered when using CT attenuation values as biomarkers of sarcopenia and osteoporosis. Furthermore, CT enhancement may be significantly influenced by age, sex, and unenhanced tissue attenuation. C1 [Boutin, Robert D.; Kaptuch, Justin M.; Bateni, Cyrus P.; Chalfant, James S.] Univ Calif Davis, Sch Med, Dept Radiol, 4860 Y St,Ste 3100, Sacramento, CA 95817 USA. [Yao, Lawrence] NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. RP Boutin, RD (reprint author), Univ Calif Davis, Sch Med, Dept Radiol, 4860 Y St,Ste 3100, Sacramento, CA 95817 USA. EM rdboutin@ucdavis.edu NR 47 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2016 VL 207 IS 5 BP 1046 EP 1054 DI 10.2214/AJR.16.16387 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EB3TN UT WOS:000387289200028 PM 27556335 ER PT J AU Naran, K Moosa, A Barry, CE Boshoff, HIM Mizrahi, V Warner, DF AF Naran, Krupa Moosa, Atica Barry, Clifton E., III Boshoff, Helena I. M. Mizrahi, Valerie Warner, Digby F. TI Bioluminescent Reporters for Rapid Mechanism of Action Assessment in Tuberculosis Drug Discovery SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; LEAD OPTIMIZATION; IN-VITRO; IDENTIFICATION; INHIBITORS; ASSAY; MACROPHAGES; RESPIRATION; METABOLISM; RESISTANCE AB The tuberculosis (TB) drug discovery pipeline is fueled by compounds identified in whole-cell screens against the causative agent, Mycobacterium tuberculosis. Phenotypic screening enables the selection of molecules that inhibit essential cellular functions in live, intact bacilli grown under a chosen in vitro condition. However, deducing the mechanism of action (MOA), which is important to avoid promiscuous targets, often requires significant biological resources in a lengthy process that risks decoupling medicinal chemistry and biology efforts. Therefore, there is a need to develop methods enabling rapid MOA assessment of putative "actives" for triage decisions. Here, we describe a modified version of a bioluminescence reporter assay that allows non-destructive detection of compounds targeting either of two macromolecular processes in M. tuberculosis: cell wall biosynthesis or maintenance of DNA integrity. Coupling the luxCDABE operon from Photorhabdus luminescens to mycobacterial promoters driving expression of the iniBAC operon (PiniB-LUX) or the DNA damage-inducible genes, recA (PrecA-LUX) or radA (PradALUX), provided quantitative detection in real time of compounds triggering expression of any of these promoters over an extended 10- to 12-day incubation. Testing against known anti-TB agents confirmed the specificity of each reporter in registering the MOA of the applied antibiotic in M. tuberculosis, independent of bactericidal or bacteriostatic activity. Moreover, profiles obtained for experimental compounds indicated the potential to infer complex MOAs in which multiple cellular processes are disrupted. These results demonstrate the utility of the reporters for early triage of compounds based on the provisional MOA and suggest their application to investigate polypharmacology in known and experimental anti-B agents. C1 [Naran, Krupa; Moosa, Atica; Mizrahi, Valerie; Warner, Digby F.] Univ Cape Town, DST NRF Ctr Excellence Biomed TB Res, MRC NHLS UCT Mol Mycobacteriol Res Unit, Dept Pathol, Cape Town, South Africa. [Barry, Clifton E., III; Boshoff, Helena I. M.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD USA. [Barry, Clifton E., III; Mizrahi, Valerie; Warner, Digby F.] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa. RP Warner, DF (reprint author), Univ Cape Town, DST NRF Ctr Excellence Biomed TB Res, MRC NHLS UCT Mol Mycobacteriol Res Unit, Dept Pathol, Cape Town, South Africa.; Warner, DF (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa. EM digby.warner@uct.ac.za FU HHS \ National Institutes of Health (NIH); Howard Hughes Medical Institute (HHMI); Foundation for the National Institutes of Health (FNIH); National Research Foundation (NRF); South African Medical Research Council (SAMRC) FX This work, including the efforts of Clifton E. Barry III, was funded by HHS vertical bar National Institutes of Health (NIH). This work, including the efforts of Valerie Mizrahi, was funded by Howard Hughes Medical Institute (HHMI). This work, including the efforts of Clifton E. Barry III and Valerie Mizrahi, was funded by Foundation for the National Institutes of Health (FNIH). This work, including the efforts of Valerie Mizrahi and Digby F. Warner, was funded by National Research Foundation (NRF). This work, including the efforts of Valerie Mizrahi and Digby F. Warner, was funded by South African Medical Research Council (SAMRC). NR 53 TC 0 Z9 0 U1 5 U2 5 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 NOV PY 2016 VL 60 IS 11 BP 6748 EP 6757 DI 10.1128/AAC.01178-16 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ED7QH UT WOS:000389063500035 PM 27572410 ER PT J AU Snesrud, E He, S Chandler, M Dekker, JP Hickman, AB McGann, P Dyda, F AF Snesrud, Erik He, Susu Chandler, Michael Dekker, John P. Hickman, Alison B. McGann, Patrick Dyda, Fred TI A Model for Transposition of the Colistin Resistance Gene mcr-1 by ISApl1 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; ELEMENT AB Analysis of mcr-1-containing sequences identified a common similar to 2,607-bp DNA segment that in many cases is flanked on one or both ends by ISApl1. We present evidence that mcr-1 is mobilized by an ISApl1 composite transposon which has, in some cases, subsequently lost one or both copies of ISApl1. We also show that mcr-1 can be mobilized in some circumstances by a single upstream copy of ISApl1 in conjunction with the remnants of a downstream ISApl1. C1 [Snesrud, Erik; McGann, Patrick] Walter Reed Army Inst Res, Multidrug Resistant Organism Repository & Surveil, Silver Spring, MD USA. [He, Susu; Hickman, Alison B.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD USA. [Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, Toulouse, France. [Dekker, John P.] NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bldg 10, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD USA. EM dyda@helix.nih.gov FU HHS \ NIH \ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases; NIH Clinical Center; U. S. Army Medical Command; Global Emerging Infections Surveillance and Response System; Defense Medical Research and Development Program FX This work, including the efforts of Alison B. Hickman, was funded by HHS vertical bar NIH vertical bar National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).; This work was partially supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (S. H., A. B. H., and F. D.), the NIH Clinical Center (J. P. D.), and the U. S. Army Medical Command, the Global Emerging Infections Surveillance and Response System, and the Defense Medical Research and Development Program (P. M. and E. S.). NR 14 TC 2 Z9 2 U1 7 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 NOV PY 2016 VL 60 IS 11 BP 6973 EP 6976 DI 10.1128/AAC.01457-16 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ED7QH UT WOS:000389063500074 PM 27620479 ER PT J AU Margalit, E Biederman, I Herald, SB Yue, XM von der Malsburg, C AF Margalit, Eshed Biederman, Irving Herald, Sarah B. Yue, Xiaomin von der Malsburg, Christoph TI An applet for the Gabor similarity scaling of the differences between complex stimuli SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE 2-D shape and form; Similarity; Face perception ID OBJECT RECOGNITION; SPATIAL STRUCTURE; RECEPTIVE-FIELDS; FACE RECOGNITION; NATURAL IMAGES; CORTEX; SENSITIVITY; SHAPES AB It is widely accepted that after the first cortical visual area, V1, a series of stages achieves a representation of complex shapes, such as faces and objects, so that they can be understood and recognized. A major challenge for the study of complex shape perception has been the lack of a principled basis for scaling of the physical differences between stimuli so that their similarity can be specified, unconfounded by early-stage differences. Without the specification of such similarities, it is difficult to make sound inferences about the contributions of later stages to neural activity or psychophysical performance. A Web-based app is described that is based on the Malsburg Gabor-jet model (Lades et al., 1993), which allows easy specification of the V1 similarity of pairs of stimuli, no matter how intricate. The model predicts the psycho physical discriminability of metrically varying faces and complex blobs almost perfectly (Yue, Biederman, Mangini, von der Malsburg, & Amir, 2012), and serves as the input stage of a large family of contemporary neurocomputational models of vision. C1 [Margalit, Eshed; Biederman, Irving] Univ Southern Calif, Neurosci Program, Los Angeles, CA USA. [Biederman, Irving] Univ Southern Calif, Dept Psychol, Los Angeles, CA USA. [Herald, Sarah B.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. [Yue, Xiaomin] Natl Inst Mental Hlth, Lab Brain & Cognit, Bethesda, MD USA. [von der Malsburg, Christoph] Frankfurt Inst Adv Studies, Frankfurt, Germany. RP Biederman, I (reprint author), Univ Southern Calif, Neurosci Program, Los Angeles, CA USA.; Biederman, I (reprint author), Univ Southern Calif, Dept Psychol, Los Angeles, CA USA. EM bieder@usc.edu FU NSF [BCS 0617699]; Dornsife Research Fund FX This research was supported by NSF Grant No. BCS 0617699 and by the Dornsife Research Fund. Our 2-D FFT code utilizes a 1-D FFT implementation by Nayuki, which can be found at https://www.nayuki.io/page/free-small-fft-in-multiple-languages. Our code for resizing images, along with a fix for iPhone camera images, uses an image-rendering library by Shinichi Tomita, https://github.com/stomita/ios-imagefile-megapixel. Line charts were created with Chart.js, www.chartjs.org/. NR 25 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 EI 1943-393X J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD NOV PY 2016 VL 78 IS 8 BP 2298 EP 2306 DI 10.3758/s13414-016-1191-7 PG 9 WC Psychology; Psychology, Experimental SC Psychology GA EC0WW UT WOS:000387823300003 PM 27557818 ER PT J AU Ding, R Zhang, T Xie, JS Williams, J Ye, YH Chen, LQ AF Ding, Rui Zhang, Ting Xie, Jiashu Williams, Jessica Ye, Yihong Chen, Liqiang TI Eeyarestatin I derivatives with improved aqueous solubility SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE p97; Valosin-containing protein; VCP; Eeyarestatin I; EerI; Solubility ID AAA ATPASE P97; ENDOPLASMIC-RETICULUM; CHAPERONE P97; ER STRESS; INHIBITORS; CANCER; MECHANISM; DISCOVERY; PROTEINS; VALOSINE AB Inhibition of p97 (also known as valosin-containing protein (VCP)), has been validated as a promising strategy for cancer therapy. Eeyarestatin I (EerI) blocks p97 through a novel mechanism of action and has favorable anti-cancer activities against cultured cancer cells. However, its poor aqueous solubility severely limits its in vivo applications. To circumvent this problem, we have identified EerI derivatives that possess improved aqueous solubility by introducing a single solubilizing group. These modified compounds preserved endoplasmic reticulum (ER) stress-inducing and antiproliferative activities as well as generally good in vitro metabolic properties, suggesting that these Eerl derivatives could serve as candidates for further optimization. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Ding, Rui; Xie, Jiashu; Williams, Jessica; Chen, Liqiang] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. [Zhang, Ting; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, LQ (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. EM chenx462@umn.edu FU Center for Drug Design in the Academic Health Center of the University of Minnesota FX This work was supported by the Center for Drug Design in the Academic Health Center of the University of Minnesota (to L. C.). NR 30 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2016 VL 26 IS 21 BP 5177 EP 5181 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA ED7DG UT WOS:000389015300007 PM 27729187 ER PT J AU Alonzo, A Aaronson, S Bikson, M Husain, M Lisanby, S Martin, D McClintock, SM McDonald, WM O'Reardon, J Esmailpoor, Z Loo, C AF Alonzo, Angelo Aaronson, Scott Bikson, Marom Husain, Mustafa Lisanby, Sarah Martin, Donel McClintock, Shawn M. McDonald, William M. O'Reardon, John Esmailpoor, Zeinab Loo, Colleen TI Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression SO Contemporary Clinical Trials LA English DT Article DE Transcranial direct current stimulation; Depression; Bipolar; Neurostimulation ID SHAM-CONTROLLED TRIAL; ELECTROCONVULSIVE-THERAPY; MAJOR DEPRESSION; DOUBLE-BLIND; TDCS; HEALTHY; PHARMACOTHERAPY; METAANALYSIS; GUIDELINES; DISORDER AB Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5 mA, 20 sessions of 30 min duration over 4 weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. (C) 2016 Elsevier Inc. All rights reserved. C1 [Alonzo, Angelo; Martin, Donel; Loo, Colleen] Univ New South Wales, Sch Psychiat, Black Dog Inst, Sydney, NSW, Australia. [Aaronson, Scott] Sheppard Pratt Hlth Syst, Clin Res Programs, Baltimore, MD USA. [Bikson, Marom; Esmailpoor, Zeinab] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA. [Husain, Mustafa; McClintock, Shawn M.] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Husain, Mustafa; Lisanby, Sarah; McClintock, Shawn M.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Lisanby, Sarah] NIMH, Div Translat Res, NIH, Bethesda, MD 20892 USA. [Lisanby, Sarah] NIMH, Noninvas Neuromodulat Unit, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [McDonald, William M.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [O'Reardon, John] Rowan Univ, Sch Osteopath Med, Cherry Hill, NJ USA. RP Alonzo, A (reprint author), UNSW Black Dog Inst, Sch Psychiat, Hosp Rd, Randwick, NSW 2031, Australia. EM a.alonzo@unsw.edu.au FU Stanley Medical Research Institute [11T-005] FX This work was supported by the Stanley Medical Research Institute (grant number: 11T-005). NR 59 TC 0 Z9 0 U1 8 U2 8 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 NOV PY 2016 VL 51 BP 65 EP 71 DI 10.1016/j.cct.2016.10.002 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ED9BW UT WOS:000389166100009 PM 27756567 ER PT J AU Wu, LT McNeely, J Subramaniam, GA Sharma, G Van Veldhuisen, P Schwartz, RP AF Wu, Li-Tzy McNeely, Jennifer Subramaniam, Geetha A. Sharma, Gaurav Van Veldhuisen, Paul Schwartz, Robert P. TI Design of the NIDA clinical trials network validation study of tobacco, alcohol, prescription medications, and substance use/misuse (TAPS) tool (vol 19, pg 90, 2016) SO Contemporary Clinical Trials LA English DT Correction C1 [Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3903, Durham, NC 27708 USA. [Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Wu, Li-Tzy] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Wu, Li-Tzy] Duke Univ, Ctr Child & Family Policy, Durham, NC USA. [McNeely, Jennifer] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Subramaniam, Geetha A.] Natl Inst Drug Abuse, Bethesda, MD USA. [Sharma, Gaurav; Van Veldhuisen, Paul] EMMES Corp, Rockville, MD USA. [Schwartz, Robert P.] Friends Res Inst Inc, Baltimore, MD USA. RP Wu, LT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3903, Durham, NC 27708 USA. EM Litzy.wu@duke.edu FU NIDA NIH HHS [R01 DA019623, UG1 DA040317]; NIMHD NIH HHS [R01 MD007658] NR 1 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 NOV PY 2016 VL 51 BP 98 EP 98 DI 10.1016/j.cct.2016.09.001 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ED9BW UT WOS:000389166100015 PM 27665683 ER PT J AU Dunay, GA Toth, I Eberhard, JM Degen, O Tolosa, E van Lunzen, J Hauber, J zur Wiesch, JS AF Dunay, Gabor A. Toth, Ilona Eberhard, Johanna M. Degen, Olaf Tolosa, Eva van Lunzen, Jan Hauber, Joachim zur Wiesch, Julian Schulze TI Parallel Assessment of Th17 Cell Frequencies by Surface Marker Co-Expression Versus Ex Vivo IL-17 Production in HIV-1 Infection SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE Th17; CCR6; CD161; HIV; CXCR3; CCR4; CD4; flow cytometry; IL17 ID REGULATORY T-CELLS; MEMORY CELLS; PHENOTYPE; DISTINCT; LINEAGE; INTERLEUKIN-17; EXPRESSION; DEPLETION; FEATURES; TISSUE AB Introduction: Th17 cells can either be identified by co-staining of surface markers or by intracellular cytokine staining (ICS) for IL-17 production. Discrepancies regarding the published frequencies of Th17 cells in peripheral blood mononuclear cells (PBMC) of HIV patients may partly be due to the different methodologies used. Methods: Cryopreserved PBMC from healthy controls and HIV-infected subjects, including treated (cART) and viremic patients, were split and analyzed side-by-side by flow cytometry for expression of surface markers CCR6, CXCR3, CCR4, and CD161, or for intracellular expression of IL-17A and IFN gamma after stimulation. Results: The characterization of Th17 cells as CXCR3-CCR6+CCR4+CD161+ yielded considerably higher frequencies than the corresponding frequencies obtained by characterization via cytokines (IL-17+IFN gamma-), regardless of the HIV status. However, the overall frequencies delivered by the two methods significantly correlated. The relative frequency of Th17 cells within the CD4+ T cell compartment was preserved in HIV infection but there was a significant decrease in the absolute Th17 number, which was restored after initiation of cART, paralleling CD4+ T cell recovery. Absolute Th17 numbers inversely correlated with HIV viral load. Conclusion: The definition of Th17 cells by surface markers might overestimate their frequency in comparison to functional assessment of IL-17 production by ICS, regardless of the HIV infection status. However, both methods yield proportionate results with reduced absolute numbers of Th17 cells in untreated HIV disease, reflecting the depletion of total CD4+ T cells in viremic HIV patients, and restoration with cART. (C) 2016 International Clinical Cytometry Society C1 [Dunay, Gabor A.; Eberhard, Johanna M.; van Lunzen, Jan; Hauber, Joachim; zur Wiesch, Julian Schulze] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany. [Toth, Ilona; Eberhard, Johanna M.; zur Wiesch, Julian Schulze] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Martinistr 52, D-20246 Hamburg, Germany. [Tolosa, Eva] Univ Med Ctr Hamburg Eppendorf, Dept Immunol, Hamburg, Germany. [Degen, Olaf; van Lunzen, Jan] Univ Med Ctr Hamburg Eppendorf, Hlth Care Ctr, Hamburg, Germany. [Dunay, Gabor A.; Degen, Olaf; van Lunzen, Jan; Hauber, Joachim; zur Wiesch, Julian Schulze] DZIF Partner Site German Ctr Infect Res, Hamburg, Germany. [Toth, Ilona] NIAID, NIH, Vaccine Res Ctr, Human Immunol Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP zur Wiesch, JS (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Martinistr 52, D-20246 Hamburg, Germany. EM julianszw@gmail.com FU German Research Agency [SFB841]; DZIF FX Grant sponsor: German Research Agency; Grant number: SFB841 project A6.; Grant sponsor: DZIF. NR 32 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2016 VL 90 IS 6 BP 486 EP 492 DI 10.1002/cyto.b.21352 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA ED8PR UT WOS:000389133900003 PM 26666875 ER PT J AU Lombo, TB Ganguly, A Tagle, DA AF Lombo, Tania B. Ganguly, Aniruddha Tagle, Danilo A. TI Diagnostic potential of extracellular RNA from biofluids SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE Biomarkers; extracellular RNA; liquid biopsy; cancer biomarkers; ExRNA Communication Program ID COMMUNICATION CONSORTIUM; CIRCULATING MICRORNAS; PROSTATE-CANCER; NONCODING RNAS; DISEASE; CHALLENGES; BIOMARKERS; MARKERS; BIOPSY; PLASMA C1 [Lombo, Tania B.; Tagle, Danilo A.] NIH, Off Director, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Ganguly, Aniruddha] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Tagle, DA (reprint author), NIH, Off Director, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. EM Danilo.Tagle@nih.gov NR 20 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7159 EI 1744-8352 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD NOV PY 2016 VL 16 IS 11 BP 1135 EP 1138 DI 10.1080/14737159.2016.1241146 PG 4 WC Pathology SC Pathology GA ED5ZA UT WOS:000388931600001 PM 27682891 ER PT J AU Teixeira, AL Salem, H Frey, BN Barbosa, IG Machado-Vieira, R AF Teixeira, Antonio L. Salem, Haitham Frey, Benicio N. Barbosa, Izabela G. Machado-Vieira, Rodrigo TI Update on bipolar disorder biomarker candidates SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE Bipolar disorder; biomarkers; neuroimaging; peripheral markers; genomic analysis ID MAJOR DEPRESSIVE DISORDER; C-REACTIVE PROTEIN; MAGNETIC-RESONANCE-SPECTROSCOPY; GENOME-WIDE ASSOCIATION; WORKING-MEMORY TASK; NEUROTROPHIC FACTOR; PROPHYLACTIC LITHIUM; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; TELOMERE LENGTH AB Introduction: Bipolar disorder is a chronic and disabling mood disorder with a complex pathophysiological basis. A significant percentage of patients do not receive correct diagnosis which directly influences therapeutic response, rendering recovery troublesome. There is a long-standing need for proper non-clinically based tools for diagnosis, treatment selection and follow-up of such patients.Areas covered: In the past decade, the scientific community has shown a great interest in biomarker development. Here, we highlight the different potential biomarkers and we discuss their feasibility and their possible clinical relevance.Expert commentary: To date, despite the major ongoing trials and consortia with promising future perspectives, no reliable biomarker of bipolar disorder has been fully defined. C1 [Teixeira, Antonio L.; Salem, Haitham] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Frey, Benicio N.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Frey, Benicio N.] St Josephs Healthcare Hamilton, Mood Disorders Program, Hamilton, ON, Canada. [Frey, Benicio N.] St Josephs Healthcare Hamilton, Womens Hlth Concerns Clin, Hamilton, ON, Canada. [Barbosa, Izabela G.] Univ Fed Minas Gerais, Sch Med, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil. [Machado-Vieira, Rodrigo] NIH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA. RP Teixeira, AL (reprint author), Dept Psychiat & Behav Sci, Room BBS 3140,1941 East Rd, Houston, TX 77054 USA. EM Antonio.L.Teixeira@uth.tmc.edu FU Alternative Funding Plan Innovations Award; Brain and Behavior Research Foundation; Canadian Institutes of Health Research; Hamilton Health Sciences Foundation; J.P. Bickell Foundation; Ontario Brain Institute; Ontario Mental Health Foundation; Society for Women's Health Research; Teresa Cascioli Charitable Foundation; Eli Lilly; Pfizer; AstraZeneca; Bristol-Myers Squibb; Canadian Psychiatric Association; CANMAT; Daiichi Sankyo; Lundbeck; Servier; Sunovion; Department of Psychiatry and Behavioral Sciences, UT Health Houston FX B.N. Frey has received grant/research support from Alternative Funding Plan Innovations Award, Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Hamilton Health Sciences Foundation, J.P. Bickell Foundation, Ontario Brain Institute, Ontario Mental Health Foundation, Society for Women's Health Research, Teresa Cascioli Charitable Foundation, Eli Lilly and Pfizer, and has received consultant and/or speaker fees from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, CANMAT, Daiichi Sankyo, Lundbeck, Pfizer, Servier and Sunovion. A.L. Teixeira has received grant/research support from Brazilian Funding Agencies and the Department of Psychiatry and Behavioral Sciences, UT Health Houston. 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 135 TC 2 Z9 2 U1 4 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7159 EI 1744-8352 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD NOV PY 2016 VL 16 IS 11 BP 1209 EP 1220 DI 10.1080/14737159.2016.1248413 PG 12 WC Pathology SC Pathology GA ED5ZA UT WOS:000388931600010 PM 27737600 ER PT J AU Gilliland, WD May, DP Colwell, EM Kennison, JA AF Gilliland, William D. May, Dennis P. Colwell, Eileen M. Kennison, James A. TI A Simplified Strategy for Introducing Genetic Variants into Drosophila Compound Autosome Stocks SO G3-GENES GENOMES GENETICS LA English DT Article DE aneuploidy; C(2)EN; long chromosome; meiosis; segregation ID FEMALE MEIOSIS I; METAPHASE ARREST; MELANOGASTER; OOCYTES AB Drosophila stocks bearing compound chromosomes, single molecules of DNA that carry the genomic complement of two chromosomes, are useful tools for studying meiosis and mitosis. However, these stocks cannot easily be crossed to stocks with regular chromosomes, due to the lethality of the resulting whole-chromosome aneuploidy. This prevents the examination of interesting genetic variants in a compound chromosome background. Methods to circumvent this difficulty have included the use of triploid females or nondisjunction (caused by either cold-induced microtubule depolymerization or meiotic mutants). Here, we present a new approach for crossing compound chromosomes that takes advantage of the nonhomologous segregations that result when multiple chromosomes in the same genome are prevented from meiotic crossing over by heterozygosity for balancer chromosomes. This approach gives higher yields of the desired progeny in fewer generations of crossing. Using this technique, we have created and validated stocks carrying both a compound-X and compound-2, as well as compound-2 stocks carrying the meiotic mutant nod. C1 [Gilliland, William D.; May, Dennis P.; Colwell, Eileen M.] Depaul Univ, Dept Biol Sci, Chicago, IL 60626 USA. [Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD 20892 USA. RP Gilliland, WD (reprint author), Depaul Univ, Dept Biol Sci, 2325 N Clifton Ave, Chicago, IL 60614 USA. EM wgillila@depaul.edu FU National Institutes of Health (National Institute of General Medical Science) [1R15GM099054-01]; DePaul College of Science and Health; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX This work was supported by the National Institutes of Health (National Institute of General Medical Science award 1R15GM099054-01 to W.D.G.), the DePaul College of Science and Health, and the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. NR 23 TC 0 Z9 0 U1 1 U2 1 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD NOV PY 2016 VL 6 IS 11 BP 3749 EP 3755 DI 10.1534/g3.116.035634 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ED2LY UT WOS:000388678000031 ER PT J AU Ikawa, Y Uchiyama, T Jagadeesh, GJ Candotti, F AF Ikawa, Y. Uchiyama, T. Jagadeesh, G. J. Candotti, F. TI The long terminal repeat negative control region is a critical element for insertional oncogenesis after gene transfer into hematopoietic progenitors with Moloney murine leukemia viral vectors SO GENE THERAPY LA English DT Article ID FOAMY VIRUS; TRANSGENE EXPRESSION; MOUSE MODEL; CELLS; THERAPY; IMMORTALIZATION; DISEASE AB Integrating vectors based on gamma-retroviruses and containing full-length long terminal repeats (LTRs) have been associated with activation of oncogene expression and leukemogenesis in human gene therapy trials. Identification of the specific molecular elements of the LTRs that have a role in insertional oncogenesis events is important as it can lead to the development of safer gene transfer vectors. The negative control region (NCR) of the LTR is a particularly well-conserved sequence among mammalian gamma-retroviruses with demonstrated regulatory activity of gene transcription in hematopoietic cells, which led us to hypothesize that this region may have a role in insertional oncogenesis after gamma-retroviral vector (GV)-mediated gene transfer into hematopoietic progenitors. We used an in vitro assay of murine bone marrow cell immortalization to compare the immortalization capabilities of a series of GVs carrying murine leukemia virus (MLV) LTR deletion mutants. Compared with GV carrying the full-length MLV LTR, deletion of the complete LTR enhancer sequence showed significant reduction of immortalization rates. However, the use of a mutant LTR deleted of the enhancer sequence, with exception of the NCR, did not affect immortalization. Importantly, the inclusion of an LTR mutant devoid only of the NCR did show significant reduction of immortalization rates compared with the full LTR sequence. Therefore, our data point to the NCR as a key element for immortalization and justify additional studies to evaluate its specific role in MLV-mediated insertional oncogenesis. C1 [Ikawa, Y.; Uchiyama, T.; Jagadeesh, G. J.; Candotti, F.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Ikawa, Y.] Kanazawa Univ Hosp, Dept Pediat, Kanazawa, Ishikawa, Japan. [Uchiyama, T.] Natl Res Inst Child Hlth & Dev, Dept Human Genet, Tokyo, Japan. [Candotti, F.] Univ Lausanne Hosp, Div Immunol & Allergy, Rue Bugnon 46,BH10-527, CH-1011 Lausanne, Switzerland. RP Candotti, F (reprint author), Univ Lausanne Hosp, Div Immunol & Allergy, Rue Bugnon 46,BH10-527, CH-1011 Lausanne, Switzerland. EM Fabio.Candotti@chuv.ch FU NHGRI intramural program; UNIL-CHUV research grant FX We thank Drs Adrian J Thrasher (University College London, London, UK) and David W Russell (University of Washington, Seattle, WA, USA) for sharing reagents, and the NIH Building 49 Animal Care Staff for excellent and humane care of laboratory animals. This research was supported by funding from the NHGRI intramural program and by a UNIL-CHUV research grant (to FC). NR 21 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD NOV PY 2016 VL 23 IS 11 BP 815 EP 818 DI 10.1038/gt.2016.51 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ED4IJ UT WOS:000388811000006 PM 27487944 ER PT J AU Bastide, H Lange, JD Lack, JB Yassin, A Pool, JE AF Bastide, Heloise Lange, Jeremy D. Lack, Justin B. Yassin, Amir Pool, John E. TI A Variable Genetic Architecture of Melanic Evolution in Drosophila melanogaster SO GENETICS LA English DT Article DE Drosophila melanogaster; pigmentation; parallel evolution; bulk segregant analysis; standing genetic variation; adaptation ID THORACIC TRIDENT PIGMENTATION; DNA-SEQUENCING DATA; ABDOMINAL PIGMENTATION; INDIAN POPULATIONS; LOCAL ADAPTATION; CLINAL VARIATION; EVO-DEVO; PATTERNS; DIFFERENTIATION; EBONY AB Unraveling the genetic architecture of adaptive phenotypic divergence is a fundamental quest in evolutionary biology. In Drosophila melanogaster, high-altitude melanism has evolved in separate mountain ranges in sub-Saharan Africa, potentially as an adaptation to UV intensity. We investigated the genetic basis of this melanism in three populations using a new bulk segregant analysis mapping method. We identified 19 distinct QTL regions from nine mapping crosses, with several QTL peaks overlapping between two or all populations, and yet different crosses involving the same melanic population commonly yielded distinct QTL. The strongest QTL often overlapped well-known pigmentation genes, but we typically did not find wide signals of genetic differentiation (F-ST) between lightly and darkly pigmented populations at these genes. Instead, we found small numbers of highly differentiated SNPs at the probable causative genes. A simulation analysis showed that these patterns of polymorphism were consistent with selection on standing genetic variation. Overall, our results suggest that, even for potentially simpler traits like pigmentation, the complexity of adaptive trait evolution poses important challenges for QTL mapping and population genetic analysis. C1 [Bastide, Heloise; Lange, Jeremy D.; Lack, Justin B.; Yassin, Amir; Pool, John E.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Lack, Justin B.] NIH, NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pool, JE (reprint author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. EM jpool@wisc.edu FU National Science Foundation [DEB-1049777]; National Institutes of Health [R01 GM-111797] FX We thank two anonymous reviewers for helping us to improve this manuscript. This work was funded by National Science Foundation grant DEB-1049777 and National Institutes of Health grant R01 GM-111797 to J.E.P. NR 69 TC 0 Z9 0 U1 18 U2 18 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD NOV PY 2016 VL 204 IS 3 BP 1307 EP + DI 10.1534/genetics.116.192492 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA EC9ZN UT WOS:000388502900037 PM 27638419 ER PT J AU Pinsky, PF Yu, K Kramer, BS Black, A Buys, SS Partridge, E Gohagan, J Berg, CD Prorok, PC AF Pinsky, Paul F. Yu, Kelly Kramer, Barnett S. Black, Amanda Buys, Saundra S. Partridge, Edward Gohagan, John Berg, Christine D. Prorok, Philip C. TI Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up SO GYNECOLOGIC ONCOLOGY LA English DT Article AB Background. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial originally reported no mortality benefit of ovarian cancer screening after a median of 12.4 years of follow-up. The UKCTOCS screening trial failed to show a statistically significant mortality reduction in the primary analysis but reported an apparent increased mortality benefit in trial years 7-14 compared to 0-7. Here we report an updated analysis of PLCO with extended mortality follow-up. Methods. Participants were randomized from 1993 to 2001 at ten U.S. centers to an intervention or usual care arm. Intervention arm women were screened for ovarian cancer with annual trans-vaginal ultrasound (TVU) (4 years) and CA-125 (6 years), with a fixed cutoff at 35 U/mL for CA-125. The original follow-up period was for up to 13 years (median follow-up 12.4 years); in this analysis follow-up for mortality was extended by up to 6 years. Results. 39,105 (intervention) and 39,111 (usual care) women were randomized, of which 34,253 and 34,304, respectively, had at least one ovary at baseline. Median follow-up was 14.7 years in each arm and maximum follow-up 19.2 years in each arm. A total of 187 (intervention) and 176 (usual care) deaths from ovarian cancer were observed, for a risk-ratio of 1.06 (95% Cl: 0.87-1.30). Risk-ratios were similar for study years 0-7 (RR = 1.04), 7-14 (RR = 1.06) and 14+ (RR = 1.09). The risk ratio for all-cause mortality was 1.01 (95% CI: 0.97-1.05). Ovarian cancer specific survival was not significantly different across trial arms (p = 0.16). Conclusion. Extended follow-up of PLCO indicated no mortality benefit from screening for ovarian cancer with CA-125 and TVU. Published by Elsevier Inc. C1 [Pinsky, Paul F.; Kramer, Barnett S.; Prorok, Philip C.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Yu, Kelly; Black, Amanda; Berg, Christine D.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Buys, Saundra S.] Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. [Partridge, Edward] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Gohagan, John] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, 9609 Med Ctr Dr,Rm 5E108, Bethesda, MD 20892 USA. EM pp4f@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 13 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2016 VL 143 IS 2 BP 270 EP 275 DI 10.1016/j.ygyno.2016.08.334 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA EA6MS UT WOS:000386743900010 PM 27615399 ER PT J AU Collins, MT Stratakis, CA AF Collins, M. T. Stratakis, C. A. TI Bone Formation, Growth, and Repair SO HORMONE AND METABOLIC RESEARCH LA English DT Editorial Material ID STEM-CELLS; RATS; WOMEN C1 [Collins, M. T.] NIDCR, Sect Skeletal Dis & Mineral Homeostasis, NIH, 30 Convent Dr Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. [Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. RP Collins, MT (reprint author), NIDCR, Sect Skeletal Dis & Mineral Homeostasis, NIH, 30 Convent Dr Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov NR 20 TC 0 Z9 0 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 687 EP 688 DI 10.1055/s-0042-119907 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000001 PM 27871113 ER PT J AU Liu, S Shapiro, JM Saloustros, E Stratakis, CA AF Liu, S. Shapiro, J. M. Saloustros, E. Stratakis, C. A. TI Bone Abnormalities in Mice with Protein Kinase A (PKA) Defects Reveal a Role of Cyclic AMP Signaling in Bone Stromal Cell-Dependent Tumor Development SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE cyclic AMP; bone tumors; fibrous dysplasia; carney complex ID MESENCHYMAL STEM-CELLS; NODULAR ADRENOCORTICAL DISEASE; CATALYTIC SUBUNIT-BETA; FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; INHIBITS OSTEOGENIC DIFFERENTIATION; CAMP-SPECIFIC PHOSPHODIESTERASE; TO-EPITHELIAL TRANSITION; ALPHA REGULATORY SUBUNIT; CARNEY COMPLEX; FIBROUS DYSPLASIA AB Protein kinase A (PKA) is an important enzyme for all eukaryotic cells. PKA phosphorylates other proteins, thus, it is essential for the regulation of many diverse cellular functions, including cytoplasmic trafficking and signaling, organelle structure and mitochondrial oxidation, nuclear gene expression, the cell cycle, and cellular division. The PKA holoenzyme is composed of 2 regulatory and 2 catalytic subunits. Four regulatory (R1 alpha, R1 beta, R2 alpha, and R2 beta) and 4 catalytic subunits (C alpha, C beta, C gamma, and Prkx) have been identified, giving rise to mainly PKA-I (when the 2 regulatory subunits are either R1 alpha or R1 beta), or PKA-II (when the 2 regulatory subunits are either R2 alpha or R2 beta). Mutations in the PKA subunits can lead to altered total PKA activity or abnormal PKA-I to PKA-II ratio, leading to various abnormalities in both humans and mice. These effects can be tissue-specific. We studied the effect of PKA subunit defects on PKA activity and bone morphology of mice that were single or double heterozygous for null alleles of the various PKA subunit genes. Bone lesions including fibrous dysplasia, myxomas, osteo-sarcomas, -chondromas and -chondrosarcomas were found in these mice. Observational and molecular studies showed that these lesions were derived from bone stromal cells (BSCs). We conclude that haploinsufficiency for different PKA subunit genes affected bone lesion formation, new bone generation, organization, and mineralization in variable ways. This work identified a PKA subunit-and activity-dependent pathway of bone lesion formation from BSCs with important implications for understanding how cyclic AMP affects the skeleton and its tumorigenesis. C1 [Liu, S.; Shapiro, J. M.; Saloustros, E.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, NIH, Bethesda, MD USA. [Shapiro, J. M.] Univ Cambridge, Dept Engn, Cambridge, England. RP Stratakis, CA (reprint author), NICHD, SEGEN, NIH, Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU NICHD, NIH FX This work was supported by the Intramural Research Program, NICHD, NIH. NR 143 TC 1 Z9 1 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 714 EP 725 DI 10.1055/s-0042-117111 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000004 PM 27728928 ER PT J AU Shapiro, JM Oyen, ML AF Shapiro, J. M. Oyen, M. L. TI Engineering Approaches for Understanding Osteogenesis: Hydrogels as Synthetic Bone Microenvironments SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE biomaterials; tissue engineering; extracellular matrix ID MESENCHYMAL STEM-CELLS; IN-VITRO; EXTRACELLULAR-MATRIX; BIODEGRADABLE HYDROGEL; GROWTH-FACTOR; ALGINATE HYDROGELS; ADIPOSE-TISSUE; PEG HYDROGELS; DIFFERENTIATION; MARROW AB The microenvironment, which can be considered the sum of all the components and conditions surrounding a particular cell, is critical to moderating cellular behavior. In bone, interactions with the microenvironment can influence osteogenic differentiation, and subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs, can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic polymer networks, are popularly used for cell culture constructs due to their substantial water content and their ability to be tailored for specific applications. As synthetic microenvironments, a level of control can be exerted on the hydrogel structure and material properties, such that individual contributions from the scaffold on cellular behavior can be observed. Both bio-chemical and mechanical stimuli have been shown to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive ligands, include osteoinductive moieties, vary mechanical properties, and be subject to external mechanical stimulation, all of which have been shown to affect osteogenic differentiation. Following "bottom-up" fabrication methods, levels of complexity can be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic bone microenvironments to observe both individual and synergistic effects from biochemical and mechanical signals on osteogenic differentiation. Ultimately, a better understanding of how material properties can influence cellular behavior will better inform design of tissue engineering scaffolds, not just for studying cell behavior, but also for regenerative medicine purposes. C1 [Shapiro, J. M.; Oyen, M. L.] Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England. [Shapiro, J. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Oyen, ML (reprint author), Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England. EM mlo29@cam.ac.uk FU NICHD, NIH FX The work was funded in part by the Intramural Research Program, NICHD, NIH NR 108 TC 1 Z9 1 U1 4 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 726 EP 736 DI 10.1055/s-0042-100469 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000005 PM 27077459 ER PT J AU Nilsson, O Isoherranen, N Guo, MH Lui, JC Jee, YH Guttmann-Bauman, I Acerini, C Lee, W Allikmets, R Yanovski, JA Dauber, A Baron, J AF Nilsson, O. Isoherranen, N. Guo, M. H. Lui, J. C. Jee, Y. H. Guttmann-Bauman, I. Acerini, C. Lee, W. Allikmets, R. Yanovski, J. A. Dauber, A. Baron, J. TI Accelerated Skeletal Maturation in Disorders of Retinoic Acid Metabolism: A Case Report and Focused Review of the Literature SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE retinoic acid; bone age; growth plate; growth ID LONGITUDINAL BONE-GROWTH; DNA-SEQUENCING DATA; EPIPHYSEAL FUSION; NEUROBEHAVIORAL TERATOLOGY; PLATE CHONDROGENESIS; HEDGEHOG EXPRESSION; MATRIX-HOMEOSTASIS; LIMB DEVELOPMENT; BINDING-PROTEIN; INDIAN HEDGEHOG AB Nutritional excess of vitamin A, a precursor for retinoic acid (RA), causes premature epiphyseal fusion, craniosynostosis, and light-dependent retinopathy. Similarly, homozygous loss-of-function mutations in CYP26B1, one of the major RA-metabolizing enzymes, cause advanced bone age, premature epiphyseal fusion, and craniosynostosis. In this paper, a patient with markedly accelerated skeletal and dental development, retinal scarring, and autism-spectrum disease is presented and the role of retinoic acid in longitudinal bone growth and skeletal maturation is reviewed. Genetic studies were carried out using SNP array and exome sequencing. RA isomers were measured in the patient, family members, and in 18 age-matched healthy children using high-performance liquid chromatography coupled to tandem mass spectrometry. A genomic SNP array identified a novel 8.3 megabase microdeletion on chromosome 10q23.2-23.33. The 79 deleted genes included CYP26A1 and C1, both major RA-metabolizing enzymes. Exome sequencing did not detect any variants that were predicted to be deleterious in the remaining alleles of these genes or other known retinoic acid-metabolizing enzymes. The patient exhibited elevated plasma total RA (16.5 vs. 12.6 +/- 1.5 nM, mean +/- SD, subject vs. controls) and 13-cisRA (10.7 nM vs. 6.1 +/- 1.1). The findings support the hypothesis that elevated RA concentrations accelerate bone and dental maturation in humans. CYP26A1 and C1 haploinsufficiency may contribute to the elevated retinoic acid concentrations and clinical findings of the patient, although this phenotype has not been reported in other patients with similar deletions, suggesting that other unknown genetic or environmental factors may also contribute. Supporting Information for this article is available online at http://www.thieme-connect.de/products C1 [Nilsson, O.; Lui, J. C.; Jee, Y. H.; Yanovski, J. A.; Baron, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Nilsson, O.] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Nilsson, O.] Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Endocrinol Unit, Stockholm, Sweden. [Nilsson, O.] Karolinska Univ Hosp, Stockholm, Sweden. [Isoherranen, N.] Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA. [Guo, M. H.] Harvard Med Sch, Program Biol & Biomed Sci, Boston, MA USA. [Guo, M. H.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Guo, M. H.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Guttmann-Bauman, I.] Oregon Hlth & Sci Univ, Harold Schnitzer Diabet Hlth Ctr, Portland, OR 97201 USA. [Acerini, C.] Univ Cambridge, Dept Paediat, Cambridge, England. [Lee, W.; Allikmets, R.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. [Allikmets, R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Dauber, A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati Ctr Growth Disorders, Div Endocrinol, Cincinnati, OH 45229 USA. RP Nilsson, O (reprint author), Karolinska Inst, Dept Womens & Childrens Hlth, Div Pediat Endocrinol, Q2 08, S-17176 Stockholm, Sweden.; Nilsson, O (reprint author), Univ Hosp, Q2 08, S-17176 Stockholm, Sweden. EM ola.nilsson@ki.se FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [Z1AHD00641, Z1AHD00640]; US National Institutes of Health [R01 GM111772]; Swedish Research Council [521-2014-3063, 2015-02227]; Swedish Governmental Agency for Innovation Systems (Vinnova) [2014-01438]; Marianne and Marcus Wallenberg Foundation; Stockholm County Council; Swedish Society of Medicine; Byggmastare Olle Engkvist's Foundation; HKH Kronprinsessan Lovisas forening for barnasjukvard; Sallskapet Barnavard; Stiftelsen Frimurare Barnhuset i Stockholm; Karolinska Institutet; Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [1K23HD073351] FX We thank the patient, his family, and all healthy volunteers for their participation in the study. The work of ON, YHJ, JCL, JAY, and JB was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Grant no. Z1AHD00641 and Z1AHD00640). NI was supported by extramural funding from the US National Institutes of Health (Grant no R01 GM111772). ON was supported by grants from the Swedish Research Council (Grant no. 521-2014-3063 and 2015-02227), the Swedish Governmental Agency for Innovation Systems (Vinnova) (2014-01438), Marianne and Marcus Wallenberg Foundation, the Stockholm County Council, the Swedish Society of Medicine, Byggmastare Olle Engkvist's Foundation, HKH Kronprinsessan Lovisas forening for barnasjukvard, Sallskapet Barnavard, Stiftelsen Frimurare Barnhuset i Stockholm, and Karolinska Institutet. This work was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (1K23HD073351). NR 50 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 737 EP 744 DI 10.1055/s-0042-114038 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000006 PM 27589347 ER PT J AU Tack, LJW Tatsi, C Stratakis, CA Lodish, MB AF Tack, L. J. W. Tatsi, C. Stratakis, C. A. Lodish, M. B. TI Effects of Glucocorticoids on Bone: What we can Learn from Pediatric Endogenous Cushing's Syndrome SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE glucocorticoids; Cushing's syndrome; stem cells; glucocorticoid-induced osteoporosis; pediatrics ID QUANTITATIVE COMPUTED-TOMOGRAPHY; GROWTH-HORMONE-SECRETION; BODY-MASS INDEX; INDUCED OSTEOPOROSIS; MINERAL DENSITY; SKELETAL MATURATION; VERTEBRAL FRACTURES; SURGICAL CURE; OSTEOBLAST DIFFERENTIATION; CHILDHOOD-ONSET AB Chronic exposure to supraphysiologic levels of glucocorticoids (GCs) is associated with impaired bone mineral density, an increase in fracture rates, and, in growing children, compromised linear growth. GCs inhibit bone formation in part by decreasing the number of osteoblasts and by increasing bone resorption by stimulating osteoclasts. While GCs are used to treat many chronic diseases, it is difficult to isolate the effects of the steroids on the bone from the effects of the underlying disease itself. Investigation into the effects of GC exposure on the bone in endogenous Cushing syndrome have contributed to our understanding of bone microarchitecture, growth, healing, and regeneration. We now know that GCs negatively impact bone marrow derived-mesenchymal stromal cells. In children with Cushing syndrome, the potential reversibility of deleterious effects of chronic GC exposure on bone provides insight into the pathophysiology behind pure GC excess. C1 [Tack, L. J. W.] Ghent Univ Hosp, Div Pediat Endocrinol & Diabetol, Dept Pediat & Genet, Ghent, Belgium. [Tatsi, C.; Stratakis, C. A.; Lodish, M. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. RP Lodish, MB (reprint author), Bldg 10,Room 9D42,10 Ctr Dr MSC 1830, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov NR 103 TC 1 Z9 1 U1 2 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 764 EP 770 DI 10.1055/s-0042-117721 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000009 PM 27728929 ER PT J AU Jha, S Blau, JE Bhattacharyya, T AF Jha, S. Blau, J. E. Bhattacharyya, T. TI Normal and Delayed Fracture Healing: Symphony and Cacophony SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE skeletal injury; bone repair; callus formation ID SOFT-TISSUE INJURY; BONE-FORMATION; OSTEOPOROSIS INFLUENCES; OSTEOBLAST-LINEAGE; OSTEOTOMY GAP; HIP FRACTURE; TIBIAL SHAFT; DOUBLE-BLIND; LONG BONES; STEM-CELLS AB The incidence of any fracture in the US is estimated to be 2 704 fractures per 100,000 person-years. Approximately 10 percent of these fractures develop complications of healing. The processes that occur during fracture healing mimic the processes that take place in the growth plate during development. The study of fracture healing represents a window to enhance our understanding of the processes of growth and development of bones and its reparative biology. This review is aimed for clinicians evaluating non-unions as an overview of different factors that inhibit fracture healing. C1 [Jha, S.; Bhattacharyya, T.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Blau, J. E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Jha, S (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 4-1341, Bethesda, MD 20892 USA. EM smita.jha@nih.gov NR 79 TC 1 Z9 1 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 2016 VL 48 IS 11 BP 779 EP 784 DI 10.1055/s-0042-117636 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ED3EK UT WOS:000388732000011 PM 27728927 ER PT J AU Arnspang, EC Login, FH Koffman, JS Sengupta, P Nejsum, LN AF Arnspang, Eva C. Login, Frederic H. Koffman, Jennifer S. Sengupta, Prabuddha Nejsum, Lene N. TI AQP2 Plasma Membrane Diffusion Is Altered by the Degree of AQP2-S256 Phosphorylation SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE diffusion coefficients; kICS: k-space Image Correlation Spectroscopy; MDCK; AQP2; kidney; urine; phosphorylation ID NEPHROGENIC DIABETES-INSIPIDUS; AQUAPORIN-2 WATER CHANNEL; MEDULLARY COLLECTING DUCT; EPITHELIAL-CELLS; RAT-KIDNEY; APICAL MEMBRANE; 2 CHIMERA; VASOPRESSIN; LOCALIZATION; TRAFFICKING AB Fine tuning of urine concentration occurs in the renal collecting duct in response to circulating levels of arginine vasopressin (AVP). AVP stimulates intracellular cAMP production, which mediates exocytosis of sub-apical vesicles containing the water channel aquaporin-2 (AQP2). Protein Kinase A (PKA) phosphorylates AQP2 on serine-256 (S256), which triggers plasma membrane accumulation of AQP2. This mediates insertion of AQP2 into the apical plasma membrane, increasing water permeability of the collecting duct. AQP2 is a homo-tetramer. When S256 on all four monomers is changed to the phosphomimic aspartic acid (S256D), AQP2-S256D localizes to the plasma membrane and internalization is decreased. In contrast, when S256 is mutated to alanine (S256A) to mimic non-phosphorylated AQP2, AQP2-S256A localizes to intracellular vesicles as well as the plasma membrane, with increased internalization from the plasma membrane. S256 phosphorylation is not necessary for exocytosis and dephosphorylation is not necessary for endocytosis, however, the degree of S256 phosphorylation is hypothesized to regulate the kinetics of AQP2 endocytosis and thus, retention time in the plasma membrane. Using k-space Image Correlation Spectroscopy (kICS), we determined how the number of phosphorylated to non-phosphorylated S256 monomers in the AQP2 tetramer affects diffusion speed of AQP2 in the plasma membrane. When all four monomers mimicked constitutive phosphorylation (AQP2-S256D), diffusion was faster than when all four were non-phosphorylated (AQP2-S256A). AQP2-WT diffused at a speed similar to that of AQP2-S256D. When an average of two or three monomers in the tetramer were constitutively phosphorylated, the average diffusion coefficients were not significantly different to that of AQP2-S256D. However, when only one monomer was phosphorylated, diffusion was slower and similar to AQP2-S256A. Thus, AQP2 with two to four phosphorylated monomers has faster plasma membrane kinetics, than the tetramer which contains just one or no phosphorylated monomers. This difference in diffusion rate may reflect behavior of AQP2 tetramers destined for either plasma membrane retention or endocytosis. C1 [Arnspang, Eva C.; Login, Frederic H.; Nejsum, Lene N.] Aarhus Univ, Dept Clin Med, DK-8000 Aarhus C, Denmark. [Arnspang, Eva C.; Sengupta, Prabuddha] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Koffman, Jennifer S.] Aarhus Univ, Dept Interdisciplinary, Nanosci Ctr, DK-8000 Aarhus C, Denmark. [Arnspang, Eva C.] Univ Southern Denmark, Dept Chem Engn Biotechnol & Environm Technol, Campusvej 55, DK-5230 Odense M, Denmark. [Sengupta, Prabuddha] Janelia Res Campus, Ashburn, VA 20147 USA. RP Nejsum, LN (reprint author), Aarhus Univ, Dept Clin Med, DK-8000 Aarhus C, Denmark. EM arnspang@kbm.sdu.dk; frederic.login@clin.au.dk; jenniferkoffman@gmail.com; prabuddha.sengupta@gmail.com; nejsum@clin.au.dk OI Christensen, Eva Arnspang/0000-0002-3095-4070; Nejsum, Lene Niemann/0000-0003-4368-8821 FU Lundbeck Junior Group Leader Fellowship from the Lundbeck Foundation; Carlsberg Foundation; MEMBRANES; Danish Council for Independent Research\Natural Sciences [0602-02518B] FX We thank Dennis Brown, Harvard University for the AQP2-EGFP and AQP2 plasmids. We thank Gitte Albinus Pedersen for technical help and Jennifer Lippincott-Schwartz for excellent guidance in PALM microscopy and the PAGFP plasmid. This work was supported by a Lundbeck Junior Group Leader Fellowship from the Lundbeck Foundation to LNN, The Carlsberg Foundation to LNN, MEMBRANES to LNN, and funding from The Danish Council for Independent Research vertical bar Natural Sciences to EAC (grant number 0602-02518B). NR 55 TC 0 Z9 0 U1 3 U2 3 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD NOV PY 2016 VL 17 IS 11 AR 1804 DI 10.3390/ijms17111804 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA ED4HV UT WOS:000388809600038 ER PT J AU Narva, AS AF Narva, Andrew S. TI A model for improving CKD outcomes SO JAAPA-JOURNAL OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS LA English DT Editorial Material C1 [Narva, Andrew S.] NIDDK, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA. RP Narva, AS (reprint author), NIDDK, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1547-1896 EI 0893-7400 J9 JAAPA-J AM ACAD PHYS JI JAAPA-J. Am. Acad. Physician Assist. PD NOV PY 2016 VL 29 IS 11 BP 14 EP 14 DI 10.1097/01.JAA.0000502869.51469.bf PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ED4OX UT WOS:000388830600010 PM 27741025 ER PT J AU Hardy, TM McCarthy, DO Fourie, NH Henderson, WA AF Hardy, Theresa M. McCarthy, Donna O. Fourie, Nicolaas H. Henderson, Wendy A. TI Anti-Mullerian Hormone Levels and Urinary Cortisol in Women With Chronic Abdominal Pain SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE AMH; chronic abdominal pain; ovarian reserve; reproductive health ID SERUM ANTIMULLERIAN HORMONE; PSYCHOLOGICAL STRESS; OVARIAN RESERVE; PREMENOPAUSAL WOMEN; PSYCHOSOCIAL STRESS; GENE-EXPRESSION; CHILDHOOD; GLUCOCORTICOIDS; REPRODUCTION; DEPRESSION AB Objective: To explore the association of hypothalamic-pituitary-adrenal activity with ovarian functioning in women with and without chronic abdominal pain (CAP). Design and Setting: A secondary data analysis was performed with data from female participants in a natural history protocol at the National Institutes of Health. Participants: A total of 36 women (age range = 19-39 years, mean = 27.11 years) were included in the study. Methods: This pilot study was conducted with a subset of participants enrolled in a natural history protocol conducted in the Hatfield Clinical Research Center at the National Institutes of Health. The parent study included participants with and without CAP who provided a 5-hour urine sample for determination of cortisol levels and serum samples for determination of circulating levels of cortisol, luteinizing hormone, and follicle-stimulating hormone. CAP was defined as presence or absence of chronic pain for at least 6 months and was determined via self-report. Results: Anti-Mullerian hormone (AMH) concentrations declined significantly with age as expected. When AMH levels were dichotomized as normal or abnormal (defined as higher or lower than age-specific normative ranges, respectively), there were significant associations between abnormal AMH levels and CAP and urine cortisol levels. Participants with CAP or low urine cortisol levels were significantly more likely to have abnormal AMH levels. Conclusion: Results suggest that chronic abdominal pain and hypothalamic-pituitary-adrenal dysregulation may be associated with abnormal AMH levels. C1 [Hardy, Theresa M.; McCarthy, Donna O.] Marquette Univ, Coll Nursing, Milwaukee, WI USA. [Fourie, Nicolaas H.] NINR, Div Intramural Res, Bethesda, MD 20892 USA. [Henderson, Wendy A.] NINR, Biobehav Branch, Bethesda, MD 20892 USA. [Henderson, Wendy A.] NINR, Digest Disorders Unit, Div Intramural Res, Bethesda, MD 20892 USA. RP Henderson, WA (reprint author), NINR, Div Intramural Res, NIH, 10 Ctr Dr,2-1341, Bethesda, MD 20892 USA. EM hendersw@mail.nih.gov FU National Institute of Nursing Research [1ZIANR000018-01-04] FX Supported by the Division of Intramural Research, National Institute of Nursing Research (1ZIANR000018-01-04, Summer Internship Program, and Intramural Research Training Award). The authors thank Angela Martino, Dr. Joan K. Austin, and Dr. Ann K. Cashion for their assistance. NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0884-2175 EI 1552-6909 J9 JOGNN-J OBST GYN NEO JI JOGNN PD NOV-DEC PY 2016 VL 45 IS 6 BP 772 EP 780 DI 10.1016/j.jogn.2016.06.012 PG 9 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA ED4UF UT WOS:000388846500004 PM 27639111 ER PT J AU Eisenberg, MH Lipsky, LM Dempster, KW Liu, AY Nansel, TR AF Eisenberg, Miriam H. Lipsky, Leah M. Dempster, Katherine W. Liu, Aiyi Nansel, Tonja R. TI I Should but I Can't: Controlled Motivation and Self-Efficacy Are Related to Disordered Eating Behaviors in Adolescents With Type 1 Diabetes SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Disordered eating behaviors; Type 1 diabetes; Controlled motivation; Autonomous motivation; Self-efficacy; Insulin restriction; Self-determination theory ID PHYSICAL-ACTIVITY; EXERCISE; WEIGHT; OUTCOMES; HEALTH; INTERVENTION; PERSPECTIVE; APPEARANCE; STRATEGIES; DURATION AB Purpose: Among adolescents with type 1 diabetes, disordered eating behaviors (DEBs) are more prevalent and have more serious health implications than in adolescents without diabetes, necessitating identification of modifiable correlates of DEB in this population. This study hypothesized that (1) autonomous motivation and (2) controlled motivation for healthy eating (i.e., eating healthfully because it is important to oneself vs. important to others, respectively) are associated with DEB among adolescents with type 1 diabetes. The third hypothesis was that baseline healthy eating self-efficacy moderates these associations. Methods: Adolescents with type 1 diabetes (n = 90; 13-16 years) participating in a behavioral nutrition intervention efficacy trial reported DEB, controlled and autonomous motivation, and self-efficacy at baseline, 6, 12, and 18 months. Linear-mixed models estimated associations of controlled and autonomous motivation with DEB, adjusting for treatment group, body mass index, socioeconomic status, age, and gender. Separate models investigated the interaction of self-efficacy with each motivation type. Results: Controlled motivation was positively associated with DEB (B = 2.18 +/- .33, p < .001); the association was stronger for those with lower self-efficacy (B = 3.33 +/- .55, p < .001) than those with higher self-efficacy (B = 1.36 +/- .36, p < .001). Autonomous motivation was not associated with DEB (B = -.70 +/- .43, p = .11). Conclusions: Findings identify controlled motivation for healthy eating as a novel correlate of DEB among adolescents with type 1 diabetes and show that self-efficacy can modify this association. Motivation and self-efficacy for healthy eating represent potential intervention targets to reduce DEB in adolescents with type 1 diabetes. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Eisenberg, Miriam H.; Lipsky, Leah M.; Dempster, Katherine W.; Nansel, Tonja R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. RP Eisenberg, MH (reprint author), 6100 Execut Blvd,Room 7B13B, Bethesda, MD 20892 USA. EM miriam.eisenberg@nih.gov OI Eisenberg, Miriam/0000-0002-7133-8805; Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082; Lipsky, Leah/0000-0003-2645-4388 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C, HHSN2752008000031/HHSN275002]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract numbers #HHSN267200703434C and #HHSN2752008000031/HHSN275002. All the authors were funded solely by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 34 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD NOV PY 2016 VL 59 IS 5 BP 537 EP 542 DI 10.1016/j.jadohealth.2016.06.008 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA EE3RC UT WOS:000389512700009 PM 27567063 ER PT J AU Guasch, L Yapamudiyansel, W Peach, ML Kelley, JA Barchi, JJ Nicklaus, MC AF Guasch, Laura Yapamudiyansel, Waruna Peach, Megan L. Kelley, James A. Barchi, Joseph J., Jr. Nicklaus, Marc C. TI Experimental and Chemoinformatics Study of Tautomerism in a Database of Commercially Available Screening Samples SO Journal of Chemical Information and Modeling LA English DT Article ID INCHI; IDENTIFIER; MANAGEMENT; DESIGN; SYSTEM; RULES AB We investigated how many cases of the same chemical sold as different products (at possibly different prices) occurred in a prototypical large aggregated database and simultaneously tested the tautomerism definitions in the chemoinformatics toolkit CACTVS. We applied the standard CACTVS tautomeric transforms plus a set of recently developed ring chain transforms to the Aldrich Market Select (AMS) database of 6 million screening samples and building blocks. In 30 000 cases, two or more AMS products were found to be just different tautomeric forms of the same compound. We purchased and analyzed 166 such tautomer pairs and triplets by H-1 and C-13 NMR to determine whether the CACTVS transforms accurately predicted what is the same "stuff in the bottle". Essentially all prototropic transforms with examples in the AMS were confirmed. Some of the ring chain transforms were found to be too "aggressive", i.e. to equate structures with one another that were different compounds. C1 [Guasch, Laura; Yapamudiyansel, Waruna; Kelley, James A.; Barchi, Joseph J., Jr.; Nicklaus, Marc C.] NCI, Chem Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Peach, Megan L.] Leidos Biomed Inc, Basic Sci Program, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Nicklaus, MC (reprint author), NCI, Chem Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM mnl@helix.nih.gov FU National Institutes of Health, at the Center for Cancer Research, National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank Dr. Wolf-Dietrich Ihlenfeldt for his help with the chemoinformatics toolkit CACTVS, and Dr. Markus Sitzmann for his help with the calculation of identifiers for the AMS database. We also gratefully acknowledge Dr. Christopher C. Lai for his expert assistance in analytical sample preparation and for LC/MS analysis of a portion of the samples. This work was funded in part by the Intramural Research Program of the National Institutes of Health, at the Center for Cancer Research, National Cancer Institute, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. 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 25 TC 0 Z9 0 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 EI 1549-960X J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD NOV PY 2016 VL 56 IS 11 BP 2149 EP 2161 DI 10.1021/acs.jcim.6b00338 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA ED8IW UT WOS:000389116200004 PM 27669079 ER PT J AU Costanzo, ME VanMeter, JW Janelle, CM Braun, A Miller, MW Oldham, J Russell, BAH Hatfield, BD AF Costanzo, Michelle E. VanMeter, John W. Janelle, Christopher M. Braun, Allen Miller, Matthew W. Oldham, Jessica Russell, Bartlett A. H. Hatfield, Bradley D. TI Neural Efficiency in Expert Cognitive-Motor Performers During Affective Challenge SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE emotional reactivity; experts; fMRI; neural efficiency ID HIGH-RESOLUTION EEG; PREFRONTAL CORTEX; WORKING-MEMORY; EMOTION REGULATION; PHYSICAL-EXERCISE; NEGATIVE EMOTION; ATHLETES BRAIN; ALPHA RHYTHMS; AMYGDALA; STRESS AB Skilled individuals demonstrate a spatially localized or relatively lower response in brain activity characterized as neural efficiency when performing within their domain of expertise. Elite athletes are experts in their chosen sport and thus must be not only adept in the motor domain but must be resilient to performing under the stress of high-level competition. Such stability of performance suggests this population processes emotion and mental stress in an adaptive and efficient manner. This study sought to determine if athletes with a history of successful performance under circumstances of mental stress demonstrate neural efficiency during affective challenges compared to age-matched controls. Using functional magnetic resonance imaging, the blood-oxygen level-dependent response was recorded during emotional challenge induced by sport-specific and general unpleasant images. The athletes demonstrated neural efficiency in brain regions critical to emotion regulation (prefrontal cortex) and affect (insula) independently of their domain of expertise, suggesting adaptive processing of negative events and less emotional reactivity to unpleasant stimuli. C1 [Costanzo, Michelle E.; Miller, Matthew W.; Russell, Bartlett A. H.; Hatfield, Bradley D.] Univ Maryland, Dept Kinesiol, Sch Publ Hlth, 2351 SPH Bldg, College Pk, MD 20742 USA. [Costanzo, Michelle E.; Miller, Matthew W.; Oldham, Jessica; Russell, Bartlett A. H.; Hatfield, Bradley D.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [VanMeter, John W.] Georgetown Univ, Med Ctr, Ctr Funct & Mol Imaging, Washington, DC 20007 USA. [Janelle, Christopher M.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL USA. [Braun, Allen] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD USA. [Russell, Bartlett A. H.; Hatfield, Bradley D.] Univ Maryland, Ctr Adv Study Language, College Pk, MD 20742 USA. RP Hatfield, BD (reprint author), Univ Maryland, Dept Kinesiol, Sch Publ Hlth, 2351 SPH Bldg, College Pk, MD 20742 USA. EM bhatfiel@umd.edu NR 83 TC 0 Z9 0 U1 5 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0022-2895 EI 1940-1027 J9 J MOTOR BEHAV JI J. Mot. Behav. PD NOV-DEC PY 2016 VL 48 IS 6 BP 573 EP 588 DI 10.1080/00222895.2016.1161591 PG 16 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA EC0IU UT WOS:000387784500012 PM 27715496 ER PT J AU Berlowitz, DR Breaux-Shropshire, T Foy, CG Gren, LH Kazis, L Lerner, AJ Newman, JC Powell, JR Riley, WT Rosman, R Wadley, VG Williams, JA AF Berlowitz, Dan R. Breaux-Shropshire, Tonya Foy, Capri G. Gren, Lisa H. Kazis, Lewis Lerner, Alan J. Newman, Jill C. Powell, James R. Riley, William T. Rosman, Robert Wadley, Virginia G. Williams, Julie A. CA SPRINT Res Grp TI Hypertension Treatment and Concern About Falling: Baseline Data from the Systolic Blood Pressure Intervention Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hypertension; falls; concern about falling ID OLDER-PEOPLE; FES-I; FEAR; PREVALENCE; HEALTH; POPULATION; VALIDITY AB ObjectivesTo determine the extent of concern about falling in older adults with hypertension, whether lower blood pressure (BP) and greater use of antihypertensive medications are associated with greater concern about falling, and whether lower BP has a greater effect on concern about falling in older and more functionally impaired individuals. DesignSecondary analysis involving cross-sectional study of baseline characteristics of participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). SettingApproximately 100 outpatient sites. ParticipantsSPRINT enrollees aged 50 and older (mean age 69) diagnosed with hypertension (N=2,299). MeasurementsConcern about falling was determined using the shortened version of the Falls Efficacy Scale International as measured at the baseline examination. ResultsMild concern about falling was present in 29.3% of participants and moderate to severe concern in 17.9%. Neither low BP (systolic BP<120mmHg, diastolic BP <70mmHg) nor orthostatic hypotension was associated with concern about falling (P>.10). Participants with moderate to severe concern about falling were taking significantly more antihypertensive medications than those with mild or no concern. After adjusting for baseline characteristics, no associations were evident between BP, medications, and concern about falling. Results were similar in older and younger participants; interactions between BP and age and functional status were not significantly associated with concern about falling. ConclusionAlthough concern about falling is common in older adults with hypertension, it was not found to be associated with low BP or use of more antihypertensive medications in baseline data from SPRINT. C1 [Berlowitz, Dan R.; Kazis, Lewis] Bedford Vet Affairs Hosp, Bedford, MA USA. [Berlowitz, Dan R.; Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA USA. [Breaux-Shropshire, Tonya] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Breaux-Shropshire, Tonya; Wadley, Virginia G.] Univ Alabama Birmingham, Birmingham, AL USA. [Foy, Capri G.; Newman, Jill C.] Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA. [Gren, Lisa H.] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT USA. [Lerner, Alan J.] Case Western Reserve Univ, Sch Med, Dept Neurol, Cleveland, OH USA. [Powell, James R.] East Carolina Univ, Brody Sch Med, Div Gen Internal Med, Greenville, NC USA. [Riley, William T.] NIH, Off Behav & Social Sci Res, Bethesda, MD USA. [Rosman, Robert] Univ Illinois, Div Acad Internal Med & Geriatr, Coll Med, Chicago, IL USA. [Williams, Julie A.] Wake Forest Univ, Sch Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. RP Berlowitz, DR (reprint author), Bedford VA Hosp, 200 Springs Rd, Bedford, MA 01730 USA. EM dan.berlowitz@va.gov FU National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute on Aging (NIA); National Institute of Neurological Disorders and Stroke (NINDS) [HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C]; CTSAs funded by NCATS [UL1TR000439, UL1RR025755, UL1RR024134, UL1TR000003, UL1RR025771, UL1TR000093, UL1RR025752, UL1TR000073, UL1TR001064, UL1TR000050, UL1TR000005, 9U54TR 000017-06, UL1TR000105-05, UL1TR000445, UL1TR000075, UL1TR000002, UL1TR000064, UL1TR000433, P30GM103337]; [A-HL-13-002-001] FX SPRINT is funded with funds from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), under Contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement A-HL-13-002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. The investigators designed and implemented all components of the SPRINT protocol. The investigative team collected, analyzed, and interpreted the data. For a full list of contributors to SPRINT, please see the supplementary acknowledgment list. We also acknowledge the support from the following CTSAs funded by NCATS: CWRU: UL1TR000439, OSU: UL1RR025755, U Penn: UL1RR024134 & UL1TR000003, U Boston: UL1RR025771, U Stanford: UL1TR000093, U Tufts: UL1RR025752, UL1TR000073 & UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern: 9U54TR 000017-06, University of Utah: UL1TR000105-05, Vanderbilt University: UL1TR000445, George Washington University: UL1TR000075, University of CA, Davis: UL1TR000002, University of Florida: UL1TR000064, University of Michigan: UL1TR000433, Tulane University: P30GM103337 COBRE Award NIGMS. NR 18 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2016 VL 64 IS 11 BP 2302 EP 2306 DI 10.1111/jgs.14441 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EC7QO UT WOS:000388335600045 PM 27640987 ER PT J AU Rathbun, AM Shardell, M Orwig, D Gruber-Baldini, AL Ostir, G Hicks, GE Miller, RR Hochberg, MC Magaziner, J AF Rathbun, Alan M. Shardell, Michelle Orwig, Denise Gruber-Baldini, Ann L. Ostir, Glenn Hicks, Gregory E. Miller, Ram R. Hochberg, Marc C. Magaziner, Jay TI Effects of Prefracture Depressive Illness and Postfracture Depressive Symptoms on Physical Performance After Hip Fracture SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hip fracture; depression; physical performance ID FUNCTIONAL RECOVERY; COGNITIVE IMPAIRMENT; ELDERLY PERSONS; OLDER-ADULTS; LIFE; REHABILITATION; ASSOCIATION; MORTALITY; HISTORY; STRESS AB ObjectivesTo compare the effect of prefracture depressive illness and postfracture depressive symptoms on changes in physical performance after hip fracture. DesignLongitudinal observational cohort. SettingBaltimore metropolitan area. ParticipantsOlder adults with hip fracture (N = 255). MeasurementsPrefracture depressive illness (from medical records) at baseline and postfracture depressive symptoms at 2 months (using the Center for Epidemiologic Studies Depression Scale) were measured. Physical performance was measured 2, 6, and 12 months after fracture using the Short Physical Performance Battery (SPPB), a composite metric of functional status with a score ranging from 0 to 12. Weighted estimating equations were used to assess mean SPPB over time, comparing participants with and without prefracture depressive illness and subjects with and without postfracture depressive symptoms. ResultsParticipants with prefracture depressive illness had an SPPB increase of 0.4 units (95% confidence interval (CI) = -0.5-1.3) from 2 to 6 months, smaller than the increase of 1.0 SPPB unit (95% CI = 0.4-1.6) in those without prefracture depressive illness. Participants with postfracture depressive symptoms had an SPPB increase of 0.2 units (95% CI = -1.0-1.5) from 2 to 12 months, and those without postfracture depressive symptoms had a larger increase of 1.2 units (95% CI = 0.6-1.8) over the same period. Nevertheless, prefracture depressive illness and postfracture depressive symptoms were not significantly associated with SPPB. ConclusionsNeither prefracture depressive illness nor postfracture depressive symptoms were significantly associated with changes in physical performance after hip fracture, but the magnitude of estimates suggested possible clinically meaningful effects on functional recovery. C1 [Rathbun, Alan M.; Orwig, Denise; Gruber-Baldini, Ann L.; Ostir, Glenn; Hochberg, Marc C.; Magaziner, Jay] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Howard Hall Suite 200,660 W Redwood St, Baltimore, MD 21201 USA. [Shardell, Michelle] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE USA. [Miller, Ram R.] Novartis Inst BioMed Res, Cambridge, MA USA. RP Rathbun, AM (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Howard Hall Suite 200,660 W Redwood St, Baltimore, MD 21201 USA. EM arathbun@epi.umaryland.edu FU Gerontological Society of America Emerging Scholar and Professional Organization FX These findings were presented in part at the 2015 annual meeting of the Gerontological Society of America, Orlando, Florida, and Dr. Alan M. Rathbun received a poster award for this research from the Gerontological Society of America Emerging Scholar and Professional Organization. NR 30 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2016 VL 64 IS 11 BP E171 EP E176 DI 10.1111/jgs.14487 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EC7QO UT WOS:000388335600009 PM 27673273 ER PT J AU Margossian, R Sleeper, LA Pearson, GD Barker, PC Mertens, L Quartermain, MD Su, JT Shirali, G Chen, S Colan, SD AF Margossian, Renee Sleeper, Lynn A. Pearson, Gail D. Barker, Piers C. Mertens, Luc Quartermain, Michael D. Su, Jason T. Shirali, Girish Chen, Shan Colan, Steven D. CA Pediat Heart Network Investigators TI Assessment of Diastolic Function in Single-Ventricle Patients After the Fontan Procedure SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Congenital heart disease; Single ventricle; Fontan; Diastolic function ID DOPPLER-ECHOCARDIOGRAPHY; EXERCISE PERFORMANCE; PRELOAD RESERVE; OPERATION; CIRCULATION; CHILDREN; VOLUME; FAILURE; DISEASE AB Background: Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status. Methods: Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored. Results: DFG was calculable in 326 of 546 subjects (60%) (mean age, 11.7 +/- 3.3 years). Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3 diastolic function. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (P < .001); this association remained significant when using Z scores adjusted for age (P < .001). DFG was associated with achieving maximal effort on exercise testing (P = .004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3. No additional significant associations of DFG with laboratory or clinical measures were identified. Conclusions: Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but few clinically or statistically significant associations were found. This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles. C1 [Margossian, Renee; Colan, Steven D.] Boston Childrens Hosp, Boston, MA USA. [Margossian, Renee; Colan, Steven D.] Harvard Med Sch, Boston, MA USA. [Sleeper, Lynn A.; Chen, Shan] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. [Pearson, Gail D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Barker, Piers C.] Duke Univ, Med Ctr, Durham, NC USA. [Mertens, Luc] Hosp Sick Children, Toronto, ON, Canada. [Quartermain, Michael D.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Su, Jason T.] Univ Utah, Salt Lake City, UT USA. [Shirali, Girish] Med Univ South Carolina, Charleston, SC USA. RP Margossian, R (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM renee.margossian@cardio.chboston.org FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288] FX This work was 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 or the National Heart, Lung, and Blood Institute. ClinicalTrials.gov identifier: NCT00132782. NR 29 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 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2016 VL 29 IS 11 BP 1066 EP 1073 DI 10.1016/j.echo.2016.07.016 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EE3SY UT WOS:000389519900006 PM 27624592 ER PT J AU Khanna, S Thomas, A Abate-Daga, D Zhang, JL Morrow, B Steinberg, SM Orlandi, A Ferroni, P Schlom, J Guadagni, F Hassan, R AF Khanna, Swati Thomas, Anish Abate-Daga, Daniel Zhang, Jingli Morrow, Betsy Steinberg, Seth M. Orlandi, Augusto Ferroni, Patrizia Schlom, Jeffrey Guadagni, Fiorella Hassan, Raffit TI Malignant Mesothelioma Effusions Are Infiltrated by CD3(+) T Cells Highly Expressing PD-L1 and the PD-L1(+) Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE PD-1-PD-L1; Mesothelioma; Avelumab; ADCC ID LUNG-CANCER; PLEURAL MESOTHELIOMA; OVARIAN-CANCER; MEDIATED CYTOTOXICITY; PROGNOSTIC-FACTORS; B7 FAMILY; B7-H1; MSB0010718C; SAFETY; LYMPHOCYTES AB Introduction: The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Methods: Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Results: Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1 positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-gamma-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Conclusions: Most pleural as well as peritoneal mesotheliomas express PD-L1. Malignant effusions in this disease are characterized by the presence of tumor cells and CD3-positive T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by the anti-PD-L1 antibody avelumab. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. C1 [Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Hassan, Raffit] NCI, Thorac & GI Oncol 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. [Orlandi, Augusto] Univ Roma Tor Vergata, Dept Biomed & Prevent, Anat Pathol, Rome, Italy. [Ferroni, Patrizia; Guadagni, Fiorella] San Raffaele Roma Open Univ, Rome, Italy. [Ferroni, Patrizia; Guadagni, Fiorella] IRCCS San Raffaele Pisana, SR Res Ctr, BioBIM Interinst Multidisciplinary BioBank, Rome, Italy. [Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Hassan, R (reprint author), NCI, Thorac & GI Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov RI Ferroni, Patrizia/C-2705-2017 OI Ferroni, Patrizia/0000-0002-9877-8712 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; EMD Serono; National Cancer Institute; European Social Fund, Italian Ministry of Education, University and Research [PON03PE_00146_1/10 BIBIOFAR (CUP B88F12000730005)] FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, as well as by a cooperative research and development agreement between EMD Serono and the National Cancer Institute. The work was also partially supported by the European Social Fund, Italian Ministry of Education, University and Research PON03PE_00146_1/10 BIBIOFAR grant (CUP B88F12000730005) to Dr. Guadagni. NR 39 TC 3 Z9 3 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2016 VL 11 IS 11 BP 1993 EP 2005 DI 10.1016/j.jtho.2016.07.033 PG 13 WC Oncology; Respiratory System SC Oncology; Respiratory System GA EA6NI UT WOS:000386745500020 PM 27544053 ER PT J AU Wibmer, CK Gorman, J Anthony, CS Mkhize, NN Druz, A York, T Schmidt, SD Labuschagne, P Louder, MK Bailer, RT Karim, SSA Mascola, JR Williamson, C Moore, PL Kwong, PD Morris, L AF Wibmer, Constantinos Kurt Gorman, Jason Anthony, Colin S. Mkhize, Nonhlanhla N. Druz, Aliaksandr York, Talita Schmidt, Stephen D. Labuschagne, Phillip Louder, Mark K. Bailer, Robert T. Karim, Salim S. Abdool Mascola, John R. Williamson, Carolyn Moore, Penny L. Kwong, Peter D. Morris, Lynn TI Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN GP120; SUBTYPE-C INFECTION; MONOCLONAL-ANTIBODIES; POTENT NEUTRALIZATION; MATURATION PATHWAY; HUMORAL IMMUNITY; B-CELLS; BROAD; ESCAPE AB All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/ founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/ founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycandependent CD4 binding site B-cell lineage. IMPORTANCE The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site. C1 [Wibmer, Constantinos Kurt; Mkhize, Nonhlanhla N.; Moore, Penny L.; Morris, Lynn] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr HIV & STIs, Johannesburg, South Africa. [Wibmer, Constantinos Kurt; Mkhize, Nonhlanhla N.; Moore, Penny L.; Morris, Lynn] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa. [Wibmer, Constantinos Kurt; Gorman, Jason; Druz, Aliaksandr; Schmidt, Stephen D.; Louder, Mark K.; Bailer, Robert T.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Anthony, Colin S.; York, Talita; Williamson, Carolyn] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa. [Anthony, Colin S.; York, Talita; Williamson, Carolyn] Univ Cape Town, Div Med Virol, Cape Town, South Africa. [Anthony, Colin S.; York, Talita; Williamson, Carolyn] Natl Hlth Lab Serv, Cape Town, South Africa. [Labuschagne, Phillip] Univ Western Cape, South African Natl Bioinformat Inst, Cape Town, South Africa. [Karim, Salim S. Abdool; Williamson, Carolyn; Moore, Penny L.; Morris, Lynn] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, Durban, South Africa. [Karim, Salim S. Abdool] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Morris, L (reprint author), Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr HIV & STIs, Johannesburg, South Africa.; Morris, L (reprint author), Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.; Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Morris, L (reprint author), Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, Durban, South Africa. EM pdkwong@nih.gov; lynnm@nicd.ac.za OI Wibmer, Constantinos Kurt/0000-0003-2329-2280 FU Strategic Health Innovation Partnership (SHIP) of the South African Medical Research Council (MRC); MRC South African HIV/AIDS Research and Innovation Platform (SHARP) via the South African Department of Science and Technology (DST); U.S. National Institutes of Health (NIH) through a U01 [AI116086-01]; Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH; SHARP; DST; NIAID, NIH, U.S. Department of Health and Human Services [U19 AI51794]; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; South African Research Chairs Initiative of the DST; National Research Foundation (NRF) of South Africa [98341]; Fogarty International Center, NIH [5 D43 TW000231] FX This research was supported by the Strategic Health Innovation Partnership (SHIP) of the South African Medical Research Council (MRC) and the MRC South African HIV/AIDS Research and Innovation Platform (SHARP) via the South African Department of Science and Technology (DST). Funding from the U.S. National Institutes of Health (NIH) was obtained through a U01 grant (AI116086-01) and the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. CAPRISA is funded by SHARP and the DST and was initially supported by NIAID, NIH, U.S. Department of Health and Human Services grant U19 AI51794. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. Penny L. Moore is supported by the South African Research Chairs Initiative of the DST and the National Research Foundation (NRF) of South Africa (grant no. 98341). Constantinos Kurt Wibmer received bursaries from the NRF and the Poliomyelitis Research Foundation (PRF) as well as a traineeship through the Fogarty International Center, NIH grant 5 D43 TW000231. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 1 Z9 1 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 22 BP 10220 EP 10235 DI 10.1128/JVI.01357-16 PG 16 WC Virology SC Virology GA EC9MN UT WOS:000388468800016 PM 27581986 ER PT J AU Thomas, JA Quintana, ADB Bosch, MA De Pena, AC Aguilera, E Coulibaly, A Wu, WM Osier, MV Hudson, AO Weintraub, ST Blacke, LW AF Thomas, Julie A. Quintana, Andrea Denisse Benitez Bosch, Martine A. De Pena, Adriana Coll Aguilera, Elizabeth Coulibaly, Assitan Wu, Weimin Osier, Michael V. Hudson, Andre O. Weintraub, Susan T. Blacke, Lindsay W. TI Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly SO JOURNAL OF VIROLOGY LA English DT Article ID BACTERIOPHAGE-PHI-KZ; COMPLETE GENOME SEQUENCE; PSEUDOMONAS-AERUGINOSA; RNA-POLYMERASE; INNER BODY; CRYSTAL-STRUCTURE; DNA; INFECTIONS; EVOLUTION; PHI-R1-37 AB Giant tailed bacterial viruses, or phages, such as Pseudomonas aeruginosa phage phi KZ, have long genomes packaged into large, atypical virions. Many aspects of phi KZ and related phage biology are poorly understood, mostly due to the fact that the functions of the majority of their proteins are unknown. We hypothesized that the Salmonella enterica phage SPN3US could be a useful model phage to address this gap in knowledge. The 240-kb SPN3US genome shares a core set of 91 genes with phi KZ and related phages, similar to 61 of which are virion genes, consistent with the expectation that virion complexity is an ancient, conserved feature. Nucleotide sequencing of 18 mutants enabled assignment of 13 genes as essential, information which could not have been determined by sequence-based searches for 11 genes. Proteome analyses of two SPN3US virion protein mutants with knockouts in 64 and 241 provided new insight into the composition and assembly of giant phage heads. The 64 mutant analyses revealed all the genetic determinants required for assembly of the SPN3US head and a likely head-tail joining role for gp64, and its homologs in related phages, due to the tailless-particle phenotype produced. Analyses of the mutation in 241, which encodes an RNA polymerase beta subunit, revealed that without this subunit, no other subunits are assembled into the head, and enabled identification of a "missing" beta' subunit domain. These findings support SPN3US as an excellent model for giant phage research, laying the groundwork for future analyses of their highly unusual virions, host interactions, and evolution. IMPORTANCE In recent years, there has been a paradigm shift in virology with the realization that extremely large viruses infecting prokaryotes (giant phages) can be found in many environments. A group of phages related to the prototype giant phage phi KZ are of great interest due to their virions being among the most complex of prokaryotic viruses and their potential for biocontrol and phage therapy applications. Our understanding of the biology of these phages is limited, as a large proportion of their proteins have not been characterized and/or have been deemed putative without any experimental verification. In this study, we analyzed Salmonella phage SPN3US using a combination of genomics, genetics, and proteomics and in doing so revealed new information regarding giant phage head structure and assembly and virion RNA polymerase composition. Our findings demonstrate the suitability of SPN3US as a model phage for the growing group of phages related to phi KZ. C1 [Thomas, Julie A.; Quintana, Andrea Denisse Benitez; Bosch, Martine A.; De Pena, Adriana Coll; Osier, Michael V.; Hudson, Andre O.] Rochester Inst Technol, Thomas H Gosnell Sch Life Sci, Rochester, NY 14623 USA. [Aguilera, Elizabeth; Coulibaly, Assitan] Baltimore City Community Coll, Nat & Phys Sci, Baltimore, MD USA. [Wu, Weimin] NIAMSD, NIH, Bethesda, MD 20892 USA. [Weintraub, Susan T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Blacke, Lindsay W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Thomas, JA (reprint author), Rochester Inst Technol, Thomas H Gosnell Sch Life Sci, Rochester, NY 14623 USA. EM jatsbi@rit.edu FU Thomas H. Gosnell School of Life Sciences; HHS \ National Institutes of Health (NIH) [AI11676, 1S10RR025111-01] FX This work, including the efforts of Julie A. Thomas, was funded by Thomas H. Gosnell School of Life Sciences. This work, including the efforts of Lindsay W. Black, was funded by HHS vertical bar National Institutes of Health (NIH) (AI11676). This work, including the efforts of Susan T. Weintraub, was funded by HHS vertical bar National Institutes of Health (NIH) (1S10RR025111-01). NR 60 TC 1 Z9 1 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 22 BP 10284 EP 10298 DI 10.1128/JVI.01492-16 PG 15 WC Virology SC Virology GA EC9MN UT WOS:000388468800021 PM 27605673 ER PT J AU Keating, SM Heitman, JW Wu, SQ Deng, XT Stacey, AR Zahn, RC de la Rosa, M Finstad, SL Lifson, JD Piatak, M Gauduin, MC Kessler, BM Ternette, N Carville, A Johnson, RP Desrosiers, RC Letvin, NL Borrow, P Norris, PJ Schmitz, JE AF Keating, Sheila M. Heitman, John W. Wu, Shiquan Deng, Xutao Stacey, Andrea R. Zahn, Roland C. de la Rosa, Maurus Finstad, Samantha L. Lifson, Jeffrey D. Piatak, Michael, Jr. Gauduin, Marie-Claire Kessler, Benedikt M. Ternette, Nicola Carville, Angela Johnson, R. Paul Desrosiers, Ronald C. Letvin, Norman L. Borrow, Persephone Norris, Philip J. Schmitz, Joern E. TI Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; PRIMARY SIV INFECTION; VIRAL SET-POINT; CD4(+) T-CELLS; RHESUS MACAQUES; IN-VIVO; DISEASE PROGRESSION; IMMUNE-RESPONSES; TYPE-1 INFECTION; INTERFERON-GAMMA AB Acute human immunodeficiency virus (HIV) infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in nonprogressive and progressive nonhuman primate (NHP) infection models can provide significant insight into critical events occurring during this time. Cytokines, chemokines, and other soluble immune factors were measured in longitudinal samples from rhesus macaques infected with either SIVmac251 (progressive infection) or SIVmac239 Delta nef (attenuated/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 beta (MIP-1 beta), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239 Delta nef or SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression. IMPORTANCE NHP models of HIV infection constitute a powerful tool with which to study viral pathogenesis in order to gain critical information for a better understanding of HIV infection in humans. Here we studied progressive and nonprogressive simian immunodeficiency virus (SIV) infection models in both natural and nonnatural host NHP species. Regardless of the pathogenicity of the virus infection and regardless of the NHP species studied, the magnitude of viremia, as measured by area under the curve, during the first 4 weeks of infection correlated positively with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between nonprogressive and progressive SIV infection models. The qualitative differences in the early immune response in pathogenic and nonpathogenic infections identified here may be important determinants of the subsequent disease course. C1 [Keating, Sheila M.; Heitman, John W.; Wu, Shiquan; Deng, Xutao; Norris, Philip J.] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Keating, Sheila M.; Norris, Philip J.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Norris, Philip J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Stacey, Andrea R.; Ternette, Nicola] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Kessler, Benedikt M.; Ternette, Nicola] Univ Oxford, Target Discovery Inst, Oxford, England. [Zahn, Roland C.; de la Rosa, Maurus; Finstad, Samantha L.; Letvin, Norman L.; Schmitz, Joern E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Lifson, Jeffrey D.; Piatak, Michael, Jr.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Gauduin, Marie-Claire] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Gauduin, Marie-Claire] Southwest Natl Primate Res Ctr San, San Antonio, TX USA. [Carville, Angela] New England Primate Res Ctr, Dept Primate Resources, Southborough, MA USA. [Johnson, R. Paul] New England Primate Res Ctr, Dept Immunol, Southborough, MA USA. [Desrosiers, Ronald C.] New England Primate Res Ctr, Dept Microbiol, Southborough, MA USA. [Stacey, Andrea R.] Immunocore, Abingdon, Oxon, England. [Zahn, Roland C.] Janssen Infect Dis & Vaccines, Leiden, Netherlands. [de la Rosa, Maurus] Baxter Innovat GmbH, Vienna, Austria. [Finstad, Samantha L.] NCI, NIH, Bethesda, MD 20892 USA. [Carville, Angela] Biomed Res Models, Worcester, MA USA. [Johnson, R. Paul] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Desrosiers, Ronald C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Schmitz, Joern E.] Inst Mol Biol & Appl Ecol IME, Aachen, Germany. RP Keating, SM (reprint author), Blood Syst Res Inst, San Francisco, CA 94118 USA.; Keating, SM (reprint author), Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. EM skeating@bloodsystems.org OI Kessler, Benedikt/0000-0002-8160-2446 FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [AI0678501, AI065335]; Harvard University Center for AIDS Research (HU CFAR) [P30-AI060354] FX This work, including the efforts of Sheila M. Keating, John W. Heitman, Shiquan Wu, Xutao Deng, Andrea R. Stacey, Roland C. Zahn, Maurus de la Rosa, Samantha L. Finstad, Jeffrey D. Lifson, Michael Piatak, Jr., Benedikt M. Kessler, Nicola Ternette, Angela Carville, R. Paul Johnson, Ronald C. Desrosiers, Norman L. Letvin, Persephone Borrow, Philip J. Norris, and Joern E. Schmitz, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (AI0678501 and AI065335). This work, including the efforts of Roland C. Zahn, Maurus de la Rosa, Samantha L. Finstad, and Joern E. Schmitz, was funded by Harvard University Center for AIDS Research (HU CFAR) (P30-AI060354). NR 47 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 22 BP 10339 EP 10350 DI 10.1128/JVI.01061-16 PG 12 WC Virology SC Virology GA EC9MN UT WOS:000388468800026 PM 27630228 ER PT J AU Thomas, A Chen, YB Berman, A Schrump, DS Giaccone, G Pastan, I Venzon, DJ Liewehr, DJ Steinberg, SM Miettinen, M Hassan, R Rajan, A AF Thomas, Anish Chen, Yuanbin Berman, Arlene Schrump, David S. Giaccone, Giuseppe Pastan, Ira Venzon, David J. Liewehr, David J. Steinberg, Seth M. Miettinen, Markku Hassan, Raffit Rajan, Arun TI Expression of mesothelin in thymic carcinoma and its potential therapeutic significance SO LUNG CANCER LA English DT Article DE Thymic carcinoma; Mesothelin; Immunohistochemistry; Therapeutic target; Immunotherapy ID EPITHELIAL TUMORS; OVARIAN-CANCER; PHASE-I; SERUM MESOTHELIN; OPEN-LABEL; THYMOMA; TRIAL; MARKER; DIFFERENTIATION; BELINOSTAT AB Objectives: Advanced thymic epithelial tumors (TETs) lack adequate treatment options in part due to absence of well characterized tumor-specific antigens. Mesothelin, a cell surface antigen, has been used successfully as a target for tumor-directed therapy. We sought to determine tumor expression and serum levels of mesothelin in patients with TETs. Patients and methods: Tissue samples were obtained from 71 patients with histologically confirmed, unresectable advanced TETs and evaluated for mesothelin expression by immunohistochemistry. The evaluation was blinded for clinical data and outcome. Mesothelin expression and its association with clinico-pathological parameters and survival were assessed. Results: Thymic carcinoma, thymoma, and thymic neuroendocrine tumors (NETs) accounted for 34 (48%), 29 (41%), and 8 (11%) cases respectively. Mesothelin expression was seen in a significantly larger proportion of thymic carcinoma (27/34, 79%) than thymoma (3/29, 10%) (P < 0.0001) and was absent in thymic NETs. Among thymic carcinomas 13/34 (38%) showed expression in nearly all tumor cells. Immunoreactivity was membranous, strong, and homogenous. Patients with thymic carcinoma and high mesothelin expression (in >50% of tumor cells) had significantly improved overall survival (median not reached, n=19) compared to patients with no or low mesothelin expression (1.60 years; 95% CI: 1.24-4.94 years; n =15; HR= 4.46, 95% CI: 1.55-12.80; p = 0.0026). Conclusion: Mesothelin expression is frequently observed in advanced thymic carcinomas, infrequently in thymomas and is absent in thymic NETs. Due to strong, membranous expression mesothelin is a potential therapeutic target in thymic carcinoma. Published by Elsevier Ireland Ltd. C1 [Thomas, Anish; Chen, Yuanbin; Berman, Arlene; Schrump, David S.; Hassan, Raffit; Rajan, Arun] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA. [Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Venzon, David J.; Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Miettinen, Markku] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rajan, A (reprint author), NCI, Thorac & GI Oncol Branch, NIH, Room 4-5330,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM rajana@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD NOV PY 2016 VL 101 BP 104 EP 110 DI 10.1016/j.lungcan.2016.09.015 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA EC3SN UT WOS:000388046700017 PM 27794397 ER PT J AU Singh, SK Lupo, PJ Scheurer, ME Saxena, A Kennedy, AE Ibrahimou, B Barbieri, MA Mills, KI McCauley, JL Okcu, MF Dorak, MT AF Singh, Sandeep K. Lupo, Philip J. Scheurer, Michael E. Saxena, Anshul Kennedy, Amy E. Ibrahimou, Boubakari Barbieri, Manuel Alejandro Mills, Ken I. McCauley, Jacob L. Okcu, Mehmet Fatih Dorak, Mehmet Tevfik TI A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants SO MEDICINE LA English DT Article DE acute lymphoblastic leukemia; case-only study; effect modification; expression quantitative trait loci; gene expression regulation; genome-wide association study; sex-specific association ID SYSTEMATIC IDENTIFICATION; FUNCTIONAL ANNOTATION; DISEASE ASSOCIATIONS; ESTROGEN-RECEPTOR; COMPLEX DISEASES; GENETIC-VARIANTS; EARLY INFANCY; RAS PATHWAY; TRAIT LOCI; CANCER AB Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex. The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P<0.05). The statistically most significant sex-specific association (P=4 x 10(-6)) was with the single nucleotide polymorphism (SNP) rs4813720 (RASSF2), an expression quantitative trait locus (eQTL) for RASSF2 in peripheral blood. rs4813720 is also a strong methylation QTL (meQTL) for a CpG site (cg22485289) within RASSF2 in pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] similar to 14; P<0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1*01 and confirmed the previously reported male-specific association with DQA1*01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels. Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormonerelated mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by sex hormones when hormone levels show a large variation. C1 [Singh, Sandeep K.] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Environm & Occupat Hlth, Miami, FL 33199 USA. [Singh, Sandeep K.; Barbieri, Manuel Alejandro] Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. [Lupo, Philip J.] Texas Childrens Canc Ctr, Dept Pediat, Sect Hematol Oncol, Houston, TX USA. [Scheurer, Michael E.; Okcu, Mehmet Fatih] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA. [Saxena, Anshul] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, Miami, FL 33199 USA. [Kennedy, Amy E.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Ibrahimou, Boubakari] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Biostat, Miami, FL 33199 USA. [Mills, Ken I.] Queens Univ Belfast, CCRCB, Belfast, Antrim, North Ireland. [McCauley, Jacob L.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom,Dept Human Genet, Dr John T Macdonald Fdn,Biorepository Facil,Ctr G, Miami, FL 33136 USA. [Dorak, Mehmet Tevfik] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Epidemiol, Miami, FL 33199 USA. RP Dorak, MT (reprint author), Liverpool Hope Univ, Sch Hlth Sci, Liverpool L16 9JD, Merseyside, England. EM dorakm@hope.ac.uk FU Robert Stempel College of Public Health and Social Work, Florida International University FX This work has been supported by funds from the Robert Stempel College of Public Health and Social Work, Florida International University. NR 68 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2016 VL 95 IS 46 AR e5300 DI 10.1097/MD.0000000000005300 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ED3DV UT WOS:000388730500027 PM 27861356 ER PT J AU Ebben, JD Lubet, RA Gad, E Disis, ML You, M AF Ebben, Johnathan D. Lubet, Ronald A. Gad, Ekram Disis, Mary L. You, Ming TI Epidermal Growth Factor Receptor Derived Peptide Vaccination to Prevent Lung Adenocarcinoma Formation: An In Vivo Study in a Murine Model of EGFR Mutant Lung Cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE cancer prevention; lung cancer; peptide vaccine ID PROGRESSION; INHIBITOR; VACCINES; DISEASE; TARGET; TUMORS; MICE AB The ability to prevent disease is the holy grail of medicine. For decades, efforts have been made to extend the successes seen with vaccination against infectious diseases to cancer. In some instances, preventive vaccination against viruses (prototypically HPV) has successfully prevented tumorigenesis and will make a major impact on public health in the decades to come. However, the majority of cancers that arise are a result of genetic mutation within the host, or non-viral environmental exposures. We present compelling evidence that vaccination against an overexpressed self-tumor oncoprotein has the potential to prevent tumor development. Vaccination against the Epidermal Growth Factor Receptor (EGFR) using a multipeptide vaccine in a preventive setting decreased EGFR-driven lung carcinogenesis by 76.4% in a mouse model of EGFR-driven lung cancer. We also demonstrate that anti-EGFR vaccination primes the development of a robust immune response in vivo. This study provides proof of concept for the first time that targeting tumor drivers in a preventive setting in lung cancer using peptide vaccination can inhibit tumorigenesis and may provide useful clinical insights into the development of strategies to vaccinate against EGFR in populations where EGFR-mutant disease is highly prevalent. (C) 2015 Wiley Periodicals, C1 [Ebben, Johnathan D.; You, Ming] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Ctr Canc, Milwaukee, WI 53226 USA. [Lubet, Ronald A.] NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. [Gad, Ekram; Disis, Mary L.] Univ Washington, Tumor Vaccine Grp, Ctr Translat Med Womens Hlth, Seattle, WA 98195 USA. RP You, M (reprint author), Med Coll Wisconsin, Ctr Canc, 8701 Watertown Plank Rd,TBRC C4795, Milwaukee, WI 53226 USA. FU NCI [HHSN261200433001C, HHSN261201200013I]; Athena Distinguished Professorship of Breast Cancer Research; DOD Breast Cancer Program [W81XWH-11-1-0760] FX Grant sponsor: NCI; Grant number: HHSN261200433001C; Grant sponsor: Athena Distinguished Professorship of Breast Cancer Research; Grant sponsor: DOD Breast Cancer Program; Grant number: #W81XWH-11-1-0760; Grant sponsor: NCI; Grant number: HHSN261201200013I NR 22 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 2016 VL 55 IS 11 BP 1517 EP 1525 DI 10.1002/mc.22405 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA EC1GP UT WOS:000387853200003 PM 26346412 ER PT J AU Cho, J Lee, CJ Zhao, JS Young, HE Zhou, P AF Cho, Jae Lee, Chul-Jin Zhao, Jinshi Young, Hayley E. Zhou, Pei TI Structure of the essential Haemophilus influenzae UDP-diacylglucosamine pyrophosphohydrolase LpxH in lipid A biosynthesis SO Nature Microbiology LA English DT Article ID ESCHERICHIA-COLI; UDP-2,3-DIACYLGLUCOSAMINE; PRECURSOR; GENE AB In most Gram-negative pathogens, the hydrolysis of UDP-2,3diacylglucosamine to generate lipid X in lipid A biosynthesis is catalysed by the membrane-associated enzyme LpxH. We report the crystal structure of LpxH in complex with its product, lipid X, unveiling a unique insertion lid above the conserved architecture of calcineurin-like phosphoesterases. This structure reveals elaborate interactions surrounding lipid X and provides molecular insights into the substrate selectivity, catalysis and inhibition of LpxH. C1 [Cho, Jae; Lee, Chul-Jin; Zhao, Jinshi; Young, Hayley E.; Zhou, Pei] Duke Univ, Dept Biochem, Med Ctr, Res Dr, Durham, NC 27710 USA. [Lee, Chul-Jin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Zhou, P (reprint author), Duke Univ, Dept Biochem, Med Ctr, Res Dr, Durham, NC 27710 USA. EM peizhou@biochem.duke.edu OI Zhou, Pei/0000-0002-7823-3416 FU National Institute of General Medical Sciences (NIGMS) [GM115355, GM51310]; NIGMS [GM103403]; NIH-ORIP HEI grant [RR029205]; DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357] FX This work was supported by grants from the National Institute of General Medical Sciences (NIGMS) (to P. Z., GM115355 and GM51310). Diffraction data were collected at the Northeastern Collaborative Access Team beamlines (24-ID-C and 24-ID-E) funded by NIGMS (GM103403). The Pilatus 6M detector on the 24-ID-C beam line is funded by a NIH-ORIP HEI grant (RR029205). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory (contract no. DE-AC02-06CH11357). The authors thank Ziqiang Guan for assistance with mass spectrometry analysis and Brian Coggins for critical reading of this manuscript. NR 21 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2058-5276 J9 NAT MICROBIOL JI NAT. MICROBIOL PD NOV PY 2016 VL 1 IS 11 AR 16154 DI 10.1038/NMICROBIOL.2016.154 PG 4 WC Microbiology SC Microbiology GA ED8RV UT WOS:000389139500009 PM 27780190 ER PT J AU Philpott, CC Protchenko, O AF Philpott, Caroline C. Protchenko, Olga TI Robbing the bank of haem iron SO Nature Microbiology LA English DT News Item ID STRUCTURAL BASIS; ACQUISITION; HEMOPEXIN; PIRACY C1 [Philpott, Caroline C.; Protchenko, Olga] NIDDK, NIH, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov NR 11 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2058-5276 J9 NAT MICROBIOL JI NAT. MICROBIOL PD NOV PY 2016 VL 1 IS 11 AR 16179 DI 10.1038/NMICROBIOL.2016.179 PG 2 WC Microbiology SC Microbiology GA ED8RV UT WOS:000389139500015 PM 27782142 ER PT J AU Polidori, D Sanghvi, A Seeley, RJ Hall, KD AF Polidori, David Sanghvi, Arjun Seeley, Randy J. Hall, Kevin D. TI How Strongly Does Appetite Counter Weight Loss? Quantification of the Feedback Control of Human Energy Intake SO Obesity LA English DT Article ID COTRANSPORTER 2 INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; EATING AD-LIBITUM; FOOD-INTAKE; BODY-WEIGHT; COVERT MANIPULATION; DIETARY-FAT; BALANCE; MEN; CANAGLIFLOZIN AB Objective: To quantify the feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans. Methods: A validated mathematical method was used to calculate energy intake changes during a 52-week placebo-controlled trial in 153 patients treated with canagliflozin, a sodium glucose co-transporter inhibitor that increases urinary glucose excretion, thereby resulting in weight loss without patients being directly aware of the energy deficit. The relationship between the body weight time course and the calculated energy intake changes was analyzed using principles from engineering control theory. Results: It was discovered that weight loss leads to a proportional increase in appetite resulting in eating above baseline by similar to 100 kcal/day per kilogram of lost weight-an amount more than threefold larger than the corresponding energy expenditure adaptations. Conclusions: While energy expenditure adaptations have often been considered the main reason for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult. C1 [Polidori, David] Janssen Res & Dev LLC, San Diego, CA USA. [Sanghvi, Arjun; Hall, Kevin D.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Seeley, Randy J.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Hall, KD (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov FU Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases; Janssen Research & Development, LLC FX This research was supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases, using data from a study sponsored by Janssen Research & Development, LLC. NR 40 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD NOV PY 2016 VL 24 IS 11 BP 2289 EP 2295 DI 10.1002/oby.21653 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA ED8VG UT WOS:000389148400006 PM 27804272 ER PT J AU Qi, QB Gogarten, SM Emery, LS Louie, T Stilp, A Cai, J Schneiderman, N Aviles-Santa, ML Kaplan, RC North, KE Laurie, CC Loos, RJF Isasi, CR AF Qi, Qibin Gogarten, Stephanie M. Emery, Leslie S. Louie, Tin Stilp, Adrienne Cai, Jianwen Schneiderman, Neil Aviles-Santa, M. Larissa Kaplan, Robert C. North, Kari E. Laurie, Cathy C. Loos, Ruth J. F. Isasi, Carmen R. TI Genetic Variation near IRS1 is Associated with Adiposity and a Favorable Metabolic Profile in US Hispanics/Latinos SO Obesity LA English DT Article ID BODY-MASS INDEX; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; OPPOSITE ASSOCIATIONS; GENOMIC LOCI; FAT; OBESITY; POPULATIONS; VARIANTS AB Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. Results: The C-allele (frequency=26%) of rs2943650 was significantly associated with higher BF% overall (beta = 0.34+/-0.11% per allele; P=0.002) and in women (beta = 0.41+/-0.14% per C-allele; P=0.003), but not in men (beta = 0.28+/-0.18% per C-allele; P=0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (beta = 0.054+/-0.018SD vs. beta = 0.008+/-0.011SD per C-allele; P=0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P<0.05). Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women. C1 [Qi, Qibin; Kaplan, Robert C.; Isasi, Carmen R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Gogarten, Stephanie M.; Emery, Leslie S.; Louie, Tin; Stilp, Adrienne; Laurie, Cathy C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Cai, Jianwen] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Cai, Jianwen] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Schneiderman, Neil] Univ Miami, Dept Psychol, Miami, FL USA. [Aviles-Santa, M. Larissa] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. RP Qi, QB (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. EM qibin.qi@einstein.yu.edu OI Gogarten, Stephanie/0000-0002-7231-9745 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI; NIDCR [HHSN268201300005C AM03, MOD03]; NHLBI [HSN 26220/20054C]; NCATS CTSI grant [UL1TR000123]; NIDDK Diabetes Research Center (DRC) grant [DK063491]; Scientist Development Award from the NHLBI [K01HL129892] FX The baseline examination of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. QQ is supported by a Scientist Development Award (K01HL129892) from the NHLBI. This manuscript has been reviewed by the HCHS/SOL Publications Committee for scientific content and consistency of data interpretation with previous HCHS/SOL publications. NR 40 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD NOV PY 2016 VL 24 IS 11 BP 2407 EP 2413 DI 10.1002/oby.21624 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA ED8VG UT WOS:000389148400022 PM 27663718 ER PT J AU Wei, BR Michael, HT Halsey, CH Peer, CJ Adhikari, A Dwyer, JE Hoover, SB Meskini, R Kozlov, S Ohler, Z Figg, WD Merlino, G Simpson, RM AF Wei, Bih-Rong Michael, Helen T. Halsey, Charles H. C. Peer, Cody J. Adhikari, Amit Dwyer, Jennifer E. Hoover, Shelley B. El Meskini, Rajaa Kozlov, Serguei Weaver Ohler, Zoe Figg, William. D. Merlino, Glenn Simpson, R. Mark TI Synergistic targeted inhibition of MEK and dual PI3K/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE trametinib; dactolisib; BRAF and NRAS wild type; preclinical model; dog; melanoma ID PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; ORAL MALIGNANT MELANOMAS; EXON 11 MUTATIONS; MELANOCYTIC NEOPLASMS; RAPAMYCIN INHIBITOR; METASTATIC MELANOMA; SOLID TUMORS; CANCER; KIT; BRAF AB Human mucosal melanoma (MM), an uncommon, aggressive and diverse subtype, shares characteristics with spontaneous MM in dogs. Although BRAF and N-RAS mutations are uncommon in MM in both species, the majority of human and canine MM evaluated exhibited RAS/ERK and/or PI3K/mTOR signaling pathway activation. Canine MM cell lines, with varying ERK and AKT/mTOR activation levels reflective of naturally occurring differences in dogs, were sensitive to the MEK inhibitor GSK1120212 and dual PI3K/mTOR inhibitor NVP-BEZ235. The two-drug combination synergistically decreased cell survival in association with caspase 3/7 activation, as well as altered expression of cell cycle regulatory proteins and Bcl-2 family proteins. In combination, the two drugs targeted their respective signaling pathways, potentiating reduction of pathway mediators p-ERK, p-AKT, p-S6, and 4E-BP1 invitro, and in association with significantly inhibited solid tumor growth in MM xenografts in mice. These findings provide evidence of synergistic therapeutic efficacy when simultaneously targeting multiple mediators in melanoma with Ras/ERK and PI3K/mTOR pathway activation. C1 [Wei, Bih-Rong; Michael, Helen T.; Halsey, Charles H. C.; Dwyer, Jennifer E.; Hoover, Shelley B.; Merlino, Glenn; Simpson, R. Mark] Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD USA. [Wei, Bih-Rong; Adhikari, Amit; El Meskini, Rajaa; Kozlov, Serguei; Weaver Ohler, Zoe] Leidos Biomed Res Inc, Frederick, MD USA. [Peer, Cody J.; Figg, William. D.] Natl Canc Inst, Genitourinary Malignancies Branch Ctr Canc Res, Bethesda, MD USA. [Adhikari, Amit; El Meskini, Rajaa; Kozlov, Serguei; Weaver Ohler, Zoe] Frederick Natl Lab Canc Res, Ctr Adv Preclin Res, Frederick, MD USA. RP Simpson, RM (reprint author), Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD USA. EM ms43b@nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland FX This research was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. Kind support is acknowledged from the Animal Cancer Foundation and from the Canine Comparative Oncology and Genomics Consortium Biorepository. HTM is a molecular pathology fellow in the NIH Comparative Biomedical Scientist Training Program, an NCI-administered Graduate Partnership Program in partnership with the University of Maryland. CHCH is currently at Pfizer, Inc., Groton, CT. AA is currently at Meso Scale Discovery, LLC, Rockville, MD. We thank Amy K. LeBlanc for critical reading of the manuscript. We thank Terry Van Dyke for input into experimental design. NR 55 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD NOV PY 2016 VL 29 IS 6 BP 643 EP 655 DI 10.1111/pcmr.12512 PG 13 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA EC7JH UT WOS:000388312900007 PM 27463366 ER PT J AU Izar, B Joyce, CE Goff, S Cho, NL Shah, PM Sharma, G Li, JJ Ibrahim, N Gold, J Hodi, FS Garraway, LA Novina, CD Bertagnolli, MM Yoon, CH AF Izar, Benjamin Joyce, Cailin E. Goff, Stephanie Cho, Nancy L. Shah, Parin M. Sharma, Gaurav Li, Jingjing Ibrahim, Nageatte Gold, Jason Hodi, F. Stephen Garraway, Levi A. Novina, Carl D. Bertagnolli, Monica M. Yoon, Charles H. TI Bidirectional cross talk between patient-derived melanoma and cancer-associated fibroblasts promotes invasion and proliferation SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE melanoma; tumor stroma; CAFs; metastasis; TGF; EGFR ID CARCINOMA-ASSOCIATED FIBROBLASTS; CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; TUMOR MICROENVIRONMENT; STROMAL FIBROBLASTS; COLORECTAL-CANCER; MESENCHYMAL TRANSITION; METASTATIC MELANOMA; PANCREATIC-CANCER; POOR-PROGNOSIS AB Tumor-stroma interactions are critical for epithelial-derived tumors, and among the stromal cell types, cancer-associated fibroblasts (CAFs) exhibit multiple functions that fuel growth, dissemination, and drug resistance. However, these interactions remain insufficiently characterized in non-epithelial tumors such as malignant melanoma. We generated monocultures of melanoma cells and matching CAFs from patients' metastatic lesions, distinguished by oncogenic drivers and immunoblotting of characteristic markers. RNA sequencing of CAFs revealed a homogenous epigenetic program that strongly resembled the signatures from epithelial cancers, including enrichment for an epithelial-to-mesenchymal transition (EMT). Melanoma CAFs in monoculture displayed robust invasive behavior while patient-derived melanoma monocultures showed very little invasiveness. Instead, melanoma cells showed increased invasion when co-cultured with CAFs. In turn, CAFs showed increased proliferation when exposed to melanoma conditioned media (CM), mediated in part by melanoma-secreted transforming growth factor-alpha that acted on CAFs via the epidermal growth factor receptor. This study provides evidence that bidirectional interactions between melanoma and CAFs regulate progression of metastatic melanoma. C1 [Izar, Benjamin; Goff, Stephanie; Cho, Nancy L.; Sharma, Gaurav; Bertagnolli, Monica M.; Yoon, Charles H.] Brigham & Womens Hosp, Div Surg Oncol, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Izar, Benjamin; Joyce, Cailin E.; Shah, Parin M.; Garraway, Levi A.; Novina, Carl D.] Broad Inst & Harvard, Cambridge, MA USA. [Izar, Benjamin; Shah, Parin M.; Li, Jingjing; Ibrahim, Nageatte; Hodi, F. Stephen; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Joyce, Cailin E.; Novina, Carl D.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Gold, Jason] VA Boston Hlth Care Serv, Surg Serv, Dept Surg, West Roxbury, MA USA. [Goff, Stephanie] Natl Canc Inst, Surg Branch, NIH, 10-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. [Ibrahim, Nageatte] Merck Res Labs, Oncol, 351 North Sumneytown Pike, N Wales, PA 19454 USA. RP Yoon, CH (reprint author), Brigham & Womens Hosp, Div Surg Oncol, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM chyoon@bics.bwh.harvard.edu NR 65 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD NOV PY 2016 VL 29 IS 6 BP 656 EP 668 DI 10.1111/pcmr.12513 PG 13 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA EC7JH UT WOS:000388312900008 PM 27482935 ER PT J AU Chaitankar, V Karakulah, G Ratnapriya, R Giuste, FO Brooks, MJ Swaroop, A AF Chaitankar, Vijender Karakulah, Gokhan Ratnapriya, Rinki Giuste, Felipe O. Brooks, Matthew J. Swaroop, Anand TI Next generation sequencing technology and genomewide data analysis: Perspectives for retinal research SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE ChIP-seq; Chromatin; Epigenetics; Gene regulatory network; Genomics; High throughput data; Network analysis; Photoreceptor; Retina; Retinal disease; RNA-Seq; Systems biology; Transcriptome; Vision; Whole exome sequencing; Whole genome sequencing; NGS data integration ID RNA-SEQ DATA; PROTEIN-DNA INTERACTIONS; DIFFERENTIAL EXPRESSION ANALYSIS; ACCESSIBLE CHROMATIN LANDSCAPE; DISEASE GENE DISCOVERY; I HYPERSENSITIVE SITES; CHIP-SEQ; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; INTEGRATIVE ANALYSIS AB The advent of high throughput next generation sequencing (NGS) has accelerated the pace of discovery of disease-associated genetic variants and genomewide profiling of expressed sequences and epigenetic marks, thereby permitting systems-based analyses of ocular development and disease. Rapid evolution of NGS and associated methodologies presents significant challenges in acquisition, management, and analysis of large data sets and for extracting biologically or clinically relevant information. Here we illustrate the basic design of commonly used NGS-based methods, specifically whole exome sequencing, transcriptome, and epigenome profiling, and provide recommendations for data analyses. We briefly discuss systems biology approaches for integrating multiple data sets to elucidate gene regulatory or disease networks. While we provide examples from the retina, the NGS guidelines reviewed here are applicable to other tissues/cell types as well. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. C1 [Chaitankar, Vijender; Karakulah, Gokhan; Ratnapriya, Rinki; Giuste, Felipe O.; Brooks, Matthew J.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. RP Swaroop, A (reprint author), Neurobiol Neurodegenerat & Repair Lab, Bldg 6-338,6 Ctr Dr, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov OI Swaroop, Anand/0000-0002-1975-1141; Karakulah, Gokhan/0000-0001-6706-1375 FU Intramural Research Program of the National Eye Institute, National Institutes of Health [EY000450, EY000474, EY000546] FX We thank Jung-Woong Kim, Hyun-jin Yang, Tiziana Cogliati and Lina Zelinger for discussions and comments on the manuscript. Our work is supported by the Intramural Research Program of the National Eye Institute (grant nos: EY000450, EY000474, EY000546), National Institutes of Health. Some of the NGS analysis required the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). NR 233 TC 1 Z9 1 U1 10 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD NOV PY 2016 VL 55 BP 1 EP 31 DI 10.1016/j.preteyeres.2016.06.001 PG 31 WC Ophthalmology SC Ophthalmology GA ED8CA UT WOS:000389098300001 PM 27297499 ER PT J AU Minegishi, Y Nakayama, M Iejima, D Kawase, K Iwata, T AF Minegishi, Yuriko Nakayama, Mao Iejima, Daisuke Kawase, Kazuhide Iwata, Takeshi TI Significance of optineurin mutations in glaucoma and other diseases SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Optineurin; Glaucoma; TANK binding kinase I (TBK1); Knock-in mouse iPS cells; Retinal ganglion cells; TBK1 inhibitor; BX795; Amlexanox ID OPEN-ANGLE GLAUCOMA; AMYOTROPHIC-LATERAL-SCLEROSIS; NORMAL-TENSION GLAUCOMA; NF-KAPPA-B; RETINAL GANGLION-CELLS; GENOME-WIDE ASSOCIATION; ANHIDROTIC ECTODERMAL DYSPLASIA; AUTOPHAGY RECEPTOR OPTINEURIN; PLURIPOTENT STEM-CELLS; COPY NUMBER VARIATIONS AB Glaucoma is one of the leading causes of bilateral blindness, affecting nearly 57 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells and is often associated with intraocular pressure (IOP). Normal tension glaucoma (NTG), marked by normal IOP but progressive glaucoma, is incompletely understood. In 2002, Sarfarazi et al. identified FIP-2 gene mutations responsible for hereditary NTG, renaming this gene "optineurin" (OPTN). Further investigations by multiple groups worldwide showed that OPTN is involved in several critical cellular functions, such as NF-icB regulation, autophagy, and vesicle transport. Recently, OPTN mutations were found to cause amyotrophic lateral sclerosis (ALS). Surprisingly, a mutation in the OPTN interacting protein, i.e., the duplication of TANK binding protein 1 (TBK1) gene, also can cause both NTG and ALS. These phenotypically distinct neuronal diseases are now merging into one common pathological mechanism by these two genes. TBK1 inhibition has emerged as a potential therapy for NTG. In this manuscript, we focus on the OPTN E5OK mutation, the most common mutation for NTG, to describe the molecular mechanism of NTG by expressing a mutant Optn gene in cells and genetically modified mice. Patient iPS cells were developed and differentiated into neural cells to observe abnormal behavior and the impact of the E5OK mutation. These in vitro studies were further extended to identify the inhibitors BX795 and amlexanox, which have the potential to reverse the disease-causing phenomenon in patient's neural cells. Here we show for the first time that amlexanox protects RGC5 in Optn E5OK knock-in mice. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Minegishi, Yuriko; Nakayama, Mao; Iejima, Daisuke; Iwata, Takeshi] Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol, Tokyo, Japan. [Kawase, Kazuhide] Gifu Univ, Dept Ophthalmol, Sch Med, Gifu, Japan. [Minegishi, Yuriko] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Iwata, T (reprint author), Natl Hosp Org Tokyo Med Ctr, Div Mol & Cellular Biol, Natl Inst Sensory Organs, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan. EM takeshi.iwata@kankakuki.go.jp FU Japanese Ministry of Health, Labour and Welfare [H18-KANKAKU-IPPAN-002, H22-KANKAKU-IPPAN-002, H26-ITAKU(NAN)-IPPAN-087]; Japan Agency for Medical Research and Development [16ek0109072h0003]; Japan Society for the Promotion of Science [16591779, 21390471, 24791885, 26861481] FX The authors greatly appreciate all patients and family member who participated in this study. The authors are also grateful to Tomoko Saito and Yoshikazu Totsuka (Institute of Immunology Co., LTD.) for generating the novel OPTN E50K knock-in mice, Megumi Yamamoto (Tokyo Medical Center) for mating and maintaining the mice, John A. Loudon (University of Sydney) for the introduction and encouragement to test the TBK1 inhibitor amlexanox for OPTN ESOK related experiments, and Luis Bonet-Ponce (National Eye Institute, NIH) for discussions about autophagy. This study was funded in part by grants to Takeshi Iwata by the Japanese Ministry of Health, Labour and Welfare (H18-KANKAKU-IPPAN-002, H22-KANKAKU-IPPAN-002, H26-ITAKU(NAN)-IPPAN-087), a grant to Takeshi Iwata by the Japan Agency for Medical Research and Development (16ek0109072h0003), and grants to Takeshi Iwata (16591779, 21390471) and Yuriko Minegishi (24791885, 26861481) by the Japan Society for the Promotion of Science. NR 180 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD NOV PY 2016 VL 55 BP 149 EP 181 DI 10.1016/j.preteyeres.2016.08.002 PG 33 WC Ophthalmology SC Ophthalmology GA ED8CA UT WOS:000389098300006 PM 27693724 ER PT J AU Torrisi, S Robinson, O O'Connell, K Davis, A Balderston, N Ernst, M Grillon, C AF Torrisi, Salvatore Robinson, Oliver O'Connell, Katherine Davis, Andrew Balderston, Nicholas Ernst, Monique Grillon, Christian TI The neural basis of improved cognitive performance by threat of shock SO Social Cognitive and Affective Neuroscience LA English DT Article DE sustained attention; response inhibition; Go; NoGo; threat of shock; fMRI ID ATTENTIONAL CONTROL-THEORY; VENTRAL TEGMENTAL AREA; SUSTAINED ATTENTION; RESPONSE-INHIBITION; FUNCTIONAL CONNECTIVITY; TARGET DETECTION; ANXIETY; TASK; STIMULI; CORTEX AB Anxiety can have both detrimental and facilitatory cognitive effects. This study investigates the neural substrates of a replicated facilitatory effect of anxiety on sustained attention and response inhibition. This effect consisted of improved performance on the Sustained Attention to Response Task (a Go-NoGo task consisting of 91% Go and 9% NoGo trials) in threat (unpredictable electrical shock) vs safe (no shock) conditions. This study uses the same experimental design with fMRI and relies on an event-related analysis of BOLD signal changes. Findings reveal that threat-related cognitive facilitation (improved NoGo accuracy) is associated with greater activation of a right-lateralized frontoparietal group of regions previously implicated in sustained attention and response inhibition. Moreover, these same regions show decreased activation in the Go trials preceding NoGo errors. During NoGo trials, striatal activity is also greater in the threat vs safe condition, consistent with the notion of enhanced inhibitory processing under threat. These findings identify potential mechanisms by which threat of unpredictable shock can facilitate distinct cognitive functions. A greater understanding of the complex interaction of the anxious state and cognitive processes may have critical clinical implications. C1 [Torrisi, Salvatore; O'Connell, Katherine; Davis, Andrew; Balderston, Nicholas; Ernst, Monique; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. [Robinson, Oliver] UCL, Inst Cognit Neurosci, London, England. RP Torrisi, S (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. EM sam.torrisi@nih.gov FU Intramural Research Program of the National Institutes of Mental Health [MH002798, 02-M-0321]; Medical Research Council Career Development award [MR/K024280/1] FX This study was supported by the Intramural Research Program of the National Institutes of Mental Health; Grant Numbers MH002798 (Protocol 02-M-0321; NCT00047853) to C.G. O.J.R. is funded by a Medical Research Council Career Development award (MR/K024280/1). NR 71 TC 1 Z9 1 U1 7 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD NOV PY 2016 VL 11 IS 11 BP 1677 EP 1686 DI 10.1093/scan/nsw088 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ED6BT UT WOS:000388940000001 PM 27369069 ER PT J AU Jenkins, GR Lee, T Moland, CL Vijay, V Herman, EH Lewis, SM Davis, KJ Muskhelishvili, L Kerr, S Fuscoe, JC Desai, VG AF Jenkins, G. Ronald Lee, Taewon Moland, Carrie L. Vijay, Vikrant Herman, Eugene H. Lewis, Sherry M. Davis, Kelly J. Muskhelishvili, Levan Kerr, Susan Fuscoe, James C. Desai, Varsha G. TI Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F(1) mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Doxorubicin; Cardiotoxicity; Sex-based differences; Mouse model; Apoptosis; DNA damage ID CARDIAC TROPONIN-T; SPONTANEOUSLY HYPERTENSIVE-RATS; CONGESTIVE-HEART-FAILURE; DOUBLE-STRAND BREAKS; RISK-FACTORS; IN-VIVO; INDUCED CARDIOMYOPATHY; RADICAL FORMATION; CHILDHOOD-CANCER; ORGAN WEIGHT AB Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F(1) mice were dosed with 3 mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27 mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24 mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21 mg/kg cumulative dose. DOX-treated male mice also had an increased number of gamma-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27 mg/kg cumulative dose and right atrium at 21 and 27 mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. Published by Elsevier Inc. C1 [Jenkins, G. Ronald; Moland, Carrie L.; Vijay, Vikrant; Fuscoe, James C.; Desai, Varsha G.] US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lee, Taewon] Korea Univ, Dept Math, Sejong, South Korea. [Herman, Eugene H.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Davis, Kelly J.; Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Kerr, Susan] Arkansas Heart Hosp, Little Rock, AR 72211 USA. RP Desai, VG (reprint author), US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov RI Vijay, Vikrant/E-7651-2010 OI Vijay, Vikrant/0000-0001-8425-1285 NR 74 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2016 VL 310 BP 159 EP 174 DI 10.1016/j.taap.2016.09.012 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA EA6NM UT WOS:000386745900017 PM 27644598 ER PT J AU Goldman, M Magnussen, K Gorlin, J Lozano, M Speedy, J Keller, A Pink, J Leung, JNS Chu, CCY Lee, CK Faed, J Chay, J Tan, HH Teo, D Djoudi, R Woimant, G Fillet, AM Castren, J Miflin, G Vandewalle, GC Compernolle, V Cardenas, JM Infanti, L Holbro, A Buser, A van den Hurk, K Yahalom, VJ Gendelman, V Shinar, E Eder, AF Steele, WR O'Neill, EM Kamel, H Vassallo, R Delage, G Lebrun, A Robillard, P Germain, M Gandhi, M West, KA Klein, HG AF Goldman, M. Magnussen, K. Gorlin, J. Lozano, M. Speedy, J. Keller, A. Pink, J. Leung, J. N. S. Chu, C. C. Y. Lee, C. -K. Faed, J. Chay, J. Tan, H. H. Teo, D. Djoudi, R. Woimant, G. Fillet, A. -M. Castren, J. Miflin, G. Vandewalle, G. C. Compernolle, V. Cardenas, J. M. Infanti, L. Holbro, A. Buser, A. van den Hurk, K. Yahalom, V. J. Gendelman, V. Shinar, E. Eder, A. F. Steele, W. R. O'Neill, E. M. Kamel, H. Vassallo, R. Delage, G. Lebrun, A. Robillard, P. Germain, M. Gandhi, M. West, K. A. Klein, H. G. TI International Forum regarding practices related to donor haemoglobin and iron SO VOX SANGUINIS LA English DT Article ID WHOLE-BLOOD DONORS; CARBONYL IRON; 45 MG; DEFICIENCY; SUPPLEMENTATION; DONATION; ANEMIA; TRIAL; POPULATION; PREDICTORS C1 [Goldman, M.] Canadian Blood Serv, Med Serv & Innovat, Ottawa, ON, Canada. [Magnussen, K.] Copenhagen Univ Hosp, Clin Immunol Blood Ctr, Hvidovre, Denmark. [Gorlin, J.] Innovat Blood Ctr, Serv Phys, St Paul, MN USA. [Lozano, M.] Hosp Clin Barcelona, Dept Hemotherapy & Hemostasis, Barcelona, Spain. [Speedy, J.] Australian Red Cross Blood Serv, Adelaide, SA, Australia. [Keller, A.] Australian Red Cross Soc, Perth, WA, Australia. [Pink, J.] Australian Red Cross Blood Serv, Stafford, Qld, Australia. [Leung, J. N. S.; Chu, C. C. Y.; Lee, C. -K.] Hong Kong Red Cross Blood Transfus Serv, Blood Collect & Donor Recruitment Dept, Kowloon, Hong Kong, Peoples R China. [Faed, J.] Univ Otago, New Zealand Blood Serv, Dept Haematol, Otago Site, Dunedin, New Zealand. [Chay, J.; Tan, H. H.] Hlth Sci Author, Blood Serv Grp, 11 Outram Rd, Singapore 169078, Singapore. [Teo, D.] Ctr Transfus Med, Singapore, Singapore. [Djoudi, R.] Qualificat Biol Don Etab Francais Sang, St Denis, France. [Woimant, G.] EFS, Med Rech & Innovat, La Plaine St Denis, France. [Fillet, A. -M.] Etablisement Francais Sang, Dept Med, 20 Ave Stade France, F-93218 La Plaine St Denis, France. [Castren, J.] Finnish Red Cross Blood Serv, Med Support Blood Donat, Kivihaantie 7, FI-00310 Helsinki, Finland. [Miflin, G.] NHS Blood & Transplant, Watford, England. [Vandewalle, G. C.] Belgian Red Cross Flanders, Blood Transfus, Mechelen, Belgium. [Compernolle, V.] Belgian Red Cross, Blood Serv, Ottergemsesteenweg 413, B-9000 Ghent, Belgium. [Cardenas, J. M.] Tejidos Humanos, Ctr Vasco Transfus & Tejidos Humanos, Labeaga S-N, Galdakao 48960, Spain. [Infanti, L.; Holbro, A.; Buser, A.] Swiss Red Cross, Blood Donat Ctr, Hebelstr 10, CH-4031 Basel, Switzerland. [Holbro, A.; Buser, A.] Univ Basel Hosp, Dept Hematol, Basel, Switzerland. [van den Hurk, K.] Sanquin Res, Donor Studies, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. [Yahalom, V. J.; Gendelman, V.; Shinar, E.] Magen David Adom Natl Blood Serv, Natl Blood Serv, IL-5262100 Ramat Gan, Israel. [Eder, A. F.] Amer Red Cross, Biomed Headquarters, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. [Steele, W. R.] Amer Red Cross, Transmissible Dis Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. [O'Neill, E. M.] Amer Red Cross, Natl Headquarters Biomed Serv, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. [Kamel, H.] Blood Syst Inc, Corp Med Director Med Affairs, 6210 E Oak St, Scottsdale, AZ 85257 USA. [Vassallo, R.] Blood Syst Inc, 6210 E Oak St, Scottsdale, AZ 85257 USA. [Delage, G.; Lebrun, A.; Robillard, P.; Germain, M.] Hema Quebec, Med Affairs, 4045 Boul Cote Vertu, Montreal, PQ, Canada. [Gandhi, M.] Mayo Clin Minnesota, Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. [West, K. A.] NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,Room 1N226, Bethesda, MD 20892 USA. [Klein, H. G.] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, 10 Ctr Dr,Room IC711, Bethesda, MD 20892 USA. RP Speedy, J (reprint author), Australian Red Cross Blood Serv, Adelaide, SA, Australia. EM jspeedy@redcrossblood.org.au; ckleea@ha.org.hk; jim.faed@nzblood.co.nz; jason_chay@hsa.gov.sg; rachid.djoudi@efs.sante.fr; johanna.castren@bloodservice.fi; gail.miflin@nhsbt.nhs.uk; veerle.compernolle@rodekruis.be; josemanuel.cardenasdiazdeespada@osakidetza.eus; andreas.buser@usb.ch; k.vandenhurk@sanquin.nl; anne.eder@redcross.org; hkamel@bloodsystems.org; rvassallo@bloodsystems.org; gilles.delage@hema-quebec.qc.ca; gandhi.manish@mayo.edu; kamille.west@nih.gov; hklein@cc.nih.gov RI Buser, Andreas/A-2660-2008; OI Buser, Andreas/0000-0002-7942-6746; Lozano, Miguel/0000-0003-2593-833X NR 31 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 EI 1423-0410 J9 VOX SANG JI Vox Sang. PD NOV PY 2016 VL 111 IS 4 BP 449 EP 473 DI 10.1111/vox.12431 PG 25 WC Hematology SC Hematology GA EC6XS UT WOS:000388280600019 PM 27564140 ER PT J AU Roark, B Tan, JA Ivanina, A Chandler, M Castaneda, J Kim, HS Jawahar, S Viard, M Talic, S Wustholz, KL Yingling, YG Jones, M Afonin, KA AF Roark, Brandon Tan, Jenna A. Ivanina, Anna Chandler, Morgan Castaneda, Jose Kim, Ho Shin Jawahar, Shriram Viard, Mathias Talic, Strahina Wustholz, Kristin L. Yingling, Yaroslava G. Jones, Marcus Afonin, Kirill A. TI Fluorescence Blinking as an Output Signal for Biosensing SO ACS SENSORS LA English DT Article DE fluorescence blinking; quantum dots; lattices; biosensors; K-ras; nucleic acid engineering; strand displacement ID FUNCTIONALIZED QUANTUM DOTS; DNA STRAND DISPLACEMENT; IN-SITU HYBRIDIZATION; SPLIT FUNCTIONALITIES; GOLD NANOPARTICLES; LOGIC-CIRCUITS; RNA; NANOTECHNOLOGY; DESIGN; AMPLIFICATION AB We demonstrate the first biosensing strategy that relies on quantum dot (QD) fluorescence blinking to report the presence of a target molecule. Unlike other biosensors that utilize QDs, our method does not require the analyte to induce any fluorescence intensity or color changes, making it readily applicable to a wide range of target species. Instead, our approach relies on the understanding that blinking, a single particle phenomenon, is obscured when several QDs lie within the detection volume of a confocal microscope. If QDs are engineered to aggregate when they encounter a particular target molecule, the observation of quasi-continuous emission should indicate its presence. As proof of concept, we programmed DNAs to drive rapid isothermal assembly of QDs in the presence of a target strand (oncogene K-ras). The assemblies, confirmed by various gel techniques, contained multiple QDs and were readily distinguished from free QDs by the absence of blinking. C1 [Roark, Brandon; Ivanina, Anna; Chandler, Morgan; Castaneda, Jose; Jawahar, Shriram; Talic, Strahina; Jones, Marcus; Afonin, Kirill A.] Univ North Carolina Charlotte, Dept Chem, 9201 Univ City Blvd, Charlotte, NC 28223 USA. [Tan, Jenna A.] Coll William & Mary, Dept Chem, Williamsburg, VA 23185 USA. [Kim, Ho Shin; Yingling, Yaroslava G.] North Carolina State Univ, Dept Mat Sci & Engn, Raleigh, NC 27695 USA. [Viard, Mathias] Leidos Biomed Res Inc, Basic Sci Program, RNA Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Jones, Marcus; Afonin, Kirill A.] Univ North Carolina Charlotte, Nanoscale Sci Program, Charlotte, NC 28223 USA. [Jones, Marcus; Afonin, Kirill A.] Univ North Carolina Charlotte, Ctr Biomed Engn & Sci, Charlotte, NC 28223 USA. RP Jones, M; Afonin, KA (reprint author), Univ North Carolina Charlotte, Dept Chem, 9201 Univ City Blvd, Charlotte, NC 28223 USA.; Jones, M; Afonin, KA (reprint author), Univ North Carolina Charlotte, Nanoscale Sci Program, Charlotte, NC 28223 USA.; Jones, M; Afonin, KA (reprint author), Univ North Carolina Charlotte, Ctr Biomed Engn & Sci, Charlotte, NC 28223 USA. EM marcus.jones@uncc.edu; kafonin@uncc.edu RI Jones, Marcus/B-3291-2008 OI Jones, Marcus/0000-0001-9912-1168 FU UNC Charlotte; NSF [CMMI-1150682]; Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN26120080001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Dr. Troutman (UNC Charlotte) for helpful discussion. This publication was funded with the start-up funds provided by UNC Charlotte to K.A.A. H.S.K. and Y.G.Y. acknowledge support by NSF (CMMI-1150682). The computer support was provided by High Performance Computing (HPC) center at North Carolina State University. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN26120080001E. 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 Research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 48 TC 0 Z9 0 U1 11 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2379-3694 J9 ACS SENSORS JI ACS Sens. PD NOV PY 2016 VL 1 IS 11 BP 1295 EP 1300 DI 10.1021/acssensors.6b00352 PG 6 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Chemistry; Science & Technology - Other Topics GA ED5TI UT WOS:000388914800005 ER PT J AU Grodin, EN Steckler, LE Momenan, R AF Grodin, Erica N. Steckler, Leah E. Momenan, Reza TI Altered Striatal Response During Effort-Based Valuation and Motivation in Alcohol-Dependent Individuals SO ALCOHOL AND ALCOHOLISM LA English DT Article ID INCENTIVE SENSITIZATION; DETOXIFIED ALCOHOLICS; NICOTINE DEPENDENCE; NONDRUG REWARDS; DRUG-ADDICTION; BRAIN; AMPHETAMINE; DOPAMINE; VISUALIZATION; DYSREGULATION AB To use functional magnetic resonance imaging (fMRI) to investigate the neural circuitry behind effort-related valuation and motivation in a population of alcohol-dependent participants and healthy controls. Seventeen alcohol-dependent participants and a comparison group of 17 healthy control participants completed an effort-based motivation paradigm during an fMRI scan, in which they were required to exert effort at varying levels in order to earn a monetary reward. We found that alcohol-dependent participants were less motivated during trials requiring high levels of effort. The whole-brain fMRI analysis revealed that alcohol-dependent participants displayed an increased blood-oxygen-level dependent (BOLD) signal during low and unknown effort cues in the dorsal and ventral striatum compared with healthy controls. These findings provide the first evidence that alcohol-dependent participants and healthy controls differ in their effort-based valuation and motivation processing. Alcohol-dependent participants displayed a hyperactive mesolimbic reward circuitry recruited by non-drug rewards, potentially reflecting a sensitization to reward in this patient population. C1 [Grodin, Erica N.; Steckler, Leah E.; Momenan, Reza] Natl Inst Alcohol Abuse & Alcoholism, Clin NeuroImaging Res Core, Natl Inst Hlth, Bethesda, MD USA. [Grodin, Erica N.] Brown Natl Inst Hlth, Grad Partnership Program, Bethesda, MD USA. RP Momenan, R (reprint author), 10 Ctr Dr,MSC1108, Bethesda, MD 20892 USA. EM rezam@nih.gov OI Grodin, Erica/0000-0001-5528-4918 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health. NR 40 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV PY 2016 VL 51 IS 6 BP 638 EP 646 DI 10.1093/alcalc/agw003 PG 9 WC Substance Abuse SC Substance Abuse GA ED0HQ UT WOS:000388524000002 PM 26893259 ER PT J AU Qu, FL Yang, MH Rasooly, A AF Qu, Fengli Yang, Minghui Rasooly, Avraharn TI Dual Signal Amplification Electrochemical Biosensor for Monitoring the Activity and Inhibition of the Alzheimer's Related Protease beta-Secretase SO ANALYTICAL CHEMISTRY LA English DT Article ID ENZYME 1 BACE1; AMYLOID-BETA; CHARGE-TRANSFER; DRUG-DELIVERY; DISEASE; HYDROXYAPATITE; CELL; NANOPARTICLES; GENERATION; MEMAPSIN-2 AB The protease BACE1 (the beta-site amyloid precursor protein cleaving enzyme 1) catalyzes the first step in the synthesis of beta-amyloids (A beta), peptides that accumulate in the brain in Alzheimers disease (AD). Measurement of BACE1 activity is important for the development of BACE1 inhibitors to slow or stop AD. To measure BACE1 cleavage of the electrode-immobilized substrate peptide, we developed a redox-generating hydroxyapatite (HAP) probe which generates electrochemical current by reaction of the nanoparticle with molybdate (MoO42- The probe combines alkaline phosphatase (ALP) for dual signal amplification and A beta antibody to bind the probe to the immobilized peptide substrate on the surface of the electrode. We measured the activity of BACE1 at concentrations ranging from 0.25 to 100 U/mL. The use of the dual-signal HAP-ALP probe increased the signal by an order of magnitude compared to HAP-only probe, enabling detection limits as low as 0.1 U/mL. To measure the inhibition of BACE1 activity, the BACE1 inhibitor OM99-2 was added to 25 U/mL of BACE1 in concentrations ranging from 5 to 150 nM. The observed detection limit of inhibition is 10 nM of OM99-2. These results demonstrate the capabilities of this novel biosensor to measure BACE1 activity and inhibitors of BACE1 activity. To the best of our knowledge this is the first report that reaction of HAP nanoparticles with molybdate can generate electrochemical current. This dual signal amplification strategy can be extended to other electrochemical assays and adapted for wide applications. C1 [Qu, Fengli; Yang, Minghui] Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Peoples R China. [Qu, Fengli] Qufu Normal Univ, Coll Chem & Chem Engn, Qufu 273165, Shandong, Peoples R China. [Rasooly, Avraharn] NCI, NIH, Rockville, MD 20850 USA. RP Yang, MH (reprint author), Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Peoples R China.; Rasooly, A (reprint author), NCI, NIH, Rockville, MD 20850 USA. EM yangminghui@csu.edu.cn; rasoolya@mail.nih.gov FU National Natural Science Foundation of China [21575165, 21375076]; Natural Science Foundation of Hunan province [2015JJ1019] FX This work was supported by a Grant from the National Natural Science Foundation of China (No. 21575165, 21375076) and the Natural Science Foundation of Hunan province (No. 2015JJ1019). NR 43 TC 3 Z9 3 U1 21 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2016 VL 88 IS 21 BP 10559 EP 10565 DI 10.1021/acs.analchem.6b02659 PG 7 WC Chemistry, Analytical SC Chemistry GA EA9UW UT WOS:000386991200033 PM 27650354 ER PT J AU Forbang, NI Michos, ED McClelland, RL Remigio-Baker, RA Allison, MA Sandfort, V Ix, JH Thomas, I Rifkin, DE Criqui, MH AF Forbang, Nketi I. Michos, Erin D. McClelland, Robyn L. Remigio-Baker, Rosemay A. Allison, Matthew A. Sandfort, Veit Ix, Joachim H. Thomas, Isac Rifkin, Dena E. Criqui, Michael H. TI Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk MESA (Multi-Ethnic Study of Atherosclerosis) SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE abdominal aorta; atherosclerosis; cardiovascular disease; computed tomography; coronary arteries; coronary heart disease ID CORONARY-ARTERY CALCIUM; CALCIFIED ATHEROSCLEROSIS; COMPUTED-TOMOGRAPHY; MORTALITY; ANGIOGRAPHY; PREDICTION; MORBIDITY; LESIONS; EVENTS; SCORE AB Background-Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Methods and Results-Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66 +/- 9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. Conclusions-The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries. C1 [Forbang, Nketi I.; Remigio-Baker, Rosemay A.; Allison, Matthew A.; Ix, Joachim H.; Thomas, Isac; Rifkin, Dena E.; Criqui, Michael H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr,MC 0965, La Jolla, CA 92093 USA. [Michos, Erin D.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Allison, Matthew A.; Ix, Joachim H.; Rifkin, Dena E.] Vet Adm San Diego Healthcare Syst, La Jolla, CA USA. [Sandfort, Veit] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Forbang, NI (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr,MC 0965, La Jolla, CA 92093 USA. EM nforbang@gmail.com OI Allison, Matthew/0000-0003-0777-8272 FU National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD [HL072403, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR [UL1-TR-000040, UL1-TR-001079] FX This study was supported by grant HL072403 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD, and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR. We thank the other investigators, the staff, and the participants of MESA for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. NR 20 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2016 VL 9 IS 11 AR e005138 DI 10.1161/CIRCIMAGING.116.005138 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA EC9RS UT WOS:000388482500008 ER PT J AU Penagaluri, A Higgins, AY Vavere, AL Miller, JM Arbab-Zadeh, A Betoko, A Steveson, C Zimmermann, E Cox, C Rochitte, CE Dewey, M Kofoed, KF Niinuma, H Di Carli, MF Lima, JAC Chen, MY AF Penagaluri, Ashritha Higgins, Angela Y. Vavere, Andrea L. Miller, Julie M. Arbab-Zadeh, Armin Betoko, Aisha Steveson, Chloe Zimmermann, Elke Cox, Christopher Rochitte, Carlos E. Dewey, Marc Kofoed, Klaus F. Niinuma, Hiroyuki Di Carli, Marcelo F. Lima, Joao A. C. Chen, Marcus Y. TI Computed Tomographic Perfusion Improves Diagnostic Power of Coronary Computed Tomographic Angiography in Women Analysis of the CORE320 Trial (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) According to Gender SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE computed tomography; coronary angiography; gender; myocardial perfusion imaging; women ID AMERICAN-HEART-ASSOCIATION; MICROVASCULAR DYSFUNCTION; NUCLEAR CARDIOLOGY; ANGINA-PECTORIS; SEX-DIFFERENCES; CT ANGIOGRAPHY; CHEST-PAIN; DISEASE; METAANALYSIS; MANAGEMENT AB Background-Coronary computed tomographic angiography (CTA) and myocardial perfusion imaging (CTP) is a validated approach for detection and exclusion of flow-limiting coronary artery disease (CAD), but little data are available on gender-specific performance of these modalities. In this study, we aimed to evaluate the diagnostic accuracy of combined coronary CTA and CTP in detecting flow-limiting CAD in women compared with men. Methods and Results-Three hundred and eighty-one patients who underwent both CTA-CTP and single-photon emission computed tomography myocardial perfusion imaging preceding invasive coronary angiography as part of the CORE320 multicenter study (Coronary Artery Evaluation Using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) were included in this ancillary study. All 4 image modalities were analyzed in blinded, independent core laboratories. Prevalence of flow-limiting CAD defined by invasive coronary angiography equal to 50% or greater with an associated single-photon emission computed tomography myocardial perfusion imaging defect was 45% (114/252) and 23% (30/129) in males and females, respectively. Patient-based diagnostic accuracy defined by the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone in females was 0.83 (0.75-0.89) and for CTA-CTP was 0.92 (0.86-0.97; P=0.003) compared with men where the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone was 0.82 (0.77-0.87) and for CTA-CTP was 0.84 (0.80-0.89; P=0.29). Conclusions-The combination of CTA-CTP was performed similarly in men and women for identifying flow-limiting coronary stenosis; however, in women, CTP had incremental value over CTA alone, which was not the case in men. C1 [Penagaluri, Ashritha; Vavere, Andrea L.; Miller, Julie M.; Arbab-Zadeh, Armin; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Baltimore, MD USA. [Penagaluri, Ashritha; Vavere, Andrea L.; Miller, Julie M.; Arbab-Zadeh, Armin; Lima, Joao A. C.] Sch Med, Baltimore, MD USA. [Betoko, Aisha; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Higgins, Angela Y.; Chen, Marcus Y.] NHLBI, NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. [Steveson, Chloe] Toshiba Med Syst Corp, Tokyo, Japan. [Zimmermann, Elke; Dewey, Marc] Charite, Berlin, Germany. [Rochitte, Carlos E.] Univ Sao Paulo, Sch Med, Inst Heart, InCor, BR-05508 Sao Paulo, Brazil. [Kofoed, Klaus F.] Univ Copenhagen, Rigshosp, DK-1168 Copenhagen, Denmark. [Niinuma, Hiroyuki] St Lukes Int Hosp, Tokyo, Japan. [Di Carli, Marcelo F.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Chen, MY (reprint author), NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM marcus.chen@nih.gov FU Toshiba Medical Systems Corporation; National Heart, Lung and Blood Institute of the National Institutes of Health FX This study was funded by Toshiba Medical Systems Corporation and in part by the intramural research program of the National Heart, Lung and Blood Institute of the National Institutes of Health. NR 35 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2016 VL 9 IS 11 AR e005189 DI 10.1161/CIRCIMAGING.116.005189 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA EC9RS UT WOS:000388482500009 ER PT J AU Butler, J Hamo, CE Udelson, JE Pitt, B Yancy, C Shah, SJ Desvigne-Nickens, P Bernstein, HS Clark, RL Depre, C Dinh, W Hamer, A Kay-Mugford, P Kramer, F Lefkowitz, M Lewis, K Maya, J Maybaum, S Patel, MJ Pollack, PS Roessig, L Rotman, S Salsali, A Sims, JJ Senni, M Rosano, G Dunnmon, P Stockbridge, N Anker, SD Zile, MR Gheorghiade, M AF Butler, Javed Hamo, Carine E. Udelson, James E. Pitt, Bertram Yancy, Clyde Shah, Sanjiv J. Desvigne-Nickens, Patrice Bernstein, Harold S. Clark, Richard L. Depre, Christophe Dinh, Wilfried Hamer, Andrew Kay-Mugford, Patricia Kramer, Frank Lefkowitz, Martin Lewis, Kelly Maya, Juan Maybaum, Simon Patel, Mahesh J. Pollack, Pia S. Roessig, Lothar Rotman, Sarit Salsali, Afshin Sims, J. Jason Senni, Michele Rosano, Giuseppe Dunnmon, Preston Stockbridge, Norman Anker, Stefan D. Zile, Michael R. Gheorghiade, Mihai TI Exploring New Endpoints for Patients With Heart Failure With Preserved Ejection Fraction SO CIRCULATION-HEART FAILURE LA English DT Article DE aging; drug approval; heart failure; hospitalization; quality of life ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; QUALITY-OF-LIFE; CLINICAL-TRIALS; FUNCTIONAL-CAPACITY; I-PRESERVE; WALK TEST; HOSPITALIZATION; PREFERENCES; SURVIVAL; OUTCOMES AB The epidemiological, clinical, and societal implications of the heart failure (HF) epidemic cannot be overemphasized. Approximately half of all HF patients have HF with preserved ejection fraction (HFpEF). HFpEF is largely a syndrome of the elderly, and with aging of the population, the proportion of patients with HFpEF is expected to grow. Currently, there is no drug known to improve mortality or hospitalization risk for these patients. Besides mortality and hospitalization, it is imperative to realize that patients with HFpEF have significant impairment in their functional capacity and their quality of life on a daily basis, underscoring the need for these parameters to ideally be incorporated within a regulatory pathway for drug approval. Although attempts should continue to explore therapies to reduce the risk of mortality or hospitalization for these patients, efforts should also be directed to improve other patient-centric concerns, such as functional capacity and quality of life. To initiate a dialogue about the compelling need for and the challenges in developing such alternative endpoints for patients with HFpEF, the US Food and Drug Administration on November 12, 2015, facilitated a meeting represented by clinicians, academia, industry, and regulatory agencies. This document summarizes the discussion from this meeting. C1 [Butler, Javed; Hamo, Carine E.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Udelson, James E.] Tufts Univ, Sch Med, Tufts Med Ctr, Div Cardiol, Boston, MA 02111 USA. [Pitt, Bertram] Univ Michigan, Sch Med, Div Cardiol, Ann Arbor, MI USA. [Yancy, Clyde; Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Desvigne-Nickens, Patrice] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [Bernstein, Harold S.] Merck & Co Inc, Kenilworth, NJ USA. [Clark, Richard L.; Sims, J. Jason] Medtronic, Mounds View, MN USA. [Depre, Christophe; Hamer, Andrew; Maya, Juan] Amgen Inc, Thousand Oaks, CA 91320 USA. [Dinh, Wilfried; Kramer, Frank; Lewis, Kelly; Roessig, Lothar; Rotman, Sarit] Bayer Pharma AG, Wuppertal, Germany. [Dinh, Wilfried] Univ Hosp Witten Herdecke, Dept Cardiol, HELIOS Clin Wuppertal, Witten, Germany. [Kay-Mugford, Patricia; Lefkowitz, Martin; Maybaum, Simon] Novartis Pharmaceut Inc, E Hanover, NJ USA. [Patel, Mahesh J.] Merck Res Labs, Clin Res Cardiovasc Dis Div, Rahway, NJ USA. [Pollack, Pia S.] AstraZeneca Global Med Dev, Gaithersburg, MD USA. [Salsali, Afshin] Boehringer Ingelheim Pharmaceut Inc, 90 E Ridge POB 368, Ridgefield, CT 06877 USA. [Senni, Michele] Azienda Osped Papa Giovannni XXIII, Dipartimento Cardiovasc, Bergamo, Italy. [Rosano, Giuseppe] IRCCS San Raffaele Pisana, Dept Med Sci, Rome, Italy. [Rosano, Giuseppe] St Georges Univ London, Cardiovasc & Cell Sci Inst, London, England. [Dunnmon, Preston; Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. [Anker, Stefan D.] Univ Med Ctr Gottingen UMG, Innovat Clin Trials, Dept Cardiol & Pneumol, Gottingen, Germany. [Zile, Michael R.] Med Univ South Carolina, Charleston, SC USA. [Zile, Michael R.] RHJ Dept Vet Adm Med Ctr, Charleston, SC USA. RP Butler, J (reprint author), SUNY Stony Brook, Div Cardiol, T-16,Room 080, Stony Brook, NY 11794 USA. EM javed.butler@stonybrookmedicine.edu FU National Institutes of Health; European Union; American Heart Association; Novartis; Abbott Vascular; Vifor; Bayer Pharma; Lonestar Heart; Respicardia; ZS Pharma; Relypsa; Biotronik; Cardiorentis; Servier; National Heart, Lung, and Blood Institute; Veteran Affairs; Alere; Bayer; CVRx; Medtronic; Sanofi-Aventis FX Dr Butler reports receiving research support from the National Institutes of Health and European Union and serves as a consultant to Amgen, Bayer, Boehringer Ingelheim, Cardiocell, Celladon, Novartis, Trevena, Relypsa, Z Pharma, and Zensun. Dr Shah reports research support from the National Institutes of Health and the American Heart Association and has served as an advisory board member for Actelion, Bayer, Merck, and Novartis. Dr Bernstein is an employee of Merck. R. Clark and J.J. Sims are employees of Medtronic. Drs Depre, Hamer, and Maya are employees of Amgen. Dr Dinh, Dr Kramer, Kelly Lewis, S. Rotman, and Dr Roessig are employees of Bayer Pharma AG. P. Kay-Mugford and Dr Lefkowitz are employees of Novartis. Dr Patel is an employee of Merck. Dr Pitt has served as a consultant for Pfizer, Merck, Bayer, Relypsa, Stealth Peptides, AstraZeneca, Boehringer Ingelheim, scPharmaceuticals, PharMain, Tricida, DaVinci Therapeutics, Kbp Biosciences, and Takeda and has stock options in Tricida, Relypsa, Stealth Peptides, PharMain, scPharmaceuticals, Kbp Biosciences, and a patent pending, site-specific delivery of eplerenone to the myocardium. Dr Pollack is an employee of AstraZeneca. Dr Salsali is an employee of Boehringer Ingelheim. Dr Senni reports consulting fees for Novartis and Abbott Vascular. Dr Anker has received research grants from Vifor and Abbott Vascular and personal fees from Vifor, Abbott Vascular, Bayer Pharma, Novartis, Lonestar Heart, Respicardia, ZS Pharma, Relypsa, Biotronik, Cardiorentis, and Servier. Dr Zile has received research support from National Heart, Lung, and Blood Institute, Veteran Affairs, Alere, Bayer, CVRx, Medtronic, Novartis, Sanofi-Aventis and has served as a consultant for Abbott, Alere, Bayer, BG Med, Bristol Myers Squib, Cardiome, Celledon, CorAssist, CVRx, GE Health, HDL, Idenex, Intersection Medical, Medtronic, MicroVide, Novartis, ONO Pharma, Sanofi-Aventis, and Up-To-Date. Dr Gheorghiade reports consulting relationships with Abbott, Astellas, AstraZeneca, Bayer, Cardiorentis, CorThera, Cytokinetics, CytoPherx, DebioPharm SA, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, Johnson & Johnson, Medtronic, Merck, Novartis, Ono Pharmaceuticals, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda, and Trevena Therapeutics. The other authors report no conflicts. NR 37 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2016 VL 9 IS 11 AR e003358 DI 10.1161/CIRCHEARTFAILURE.116.003358 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ED2HH UT WOS:000388664100006 ER PT J AU Carlsten, M Korde, N Kotecha, R Reger, R Bor, S Kazandjian, D Landgren, O Childs, RW AF Carlsten, Mattias Korde, Neha Kotecha, Ritesh Reger, Robert Bor, Simona Kazandjian, Dickran Landgren, Ola Childs, Richard W. TI Checkpoint Inhibition of KIR2D with the Monoclonal Antibody IPH2101 Induces Contraction and Hyporesponsiveness of NK Cells in Patients with Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID NATURAL-KILLER-CELL; MHC CLASS-I; HIGH-AFFINITY RECEPTOR; RELAPSED/REFRACTORY MULTIPLE-MYELOMA; MISSING-SELF; MOLECULES; TRANSPLANTATION; EDUCATION; VIVO; RECOGNITION AB Purpose: Immune checkpoint inhibitors have recently revolutionized cancer immunotherapy. On the basis of data showing KIR-ligand mismatched natural killer (NK) cells reduce the risk of leukemia and multiple myeloma relapse following allogeneic hematopoietic stem cell transplantation, investigators have developed a checkpoint inhibition antibody that blocks KIR on NK cells. Although in vitro studies suggest the KIR2D-specific antibody IPH2101 induces KIR-ligand mismatched tumor killing by NK cells, our single-arm phase II clinical trial in patients with smoldering multiple myeloma was prematurely terminated due to lack of clinical efficacy. This study aimed at unveiling the underlying mechanisms behind the lack of clinical efficacy. Experimental Design: Treatment-naive patients received an intravenous infusion of 1 mg/kg IPH2101 every other month for up to a year. Peripheral blood was collected at baseline and 24 hours after first infusion, followed by weekly samples for the month and monthly samples thereafter. NK cell phenotype and function was analyzed using high-resolution flow cytometry. Results: Unexpectedly, infusion of IPH2101 resulted in rapid reduction in both NK cell responsiveness and KIR2D expression on the NK cell surface. In vitro assays revealed KIR2D molecules are removed from the surface of IPH2101-treated NK cells by trogocytosis, with reductions in NK cell function directly correlating with loss of free KIR2D surface molecules. Although IPH2101 marginally augmented the antimyeloma cytotoxicity of remaining KIR2D(dul)l patientNK cells, the overall response was diminished by significant contraction and reduced function of KIR2D-expressing NK cells. Conclusions: These data raise concerns that the unexpected biological events reported in this study could compromise antibody- based strategies designed at augmenting NK cell tumor killing via checkpoint inhibition. (C) 2016 AACR. C1 [Carlsten, Mattias; Kotecha, Ritesh; Reger, Robert; Bor, Simona; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Korde, Neha; Kazandjian, Dickran; Landgren, Ola] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NIH, 10 Ctr Dr MSC 1230,Bldg 10-CRC 3E-5332, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov FU NHLBI Division of Intramural Research (DIR); NCI DIR; Medical Research Scholars Program (MRSP) program at the NIH; Swedish Research Council FX Funding for this study was provided by the NHLBI Division of Intramural Research (DIR), the NCI DIR, the Medical Research Scholars Program (MRSP) program at the NIH, and the Swedish Research Council (to M. Carlsten). NR 43 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2016 VL 22 IS 21 BP 5211 EP 5222 DI 10.1158/1078-0432.CCR-16-1108 PG 12 WC Oncology SC Oncology GA EB5VY UT WOS:000387450000010 PM 27307594 ER PT J AU Lyle, LT Lockman, PR Adkins, CE Mohammad, AS Sechrest, E Hua, E Palmieri, D Liewehr, DJ Steinberg, SM Kloc, W Izycka-Swieszewska, E Duchnowska, R Nayyar, N Brastianos, PK Steeg, PS Gril, B AF Lyle, L. Tiffany Lockman, Paul R. Adkins, Chris E. Mohammad, Afroz Shareef Sechrest, Emily Hua, Emily Palmieri, Diane Liewehr, David J. Steinberg, Seth M. Kloc, Wojciech Izycka-Swieszewska, Ewa Duchnowska, Renata Nayyar, Naema Brastianos, Priscilla K. Steeg, Patricia S. Gril, Brunilde TI Alterations in Pericyte Subpopulations Are Associated with Elevated Blood-Tumor Barrier Permeability in Experimental Brain Metastasis of Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM METASTASES; PHASE-II; MESENCHYMAL TRANSITION; CAPECITABINE; GROWTH; COLONIZATION; ANGIOGENESIS; TEMOZOLOMIDE; INTEGRITY; SURVIVAL AB Purpose: The blood-brain barrier (BBB) is modified to a blood-tumor barrier (BTB) as a brain metastasis develops from breast or other cancers. We (i) quantified the permeability of experimental brain metastases, (ii) determined the composition of the BTB, and (iii) identified which elements of the BTB distinguished metastases of lower permeability from those with higher permeability. Experimental Design: A SUM190-BR3 experimental inflammatory breast cancer brain metastasis subline was established. Experimental brain metastases from this model system and two previously reported models (triple-negative MDA-231-BR6, HER2(+) JIMT-1-BR3) were serially sectioned; low- and high-permeability lesions were identified with systemic 3-kDa Texas Red dextran dye. Adjoining sections were used for quantitative immunofluorescence to known BBB and neuroinflammatory components. One-sample comparisons against a hypothesized value of one were performed with the Wilcoxon signed-rank test. Results: When uninvolved brain was compared with any brain metastasis, alterations in endothelial, pericytic, astrocytic, and microglial components were observed. When metastases with relatively low and high permeability were compared, increased expression of a desmin(+) subpopulation of pericytes was associated with higher permeability (231-BR6 P = 0.0002; JIMT-1-BR3 P = 0.004; SUM190-BR3 P = 0.008); desmin(+) pericytes were also identified in human craniotomy specimens. Trends of reduced CD13(+) pericytes (231-BR6 P = 0.014; JIMT-1-BR3 P = 0.002, SUM190-BR3, NS) and laminin alpha 2 (231-BR6 P = 0.001; JIMT-1-BR3 P = 0.049; SUM190-BR3 P = 0.023) were also observed with increased permeability. Conclusions: We provide the first account of the composition of the BTB in experimental brain metastasis. Desmin(+) pericytes and laminin a2 are potential targets for the development of novel approaches to increase chemotherapeutic efficacy. (C) 2016 AACR. C1 [Hua, Emily; Palmieri, Diane; Steeg, Patricia S.; Gril, Brunilde] NCI, Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD 20892 USA. [Lockman, Paul R.; Adkins, Chris E.; Mohammad, Afroz Shareef; Sechrest, Emily] West Virginia Univ, Hlth Sci Ctr, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. [Lyle, L. Tiffany; Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Kloc, Wojciech] Univ Varmia & Masuria Univ, Dept Neurol, Olsztyn, Poland. [Kloc, Wojciech] Univ Varmia & Masuria Univ, Dept Neurosurg, Olsztyn, Poland. [Kloc, Wojciech] Copernicus Hosp Gdansk, Dept Neurosurg, Gdansk, Poland. [Izycka-Swieszewska, Ewa] Med Univ Gdansk, Dept Pathol, Gdansk, Poland. [Izycka-Swieszewska, Ewa] Med Univ Gdansk, Dept Neuropathol, Gdansk, Poland. [Izycka-Swieszewska, Ewa] Copernicus Hosp, Dept Pathomorphol, Gdansk, Poland. [Duchnowska, Renata] Mil Inst Med, Dept Oncol, Warsaw, Poland. [Nayyar, Naema; Brastianos, Priscilla K.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Neurooncol, Boston, MA USA. [Palmieri, Diane] NCI, Ctr Res Strategy, NIH, Bethesda, MD 20892 USA. [Lyle, L. Tiffany] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47906 USA. RP Gril, B (reprint author), NCI, 37-1126 NIH, Bethesda, MD 20892 USA. EM grilbrun@mail.nih.gov FU Intramural Program of the NCI; U.S. Department of Defense Breast Cancer Research Program [W81 XWH-062-0033]; Inflammatory Breast Cancer Research Foundation FX This work was supported by the Intramural Program of the NCI, U.S. Department of Defense Breast Cancer Research Program, grant number: W81 XWH-062-0033, and a research grant from the Inflammatory Breast Cancer Research Foundation. NR 42 TC 2 Z9 2 U1 7 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2016 VL 22 IS 21 BP 5287 EP 5299 DI 10.1158/1078-0432.CCR-15-1836 PG 13 WC Oncology SC Oncology GA EB5VY UT WOS:000387450000018 PM 27245829 ER PT J AU Smith, PJ Chattopadhyay, PK AF Smith, Paul J. Chattopadhyay, Pratip K. TI Re-Visiting Fc-Receptor Blocking Maneuvers in Man SO CYTOMETRY PART A LA English DT Editorial Material ID NONSPECIFIC-BINDING; ANTIBODIES; IMMUNOHISTOCHEMISTRY; TARGETS C1 [Smith, Paul J.] Cardiff Univ, Sch Med, Canc & Genet Inst, Cardiff CF14 4XN, S Glam, Wales. [Chattopadhyay, Pratip K.] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Smith, PJ (reprint author), Cardiff Univ, Sch Med, Canc & Genet Inst, Canc Biol, Cardiff CF14 4XN, S Glam, Wales. EM smithpj2@cf.ac.uk OI Chattopadhyay, Pratip/0000-0002-5457-9666 NR 12 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2016 VL 89A IS 11 BP 975 EP 977 DI 10.1002/cyto.a.22998 PG 3 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ED0UA UT WOS:000388556400004 PM 27870535 ER PT J AU Cogliati, M D'Amicis, R Zani, A Montagna, MT Caggiano, G De Giglio, O Balbino, S De Donno, A Serio, F Susever, S Ergin, C Velegraki, A Ellabib, MS Nardoni, S Macci, C Oliveri, S Trovato, L Dipineto, L Rickerts, V McCormick-Smith, I Akcaglar, S Tore, O Mlinaric-Missoni, E Bertout, S Mallie, M Martins, MD Venca, ACF Vieira, ML Sampaio, AC Pereira, C Criseo, G Romeo, O Ranque, S Al-Yasiri, MHY Kaya, M Cerikcioglu, N Marchese, A Vezzulli, L Ilkit, M Desnos-Ollivier, M Pasquale, V Korem, M Polacheck, I Scopa, A Meyer, W Ferreira-Paim, K Hagen, F Theelen, B Boekhout, T Lockhart, SR Tintelnot, K Tortorano, AM Dromer, F Varma, A Kwon-Chung, KJ Inacio, J Alonso, B Colom, MF AF Cogliati, Massimo D'Amicis, Roberta Zani, Alberto Montagna, Maria Teresa Caggiano, Giuseppina De Giglio, Osvalda Balbino, Stella De Donno, Antonella Serio, Francesca Susever, Serdar Ergin, Cagri Velegraki, Aristea Ellabib, Mohamed S. Nardoni, Simona Macci, Cristina Oliveri, Salvatore Trovato, Laura Dipineto, Ludovico Rickerts, Volker McCormick-Smith, Ilka Akcaglar, Sevim Tore, Okan Mlinaric-Missoni, Emilija Bertout, Sebastien Mallie, Michele Martins, Maria da Luz Venca, Ana C. F. Vieira, Maria L. Sampaio, Ana C. Pereira, Cheila Criseo, Giuseppe Romeo, Orazio Ranque, Stephane Al-Yasiri, Mohammed H. Y. Kaya, Meltem Cerikcioglu, Nilgun Marchese, Anna Vezzulli, Luigi Ilkit, Macit Desnos-Ollivier, Marie Pasquale, Vincenzo Korem, Maya Polacheck, Itzhack Scopa, Antonio Meyer, Wieland Ferreira-Paim, Kennio Hagen, Ferry Theelen, Bart Boekhout, Teun Lockhart, Shawn R. Tintelnot, Kathrin Tortorano, Anna Maria Dromer, Francoise Varma, Ashok Kwon-Chung, Kyung J. Inacio, Joao Alonso, Beatriz Colom, Maria F. TI Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin (vol 16, 2016 ) SO FEMS YEAST RESEARCH LA English DT Correction C1 [Cogliati, Massimo; D'Amicis, Roberta; Zani, Alberto; Tortorano, Anna Maria] Univ Milan, Dip Sci Biomed Salute, Via Pascal 36, I-20133 Milan, Italy. [Montagna, Maria Teresa; Caggiano, Giuseppina; De Giglio, Osvalda; Balbino, Stella] Univ Bari Aldo Moro, Dip Sci Biomed & Oncol Umana, Piazza Giulio Cesare 11, I-70124 Bari, Italy. [De Donno, Antonella; Serio, Francesca] Univ Salento, Dip Sci & Tecnol Biol & Ambientali, Via Monteroni, I-73100 Lecce, Italy. [Susever, Serdar] Cyprus Near East Univ, Dept Nutr & Dietet, Near East Blvd, CY-99138 Nicosia, Cyprus. [Ergin, Cagri] Pamukkale Univ, Sch Med, Klin Kampusu, TR-20160 Denizli, Turkey. [Velegraki, Aristea] Univ Athens, Sch Med, Mikras Asias 75, Athens 11527, Greece. [Ellabib, Mohamed S.] Univ Tripoli, Coll Med, Tripoli Univ Rd, Tripoli, Libya. [Nardoni, Simona] Univ Pisa, Dip Sci Vet, Via Piagge 2, I-56124 Pisa, Italy. [Macci, Cristina] CNR, ISE, Via Moruzzi 1, I-56124 Pisa, Italy. [Oliveri, Salvatore; Trovato, Laura] Univ Catania, Dip Sci Microbiol & Sci Ginecol, Via Androne 81, I-95124 Catania, Italy. [Dipineto, Ludovico] Univ Naples Federico II, Dip Med Vet & Prod Anim, Cso Umberto 1 40, I-80138 Naples, Italy. [Rickerts, Volker; McCormick-Smith, Ilka; Tintelnot, Kathrin] Robert Koch Inst, Dept Infeciuos Dis, D-13302 Berlin, Germany. [Akcaglar, Sevim; Tore, Okan] Uludag Univ, Sch Med, Gorukle Kampusu, TR-16059 Bursa, Turkey. [Mlinaric-Missoni, Emilija] Croatian Natl Inst Publ Hlth, Rockefellerova 7, Zagreb 10000, Croatia. [Bertout, Sebastien; Mallie, Michele] Univ Montpellier, Unite Mixte Int Rech Translat lnfect VIH & Malad, 15 Ave Charles Flahault, F-34093 Montpellier, France. [Martins, Maria da Luz; Venca, Ana C. F.; Vieira, Maria L.] Inst Higiene & Med Trop, Rua Junqueira 100, P-1349008 Lisbon, Portugal. [Sampaio, Ana C.; Pereira, Cheila] Univ Tras Os Montes & Alto Douro, CITAB, P-5000801 Quinta Dos Prados, Vila Real, Portugal. [Criseo, Giuseppe; Romeo, Orazio] Univ Messina, Dept Chem Biol Pharmaceut & Environm Sci, Piazza Pugliatti 1, I-98122 Messina, Italy. [Ranque, Stephane; Al-Yasiri, Mohammed H. Y.] Aix Marseille Univ, IP TPT Infect Parasitaires Transmiss Pphysiopatho, 27 Blvd Jean Moulin, F-13005 Marseille, France. [Kaya, Meltem; Cerikcioglu, Nilgun] Marmara Univ, Sch Med, MU Goztepe Kampusu, TR-34722 Istanbul, Turkey. [Marchese, Anna] Univ Genoa, IRCCS San Martino IST Genova, Sez Microbiol DISC, Largo Benzi 10, I-16132 Genoa, Italy. [Vezzulli, Luigi] Univ Genoa, Dipartimento Sci Terra Ambiente & Vita DISTAV, Cso Europa 26, I-16132 Genoa, Italy. [Ilkit, Macit] Cukurova Univ Rektorlugu, Univ Cukurova Saricam, Dept Microbiol, TR-01330 Adana, Turkey. [Desnos-Ollivier, Marie; Dromer, Francoise] Inst Pasteur, CNRS, Unite Mycol Mol, 25-28 Rue Dr Roux, F-75015 Paris, France. [Pasquale, Vincenzo] Univ Napoli Parthenope, Dip Sci & Tecnol, Via Amm F Acton 38, I-80133 Naples, Italy. [Korem, Maya; Polacheck, Itzhack] Hadassah Hebrew Univ, Med Ctr, Div Microbiol & Infect Dis, POB 12271, Jerusalem, Israel. [Scopa, Antonio] Univ Basilicata, Fac Sci Agr Forestali & Ambientali, Via Nazario Sauro 85, I-85100 Potenza, Italy. [Meyer, Wieland; Ferreira-Paim, Kennio] Univ Sydney, Westmead Millennium Inst, Mol Mycol Res Lab, CIDM,MBI,Sydney Med Sch,Westmead Hosp, 176 Hawkesbury Rd, Westmead, NSW 2145, Australia. [Hagen, Ferry] Canisius Wilhelmina Hosp, Weg Door Jonkerbos 100, NL-6532 SZ Nijmegen, Netherlands. [Theelen, Bart; Boekhout, Teun] CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. [Lockhart, Shawn R.] Ctr Dis Control & Prevent, 1600 Clifton Rd, Atlanta, GA 30333 USA. [Varma, Ashok; Kwon-Chung, Kyung J.] NIAID, 31 Ctr Dr, Bethesda, MD 20892 USA. [Inacio, Joao; Alonso, Beatriz] Univ Brighton, Sch Pharm & Biomol Sci, Lewes Rd, Brighton BN2 4GJ, E Sussex, England. [Colom, Maria F.] Univ Miguel Hernandez, Sch Med, Ave Univ, Alicante 03202, Spain. RP Cogliati, M (reprint author), Univ Milan, Dip Sci Biomed Salute, Lab Micol Med, Via Pascal 36, I-20133 Milan, Italy. EM massimo.cogliati@unimi.it RI Hagen, Ferry/B-9044-2009 OI Hagen, Ferry/0000-0002-5622-1916 NR 1 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1567-1356 EI 1567-1364 J9 FEMS YEAST RES JI FEMS Yeast Res. PD NOV PY 2016 VL 16 IS 7 AR fow086 DI 10.1093/femsyr/fow086 PG 2 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA ED0VO UT WOS:000388560700012 ER PT J AU Linte, CA Yaniv, ZR AF Linte, Cristian A. Yaniv, Ziv R. TI Image-Guided Interventions We've come a long way, but are we there? SO IEEE PULSE LA English DT Article DE Medical diagnostic imaging; Government policies; Economics; Patient monitoring; Diseases; Medical treatment ID SURGERY C1 [Linte, Cristian A.] Rochester Inst Technol, Dept Biomed Engn, Rochester, NY 14623 USA. [Linte, Cristian A.] Rochester Inst Technol, Chester F Carlson Ctr Imaging Sci, Rochester, NY 14623 USA. [Yaniv, Ziv R.] TAJ Technol Inc, Mendota Hts, MN USA. [Yaniv, Ziv R.] NIH, Natl Lib Med, Off High Performance Comp & Commun, Bldg 10, Bethesda, MD 20892 USA. RP Linte, CA (reprint author), Rochester Inst Technol, Dept Biomed Engn, Rochester, NY 14623 USA.; Linte, CA (reprint author), Rochester Inst Technol, Chester F Carlson Ctr Imaging Sci, Rochester, NY 14623 USA. EM clinte@mail.rit.edu; zivyaniv@nih.gov FU Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine FX Ziv Yaniv was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine. of Technology in New York. Ziv R. Yaniv, Ph.D., (zivyaniv@nih.gov) is currently with TAJ Technologies Inc. and is also a senior computer scientist in the Office of High Performance Computing and Communications at the National Library of Medicine and the National Institutes of Health in Bethesda, Maryland. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD NOV-DEC PY 2016 VL 7 IS 6 BP 46 EP 50 DI 10.1109/MPUL.2016.2606466 PG 5 WC Engineering, Biomedical SC Engineering GA ED6KO UT WOS:000388964700012 PM 27875119 ER PT J AU Tsugawa, T Tsutsumi, H AF Tsugawa, Takeshi Tsutsumi, Hiroyuki TI Genomic changes detected after serial passages in cell culture of virulent human G1P[8] rotaviruses SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Rotavirus; Cell culture; Serial passage; Virulence; Mutation; Sequence ID REVERSE GENETICS; PORCINE ROTAVIRUS; SEQUENCE-ANALYSIS; BOVINE ROTAVIRUS; GROUP-A; VACCINE; MUTATIONS; NSP4; RESPONSES; EFFICACY AB Serial passages of a virulent mouse rotavirus in cell cultures caused a loss of virulence in mice. To gain insight into the genomic mutations in human rotavirus during cell culture and its attenuation in humans, we serially passaged three wild type human G1P[8] rotavirus strains (Wa, DC3695, DC5685) derived from diarrheal stool samples up to 60 times in two different cell cultures (human colon adenocarcinoma cell line: HT29, and primary African green monkey kidney cells: primary AGMK). We sequenced the whole genomes of 60 times-passaged strains and compared them with those of the original viruses. Most substitutions were detected in VP4, followed by substitutions in VP7 and NSP4 genes. Substitution at amino acid 385 in the putative VP4 fusion domain and substitution T45M in NSP4 genes were detected in all AGMK-passaged strains, respectively. These genomic changes are likely to correlate with a loss of rotavirus virulence in humans. (C) 2016 Published by Elsevier B.V. C1 [Tsugawa, Takeshi; Tsutsumi, Hiroyuki] Sapporo Med Univ, Sch Med, Dept Pediat, Chuo Ku, South 1 West 16, Sapporo, Hokkaido 0608543, Japan. [Tsugawa, Takeshi] NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 South Dr,MSC 8026, Bethesda, MD 20892 USA. RP Tsugawa, T (reprint author), Sapporo Med Univ, Sch Med, Dept Pediat, Chuo Ku, South 1 West 16, Sapporo, Hokkaido 0608543, Japan. EM tsugawat@sapmed.ac.jp FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX We thank R. W. Jones for expert technical assistance and Y. Hoshino for his support. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. There is no conflict of interest to declare. NR 37 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD NOV PY 2016 VL 45 BP 6 EP 10 DI 10.1016/j.meegid.2016.08.015 PG 5 WC Infectious Diseases SC Infectious Diseases GA ED0ZY UT WOS:000388574400002 PM 27543393 ER PT J AU Barreto, FK Khouri, R Rego, FFD Santos, LA de Castro-Amarante, MF Bialuk, I Pise-Masison, CA Galvao-Castro, B Gessain, A Jacobson, S Franchini, G Alcantara, LC AF Barreto, Fernanda Khouri Khouri, Ricardo de Almeida Rego, Filipe Ferreira Santos, Luciane Amorim de Castro-Amarante, Maria Fernanda Bialuk, Izabela Pise-Masison, Cynthia A. Galvao-Castro, Bernardo Gessain, Antoine Jacobson, Steven Franchini, Genoveffa Alcantara, Luiz Carlos, Jr. TI Analyses of HTLV-1 sequences suggest interaction between ORF-I mutations and HAM/TSP outcome SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE HTLV-1; ORF-1; HAM/TSP ID T-CELL LEUKEMIA; LYMPHOTROPIC-VIRUS TYPE-1; TROPICAL SPASTIC PARAPARESIS; NUCLEAR FACTOR; PROVIRAL LOAD; MESSENGER-RNA; PROTEIN; P12(I); PATHOGENESIS; PX AB The region known as pX in the 3' end of the human T-cell lymphotropic virus type 1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. HTLV-1 ORF-I produces the protein p12 and its cleavage product p8. The functions of these proteins have been linked to immune evasion and viral infectivity and persistence. It is known that the HTLV-1 infection does not necessarily imply the development of pathological processes and here we evaluated whether natural mutations in HTLV-1 ORF-I can influence the proviral load and clinical manifestation of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/ TSP). For that, we performed molecular characterization, datamining and phylogenetic analysis with HTLV-1 ORF-I sequences from 156 patients with negative or positive diagnosis for HAM/TSP. Our analyses demonstrated that some mutations may be associated with the outcome of HAM/ TSP (C39R, L40F, P45L, S69G and R88K) or with proviral load (P34L and F61L). We further examined the presence of mutations in motifs of HBZ and observed that P45L mutation is located within the HBZ nuclear localization signal and was found more frequently between patients with HAM/TSP and high proviral load. These results indicate that some natural mutations are located in functional domains of ORF-I and suggests a potential association between these mutations and the proviral loads and development of HAM/TSP. Therefore it is necessary to conduct functional studies aimed at evaluating the impact of these mutations on the virus persistence and immune evasion. (C) 2016 Elsevier B.V. All rights reserved. C1 [Barreto, Fernanda Khouri; de Almeida Rego, Filipe Ferreira; Santos, Luciane Amorim; Galvao-Castro, Bernardo; Alcantara, Luiz Carlos, Jr.] Fiocruz MS, Ctr Pesquisa Goncalo Moniz, Lab Hematol Genet & Biol Computac, Salvador, Bahia, Brazil. [Khouri, Ricardo] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, Leuven, Belgium. [de Castro-Amarante, Maria Fernanda; Pise-Masison, Cynthia A.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Bialuk, Izabela] Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. [Galvao-Castro, Bernardo] Escola Bahiana Med & Saude Publ, Salvador, Bahia, Brazil. [Gessain, Antoine] Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Dept Virol, Batiment Lwoff, Paris, France. [Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Alcantara, LC (reprint author), Fiocruz MS, Ctr Pesquisa Goncalo Moniz, Lab Hematol Genet & Biol Computac, Salvador, Bahia, Brazil. EM lalcan@bahia.fiocruz.br FU Intramural Program at the National Cancer Institute, National Institutes of Health, Bethesda, MD FX This work was supported by the Intramural Program at the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 37 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD NOV PY 2016 VL 45 BP 420 EP 425 DI 10.1016/j.meegid.2016.08.020 PG 6 WC Infectious Diseases SC Infectious Diseases GA ED0ZY UT WOS:000388574400055 PM 27553711 ER PT J AU Qin, XY Zhang, SP Cao, C Loh, YP Cheng, Y AF Qin, Xiao-Yan Zhang, Shu-Ping Cao, Chang Loh, Y. Peng Cheng, Yong TI Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease A Systematic Review and Meta-analysis SO JAMA NEUROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-ALPHA; C-REACTIVE PROTEIN; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; SERUM-LEVELS; TNF-ALPHA; DOPAMINERGIC-NEURONS; SUBSTANTIA-NIGRA AB IMPORTANCE The association of nonmotor features and Parkinson disease (PD) is increasingly recognized. Evidence suggests that inflammation may play a role in PD pathologic features and symptoms. OBJECTIVE To quantitatively summarize the peripheral inflammatory cytokine data available for patients with PD. DATA SOURCE A systematic search of peer-reviewed English-language articles from PubMed, PsycINFO, and the Cochrane Library without year limitation was performed from December 7, 2015, to March 23, 2016. The search terms included inflammation or cytokine or chemokine or tumor necrosis factor or interleukin or interferon or C-reactive protein AND Parkinson disease. STUDY SELECTION Studies were included if they provided data on peripheral blood cytokine concentrations in patients with PD and a healthy control group. Studies were excluded if they contained in vitro analysis of stimulated or unstimulated levels of cytokines, samples that overlapped with other studies, patients not diagnosed with PD at blood sampling, or if the cytokine analyzed was assessed in fewer than 3 studies. DATA EXTRACTION AND SYNTHESIS Datawere extracted from the 25 included studies encompassing 1547 unique patients with PD and 1107 unique controls by 2 independent investigators. Datawere pooled using a random-effects model with the ComprehensiveMeta-analysis software. Effect sizeswere generated as standardized mean differences of cytokine concentrations between patients with PD and healthy controls and converted to the Hedges g statistic. MAIN OUTCOMES AND MEASURES Blood cytokine concentrations in patients with PD compared with controls. Aberrations in peripheral cytokine levels were hypothesized to be related to PD. RESULTS Among the 2654 study participants, concentrations of interleukin 6 (IL-6) (Hedges g, 0.325; 95% CI, 0.007-0.643; P = .045) in 13 studies, tumor necrosis factor (Hedges g, 0.354; 95% CI, 0.144-0.563; P = .001) in 9 studies, IL-1 beta (Hedges g, 0.382; 95% CI, 0.142-0.621; P = .002) in 6 studies, C-reactive protein (Hedges g, 0.323; 95% CI, 0.052-0.593; P = .02) in 6 studies, IL-10 (Hedges g, 0.329; 95% CI, 0.051-0.607; P =.02) in 5 studies, RANTES (regulated on activation, normal T-expressed, and presumably secreted) (Hedges g, 0.605; 95% CI, 0.111-1.099; P = .02) in 5 studies, and IL-2 (Hedges g, 0.789; 95% CI, 0.105-1.472; P =.02) in 3 studies were significantly higher in patients with PD compared with healthy controls. No differences were found between patients with PD and healthy controls for concentrations of interferon-gamma (Hedges g, 0.745; 95% CI,-0.192 to 1.682; P =.12) in 5 studies, IL-4 (Hedges g, 0.031; 95% CI,-0.191 to 0.253; P = .79) in 3 studies, and IL-8 (Hedges g, 0.072; 95% CI,-0.136 to 0.279; P = .50) in 3 studies. CONCLUSIONS AND RELEVANCE The findings of the meta-analysis demonstrated higher peripheral concentrations of IL-6, tumor necrosis factor, IL-1 beta, IL-2, IL-10, C-reactive protein, and RANTES in patients with PD, strengthening the clinical evidence that PD is accompanied by an inflammatory response. C1 [Qin, Xiao-Yan; Zhang, Shu-Ping; Cao, Chang] MinZu Univ China, Ctr Translat Neurosci, Coll Life & Environm Sci, Beijing, Peoples R China. [Loh, Y. Peng; Cheng, Yong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Room 6C80, Bethesda, MD 20892 USA. RP Cheng, Y (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Room 6C80, Bethesda, MD 20892 USA. EM chengy4@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; 985 Academic Team-building Fund of MinZu University [YLDX01013, 2015MDTD13C]; 111 Project of China [B08044] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; grants YLDX01013 and 2015MDTD13C from the 985 Academic Team-building Fund of MinZu University; and the grant B08044 from the 111 Project of China. NR 73 TC 2 Z9 2 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV 1 PY 2016 VL 73 IS 11 BP 1316 EP 1324 DI 10.1001/jamaneurol.2016.2742 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA ED1BL UT WOS:000388578600012 PM 27668667 ER PT J AU Smith, DB Becher, P Bukh, J Gould, EA Meyers, G Monath, T Muerhoff, AS Pletnev, A Rico-Hesse, R Stapleton, JT Simmonds, P AF Smith, Donald B. Becher, Paul Bukh, Jens Gould, Ernest A. Meyers, Gregor Monath, Thomas Muerhoff, A. Scott Pletnev, Alexander Rico-Hesse, Rebecca Stapleton, Jack T. Simmonds, Peter TI Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; GB-VIRUS; NON-A; NONPRIMATE HEPACIVIRUSES; GENOMIC ORGANIZATION; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; B-HEPATITIS; CDNA-CLONE; IDENTIFICATION AB Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A-N) and 11 Pegivirus species (Pegivirus A-K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences for members of each proposed taxon. We propose that the species Hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimize confusion. Despite the newly documented genetic diversity of hepaciviruses and pegiviruses, members of these genera remain phylogenetically distinct, and differ in hepatotropism and the possession of a basic core protein; pegiviruses in general lack these features. However, other characteristics that were originally used to support their division into separate genera are no longer definitive; there is overlap between the two genera in the type of internal ribosomal entry site and the presence of miR-122 sites in the 5' UTR, the predicted number of N-linked glycosylation sites in the envelope E1 and E2 proteins, the presence of poly U tracts in the 3' UTR and the propensity of viruses to establish a persistent infection. While all classified hepaciviruses and pegiviruses have mammalian hosts, the recent description of a hepaci-/pegi-like virus from a shark and the likely existence of further homologues in other non-mammalian species indicate that further species or genera remain to be defined in the future. C1 [Smith, Donald B.; Simmonds, Peter] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH8 9YL, Midlothian, Scotland. [Becher, Paul] Univ Vet Med, Inst Virol, Hannover, Germany. [Bukh, Jens] Copenhagen Univ Hosp, Res Ctr, Dept Infect Dis & Clin, Copenhagen Hepatitis Program CO HEP C, Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen Hepatitis Program CO HEP C, DK-1168 Copenhagen, Denmark. [Gould, Ernest A.] Aix Marseille Univ, French Inst Res Dev IRD, EHESP French Sch Publ Hlth, EPV UMR D Emergence Pathol Virales 190, Marseille, France. [Meyers, Gregor] Fed Res Inst Anim Hlth, Friedrich Loeffler Inst, Inst Immunol, Greifswald, Germany. [Monath, Thomas] Hookipa Biotech AG, Vienna, Austria. [Monath, Thomas] PaxVax Inc, Menlo Pk, CA USA. [Monath, Thomas] PaxVax Inc, Redwood City, CA USA. [Muerhoff, A. Scott] Abbott Diagnost Res & Dev, Abbott Pk, IL USA. [Pletnev, Alexander] NIAID, Lab Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Rico-Hesse, Rebecca] Baylor Coll Med, Dept Mol Virol & microbiol, Houston, TX 77030 USA. [Rico-Hesse, Rebecca] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Stapleton, Jack T.] Iowa City Vet Affairs Med Ctr, Med Serv, Iowa City, IA USA. [Stapleton, Jack T.] Univ Iowa, Dept Internal Med, Iowa City, IA USA. [Stapleton, Jack T.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Simmonds, Peter] Univ Oxford, Nuffield Dept Med, Oxford, England. RP Smith, DB (reprint author), Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH8 9YL, Midlothian, Scotland. EM donald.smith.mail@gmail.com OI Becher, Paul/0000-0001-7857-1354 FU Wellcome Trust [095831/Z/11/Z, WT108418AIA] FX This work was supported by grants from the Wellcome Trust to the Centre for Immunity, Infection and Evolution at the University of Edinburgh (095831/Z/11/Z) and to the Nuffield Department of Medicine, University of Oxford (WT108418AIA). The authors are grateful to Troels Scheel (Copenhagen Hepatitis C Program, University of Copenhagen and Department of Infectious Diseases, Hividovre Hospital, Copenhagen, Denmark) for his helpful comments on the manuscript, and to Oliver Pybus and Julien Theze (Department of Zoology, University of Oxford, UK) for sharing their unpublished analysis of Wenling shark virus. NR 52 TC 0 Z9 0 U1 3 U2 3 PU MICROBIOLOGY SOC PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER ST, LONDON WC1N 2JU, ERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2016 VL 97 BP 2894 EP 2907 DI 10.1099/jgv.0.000612 PN 11 PG 14 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ED2LV UT WOS:000388677600010 PM 27692039 ER PT J AU Krasich, R Copeland, WC AF Krasich, Rachel Copeland, William C. TI Persistent Mitochondrial DNA Damage Due to POL gamma Disease Mutations SO MITOCHONDRION LA English DT Meeting Abstract C1 [Krasich, Rachel; Copeland, William C.] NIEHS, Mitochondrial DNA Replicat Grp, Mol Genet Lab, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2016 VL 31 MA PA-0200 BP 104 EP 104 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA EC8ZL UT WOS:000388431500052 ER PT J AU DeBalsi, KL Longley, MJ Hoff, KE Copeland, WC AF DeBalsi, Karen L. Longley, Matthew J. Hoff, Kirsten E. Copeland, William C. TI Biochemical characterization of the in cis T251I and P587L PolG disease mutations SO MITOCHONDRION LA English DT Meeting Abstract C1 [DeBalsi, Karen L.; Longley, Matthew J.; Hoff, Kirsten E.; Copeland, William C.] NIEHS, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2016 VL 31 MA PA-0206 BP 105 EP 105 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA EC8ZL UT WOS:000388431500055 ER PT J AU Hwang, SB Tarasenko, TN McGuire, PJ AF Hwang, Sun-Bin Tarasenko, Tatyana N. McGuire, Peter J. TI Tumor Necrosis Factor alpha modulates mitochondrial respiratory function in liver cells: exploring the immune basis for metabolic decompensation SO MITOCHONDRION LA English DT Meeting Abstract C1 [Hwang, Sun-Bin; Tarasenko, Tatyana N.; McGuire, Peter J.] NHGRI, Metab Infect & Immun Unity, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2016 VL 31 MA PA-0240 BP 114 EP 114 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA EC8ZL UT WOS:000388431500078 ER PT J AU Shin, EJ Dang, DK Tran, HQ Nam, Y Jeong, JH Lee, YH Park, KT Lee, YS Jang, CG Hong, JS Nabeshima, T Kim, HC AF Shin, Eun-Joo Dang, Duy-Khanh Hai-Quyen Tran Nam, Yunsung Jeong, Ji Hoon Lee, Young Hun Park, Kyung Tae Lee, Yong Sup Jang, Choon-Gon Hong, Jau-Shyong Nabeshima, Toshitaka Kim, Hyoung-Chun TI PKC delta knockout mice are protected from para-methoxymethamphetamine-induced mitochondrial stress and associated neurotoxicity in the striatum of mice SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Para-methoxymethamphetamine; Protein kinase C delta; Oxidative stress; Mitochondria; Tumor necrosis factor-alpha; Microglia ID PROTEIN-KINASE-C; DOPAMINERGIC NEURON DAMAGE; INDUCED LOCOMOTOR-ACTIVITY; NECROSIS-FACTOR-ALPHA; OXIDATIVE STRESS; IN-VIVO; MICROGLIAL ACTIVATION; SUPEROXIDE-DISMUTASE; CELL-DEATH; PROTEOLYTIC ACTIVATION AB Para-methoxymethamphetamine (PMMA) is a para-ring-substituted amphetamine derivative sold worldwide as an illegal psychotropic drug. Although PMMA use has been reported to lead to severe intoxication and even death, little is known about the mechanism(s) by which PMMA exerts its neurotoxic effects. Here we found that PMMA treatment resulted in phosphorylation of protein kinase CO (PKC delta) and subsequent mitochondrial translocation of cleaved PKCS. PMMA-induced oxidative stress was more pronounced in mitochondria than in the cytosol. Moreover, treatment with PMMA consistently resulted in significant reductions in mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial Mn superoxide dismutase-immunoreactivity. In contrast, PMMA treatment led to a significant increase in intramitochondrial Ca2+ level. Treatment with PMMA also significantly increased ionized calcium binding adaptor molecule 1 (Iba-1)-labeled microglial activation and upregulated tumor necrosis factor alpha (TNF-alpha) gene expression. PKC delta knockout attenuated these mitochondrial effects and dampened the neurotoxic effects of PMMA. Importantly, TNF-alpha knockout mice were significantly protected from PMMA-induced increases in phospho-PKC delta expression, mitochondrial translocation of cleaved PKC delta, and Iba-1-labeled microgliosis. Both rottlerin, a pharmacological inhibitor of WO, and etanercept, a pharmacological inhibitor of TNF-alpha, significantly protected against PMMA-mediated induction of apoptosis, as assessed by terminal deoxynucleotidyl transferase dUDP nick end labeling (TUNEL) assays. In addition, PKC delta knockout and TNF-alpha knockout both resulted in decreased PMMA-mediated induction of dopaminergic loss. Therefore, our results suggest that PKC delta mediates PMMA-induced neurotoxicity by facilitating oxidative stress (mitochondria > cytosol), mitochondrial dysfunction, microglial activation, and pro-apoptotic signaling. Our results also indicate that PMMA-induced PKC delta activation requires the proinflammatory cytokine TNF-alpha. (C) 2016 Published by Elsevier Ltd. C1 [Shin, Eun-Joo; Dang, Duy-Khanh; Hai-Quyen Tran; Nam, Yunsung; Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 24341, South Korea. [Jeong, Ji Hoon] Chung Ang Univ, Coll Med, Dept Pharmacol, Seoul 06974, South Korea. [Lee, Young Hun; Park, Kyung Tae; Lee, Yong Sup] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Med Chem Lab, Dept Pharm,Coll Pharm, Seoul 02447, South Korea. [Jang, Choon-Gon] Sungkyunkwan Univ, Dept Pharmacol, Sch Pharm, Suwon 16419, South Korea. [Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Nabeshima, Toshitaka] Meijo Univ, Nabeshima Lab, Grad Sch Pharmaceut Sci, Nagoya, Aichi 4688503, Japan. RP Kim, HC (reprint author), Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 24341, South Korea. EM kimhc@kangwon.ac.kr FU Korea Food and Drug Administration, Republic of Korea [14182MFDS979]; BK21 PLUS program, National Research Foundation of Korea, Republic of Korea FX This study was supported by a grant (14182MFDS979) from the Korea Food and Drug Administration, Republic of Korea. Duy-Khanh Dang, Hai-Quyen Tran, and Yunsung Nam were supported by the BK21 PLUS program, National Research Foundation of Korea, Republic of Korea. Equipment at the Institute of New Drug Development Research (Kangwon National University) was used for this study. NR 72 TC 0 Z9 0 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 EI 1872-9754 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV PY 2016 VL 100 BP 146 EP 158 DI 10.1016/j.neuint.2016.09.008 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ED3WX UT WOS:000388780300017 PM 27623093 ER PT J AU Barrett, JE McGonigle, P Clark, JE AF Barrett, James E. McGonigle, Paul Clark, Janet E. TI Graduate Education in Pharmacology: Addressing the need for specialized training for pharmaceutical and biotechnology careers SO PHARMACOLOGICAL RESEARCH LA English DT Editorial Material ID DRUG DISCOVERY C1 [Barrett, James E.; McGonigle, Paul] Drexel Univ, Coll Med, Dept Physiol & Pharmacol, Philadelphia, PA 19102 USA. [Clark, Janet E.] NIMH, Bethesda, MD 20814 USA. RP Barrett, JE (reprint author), Drexel Univ, Coll Med, Dept Physiol & Pharmacol, Philadelphia, PA 19102 USA. EM jbarrett@drexelmed.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD NOV PY 2016 VL 113 BP 327 EP 331 DI 10.1016/j.phrs.2016.08.030 PN A PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ED7XU UT WOS:000389086800031 PM 27590782 ER PT J AU Gorsich, EE Luis, AD Buhnerkempe, MG Grear, DA Portacci, K Miller, RS Webb, CT AF Gorsich, Erin E. Luis, Angela D. Buhnerkempe, Michael G. Grear, Daniel A. Portacci, Katie Miller, Ryan S. Webb, Colleen T. TI Mapping US cattle shipment networks: Spatial and temporal patterns of trade communities from 2009 to 2011 SO PREVENTIVE VETERINARY MEDICINE LA English DT Article DE Cattle shipment; Community detection; Dynamic network; Network analysis; Interstate Certificate of Veterinary; Inspection; US cattle industry ID INDIRECT CONTACT RATES; INFECTIOUS-DISEASES; MOUTH-DISEASE; MOVEMENTS; SPREAD; BEEF; CALIFORNIA; FRANCE; HERDS AB The application of network analysis to cattle shipments broadens our understanding of shipment patterns beyond pairwise interactions to the network as a whole. Such a quantitative description of cattle shipments in the U.S. can identify trade communities, describe temporal shipment patterns, and inform the design of disease surveillance and control strategies. Here, we analyze a longitudinal dataset of beef and dairy cattle shipments from 2009 to 2011 in the United States to characterize communities within the broader cattle shipment network, which are groups of counties that ship mostly to each other. Because shipments occur over time, we aggregate the data at various temporal scales to examine the consistency of network and community structure over time. Our results identified nine large (>50 counties) communities based on shipments of beef cattle in 2009 aggregated into an annual network and nine large communities based on shipments of dairy cattle. The size and connectance of the shipment network was highly dynamic; monthly networks were smaller than yearly networks and revealed seasonal shipment patterns consistent across years. Comparison of the shipment network over time showed largely consistent shipping patterns, such that communities identified on annual networks of beef and diary shipments from 2009 still represented 41-95% of shipments in monthly networks from 2009 and 41-66% of shipments from networks in 2010 and 2011. The temporal aspects of cattle shipments suggest that future applications of the U.S. cattle shipment network should consider seasonal shipment patterns. However, the consistent within-community shipping patterns indicate that yearly communities could provide a reasonable way to group regions for management. (C) 2016 Elsevier B.V. All rights reserved. C1 [Gorsich, Erin E.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Luis, Angela D.] Univ Montana, Dept Ecosyst & Conservat Sci, Missoula, MT 59812 USA. [Buhnerkempe, Michael G.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Buhnerkempe, Michael G.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Grear, Daniel A.; Portacci, Katie; Miller, Ryan S.] USDA APHIS Vet Serv, Ctr Epidemiol & Anim Hlth, Ft Collins, CO USA. RP Gorsich, EE (reprint author), Oregon State Univ, Dept Biomed Sci, Corvallis, OR 97331 USA. EM eringorsich@gmail.com OI Miller, Ryan/0000-0003-3892-0251 FU Foreign Animal Disease Modeling Program, Science and Technology Directorate; U.S. Department of Homeland Security [ST-108-000017]; USDA [13-9208-0345-CA]; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health [HSHQDC-09-X-00135] FX Funding was provided by the Foreign Animal Disease Modeling Program, Science and Technology Directorate, U.S. Department of Homeland Security (Grant ST-108-000017) and a USDA Cooperative Agreement 13-9208-0345-CA. MGB and CTW were supported by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health; through interagency agreement #HSHQDC-09-X-00135. Data were provided by the U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services. However, the analyses, views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the regulatory opinions, official policies, either expressed or implied, of the USDA-APHIS-Veterinary Services or the U.S. Department of Homeland Security. We also thank the state veterinarians and staff whose cooperation and effort made the data collection possible. NR 36 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-5877 EI 1873-1716 J9 PREV VET MED JI Prev. Vet. Med. PD NOV 1 PY 2016 VL 134 BP 82 EP 91 DI 10.1016/j.prevetmed.2016.09.023 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA ED8CV UT WOS:000389100500009 PM 27836049 ER PT J AU de Moor, JS Virgo, KS Li, CY Chawla, N Han, XS Blanch-Hartigan, D Ekwueme, DU McNeel, TS Rodriguez, JL Yabroff, KR AF de Moor, Janet S. Virgo, Katherine S. Li, Chunyu Chawla, Neetu Han, Xuesong Blanch-Hartigan, Danielle Ekwueme, Donatus U. McNeel, Timothy S. Rodriguez, Juan L. Yabroff, K. Robin TI Access to Cancer Care and General Medical Care Services Among Cancer Survivors in the United States: An Analysis of 2011 Medical Expenditure Panel Survey Data SO PUBLIC HEALTH REPORTS LA English DT Article DE cancer care; access to care; health services ID QUALITY-OF-CARE; BREAST-CANCER; HEALTH-CARE; LONG-TERM; RECEIPT; PATIENT; EXPERIENCES; DISPARITIES; CHALLENGE; PATTERNS AB Objectives: Cancer survivors require appropriate health care to manage their unique health needs. This study describes access to cancer care among cancer survivors in the United States and compares access to general medical care between cancer survivors and people who have no history of cancer. Methods: We assessed access to general medical care using the core 2011 Medical Expenditure Panel Survey (MEPS). We assessed access to cancer care using the MEPS Experiences With Cancer Survey. We used multivariable logistic regression to compare access to general medical care among 2 groups of cancer survivors (those who reported having access to all necessary cancer care [n = 1088] and those who did not [n = 70]) with self-reported access to general medical care among people who had no history of cancer (n = 22434). Results: Of the 1158 cancer survivors, 70 (6.0%) reported that they did not receive all necessary cancer care. Adjusted analyses found that cancer survivors who reported not receiving all necessary cancer care were also less likely to report receiving general medical care (78.0%) than cancer survivors who reported having access to necessary cancer care (87.1%) and people who had no history of cancer (87.8%). Conclusions: This study provides nationally representative data on the proportion of cancer survivors who have access to necessary cancer care and yields insight into factors that impede survivors' access to both cancer care and general medical care. This study is a reference for future work on access to care. C1 [de Moor, Janet S.; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Virgo, Katherine S.] Emory Univ, Rollins Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. [Li, Chunyu; Ekwueme, Donatus U.; Rodriguez, Juan L.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Chawla, Neetu] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Han, Xuesong] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA. [Blanch-Hartigan, Danielle] Bentley Univ, Dept Nat & Appl Sci, Waltham, MA USA. [McNeel, Timothy S.] Informat Management Serv Inc, Calverton, MD USA. RP de Moor, JS (reprint author), NCI, Healthcare Assessment Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM demoorjs@mail.nih.gov NR 41 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0033-3549 EI 1468-2877 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2016 VL 131 IS 6 BP 783 EP 790 DI 10.1177/0033354916675852 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ED2FN UT WOS:000388659400008 PM 28123224 ER PT J AU Ekholm, L Kahlenberg, JM Helmers, SB Tjarnlund, A Yalavarthi, S Zhao, WP Seto, N Betteridge, Z Lundberg, IE Kaplan, MJ AF Ekholm, Louise Kahlenberg, J. Michelle Helmers, Sevim Barbasso Tjarnlund, Anna Yalavarthi, Srilakshmi Zhao, Wenpu Seto, Nickie Betteridge, Zoe Lundberg, Ingrid E. Kaplan, Mariana J. TI Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis SO RHEUMATOLOGY LA English DT Article DE idiopathic inflammatory myopathies; IFN-regulated gene expression; interferon signature; IL-18; autoantibodies ID INFLAMMATORY MYOPATHIES; LUPUS; ALPHA; VASCULOGENESIS; ACTIVATION AB Objective. Alterations in phenotype and function of endothelial progenitor cells (EPCs) have been associated with poor vascular outcomes and impaired vascular repair in various conditions. Our hypothesis was that patients with PM and DM have dysregulation of EPCs driven by type I IFN and IL-18 similar to other autoimmune diseases. Methods. Quantification of circulating EPCs was performed by flow cytometry in patients with PM/DM and matched healthy controls. The ability of EPCs to differentiate into mature endothelial cells was investigated by light and fluorescence microscopy quantification in the presence or absence of PM/DM or control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum type I IFN activity was quantified by induction of type I IFN-inducible genes in HeLa cells. Circulating IL-18 concentrations were assessed by ELISA. Results. Circulating EPCs were significantly lower in PM/DM patients compared with controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature endothelial cells and PM/DM serum significantly inhibited differentiation of control EPCs. This effect was reversed in the majority of samples with neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of these antibodies. Patients with associated impairments in EPC function had higher type I IFN serum activity. Conclusion. PM/DM is associated with dysregulation of EPC phenotype and function that may be attributed, at least in part, to aberrant IL-18 and type I IFN pathways. The implication of these vasculopathic findings for disease prognosis and complications remains to be determined. C1 [Ekholm, Louise; Helmers, Sevim Barbasso; Tjarnlund, Anna; Lundberg, Ingrid E.] Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, S-17176 Solna, Sweden. [Kahlenberg, J. Michelle; Yalavarthi, Srilakshmi] Univ Michigan, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 USA. [Zhao, Wenpu; Seto, Nickie; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Betteridge, Zoe] Univ Bath, Pharm & Pharmacol, Bath, Avon, England. RP Ekholm, L (reprint author), Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, S-17176 Solna, Sweden. EM louise.ekholm@karolinska.se OI Kahlenberg, J. Michelle/0000-0002-4006-8945 FU NIAMS/NIH; Stockholm County Council; Karolinska Institute FX This study was funded in part by the intramural research program at NIAMS/NIH and in part by The regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute. NR 15 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2016 VL 55 IS 11 BP 1987 EP 1992 DI 10.1093/rheumatology/kew288 PG 6 WC Rheumatology SC Rheumatology GA ED0TN UT WOS:000388555100012 PM 27498356 ER PT J AU Falcinelli, SD Chertow, DS Kindrachuk, J AF Falcinelli, Shane D. Chertow, Daniel S. Kindrachuk, Jason TI Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections SO ACS INFECTIOUS DISEASES LA English DT Review DE emerging pathogens; kinomics; cell signaling; virology; kinases; high-consequence pathogens ID RESPIRATORY SYNDROME CORONAVIRUS; EBOLA-VIRUS INFECTION; GENE-EXPRESSION; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; PROTEIN-KINASES; HUMAN MONKEYPOX; KINOME ANALYSIS; RESTON-EBOLAVIRUS; SYNCYTIAL VIRUS AB Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. Furthermore, we will highlight the role of global investigations of host kinases, the kinome, for investigating emerging and reemerging viral pathogens from the context of characterizing cellular responses and identifying novel therapeutic targets. Lastly, we will address how increased integration of clinical and basic research will assist treatment and prevention efforts for emerging pathogens. C1 [Falcinelli, Shane D.; Chertow, Daniel S.; Kindrachuk, Jason] NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20814 USA. RP Kindrachuk, J (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20814 USA. EM kindrachuk.kenneth@nih.gov FU Intramural Research Programs of National Institute of Health (Clinical Center, Critical Care Medicine Department) FX The Intramural Research Programs of National Institute of Health (Clinical Center, Critical Care Medicine Department) supported this work. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 84 TC 0 Z9 0 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD NOV PY 2016 VL 2 IS 11 BP 787 EP 799 DI 10.1021/acsinfecdis.6b00704 PG 13 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA EC5GL UT WOS:000388161300006 PM 27933782 ER PT J AU Alkaitis, MS Ackerman, HC AF Alkaitis, Matthew S. Ackerman, Hans C. TI Tetrahydrobiopterin Supplementation Improves Phenylalanine Metabolism in a Murine Model of Severe Malaria SO ACS INFECTIOUS DISEASES LA English DT Article DE metabolism; host response; plasmodium; nitric oxide; endothelium ID NITRIC-OXIDE SYNTHASE; ELEVATED PLASMA PHENYLALANINE; HUMAN BIOCHEMICAL GENETICS; SEVERE FALCIPARUM-MALARIA; BLOOD-CELL DEFORMABILITY; L-ARGININE; ENDOTHELIAL-CELLS; PROGNOSTIC-SIGNIFICANCE; SUPEROXIDE GENERATION; PLASMODIUM-BERGHEI AB Tetrahydrobiopterin (BH4) is an essential cofactor for both phenylalanine hydroxylase and nitric oxide synthase. Patients with severe malaria have low urinary BH4, elevated plasma phenylalanine, and impaired endothelium-dependent vasodilation, suggesting that BH4 depletion may limit phenylalanine metabolism and nitric oxide synthesis. We infected C57BL/6 mice with Plasmodium berghei ANKA to characterize BH4 availability and to investigate the effects of BH4 supplementation. P. berghei ANKA infection lowered BH4 in plasma, erythrocytes, and brain tissue but raised it in aorta and liver tissue. The ratio of BH4 to 7,8-BH2 (the major product of BH4 oxidation) was decreased in plasma, erythrocytes, and brain tissue, suggesting that oxidation contributes to BH4 depletion. The continuous infusion of sepiapterin (a BH4 precursor) and citrulline (an arginine precursor) raised the concentrations of BH4 and arginine in both blood and tissue compartments. The restoration of systemic BH4 and arginine availability in infected mice produced only a minor improvement in whole blood nitrite concentrations, a biomarker of NO synthesis, and failed to prevent the onset of severe disease symptoms. However, sepiapterin and citrulline infusion reduced the ratio of phenylalanine to tyrosine in plasma, aortic tissue, and brain tissue. In summary, BH4 depletion in P. berghei infection may compromise both nitric oxide synthesis and phenylalanine metabolism; however, these findings require further investigation in human patients with severe malaria. C1 [Alkaitis, Matthew S.; Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Alkaitis, Matthew S.] Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Headington Oxford, England. [Alkaitis, Matthew S.] Harvard Med Sch, Boston, MA USA. [Ackerman, Hans C.] NHLBI, Sickle Cell Branch, Bldg 10, Bethesda, MD 20892 USA. RP Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.; Ackerman, HC (reprint author), NHLBI, Sickle Cell Branch, Bldg 10, Bethesda, MD 20892 USA. EM hans.ackerman@nih.gov FU NIAID Division of Intramural Research [AI001150-01]; NIH Oxford-Cambridge Scholars Program; National Institute of General Medical Sciences [T32GM007753] FX We thank the Twinbrook Animal Facility staff, Ivo Francischetti (NIAID/NIH) for making infusion pump and tether systems available for these studies, Laurel Mendelsohn (NHLBI/NIH) for training in the measurement of nitrite, and Keith Channon, Ashley Hale, and Mark Crabtree (Department of Cardiovascular Medicine, University of Oxford) for their guidance in setting up the HPLC assay for biopterins. We also thank David Roberts and Oliver Billker for helpful discussions about experimental design. This work was funded by the NIAID Division of Intramural Research project number AI001150-01 (HCA), the NIH Oxford-Cambridge Scholars Program (MSA), and award number T32GM007753 from the National Institute of General Medical Sciences (MSA). NR 67 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD NOV PY 2016 VL 2 IS 11 BP 827 EP 838 DI 10.1021/acsinfecdis.6b00124 PG 12 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA EC5GL UT WOS:000388161300010 PM 27641435 ER PT J AU Lusvarghi, S Lohith, K Morin-Leisk, J Ghirlando, R Hinshaw, JE Bewley, CA AF Lusvarghi, Sabrina Lohith, Katheryn Morin-Leisk, Jeanne Ghirlando, Rodolfo Hinshaw, Jenny E. Bewley, Carole A. TI Binding Site Geometry and Subdomain Valency Control Effects of Neutralizing Lectins on HIV-1 Viral Particles SO ACS INFECTIOUS DISEASES LA English DT Article DE cryo-electron microscopy (cryo-EM); envelope glycoprotein; HIV gp120 (gp120); surface plasmon resonance (SPR); electron microscopy (EM); multivalency ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN CYANOVIRIN-N; ENVELOPE GLYCOPROTEIN GP120; CARBOHYDRATE-BINDING; SEDIMENTATION-VELOCITY; STRUCTURAL BASIS; ENTRY INHIBITOR; GLYCAN SHIELD; POTENT; GRIFFITHSIN AB Carbohydrate binding proteins such as griffithsin, cyanovirin-N, and BanLec are potent HIV entry inhibitors and promising microbicides. Each binds to high-mannose glycans on the surface envelope glycoprotein gp120, yet the mechanisms by which they engage viral spikes and exhibit inhibition constants ranging from nanomolar to picomolar are not understood. To determine the structural and mechanistic basis for recognition and potency, we selected a panel of lectins possessing different valencies per subunit, oligomeric states, and relative orientations of carbohydrate binding sites to systematically probe their contributions to inhibiting viral entry. Cryo-electron micrographs and immuno gold staining of lectin-treated viral particles revealed two distinct effects namely, viral aggregation or clustering of the HIV-1 envelope on the viral membrane that were dictated by carbohydrate binding site geometry and valency. "Sandwich" surface plasmon resonance experiments revealed that a second binding event occurs only for those lectins that could aggregate viral particles. Furthermore, picomolar K-d values were observed for the second binding event, providing a mechanism by which picomolar IC50 values are achieved. We suggest that these binding and aggregation phenomena translate to neutralization potency. C1 [Lusvarghi, Sabrina; Lohith, Katheryn; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Ctr Dr, Bethesda, MD 20892 USA. [Morin-Leisk, Jeanne; Hinshaw, Jenny E.] NIDDK, Lab Cell & Mol Biol, NIH, Ctr Dr, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NIDDK, Lab Mol Biol, NIH, Ctr Dr, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Ctr Dr, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU NIH Intramural Research Program, NIDDK FX We thank J. Lifson and J. Bess for purified HIV-1 virions, B. O'Keefe for anti-GRFT antibodies, C. Soto for coordinates of fully glycosylated HIV-1 trimer model, and the NIH Intramural Research Program, NIDDK, for financial support. NR 43 TC 0 Z9 0 U1 5 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD NOV PY 2016 VL 2 IS 11 BP 882 EP 891 DI 10.1021/acsinfecdis.6b00139 PG 10 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA EC5GL UT WOS:000388161300015 PM 27669574 ER PT J AU Chen, LY Bigger, JT Hickey, KT Chen, H Lopez-Jimenez, C Banerji, MA Evans, G Fleg, JL Papademetriou, V Thomas, A Woo, V Seaquist, ER Soliman, EZ AF Chen, Lin Y. Bigger, J. Thomas Hickey, Kathleen T. Chen, Haiying Lopez-Jimenez, Carlos Banerji, Mary Ann Evans, Gregory Fleg, Jerome L. Papademetriou, Vasilios Thomas, Abraham Woo, Vincent Seaquist, Elizabeth R. Soliman, Elsayed Z. TI Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation and P-Wave Indices in the ACCORD Blood Pressure Trial SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE atrial fibrillation; blood pressure; diabetes mellitus; hypertension; left atrial abnormality; P-wave indices; randomized controlled trial ID TYPE-2 DIABETES-MELLITUS; ATHEROSCLEROSIS RISK; ISCHEMIC-STROKE; COMMUNITIES; PREVALENCE; ECG; ASSOCIATION; HEALTH; COHORT; ADULTS AB There are no proven strategies to prevent atrial fibrillation (AF) in patients with type 2 diabetes (T2DM). We compared standard blood pressure (BP) lowering vs. intensive BP lowering in reducing incidence of AF or P-wave indices (PWI-ECG markers of left atrial abnormality that are considered intermediate phenotypes of AF) in patients with T2DM. We analyzed data from the ACCORD BP trial-a randomized controlled nonblinded trial (2001-2009) which randomized patients with T2DM and systolic BP (SBP) 130-180mm Hg on a parts per thousand currency sign3 antihypertensive medications aged 40-79 years with cardiovascular disease (CVD) or aged 55-79 years with subclinical CVD or a parts per thousand yen2 CVD risk factors to standard BP lowering (SBP < 140mm Hg) vs. intensive BP lowering (SBP < 120mm Hg). The primary outcome was a composite of incident AF and PWI. Data from 3,087 participants (mean age, 62.2 years; women, 48.2%; non-White, 39.2%) were analyzed. During a mean follow-up of 4.4 years, the primary outcome occurred in 1,063 participants (incidence rate, 84.5 per 1,000 person-years in the standard-therapy group vs. 73.9 per 1,000 person-years in the intensive-therapy group). The adjusted hazard ratios (95% confidence intervals) of intensive-therapy group for the primary outcome and for incident PWI alone were 0.87 (0.77-0.98), P = 0.02 and 0.87 (0.76-0.98), P = 0.02, respectively. The effect of intensive therapy on the incidence of AF alone did not reach statistical significance. In patients with T2DM, intensive BP lowering reduces the incidence of the composite outcome of AF and PWI, suggesting a potential benefit from stringent BP control in patients with T2DM. clinical trials registration Trial Number NCT00000620. C1 [Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Cardiovasc Div, Minneapolis, MN 55455 USA. [Bigger, J. Thomas; Hickey, Kathleen T.; Lopez-Jimenez, Carlos] Columbia Univ, Dept Med, Div Cardiol, New York, NY USA. [Hickey, Kathleen T.] Columbia Univ, Sch Nursing, New York, NY USA. [Chen, Haiying; Evans, Gregory] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Banerji, Mary Ann] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [Papademetriou, Vasilios] Vet Adm Med Ctr, Washington, DC 20422 USA. [Thomas, Abraham] Henry Ford Hosp, Endocrinol Diabet Bone & Mineral Disorders Div, Detroit, MI 48202 USA. [Woo, Vincent] Univ Manitoba, Sect Endocrinol & Metab, Winnipeg, MB, Canada. [Seaquist, Elizabeth R.] Univ Minnesota, Sch Med, Dept Med, Div Diabet Endocrinol & Metab, Minneapolis, MN 55455 USA. [Soliman, Elsayed Z.] Epidemiol Cardiol Res Ctr EPICARE, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Soliman, Elsayed Z.] Wake Forest Sch Med, Cardiol Sect, Dept Med, Winston Salem, NC USA. RP Chen, LY (reprint author), Univ Minnesota, Sch Med, Dept Med, Cardiovasc Div, Minneapolis, MN 55455 USA. EM chenx484@umn.edu OI Papademetriou, Vasilios/0000-0002-2882-2757 FU National Institute on Aging [R21AG042660-01A1]; National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, Y1-HC-9035, Y1-HC-1010] FX Dr Chen receives support from National Institute on Aging (R21AG042660-01A1). The ACCORD BP trial was supported by contracts from the National Heart, Lung, and Blood Institute (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, and IAA#Y1-HC-9035 and IAA#Y1-HC-1010). NR 31 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 2016 VL 29 IS 11 BP 1276 EP 1282 DI 10.1093/ajh/hpv172 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA EC2PX UT WOS:000387967000010 ER PT J AU Mao, CY Luo, HY Yang, J Qin, J Wang, H Song, B Sun, SL Zhuang, ZP Shi, CH Xu, YM AF Mao, Chengyuan Luo, Haiyang Yang, Jing Qin, Jie Wang, Hui Song, Bo Sun, Shilei Zhuang, Zhengping Shi, Changhe Xu, Yuming TI Pseudo-Dominant Inheritance of A Novel Double GLA Mutation Associated with Fabry Disease Mimicking Familial Episodic Pain SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter C1 [Mao, Chengyuan; Luo, Haiyang; Yang, Jing; Qin, Jie; Wang, Hui; Song, Bo; Sun, Shilei; Shi, Changhe; Xu, Yuming] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, 1 Jian She East Rd, Zhengzhou 450000, Henan, Peoples R China. [Mao, Chengyuan; Luo, Haiyang; Wang, Hui; Shi, Changhe; Xu, Yuming] Zhengzhou Univ, Affiliated Hosp 1, Inst Clin Med, Zhengzhou, Henan, Peoples R China. [Zhuang, Zhengping] NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Shi, CH; Xu, YM (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, 1 Jian She East Rd, Zhengzhou 450000, Henan, Peoples R China. EM shichanghe@gmail.com; xuyuming@zzu.edu.cn NR 8 TC 0 Z9 0 U1 1 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 NOV PY 2016 VL 170 IS 11 BP 3051 EP 3053 DI 10.1002/ajmg.a.37833 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA EC5SA UT WOS:000388195300042 PM 27531472 ER PT J AU Fee, E AF Fee, Elizabeth TI Whither WHO? Our Global Health Leadershiple SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Fee, Elizabeth] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM feee@mail.nih.gov NR 2 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 NOV PY 2016 VL 106 IS 11 BP 1903 EP 1904 DI 10.2105/AJPH.2016.303481 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EC4IE UT WOS:000388090200009 PM 27715304 ER PT J AU Fee, E Cueto, M Brown, TM AF Fee, Elizabeth Cueto, Marcu Brown, Theodore M. TI At the Roots of The World Health Organization's Challenges: Politics and Regionalization SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material AB The World Health Organization's (WHO's) leadership challenges can be traced to its first decades of existence. Central to its governance and practice is regionalization: the division of its member countries into regions, each representing 1 geographical or cultural area. The particular composition of each region has varied over time-reflecting political divisions and especially decolonization. Currently, the 194 member countries belong to 6 regions: the Americas (35 countries), Europe (53 countries), the Eastern Mediterranean (21 countries), South-East Asia (11 countries), the Western Pacific (27 countries), and Africa (47 countries). The regions have considerable autonomy with their own leadership, budget, and priorities. This regional organization has been controversial since its beginnings in the first days of WHO, when representatives of the European countries believed that each country should have a direct relationship with the headquarters in Geneva, Switzerland, whereas others (especially the United States) argued in favor of the regionalization plan. Over time, regional directors have inevitably challenged the WHO directors-general over their degree of autonomy, responsibilities and duties, budgets, and national composition; similar tensions have occurred within regions. This article traces the historical roots of these challenges. C1 [Fee, Elizabeth] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Cueto, Marcu] Casa Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio De Janeiro, Brazil. [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA. [Brown, Theodore M.] Univ Rochester, Dept Publ Hlth Sci, Rochester, NY USA. RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM feee@mail.nih.gov NR 22 TC 1 Z9 1 U1 1 U2 1 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 NOV PY 2016 VL 106 IS 11 BP 1912 EP 1917 DI 10.2105/AJPH.2016.303480 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EC4IE UT WOS:000388090200015 PM 27715303 ER PT J AU Pinheiro, SP Rivera, DR Graham, DJ Freedman, AN Major, JM Penberthy, L Levenson, M Bradley, MC Wong, HL Ouellet-Hellstrom, R AF Pinheiro, Simone P. Rivera, Donna R. Graham, David J. Freedman, Andrew N. Major, Jacqueline M. Penberthy, Lynne Levenson, Mark Bradley, Marie C. Wong, Hui-Lee Ouellet-Hellstrom, Rita TI Cancer pharmacoepidemiology symposium Challenges in evaluating cancer as a clinical outcome in postapproval studies of drug safety SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Cancer epidemiology; Pharmacoepidemiology; Drug safety ID COLORECTAL-CANCER; LATENCY ANALYSIS; LUNG-CANCER; ASSOCIATION; DATABASE; MINERS; GENOME; WOMEN; RISK AB Pharmaceuticals approved in the United States are largely not known human carcinogens. However, cancer signals associated with pharmaceuticals may be hypothesized or arise after product approval. There are many study designs that can be used to evaluate cancer as an outcome in the postapproval setting. Because prospective systematic collection of cancer outcomes from a large number of individuals may be lengthy, expensive, and challenging, leveraging data from large existing databases are an integral approach. Such studies have the capability to evaluate the clinical experience of a large number of individuals, yet there are unique methodological challenges involved in their use to evaluate cancer outcomes. To discuss methodological challenges and potential solutions, the Food and Drug Administration and the National Cancer Institute convened a two-day public meeting in 2014. This commentary summarizes the most salient issues discussed at the meeting. Published by Elsevier Inc. C1 [Pinheiro, Simone P.; Graham, David J.; Major, Jacqueline M.; Bradley, Marie C.; Wong, Hui-Lee; Ouellet-Hellstrom, Rita] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rivera, Donna R.; Freedman, Andrew N.; Penberthy, Lynne; Bradley, Marie C.] NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res, Div Canc Control & Populat Sci, Rockville, MD USA. [Levenson, Mark] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Pinheiro, SP (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM simone.pinheiro@fda.hhs.gov NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2016 VL 26 IS 11 BP 735 EP 740 DI 10.1016/j.annepidem.2016.04.012 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ED0QF UT WOS:000388546300001 PM 27663208 ER PT J AU Rivera, DR McGlynn, KA Freedman, AN AF Rivera, Donna R. McGlynn, Katherine A. Freedman, Andrew N. TI Cancer pharmacoepidemiology symposium Connections between pharmacoepidemiology and cancer biology: designing biologically relevant studies of cancer outcomes SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material ID COMPOSITE END-POINTS; BREAST-CANCER; UNITED-STATES; RANDOMIZED-TRIALS C1 [Rivera, Donna R.; Freedman, Andrew N.] NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res, Div Canc Control & Populat Sci, Rockville, MD USA. [McGlynn, Katherine A.] NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Rivera, DR (reprint author), 9609 Med Ctr Dr, Rockville, MD USA. EM donna.rivera@nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2016 VL 26 IS 11 BP 741 EP 745 DI 10.1016/j.annepidem.2016.10.001 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ED0QF UT WOS:000388546300002 PM 27837786 ER PT J AU Major, JM Penberthy, L McGlynn, KA AF Major, Jacqueline M. Penberthy, Lynne McGlynn, Katherine A. TI Cancer pharmacoepidemiology symposium Data systems and record linkage: considerations for pharmacoepidemiologic studies examining cancer risk SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material C1 [Major, Jacqueline M.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Penberthy, Lynne] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Major, JM (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Jacqueline.Major@fda.hhs.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2016 VL 26 IS 11 BP 746 EP 748 DI 10.1016/j.annepidem.2016.08.015 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ED0QF UT WOS:000388546300003 PM 27639347 ER PT J AU Ng, DK Moxey-Mims, M Warady, BA Furth, SL Munoz, A AF Ng, Derek K. Moxey-Mims, Marva Warady, Bradley A. Furth, Susan L. Munoz, Alvaro TI Racial differences in renal replacement therapy initiation among children with a nonglomerular cause of chronic kidney disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Pediatric nephrology; Chronic kidney disease; Health disparities; Renal replacement therapy; Inverse probability weights ID MARGINAL STRUCTURAL MODELS; GLOMERULAR-FILTRATION-RATE; SOCIOECONOMIC-STATUS; AFRICAN-AMERICANS; RACE DISPARITIES; UNITED-STATES; CKID COHORT; TRANSPLANTATION; ACCESS; PROGRESSION AB Purpose: African American (AA) adults with chronic kidney disease (CKD) have a faster progression to end-stage renal disease and are less likely to receive a kidney transplant. It is unclear whether AA children experience renal replacement therapy (RRT) for end-stage renal disease sooner than non-AA children after accounting for socioeconomic status (SES). Methods: Among children with nonglomerular CKD in the Chronic Kidney Disease in Children study, we investigated time to RRT (i.e., first dialysis or transplant) after CKD onset using parametric survival models and accounted for SES differences by inverse probability weights. Results: Of 110 AA and 493 non-AA children (median age = 10 years), AA children had shorter time to first RRT: median time was 3.2 years earlier than non-AA children (95% CI:-6.1,-0.3). When accounting for SES, this difference was diminished and nonsignificant (-1.6 years; 95% CI:-4.6, +1.5), and its directionality was consistent with faster glomerular filtration rate decline among AA children (-6.2% vs.-4.4% per year, P =.098). When RRT was deconstructed into dialysis or transplant, the time to dialysis was 37.5% shorter for AA children and 53.7% longer for transplant. These inferences were confirmed by the frequency and timing of transplant after initiating dialysis. Conclusions: Racial differences in time to RRT were almost fully accounted for by SES, and the remaining difference was congruent with a faster glomerular filtration rate decline among AA children. Access to transplant occurred later, yet times to dialysis were shorter among AA children even when accounting for SES which may be due to a lack of organ availability. (C) 2016 Elsevier Inc. All rights reserved. C1 [Ng, Derek K.; Munoz, Alvaro] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA. [Warady, Bradley A.] Childrens Mercy Hosp, Div Pediat Nephrol, Kansas City, MO 64108 USA. [Furth, Susan L.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Furth, Susan L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Ng, DK (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St,Suite E7643, Baltimore, MD 21205 USA. EM dng3@jhu.edu OI Moxey-Mims, Marva/0000-0001-8542-9313 FU National Institute of Diabetes and Digestive and Kidney Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute [U01-DK-66143, U01-DK-66174, U01-DK-082194, U01-DK-66116] FX Data in this article were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (principal investigators) at Children's Mercy Hospital and the University of Missouri, Kansas City (Bradley Warady, MD) and Children's Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Munoz, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01-DK-082194, U01-DK-66116). The CKiD web site is located at http://www.statepi.jhsph.edu/ckid. The authors acknowledge Deidra Crews for critical input in the preparation of this article. NR 42 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2016 VL 26 IS 11 BP 780 EP 787 DI 10.1016/j.annepidem.2016.09.011 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ED0QF UT WOS:000388546300010 PM 27789133 ER PT J AU Snijders, AH Takakusaki, K Debu, B Lozano, AM Krishna, V Fasano, A Aziz, TZ Papa, SM Factor, SA Hallett, M AF Snijders, Anke H. Takakusaki, Kaoru Debu, Bettina Lozano, Andres M. Krishna, Vibhor Fasano, Alfonso Aziz, Tipu Z. Papa, Stella M. Factor, Stewart A. Hallett, Mark TI Physiology of freezing of gait SO ANNALS OF NEUROLOGY LA English DT Review ID DEEP BRAIN-STIMULATION; PEDUNCULOPONTINE NUCLEUS STIMULATION; PROGRESSIVE SUPRANUCLEAR PALSY; POSTURAL MUSCLE TONE; BASAL GANGLIA DYSFUNCTION; PARKINSONS-DISEASE; SUBTHALAMIC NUCLEUS; TEGMENTAL NUCLEUS; FREQUENCY STIMULATION; RETICULAR-FORMATION AB Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG. The outcomes of these studies point to a dynamic network of cortical areas such as the supplementary motor area, as well as subcortical areas such as the striatum and the mesencephalic locomotor region including the pedunculopontine nucleus (PPN). Additionally, we will review PPN (area) stimulation as a possible treatment for FOG, and ponder whether PPN stimulation truly is the right step forward. Ann Neurol 2016;80:644-659 C1 [Snijders, Anke H.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands. [Snijders, Anke H.] Maasziekenhuis Pantein, Boxmeer, Netherlands. [Takakusaki, Kaoru] Asahikawa Med Univ, Res Ctr Brain Funct & Med Engn, Asahikawa, Hokkaido, Japan. [Debu, Bettina] Grenoble Univ, Joseph Fourier Univ, Grenoble, France. [Lozano, Andres M.; Krishna, Vibhor] Univ Toronto, Div Neurosurg, Toronto, ON, Canada. [Krishna, Vibhor] Ohio State Univ, Dept Neurosurg, Columbus, OH 43210 USA. [Fasano, Alfonso] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON, Canada. [Fasano, Alfonso] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Univ Hlth Network, Toronto, ON, Canada. [Aziz, Tipu Z.] John Radcliffe Hosp, Oxford, England. [Papa, Stella M.; Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Jean & Paul Amos Parkinsons Dis & Movement Disord, Atlanta, GA 30322 USA. [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Snijders, AH (reprint author), Maasziekenhuis Pantein, Dept Neurol, Dokter Kopstr 1, NL-5835 DV Beugen, Netherlands. EM A.Snijders@pantein.nl FU Japan Society for the Promotion of Science [26120004, 25290001]; NIH National Institute of Neurological Disorders and Stroke Intramural Program; Sartain Lanier Family Foundation; Curtis Family Foundation FX This work was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (26120004, 25290001, K.T.), NIH National Institute of Neurological Disorders and Stroke Intramural Program (M.H.), Sartain Lanier Family Foundation (S.A.F.), and Curtis Family Foundation (S.A.F.). NR 126 TC 2 Z9 2 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2016 VL 80 IS 5 BP 644 EP 659 DI 10.1002/ana.24778 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ED0YS UT WOS:000388570800002 PM 27649270 ER PT J AU Anderson, CD Falcone, GJ Phuah, CL Radmanesh, F Brouwers, HB Battey, TWK Biffi, A Peloso, GM Liu, DJJ Ayres, AM Goldstein, JN Viswanathan, A Greenberg, SM Selim, M Meschia, JF Brown, DL Worrall, BB Silliman, SL Tirschwell, DL Flaherty, ML Kraft, P Jagiella, JM Schmidt, H Hansen, BM Jimenez-Conde, J Giralt-Steinhauer, E Elosua, R Cuadrado-Godia, E Soriano, C van Nieuwenhuizen, KM Klijn, CJM Rannikmae, K Samarasekera, N Salman, RA Sudlow, CL Deary, IJ Morotti, A Pezzini, A Pera, J Urbanik, A Pichler, A Enzinger, C Norrving, B Montaner, J Fernandez-Cadenas, I Delgado, P Roquer, J Lindgren, A Slowik, A Schmidt, R Kidwell, CS Kittner, SJ Waddy, SP Langefeld, CD Abecasis, G Willer, CJ Kathiresan, S Woo, D Rosand, J AF Anderson, Christopher D. Falcone, Guido J. Phuah, Chia-Ling Radmanesh, Farid Brouwers, H. Bart Battey, Thomas W. K. Biffi, Alessandro Peloso, Gina M. Liu, Dajiang J. Ayres, Alison M. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Selim, Magdy Meschia, James F. Brown, Devin L. Worrall, Bradford B. Silliman, Scott L. Tirschwell, David L. Flaherty, Matthew L. Kraft, Peter Jagiella, Jeremiasz M. Schmidt, Helena Hansen, Bjorn M. Jimenez-Conde, Jordi Giralt-Steinhauer, Eva Elosua, Roberto Cuadrado-Godia, Elisa Soriano, Carolina van Nieuwenhuizen, Koen M. Klijn, Catharina J. M. Rannikmae, Kristiina Samarasekera, Neshika Salman, Rustam Al-Shahi Sudlow, Catherine L. Deary, Ian J. Morotti, Andrea Pezzini, Alessandro Pera, Joanna Urbanik, Andrzej Pichler, Alexander Enzinger, Christian Norrving, Bo Montaner, Joan Fernandez-Cadenas, Israel Delgado, Pilar Roquer, Jaume Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Kidwell, Chelsea S. Kittner, Steven J. Waddy, Salina P. Langefeld, Carl D. Abecasis, Goncalo Willer, Cristen J. Kathiresan, Sekar Woo, Daniel Rosand, Jonathan CA Global Lipids Genetics Consortium Int Stroke Genetics Consortium TI Genetic variants in CETP increase risk of intracerebral hemorrhage SO ANNALS OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; CHOLESTEROL LEVELS; AGGRESSIVE REDUCTION; STROKE PREVENTION; VASCULAR EVENTS; PLASMA-LIPIDS; DISEASE; METAANALYSIS; INHIBITORS; LOCATION AB ObjectiveIn observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH. MethodsWe performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk. ResultsTwelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR]=1.25, standard error [SE]=0.06, p=6.0x10(-4)) with no heterogeneity across studies (I-2=0%). This association was replicated in patients of European ancestry (p=0.03). A genetic score of CETP variants found to increase HDL-C by approximate to 2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR=1.86, SE=0.13, p=1.39x10(-6)). InterpretationGenetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740 C1 [Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia-Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W. K.; Biffi, Alessandro; Peloso, Gina M.; Ayres, Alison M.; Kathiresan, Sekar; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St;CPZN 6818, Boston, MA 02114 USA. [Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia-Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W. K.; Biffi, Alessandro; Ayres, Alison M.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] MGH, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA USA. [Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia-Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W. K.; Rosand, Jonathan] MGH, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA USA. [Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia-Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W. K.; Biffi, Alessandro; Peloso, Gina M.; Kathiresan, Sekar; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.; Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Falcone, Guido J.; Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Biffi, Alessandro] MGH, Div Behav Neurol, Dept Neurol, Boston, MA USA. [Biffi, Alessandro] MGH, Dept Psychiat, Div Psychiat, Boston, MA USA. [Liu, Dajiang J.] Penn State Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA. [Goldstein, Joshua N.] MGH, Dept Emergency Med, Boston, MA USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, 325 9Th Ave, Seattle, WA 98104 USA. [Flaherty, Matthew L.; Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA. [Jagiella, Jeremiasz M.; Pera, Joanna; Urbanik, Andrzej; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Lund Univ, Div Neurol, Dept Clin Sci Lund, Lund, Sweden. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Skane Univ Hosp, Div Neurol, Dept Neurol & Rehabil Med, Lund, Sweden. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Autonomous Univ Barcelona, Municipal Inst Med Invest Hosp Sea, Dept Neurol, Neurovasc Res Unit, Barcelona, Spain. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Autonomous Univ Barcelona, Municipal Inst Med Invest Hosp Sea, Program Inflammat & Cardiovasc Disorders, Barcelona, Spain. [van Nieuwenhuizen, Koen M.; Klijn, Catharina J. M.] Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Klijn, Catharina J. M.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands. [Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al-Shahi; Sudlow, Catherine L.] Univ Edinburgh, Div Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Sudlow, Catherine L.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Morotti, Andrea; Pezzini, Alessandro] Univ Brescia, Dept Clin & Expt Sci, Neurol Clin, Brescia, Italy. [Pichler, Alexander; Enzinger, Christian; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Enzinger, Christian; Slowik, Agnieszka] Med Univ Graz, Div Neuroradiol, Dept Radiol, Graz, Austria. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Autonomous Univ Barcelona, Res Inst, Vall dHebron Hosp, Neurovasc Res Lab, Barcelona, Spain. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Autonomous Univ Barcelona, Res Inst, Vall dHebron Hosp, Neurovasc Unit, Barcelona, Spain. [Fernandez-Cadenas, Israel] Terrassa Mutual Hosp, Stroke Pharmacogen & Genet Terrassa Mutual Teachi, Terrassa, Spain. [Kidwell, Chelsea S.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Kittner, Steven J.] Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Waddy, Salina P.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Langefeld, Carl D.] Wake Forest Univ, Ctr Publ Hlth Genom, Winston Salem, NC 27109 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Dept Internal Med, Sch Med, Div Cardiol, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA. [Kathiresan, Sekar] MGH, Cardiovasc Dis Prevent Ctr, Boston, MA USA. RP Anderson, CD (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St;CPZN 6818, Boston, MA 02114 USA. EM cdanderson@mgh.harvard.edu RI Lee, Chaeyoung/C-7929-2012; Montaner, Joan/D-3063-2015; OI Lee, Chaeyoung/0000-0002-2940-1778; Anderson, Christopher/0000-0002-0053-2002 FU NIH National Institute of Neurological Disorders and Stroke (NINDS) [K23NS086873, R01NS059727, P50NS061343, R01NS36695, U01NS069 763, R01NS30678]; NIH National Institute on Aging [R01AG26484]; NIH National Heart, Lung, and Blood Institute [R01HL127564]; Swedish Heart and Lung Foundation; Skane University Hospital; Region Skane; Freemasons Lodge of Instruction EOS in Lund; King Gustaf V and Queen Victoria's Foundation; Lund University; Swedish Stroke Association; Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III FEDER) [RD12/0042/0020] FX This work was supported by the NIH National Institute of Neurological Disorders and Stroke (NINDS; K23NS086873, R01NS059727, P50NS061343, R01NS36695, U01NS069 763, R01NS30678) and the NIH National Institute on Aging (R01AG26484). Project support for the GLGC through C.J.W. and S.K. was provided by the NIH National Heart, Lung, and Blood Institute (R01HL127564). Lund Stroke Register has been supported by the Swedish Heart and Lung Foundation, Skane University Hospital, Region Skane, the Freemasons Lodge of Instruction EOS in Lund, King Gustaf V and Queen Victoria's Foundation, Lund University, the Swedish Stroke Association, and Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III FEDER, RD12/0042/0020). NR 47 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2016 VL 80 IS 5 BP 730 EP 740 DI 10.1002/ana.24780 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ED0YS UT WOS:000388570800010 PM 27717122 ER PT J AU Malekshah, AFT Zaroudi, M Etemadi, A Islami, F Sepanlou, S Sharafkhah, M Keshtkar, AA Khademi, H Poustchi, H Hekmatdoost, A Pourshams, A Sani, AF Jafari, E Kamangar, F Dawsey, SM Abnet, CC Pharoah, PD Berennan, PJ Boffetta, P Esmaillzadeh, A Malekzadeh, R AF Malekshah, Akbar Fazel-tabar Zaroudi, Marsa Etemadi, Arash Islami, Farhad Sepanlou, Sadaf Sharafkhah, Maryam Keshtkar, Abbas-Ali Khademi, Hooman Poustchi, Hossein Hekmatdoost, Azita Pourshams, Akram Sani, Akbar Feiz Jafari, Elham Kamangar, Farin Dawsey, Sanford M. Abnet, Christian C. Pharoah, Paul D. Berennan, Paul J. Boffetta, Paolo Esmaillzadeh, Ahmad Malekzadeh, Reza TI The Combined Effects of Healthy Lifestyle Behaviors on All-Cause Mortality: The Golestan Cohort Study SO ARCHIVES OF IRANIAN MEDICINE LA English DT Article DE Alternative healthy eating index; Golestan cohort study; life style score; mortality ID HIGH-RISK AREA; ESOPHAGEAL CANCER; NORTHERN IRAN; WOMEN; MEN; DIET; METAANALYSIS; IMPACT; ADULTS AB Background: Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of developed countries. Objectives: The aim of this study was to examine the association between combined lifestyle scores and risk of all-cause and cause specific mortality for the first time among Iranian adults. Methods: The study population included 50,045 Iranians, 40 75 years of age, who were enrolled in the Golestan Cohort Study, between 2004 and 2008. The lifestyle risk factors used in this study included cigarette smoking, physical inactivity, and Alternative Healthy Eating Index. The lifestyle score ranged from zero (non-healthy) to 3 (most healthy) points. From the study baseline up to analysis, a total of 4691 mortality cases were recorded. Participants with chronic diseases at baseline, outlier reports of calorie intake, missing data, and body mass index of less than 18.5 were excluded from the analyses. Cox regression models were fitted to establish the association between combined lifestyle scores and mortality outcomes. Results: After implementing the exclusion criteria, data from 40,708 participants were included in analyses. During 8.08 years of follow-up, 3,039 cases of all-cause mortality were recorded. The adjusted hazard ratio of a healthy lifestyle score, compared with non-healthy lifestyle score, was 0.68 (95% CI: 0.54, 0.86) for all-cause mortality, 0.53 (95% CI: 0.37, 0.77) for cardiovascular mortality, and 0.82 (95% CI: 0.53, 1.26) for mortality due to cancer. When we excluded the first two years of follow up from the analysis, the protective association between healthy lifestyle score and cardiovascular death did not change much 0.55 (95% CI: 0.36, 0.84), but the inverse association with all-cause mortality became weaker 0.72 (95% CI: 0.55, 0.94), and the association with cancer mortality was non-significant 0.92 (95% CI: 0.58, 1.48). In the gender-stratified analysis, we found an inverse strong association between adherence to healthy lifestyle and mortality from all causes and cardiovascular disease in either gender, but no significant relationship was seen with mortality from cancer in men or women. Stratified analysis of BMI status revealed an inverse significant association between adherence to healthy lifestyle and mortality from all causes, cardiovascular disease and cancer among non-obese participants. Conclusion: We found evidence indicating that adherence to a healthy lifestyle, compared to non-healthy lifestyle, was associated with decreased risk of all-cause mortality and mortality from cardiovascular diseases in Iranian adults. C1 [Malekshah, Akbar Fazel-tabar; Zaroudi, Marsa; Etemadi, Arash; Islami, Farhad; Sepanlou, Sadaf; Sharafkhah, Maryam; Khademi, Hooman; Poustchi, Hossein; Pourshams, Akram; Sani, Akbar Feiz; Jafari, Elham; Kamangar, Farin; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Inst, Shariati Hosp, Digest Oncol Res Ctr, Tehran, Iran. [Etemadi, Arash] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Islami, Farhad] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA. [Keshtkar, Abbas-Ali] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran. [Hekmatdoost, Azita] Shahid Beheshti Univ Med Sci, Natl Nutr & Food Technol Res Inst, Fac Nutr Sci & Food Technol, Dept Clin Nutr & Dietet, Tehran, Iran. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pharoah, Paul D.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Berennan, Paul J.] Int Prevent Res Inst, Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. [Esmaillzadeh, Ahmad] Univ Tehran Med Sci, Endocrinol & Metab Mol Cellular Sci Inst, Obes & Eating Habits Res Ctr, Tehran, Iran. [Esmaillzadeh, Ahmad] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran. [Esmaillzadeh, Ahmad] Univ Tehran Med Sci, Sch Nutr Sci & Dietet, Dept Community Nutr, Tehran, Iran. [Esmaillzadeh, Ahmad] Isfahan Univ Med Sci, Sch Nutr & Food Sci, Dept Community Nutr, Food Secur Res Ctr, Esfahan, Iran. RP Esmaillzadeh, A (reprint author), Isfahan Univ Med Sci, Dept Community Nutr, Esfahan, Iran.; Malekzadeh, R (reprint author), Univ Tehran Med Sci, Digest Dis Res Inst, Shariati Hosp, North Kargar St,POB 14117-13135, Tehran, Iran. EM esmaillzadeh@hlth.mui.ac.ir; Reza.Malekzadeh@gmail.com RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU Tehran University of Medical Sciences [81/15]; Cancer Research UK [C20/A5860]; Intramural Research Program of the NCI, National Institutes of Health; IARC; Social Security Organization of Iran, Golestan Branch FX The Golestan Cohort Study was supported by Tehran University of Medical Sciences (grant No: 81/15), Cancer Research UK (grant No: C20/A5860), the Intramural Research Program of the NCI, National Institutes of Health, and through various collaborative research agreements with the IARC. The study has also received special support from the Social Security Organization of Iran, Golestan Branch. NR 33 TC 0 Z9 0 U1 4 U2 4 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 EI 1735-3947 J9 ARCH IRAN MED JI Arch. Iran. Med. PD NOV PY 2016 VL 19 IS 11 BP 752 EP 761 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EC3CM UT WOS:000388002300001 ER PT J AU Hinkle, SN Sjaarda, LA Albert, PS Mendola, P Grantz, KL AF Hinkle, S. N. Sjaarda, L. A. Albert, P. S. Mendola, P. Grantz, K. L. TI Comparison of methods for identifying small-for-gestational-age infants at risk of perinatal mortality among obese mothers: a hospital-based cohort study SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Birthweight; fetal growth; obesity; small-for-gestational-age ID MATERNAL OBESITY; FETAL-GROWTH; PREGNANCY OUTCOMES; WEIGHT AB Objective To assess differences in small-for-gestational age (SGA) classifications for the detection of neonates with increased perinatal mortality risk among obese women and subsequently assess the association between prepregnancy body mass index (BMI) status and SGA. Design Hospital-based cohort. Setting Twelve US clinical centres (2002-08). Population A total of 114 626 singleton, nonanomalous pregnancies. Methods Data were collected using electronic medical record abstraction. Relative risks (RR) with 95% CI were estimated. Main outcome measures SGA trends (birthweight < 10th centile) classified using population-based (SGAPOP), intrauterine (SGAIU) and customised (SGACUST) references were assessed. The SGA-associated perinatal mortality risk was estimated among obese women. Using the SGA method most associated with perinatal mortality, the association between prepregnancy BMI and SGA was estimated. Results The overall perinatal mortality prevalence was 0.55% and this increased significantly with increasing BMI (P < 0.01). Among obese women, SGAIU detected the highest proportion of perinatal mortality cases (2.49%). Perinatal mortality was 5.32 times (95% CI 3.72-7.60) more likely among SGAIU neonates than non-SGAIU neonates. This is in comparison with the 3.71-fold (2.49-5.53) and 4.81-fold (3.41-6.80) increased risk observed when SGAPOP and SGACUST were used, respectively. Compared with women of normal weight, overweight women (RR = 0.82, 95% CI 0.78-0.86) and obese women (RR = 0.80; 95% CI 0.750.83) had a lower risk for delivering an SGAIU neonate. Conclusion Among obese women, the intrauterine reference best identified neonates at risk of perinatal mortality. Based on SGAIU, SGA is less common among obese women but these SGA babies are at a high risk of death and remain an important group for surveillance. C1 [Hinkle, S. N.; Sjaarda, L. A.; Mendola, P.; Grantz, K. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. [Albert, P. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. RP Grantz, KL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM katherine.grantz@mail.nih.gov OI Hinkle, Stefanie/0000-0003-4312-708X; Sjaarda, Lindsey/0000-0003-0539-8110; Mendola, Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract number HHSN267200603425C). NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD NOV PY 2016 VL 123 IS 12 BP 1983 EP 1988 DI 10.1111/1471-0528.13896 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EC7JW UT WOS:000388314800016 PM 26853429 ER PT J AU Chubak, J Ziebell, R Greenlee, RT Honda, S Hornbrook, MC Epstein, M Nekhlyudov, L Pawloski, PA Ritzwoller, DP Ghai, NR Feigelson, HS Clancy, HA Doria-Rose, VP Kushi, LH AF Chubak, Jessica Ziebell, Rebecca Greenlee, Robert T. Honda, Stacey Hornbrook, Mark C. Epstein, Mara Nekhlyudov, Larissa Pawloski, Pamala A. Ritzwoller, Debra P. Ghai, Nirupa R. Feigelson, Heather Spencer Clancy, Heather A. Doria-Rose, V. Paul Kushi, Lawrence H. TI The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer; Epidemiology; Health services; Integrated health care delivery systems ID BREAST-CANCER; COLORECTAL-CANCER; OLDER WOMEN; RISK; DIAGNOSIS; MORTALITY; SYSTEM AB The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States. Data were extracted from each CRN site's virtual data warehouse using a centrally written and locally executed program. We computed the percent of patients continuously enrolled aeyen1, aeyen5, and aeyen10 years before cancer diagnosis in 2012-2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after the diagnosis for patients diagnosed in 2000. Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70 % were enrolled for aeyen5 years and 56 % for aeyen10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28 % were still enrolled in 2010, 45 % had died, and 27 % had disenrolled from CRN health systems. Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs. C1 [Chubak, Jessica; Ziebell, Rebecca] Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. [Greenlee, Robert T.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Honda, Stacey] Kaiser Permanente Hawaii, Hawaii Permanente Grp, Honolulu, HI USA. [Hornbrook, Mark C.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Epstein, Mara] Univ Massachusetts, Sch Med, Dept Med, Meyers Primary Care Inst, Worcester, MA USA. [Nekhlyudov, Larissa] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Pawloski, Pamala A.] HealthPartners Inst, Minneapolis, MN USA. [Ritzwoller, Debra P.; Feigelson, Heather Spencer] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Ghai, Nirupa R.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Clancy, Heather A.; Kushi, Lawrence H.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Doria-Rose, V. Paul] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Chubak, J (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM chubak.j@ghc.org FU National Cancer Institute at the National Institutes of Health (NIH) [U24CA171524]; Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute [N01-CN-67009, N01-PC-35142]; Fred Hutchinson Cancer Research Center; State of Washington; Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427] FX This study was funded by the National Cancer Institute at the National Institutes of Health (NIH), Award Number U24CA171524 to Lawrence H. Kushi, ScD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. At Group Health, the collection of cancer incidence data used in this study was supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract Nos. N01-CN-67009 and N01-PC-35142 from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. At Marshfield Clinic Research Foundation, the project was also supported in part by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), Grant No. UL1TR000427. The authors would like to thank Dr. Virginia Quinn for comments on previous versions of the manuscript. NR 20 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2016 VL 27 IS 11 BP 1315 EP 1323 DI 10.1007/s10552-016-0808-4 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EC5NW UT WOS:000388183800004 PM 27639398 ER PT J AU Arem, H Pfeiffer, RM Moore, SC Brinton, LA Matthews, CE AF Arem, Hannah Pfeiffer, Ruth M. Moore, Steven C. Brinton, Louise A. Matthews, Charles E. TI Body mass index, physical activity, and television time in relation to mortality risk among endometrial cancer survivors in the NIH-AARP Diet and Health Study cohort SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer survivorship; Endometrial cancer; Body mass index; Physical activity; Television; Mortality ID CARDIOVASCULAR-DISEASE; NATIONAL INSTITUTES AB Endometrial cancer (EC) survivors are the second largest group of female cancer survivors in the USA, with high prevalence of obesity and physical inactivity. While higher pre-diagnosis body mass index (BMI) has been associated with higher all-cause and disease-specific mortality, pre-diagnosis physical activity has shown mixed evidence of an association with mortality. However, the association between BMI, physical activity, and TV viewing measured after diagnosis and mortality risk among EC survivors is unknown. We identified 580 women with EC in the NIH-AARP Diet and Health Study who completed a post-diagnosis questionnaire on BMI, leisure time moderate- to vigorous-intensity physical activity (MVPA), and TV viewing. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. With a median follow-up time of 7.1 years, we observed 91 total deaths. We found a positive association between BMI ( = 2.14, 95% CI 1.08-4.24 and mortality, and no statistically significant association between TV viewing (HR5+ vs. < 3 h/day = 1.46, 95% CI 0.86-2.46) and mortality nor MVPA with mortality (HR15+ vs. 0 MET h/week = 0.72, 95% CI 0.43-1.21) after adjusting for tumor characteristics and demographic factors. Further adjustment for lifestyle and health status attenuated BMI associations ( = 1.47, 95% CI 0.71-3.07), but strengthened the association between TV viewing and mortality (HR5+ vs. < 3 h/day = 2.28, 95% CI 1.05-4.95). Our results suggest that higher post-diagnosis BMI and TV viewing may be associated with higher mortality risk among EC patients, but that there may be complicated interrelationships between lifestyle factors of BMI, PA, and TV viewing and the mediating role of health status that need to be clarified. C1 [Arem, Hannah] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, 950 New Hampshire Ave NW,Off 514, Washington, DC 20052 USA. [Pfeiffer, Ruth M.; Moore, Steven C.; Brinton, Louise A.; Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Arem, H (reprint author), George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, 950 New Hampshire Ave NW,Off 514, Washington, DC 20052 USA. EM hannaharem@gwu.edu RI Moore, Steven/D-8760-2016 OI Moore, Steven/0000-0002-8169-1661 FU intramural research program at the US National Cancer Institute FX This study was funded by the intramural research program at the US National Cancer Institute. NR 17 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2016 VL 27 IS 11 BP 1403 EP 1409 DI 10.1007/s10552-016-0813-7 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EC5NW UT WOS:000388183800013 PM 27730319 ER PT J AU Pinto, C Di Fabio, F Rosati, G Lolli, IR Ruggeri, EM Ciuffreda, L Ferrari, D Lo Re, G Rosti, G Tralongo, P Ferrara, R Alabiso, O Chiara, S Ianniello, GP Frassoldati, A Bilancia, D Campanella, GA Signorelli, C Racca, P Benincasa, E Stroppolo, ME Di Costanzo, F AF Pinto, Carmine Di Fabio, Francesca Rosati, Gerardo Lolli, Ivan R. Ruggeri, Enzo M. Ciuffreda, Libero Ferrari, Daris Lo Re, Giovanni Rosti, Giovanni Tralongo, Paolo Ferrara, Raimondo Alabiso, Oscar Chiara, Silvana Ianniello, Giovanni P. Frassoldati, Antonio Bilancia, Domenico Campanella, Giovanna A. Signorelli, Carlo Racca, Patrizia Benincasa, Elena Stroppolo, Maria Elena Di Costanzo, Francesco TI Observational study on quality of life, safety, and effectiveness of first-line cetuximab plus chemotherapy in KRAS wild-type metastatic colorectal cancer patients: the ObservEr Study SO CANCER MEDICINE LA English DT Article DE Cetuximab; metastatic colorectal cancer; quality of life; skin reactions ID RAS MUTATIONS; OPEN-LABEL; TRIAL; IRINOTECAN; FLUOROURACIL; LEUCOVORIN; BEVACIZUMAB; PSORIASIS; OPUS AB Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression-free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab-specific grade >= 3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan-Incidence rate ratio [IRR] 1.72, P < 0.0001) and gender (male vs. female-IRR 1.38, P = 0.0008). Compliance at first postbaseline evaluation was 97.75%. Median overall survival was 23.6 months, median progression-free survival 8.3 months. Cetuximab plus chemotherapy did not compromise QoL in the routine clinical setting when patients receive close monitoring plus prophylactic or reactive management of skin reactions. We observed the same correlation between overall survival (OS) and skin reactions reported in controlled clinical trials, also in this setting. C1 [Pinto, Carmine] Santa Maria Nuova IRCCS Hosp, Med Oncol, Reggio Emilia, Italy. [Di Fabio, Francesca] S Orsola Malpighi Policlin Hosp, Med Oncol, Bologna, Italy. [Rosati, Gerardo; Bilancia, Domenico] San Carlo Hosp, Med Oncol, Potenza, Italy. [Lolli, Ivan R.; Campanella, Giovanna A.] Saverio Bellis IRCCS Hosp, Med Oncol, Castellana Grotte, Italy. [Ruggeri, Enzo M.; Signorelli, Carlo] Belcolle AUSL Hosp Viterbo, Med Oncol, Viterbo, Italy. [Ciuffreda, Libero; Racca, Patrizia] Citta Salute Scienza, Med Oncol, Turin, Italy. [Ciuffreda, Libero; Racca, Patrizia] San Giovanni Battista Molinette Hosp, Turin, Italy. [Ferrari, Daris] San Paolo Hosp, Med Oncol, Milan, Italy. [Lo Re, Giovanni] Pordenone AAS5 Hosp, Med Oncol, Pordenone, Italy. [Rosti, Giovanni] Treviso Reg Hosp, Med Oncol, Treviso, Italy. [Tralongo, Paolo] Umberto I RAO Hosp, Med Oncol, Siracusa, Italy. [Ferrara, Raimondo] Mons R Dimiccoli Hosp, Med Oncol, Barletta, Italy. [Alabiso, Oscar] Carita Hosp, Med Oncol, Novara, Italy. [Chiara, Silvana] San Martino IRCCS Univ Hosp, Natl Canc Inst, Med Oncol, Genoa, Italy. [Ianniello, Giovanni P.] St Anna & San Sebastiano Hosp, Med Oncol, Caserta, Italy. [Frassoldati, Antonio] Arcispedale St Anna Univ Hosp, Clin Oncol, Ferrara, Italy. [Benincasa, Elena; Stroppolo, Maria Elena] Merck Serono SpA, Rome, Italy. [Pinto, Carmine; Di Costanzo, Francesco] Careggi Univ Hosp, Florence, Italy. RP Pinto, C (reprint author), IRCCS Arcispedale S Maria Nuova, Ctr Clin Canc, Med Oncol Unit, Viale Risorgimento 80, I-42123 Reggio Emilia, Italy. EM pinto.carmine@asmn.re.it FU Merck Serono S.p.A. Italy FX The ObservEr Study was sponsored by Merck Serono S.p.A. Italy. NR 26 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD NOV PY 2016 VL 5 IS 11 BP 3272 EP 3281 DI 10.1002/cam4.888 PG 10 WC Oncology SC Oncology GA EC8DH UT WOS:000388370000027 PM 27748041 ER PT J AU Koshiol, J Wozniak, A Cook, P Adaniel, C Acevedo, J Azocar, L Hsing, AW Roa, JC Pasetti, MF Miquel, JF Levine, MM Ferreccio, C AF Koshiol, Jill Wozniak, Aniela Cook, Paz Adaniel, Christina Acevedo, Johanna Azocar, Lorena Hsing, Ann W. Roa, Juan C. Pasetti, Marcela F. Miquel, Juan F. Levine, Myron M. Ferreccio, Catterina CA Gallbladder Canc Chile Working Grp TI Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis SO CANCER MEDICINE LA English DT Article DE Chile; epidemiology; gallbladder cancer; meta-analysis; Salmonella enterica serovar Typhi; Vi antibodies ID HIGH-RISK AREA; HEPATOBILIARY CANCER; CARRIER STATE; CHILI-PEPPER; CARCINOMA; BILE; ASSOCIATION; GALLSTONES; INFECTION; FEVER AB In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association between Salmonella enterica serovar Typhi (S. Typhi) antibodies and GBC. We tested 39 GBC cases, 40 gallstone controls, and 39 population-based controls for S. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association with GBC. We also conducted a meta-analysis of > 1000 GBC cases by combining our results with previous studies. GBC cases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95% CI: 0.9-18.3), although S. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta-analysis, the summary relative risk was 4.6 (95% CI: 3.1-6.8, P-heterogeneity = 0.6) for anti-Vi and 5.0 (95% CI: 2.7-9.3, P-heterogeneity = 0.2) for bile or stool culture. Our results are consistent with the meta-analysis. Despite differences in study methods (e.g., S. Typhi detection assay), most studies found a positive association between S. Typhi and GBC. However, the mechanism underlying this association requires further investigation C1 [Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Wozniak, Aniela; Adaniel, Christina] Pontificia Univ Catolica Chile, Microbiol Lab, Santiago, Chile. [Cook, Paz; Acevedo, Johanna; Ferreccio, Catterina] Pontificia Univ Catolica Chile, ACCDiS, Escuela Med, Adv Ctr Chron Dis, Santiago, Chile. [Azocar, Lorena; Miquel, Juan F.] Pontificia Univ Catolica Chile, Sch Med, Dept Gastroenterol, Santiago, Chile. [Hsing, Ann W.] Stanford Canc Inst, Palo Alto, CA USA. [Hsing, Ann W.] Stanford Sch Med, Dept Hlth Res & Policy, Palo Alto, CA USA. [Roa, Juan C.] Pontificia Univ Catolica Chile, Sch Med, Dept Pathol, Santiago, Chile. [Pasetti, Marcela F.; Levine, Myron M.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD USA. RP Ferreccio, C (reprint author), FONDAP, ACCDiS, Marcoletta 434, Santiago, Chile. EM catferre@gmail.com FU Fondo Nacional de Investigacion y Desarrollo en Salud (FONIS) [SA11I2205]; Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1130303, 1130204, CONICYT/FONDAP/15130011]; Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Division of Cancer Epidemiology and Genetics; Office of Research on Women's Health (ORWH), NIH FX This work was supported by grants from the Fondo Nacional de Investigacion y Desarrollo en Salud (FONIS) #SA11I2205 to CF and the Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) (grant numbers 1130303 to JFM and 1130204 to JCR), CONICYT/FONDAP/15130011, and by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Office of Research on Women's Health (ORWH), NIH. NR 62 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD NOV PY 2016 VL 5 IS 11 BP 3310 EP 3325 DI 10.1002/cam4.915 PG 16 WC Oncology SC Oncology GA EC8DH UT WOS:000388370000031 PM 27726295 ER PT J AU Klein, MB Althoff, KN Jing, YZ Lau, B Kitahata, M Lo Re, V Kirk, GD Hull, M Kim, HN Sebastiani, G Moodie, EEM Silverberg, MJ Sterling, TR Thorne, JE Cescon, A Napravnik, S Eron, J Gill, MJ Justice, A Peters, MG Goedert, JJ Mayor, A Thio, CL Cachay, ER Moore, R AF Klein, Marina B. Althoff, Keri N. Jing, Yuezhou Lau, Bryan Kitahata, Mari Lo Re, Vincent, III Kirk, Gregory D. Hull, Mark Kim, H. Nina Sebastiani, Giada Moodie, Erica E. M. Silverberg, Michael J. Sterling, Timothy R. Thorne, Jennifer E. Cescon, Angela Napravnik, Sonia Eron, Joe Gill, M. John Justice, Amy Peters, Marion G. Goedert, James J. Mayor, Angel Thio, Chloe L. Cachay, Edward R. Moore, Richard CA Amer AIDS Cohort Collaboration Res TI Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; hepatitis C virus; hepatitis B virus; coinfection; end-stage liver disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIMPLE NONINVASIVE INDEX; TENOFOVIR-BASED THERAPY; B-VIRUS; INFECTED PATIENTS; SIGNIFICANT FIBROSIS; HIV/HCV COINFECTION; HBV-HIV; COHORT; DECOMPENSATION AB Background. Human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown. Methods. Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996-2000), middle (2001-2005), and modern (2006-2010) eras. Results. Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV-(8.72) and HCV-(6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy. Conclusions. Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients. C1 [Klein, Marina B.; Sebastiani, Giada; Moodie, Erica E. M.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Althoff, Keri N.; Jing, Yuezhou; Lau, Bryan; Kirk, Gregory D.; Thorne, Jennifer E.; Thio, Chloe L.; Moore, Richard] Johns Hopkins Univ, Baltimore, MD USA. [Kitahata, Mari; Kim, H. Nina] Univ Washington, Seattle, WA 98195 USA. [Lo Re, Vincent, III] Univ Penn, Philadelphia, PA 19104 USA. [Hull, Mark] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Hull, Mark] Univ British Columbia, Vancouver, BC, Canada. [Silverberg, Michael J.] Kaiser Permanente Calif, Oakland, CA USA. [Sterling, Timothy R.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Cescon, Angela] Northern Ontario Sch Med, Sudbury, ON, Canada. [Napravnik, Sonia; Eron, Joe] Univ N Carolina, Chapel Hill, NC USA. [Gill, M. John] Univ Calgary, Calgary, AB, Canada. [Justice, Amy] Yale Univ, New Haven, CT USA. [Justice, Amy] Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. [Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goedert, James J.] NCI, NIH, Bethesda, MD 20892 USA. [Mayor, Angel] Univ Cent Caribe, Retrovirus Res Ctr, Bayamon, PR USA. [Cachay, Edward R.] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Klein, MB (reprint author), McGill Univ Hlth, Chron Viral Illness Serv, Glen Site,1001 Decarie Blvd,D02-4110, Montreal, PQ H4A 3J1, Canada. EM marina.klein@mcgill.ca FU National Institutes of Health [U01-AI069918, U01-AA013566, U01-AA020790, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, UM1-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-AI69432, U01-AI69434, U01-DA036935, U01-HD32632, U10-EY08052, U10-EY08057, U10-EY08067, U24-AA020794, U54-MD007587, UL1-RR024131, UL1-TR000083, F31-DA037788, G12-MD007583]; Centers for Disease Control and Prevention [CDC200-2006-18797]; Agency for Healthcare Research and Quality [90047713]; Health Resources and Services Administration [90051652]; Canadian Institutes of Health Research, Canada [TGF-96118, HCP-97105, CBR-86906, CBR-94036]; Canadian Institutes of Health Research (CIHR) New Investigator award; Fonds de recherche Sante-Quebec/(FRQ-S)/Reseau SIDA/Maladies Infectieuses; Ontario Ministry of Health and Long Term Care; Government of Alberta, Canada; Intramural Research Program of the National Cancer Institute; FRQ-S; The National Institutes of Health [K01-AI071754, K01-AI093197, K23-EY013707, K24-DA00432, K24-AI065298, KL2-TR000421, MO1-RR-00052, N02-CP55504, P30-AI027763, P30-AI094189, P30-AI27757, P30-AI27767, P30-AI036219, P30-AI50410, P30-AI54999, P30-MH62246]; A National Institutes of Health [R01-AA16893, R01-CA165937, U01-DA036297, K24-AI118591, R01-DA11602, R01-DA12568, R24-AI067039, R56-AI102622, Z01-CP010214, Z01-CP010176] FX This work was supported by numerous grants (grants U01-AI069918, U01-AA013566, U01-AA020790, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, UM1-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-AI69432, U01-AI69434, U01-DA036935, U01-HD32632, U10-EY08052, U10-EY08057, U10-EY08067, U24-AA020794, U54-MD007587, UL1-RR024131, UL1-TR000083, F31-DA037788, G12-MD007583, K01-AI071754, K01-AI093197, K23-EY013707, K24-DA00432, K24-AI065298, KL2-TR000421, MO1-RR-00052, N02-CP55504, P30-AI027763, P30-AI094189, P30-AI27757, P30-AI27767, P30-AI036219, P30-AI50410, P30-AI54999, P30-MH62246, R01-AA16893, R01-CA165937, U01-DA036297, K24-AI118591, R01-DA11602, R01-DA12568, R24-AI067039, R56-AI102622, Z01-CP010214, and Z01-CP010176) from the National Institutes of Health; contract CDC200-2006-18797 from the Centers for Disease Control and Prevention; contract 90047713 from the Agency for Healthcare Research and Quality; contract 90051652 from the Health Resources and Services Administration; grants TGF-96118, HCP-97105, CBR-86906, CBR-94036 from the Canadian Institutes of Health Research, Canada; Canadian Institutes of Health Research (CIHR) New Investigator award (A. B.); Fonds de recherche Sante-Quebec/(FRQ-S)/Reseau SIDA/Maladies Infectieuses; Ontario Ministry of Health and Long Term Care; and the Government of Alberta, Canada. Additional support was provided by the Intramural Research Program of the National Cancer Institute and the National Institutes of Health. M. B. K. is supported by a Chercheurs nationaux career award from the FRQ-S. NR 38 TC 0 Z9 0 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 NOV 1 PY 2016 VL 63 IS 9 BP 1160 EP 1167 DI 10.1093/cid/ciw531 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EC2WY UT WOS:000387986200007 PM 27506682 ER PT J AU Amour, C Gratz, J Mduma, E Svensen, E Rogawski, ET McGrath, M Seidman, JC McCormick, BJJ Shrestha, S Samie, A Mahfuz, M Qureshi, S Hotwani, A Babji, S Trigoso, DR Lima, AAM Bodhidatta, L Bessong, P Ahmed, T Shakoor, S Kang, G Kosek, M Guerrant, RL Lang, D Gottlieb, M Houpt, ER Platts-Mills, JA AF Amour, Caroline Gratz, Jean Mduma, Estomih Svensen, Erling Rogawski, Elizabeth T. McGrath, Monica Seidman, Jessica C. McCormick, Benjamin J. J. Shrestha, Sanjaya Samie, Amidou Mahfuz, Mustafa Qureshi, Shahida Hotwani, Aneeta Babji, Sudhir Trigoso, Dixner Rengifo Lima, Aldo A. M. Bodhidatta, Ladaporn Bessong, Pascal Ahmed, Tahmeed Shakoor, Sadia Kang, Gagandeep Kosek, Margaret Guerrant, Richard L. Lang, Dennis Gottlieb, Michael Houpt, Eric R. Platts-Mills, James A. CA Etiology Risk Factors Interactions TI Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource Settings: Results From the MAL-ED Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Campylobacter; children; risk factors; growth; inflammation ID RANDOMIZED CONTROLLED-TRIAL; DEVELOPING-COUNTRIES; LINEAR GROWTH; MASS AZITHROMYCIN; EGYPTIAN CHILDREN; PERUVIAN CHILDREN; TRACHOMA CONTROL; BIRTH COHORT; ADULT HEALTH; RISK-FACTORS AB Background. Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life. Methods. Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter. Stool and blood samples were assayed for markers of intestinal permeability and inflammation. Results. A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter. We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47-.67), treatment of drinking water (0.76; 0.70-0.83), access to an improved latrine (0.89; 0.82-0.97), and recent macrolide antibiotic use (0.68; 0.63-0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (-1.82; 95% confidence interval, -1.94 to -1.70) compared with a low burden (-1.49; -1.60 to -1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation. Conclusions. Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings. C1 [Amour, Caroline; Gratz, Jean; Mduma, Estomih] Haydom Lutheran Hosp, Haydom, Tanzania. [Gratz, Jean; Rogawski, Elizabeth T.; Guerrant, Richard L.; Houpt, Eric R.; Platts-Mills, James A.] Univ Virginia, Div Infect Dis & Int Hlth, POB 801340, Charlottesville, VA 22908 USA. [McGrath, Monica; Seidman, Jessica C.; McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Lang, Dennis; Gottlieb, Michael] Fdn Natl Inst Hlth, Bethesda, MD USA. [Kosek, Margaret] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Svensen, Erling] Haukeland Hosp, Bergen, Norway. [Shrestha, Sanjaya; Bodhidatta, Ladaporn] Armed Forces Res Inst Med Sci, Bangkok, Thailand. [Samie, Amidou; Bessong, Pascal] Univ Venda, Thohoyandou, South Africa. [Mahfuz, Mustafa; Ahmed, Tahmeed] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Qureshi, Shahida; Hotwani, Aneeta; Shakoor, Sadia] Aga Khan Univ, Karachi, Pakistan. [Babji, Sudhir; Kang, Gagandeep] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Trigoso, Dixner Rengifo; Kosek, Margaret] Asociac Benef PRISMA, Iquitos, Peru. [Lima, Aldo A. M.] Univ Fed Ceara, Clin Res Unit, Fortaleza, Ceara, Brazil. [Lima, Aldo A. M.] Univ Fed Ceara, Inst Biomed, Fortaleza, Ceara, Brazil. RP Platts-Mills, JA (reprint author), Univ Virginia, Div Infect Dis & Int Hlth, POB 801340, Charlottesville, VA 22908 USA. EM jp5t@virginia.edu RI Strand, Tor/D-9836-2016 OI Strand, Tor/0000-0002-4038-151X FU Bill & Melinda Gates Foundation; Foundation for the National Institutes of Health; National Institutes of Health, Fogarty International Center; National Institutes of Health [5K23-AI114888-02] FX The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center. J. A. P. receives support from the National Institutes of Health (5K23-AI114888-02). NR 46 TC 2 Z9 2 U1 4 U2 4 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 NOV 1 PY 2016 VL 63 IS 9 BP 1171 EP 1179 DI 10.1093/cid/ciw542 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EC2WY UT WOS:000387986200009 PM 27501842 ER PT J AU Edelman, EJ Gordon, KS Tate, JP Becker, WC Bryant, K Crothers, K Gaither, JR Gibert, CL Gordon, AJ Marshall, BDL Rodriguez-Barradas, MC Samet, JH Skanderson, M Justice, AC Fiellin, DA AF Edelman, E. J. Gordon, K. S. Tate, J. P. Becker, W. C. Bryant, K. Crothers, K. Gaither, J. R. Gibert, C. L. Gordon, A. J. Marshall, B. D. L. Rodriguez-Barradas, M. C. Samet, J. H. Skanderson, M. Justice, A. C. Fiellin, D. A. TI The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy SO HIV MEDICINE LA English DT Article DE analgesics; antiretroviral therapy; CD4 lymphocyte count; disease progression; HIV; opioid ID HUMAN-IMMUNODEFICIENCY-VIRUS; ILLICIT DRUG-USE; COMMUNITY-BASED COHORT; VETERANS AGING COHORT; DISEASE PROGRESSION; TREATMENT OUTCOMES; UNINFECTED PATIENTS; RHESUS MACAQUES; INDIGENT ADULTS; IMMUNE FUNCTION AB Objectives Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. Methods Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (>= 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). Results Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/mu L; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/mu L; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count >= 500 cells/mu L (mean rise per year: 52 cells/mu L for no opioids vs. 20 cells/mu L for short-term opioids; P = 0.04); findings were otherwise unchanged. Conclusions Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART. C1 [Edelman, E. J.; Tate, J. P.; Becker, W. C.; Gaither, J. R.; Justice, A. C.; Fiellin, D. A.] Yale Univ, Sch Med, POB 208025, New Haven, CT 06520 USA. [Edelman, E. J.; Justice, A. C.; Fiellin, D. A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Gordon, K. S.; Tate, J. P.; Becker, W. C.; Gaither, J. R.; Skanderson, M.; Justice, A. C.] VA Connecticut Hlth Care Syst, West Haven, CT USA. [Bryant, K.] NIAAA, HIV AIDS Program, Bethesda, MD USA. [Crothers, K.] Univ Washington, Seattle, WA 98195 USA. [Gaither, J. R.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Gibert, C. L.] DC Vet Affairs Med Ctr, Washington, DC USA. [Gibert, C. L.] George Washington Univ, Washington, DC USA. [Gordon, A. J.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, A. J.] Univ Pittsburgh, Pittsburgh, PA USA. [Marshall, B. D. L.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Rodriguez-Barradas, M. C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Houston, TX 77030 USA. [Samet, J. H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Samet, J. H.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, POB 208025, New Haven, CT 06520 USA. EM ejennifer.edelman@yale.edu OI Edelman, E. Jennifer/0000-0002-9375-0489; Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU NCATS NIH HHS [UL1 TR000142]; NIAAA NIH HHS [U10 AA013566]; NIDA NIH HHS [K12 DA033312] NR 79 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD NOV PY 2016 VL 17 IS 10 BP 728 EP 739 DI 10.1111/hiv.12377 PG 12 WC Infectious Diseases SC Infectious Diseases GA EC9DA UT WOS:000388443100003 PM 27186715 ER PT J AU Erlandson, KM Plankey, MW Springer, G Cohen, HS Cox, C Hoffman, HJ Yin, MT Brown, TT AF Erlandson, K. M. Plankey, M. W. Springer, G. Cohen, H. S. Cox, C. Hoffman, H. J. Yin, M. T. Brown, T. T. TI Fall frequency and associated factors among men and women with or at risk for HIV infection SO HIV MEDICINE LA English DT Article DE accidental fall; dizziness; HIV; musculoskeletal equilibrium; vertigo ID ANTIRETROVIRAL THERAPY; INTERAGENCY HIV; AUTONOMIC DYSFUNCTION; POSITIVE PATIENTS; PREVALENCE; COMMUNITY; ADULTS; IMPACT; FEAR; POLYNEUROPATHY AB Objectives Falls and fall-related injuries are a major public health concern. HIV-infected adults have been shown to have a high incidence of falls. Identification of major risk factors for falls that are unique to HIV infection or similar to those in the general population will inform development of future interventions for fall prevention. Methods HIV-infected and uninfected men and women participating in the Hearing and Balance Substudy of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study were asked about balance symptoms and falls during the prior 12 months. Falls were categorized as 0, 1, or >= 2; proportional odds logistic regression models were used to investigate relationships between falls and demographic and clinical variables and multivariable models were created. Results Twenty-four per cent of 303 HIV-infected participants reported at least one fall compared with 18% of 233 HIV-uninfected participants (P = 0.27). HIV-infected participants were demographically different from HIV-uninfected participants, and were more likely to report clinical imbalance symptoms (P = 0.035). In univariate analyses, more falls were associated with hepatitis C, female sex, obesity, smoking, and clinical imbalance symptoms, but not age, HIV serostatus or other comorbidities. In multivariable analyses, female sex and imbalance symptoms were independently associated with more falls. Among HIV-infected participants, smoking, a higher number of medications, and imbalance symptoms remained independent fall predictors, while current protease inhibitor use was protective. Conclusions Similar rates of falls among HIV-infected and uninfected participants were largely explained by a high prevalence of imbalance symptoms. Routine assessment of falls and dizziness/imbalance symptoms should be considered, with interventions targeted at reducing symptomatology. C1 [Erlandson, K. M.] Univ Colorado, Dept Med, Div Infect Dis, 12700 E 19th Ave,Mail Stop B168, Aurora, CO 80045 USA. [Erlandson, K. M.] Univ Colorado, Dept Med, Div Geriatr Med, 12700 E 19th Ave,Mail Stop B168, Aurora, CO 80045 USA. [Plankey, M. W.] Georgetown Univ, Med Ctr, Dept Med, Div Infect Dis, Washington, DC 20007 USA. [Springer, G.; Cox, C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cohen, H. S.] Baylor Coll Med, Bobby R Alford Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. [Hoffman, H. J.] Natl Inst Deafness & Other Commun Disorders NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA. [Yin, M. T.] Columbia Univ, Dept Med, Div Infect Dis, Med Ctr, New York, NY USA. [Brown, T. T.] Johns Hopkins Univ, Dept Med, Div Endocrinol Diabet & Metab, Baltimore, MD USA. RP Erlandson, KM (reprint author), Univ Colorado, Dept Med, Div Infect Dis, 12700 E 19th Ave,Mail Stop B168, Aurora, CO 80045 USA.; Erlandson, KM (reprint author), Univ Colorado, Dept Med, Div Geriatr Med, 12700 E 19th Ave,Mail Stop B168, Aurora, CO 80045 USA. EM Kristine.Erlandson@ucdenver.edu FU NCATS NIH HHS [UL1 TR001079]; NCRR NIH HHS [UL1 RR025005]; NIA NIH HHS [K23 AG050260]; NIAID NIH HHS [R01 AI093520, R01 AI095089, U01 AI035004, U01 AI035039, U01 AI035042, UM1 AI035043, K24 AI120834, U01 AI034994, U01 AI042590]; NICHD NIH HHS [U01 HD032632]; NIDCD NIH HHS [R01 DC009031] NR 53 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD NOV PY 2016 VL 17 IS 10 BP 740 EP 748 DI 10.1111/hiv.12378 PG 9 WC Infectious Diseases SC Infectious Diseases GA EC9DA UT WOS:000388443100004 PM 27028463 ER PT J AU Chandler, RJ Williams, IM Incao, AA Gibson, AL Davidson, CD Hubbard, B Porter, FD Pavan, WJ Venditti, CP AF Chandler, R. J. Williams, I. M. Incao, A. A. Gibson, A. L. Davidson, C. D. Hubbard, B. Porter, F. D. Pavan, W. J. Venditti, C. P. TI Systemic AAV9 gene delivery improves the lifespan of mice with Niemann-Pick disease, type C1 SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Conference on Changing the Face of Modern Medicine - Stem Cells and Gene Therapy CY OCT 18-21, 2016 CL Florence, ITALY SP Int Soc Stem Cell Res, Assoc Biologia Cellulare & Differenziamento C1 [Chandler, R. J.; Hubbard, B.; Venditti, C. P.] NHGRI, Med Genom & Mol Genet Branch, NIH, Betrhesda, MD USA. [Williams, I. M.; Porter, F. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Translat Med, NIH, Bethesda, MD USA. [Incao, A. A.; Gibson, A. L.; Pavan, W. J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Davidson, C. D.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose F Kennedy Ctr Intellectual & Dev Disabil Res, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2016 VL 27 IS 11 MA P003 BP A46 EP A46 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA EC4QT UT WOS:000388119200156 ER PT J AU De Ravin, SS Sorrentino, BP Malech, HL AF De Ravin, S. S. Sorrentino, B. P. Malech, H. L. TI Lentiviral gene therapy with busulfan conditioning for older patients with SCID-X1 SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Conference on Changing the Face of Modern Medicine - Stem Cells and Gene Therapy CY OCT 18-21, 2016 CL Florence, ITALY SP Int Soc Stem Cell Res, Assoc Biologia Cellulare & Differenziamento C1 [De Ravin, S. S.; Malech, H. L.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Sorrentino, B. P.] St Jude Childrens Res Hosp, Garden City, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2016 VL 27 IS 11 MA OR37 BP A37 EP A37 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA EC4QT UT WOS:000388119200127 ER PT J AU Wu, C Espinoza, DA Koelle, SJ Yang, D Schlums, H Kaur, A Hammer, Q Childs, RW Romagnani, C Bryceson, YT Dunbar, CE AF Wu, C. Espinoza, D. A. Koelle, S. J. Yang, D. Schlums, H. Kaur, A. Hammer, Q. Childs, R. W. Romagnani, C. Bryceson, Y. T. Dunbar, C. E. TI Clonal expansion and long-term persistence of rhesus macaque NK cells with an adaptive phenotype as revealed by genetic barcoding SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Conference on Changing the Face of Modern Medicine - Stem Cells and Gene Therapy CY OCT 18-21, 2016 CL Florence, ITALY SP Int Soc Stem Cell Res, Assoc Biologia Cellulare & Differenziamento C1 [Wu, C.; Espinoza, D. A.; Koelle, S. J.; Yang, D.; Childs, R. W.; Dunbar, C. E.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. Univ Southern Calif, Los Angeles, CA USA. [Schlums, H.; Bryceson, Y. T.] Karolinska Inst, Stockholm, Sweden. Charite, Berlin, Germany. [Kaur, A.] Tulane Natl Primate Res Ctr, Covington, LA USA. [Hammer, Q.; Romagnani, C.] Deutsch Rheuma Forschungszentrum, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2016 VL 27 IS 11 MA INV64 BP A18 EP A18 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA EC4QT UT WOS:000388119200064 ER PT J AU Tobias, DK Zhang, C Chavarro, J Olsen, S Bao, W Bjerregaard, AA Fung, TT Manson, JE Hu, FB AF Tobias, D. K. Zhang, C. Chavarro, J. Olsen, S. Bao, W. Bjerregaard, A. A. Fung, T. T. Manson, J. E. Hu, F. B. TI Healthful dietary patterns and long-term weight change among women with a history of gestational diabetes mellitus SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID LIFE-STYLE INTERVENTION; MEDITERRANEAN DIET; PROSPECTIVE COHORT; GLUCOSE-TOLERANCE; RANDOMIZED-TRIAL; RISK-FACTORS; METAANALYSIS; PREVENTION; ADULTS; FEASIBILITY AB BACKGROUND/OBJECTIVE: Diet represents a key strategy for the prevention of obesity and type 2 diabetes among women with a history of gestational diabetes mellitus (GDM), although effective dietary patterns to prevent weight gain in the long term are largely unknown. We sought to evaluate whether improvement in overall diet quality is associated with less long-term weight gain among high-risk women with prior GDM. SUBJECTS/METHODS: Women with a history of GDM (N = 3397) were followed from 1991 to 2011, or until diagnosis of type 2 diabetes or other chronic disease. Usual diet was assessed via food frequency questionnaire every 4 years from which we calculated the Alternative Healthy Eating Index (aHEI-2010), Alternate Mediterranean Diet (AMED) and Dietary Approaches to Stop Hypertension (DASH) dietary pattern scores. Weight, lifestyle and health-related outcomes were self-reported every 2 years. We estimated the change in dietary score with change in body weight using linear regression models adjusting for age, baseline body mass index (BMI), baseline and simultaneous change in physical activity and smoking status and other risk factors. RESULTS: Women were followed up to 20 years, gaining an average 1.9 kg (s.d. = 7.0) per 4-year period. Women in the highest quintile (Q5) of diet change (most improvement in quality) gained significantly less weight per 4-year period than the lowest quintile (Q1; decrease in quality), independent of other risk factors (4-year weight change, aHEI-2010: Q5 = 1.30 kg vs Q1 = 3.27 kg; AMED: Q5 = 0.94 kg vs Q1 = 2.56 kg, DASH: Q5 = 0.64 kg vs Q1 = 2.75 kg). Significant effect modification by BMI (p-interactions o0.001) indicated a greater magnitude of weight change among women with a higher baseline BMI for all three patterns. CONCLUSIONS: Increased diet quality was associated with less weight gain, independent of other lifestyle factors. Post-partum recommendations on diet quality may provide one strategy to prevent long-term weight gain in this high-risk group. C1 [Tobias, D. K.; Manson, J. E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02115 USA. [Tobias, D. K.; Chavarro, J.; Manson, J. E.; Hu, F. B.] Harvard Med Sch, 900 Commonwealth Ave, Boston, MA 02115 USA. [Tobias, D. K.; Chavarro, J.; Olsen, S.; Fung, T. T.; Hu, F. B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Zhang, C.; Bao, W.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA. [Chavarro, J.; Hu, F. B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chavarro, J.; Hu, F. B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Olsen, S.; Bjerregaard, A. A.] Statens Serum Inst, Dept Epidemiol Res, Ctr Fetal Programming, Copenhagen, Denmark. [Bao, W.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Fung, T. T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. RP Tobias, DK (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02115 USA.; Tobias, DK (reprint author), Harvard Med Sch, 900 Commonwealth Ave, Boston, MA 02115 USA. EM dtobias@partners.org FU National Institutes of Health [HL60712, UM1 CA176726, DK58845, HSN275201000020C, P30 DK46200, 1K01DK103720]; American Diabetes Association [7-12-MN-34]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health FX This work was supported by the National Institutes of Health (HL60712, UM1 CA176726, DK58845, HSN275201000020C, P30 DK46200, 1K01DK103720) and the American Diabetes Association (7-12-MN-34). Drs Zhang and Bao are supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. NR 32 TC 0 Z9 0 U1 11 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 2016 VL 40 IS 11 BP 1748 EP 1753 DI 10.1038/ijo.2016.156 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EC4TT UT WOS:000388127600021 PM 27569683 ER PT J AU Mansouri, B Kivelevitch, D Natarajan, B Joshi, AA Ryan, C Benjegerdes, K Schussler, JM Rader, DJ Reilly, MP Menter, A Mehta, NN AF Mansouri, Bobbak Kivelevitch, Dario Natarajan, Balaji Joshi, Aditya A. Ryan, Caitriona Benjegerdes, Katie Schussler, Jeffrey M. Rader, Daniel J. Reilly, Muredach P. Menter, Alan Mehta, Nehal N. TI Comparison of Coronary Artery Calcium Scores Between Patients With Psoriasis and Type 2 Diabetes SO JAMA DERMATOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CHOLESTEROL EFFLUX CAPACITY; POPULATION-BASED COHORT; COMPUTED-TOMOGRAPHY; METABOLIC SYNDROME; VASCULAR-DISEASE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; ASYMPTOMATIC PATIENTS; RISK-FACTORS AB IMPORTANCE Psoriasis is associated with an increased risk of cardiovascular diseases. Subclinical atherosclerosis in patients with psoriasis has not been compared with other conditions associated with increased cardiovascular risk and more rigorous cardiovascular disease screening, such as type 2 diabetes. OBJECTIVE To assess the burden of asymptomatic coronary atherosclerosis measured by coronary artery calcium score in patients with moderate to severe psoriasis compared with patients with type 2 diabetes and healthy controls. DESIGN, SETTING, AND PARTICIPANTS Three single-center, cross-sectional studies were performed in patients recruited from specialty outpatient clinics with moderate to severe psoriasis without type 2 diabetes (recruited from November 1, 2013, through April 31, 2015), patients with type 2 diabetes without psoriasis or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011), and age-and sex-matched healthy controls without psoriasis, type 2 diabetes, or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011). EXPOSURES Psoriasis, type 2 diabetes, and healthy control effect on coronary artery calcium score. MAIN OUTCOMES AND MEASURES Coronary artery calcium measured by Agatston score. RESULTS A total of 387 individuals participated in the study. Mean (SD) age was 51 (7.7), 52 (8.0), and 52 (8.0) years in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively. There were 64 men (49.6%) in each group, and most patients were white (119 [ 92.2%], 123 [ 95.3%], and 128 [ 99.2%] in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively). Patients with psoriasis had low cardiovascular risk measured by the Framingham Risk Score but had a high prevalence of cardiovascular and cardiometabolic risk factors, similar to patients with type 2 diabetes. In a fully adjusted model, psoriasis was associated with coronary artery calcium (Tobit regression ratio, 0.89; P < .001) similar to the association in type 2 diabetes (Tobit regression ratio, 0.79; P = .04). Likelihood ratio testing revealed incremental value for psoriasis in a fully adjusted model (chi(2) = 4.48, P = .03) in predicting coronary artery calcium. Psoriasis was independently associated with the presence of any coronary artery calcium (odds ratio, 2.35; 95% CI, 1.12-4.94) in fully adjusted models, whereas the association of coronary artery calcium with type 2 diabetes was no longer significant after adding body mass index to the model (odds ratio, 2.18; 95% CI, 0.75-6.35). CONCLUSIONS AND RELEVANCE Patients with psoriasis have increased coronary artery calcium by mean total Agatston scores, similar to that of patients with type 2 diabetes, suggesting that patients with psoriasis harbor high rates of subclinical atherosclerosis beyond adjustment for body mass index. Major educational efforts for patients and physicians should be undertaken to reduce the burden of cardiovascular disease in patients with psoriasis. C1 [Mansouri, Bobbak; Kivelevitch, Dario; Ryan, Caitriona; Menter, Alan] Baylor Univ, Med Ctr, Div Dermatol, Dallas, TX USA. [Mansouri, Bobbak] Baylor Scott & White Hlth, Dept Dermatol, Temple, TX USA. [Kivelevitch, Dario] Baylor Inst Immunol Res, Dallas, TX USA. [Natarajan, Balaji] Univ Arizona, Coll Med South Campus, Tucson, AZ USA. [Natarajan, Balaji; Joshi, Aditya A.; Mehta, Nehal N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Benjegerdes, Katie] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [Schussler, Jeffrey M.] Baylor Univ, Med Ctr, Div Cardiol, Dallas, TX USA. [Schussler, Jeffrey M.] Baylor Jack & Jane Hamilton Heart & Vasc Hosp, Dallas, TX USA. [Schussler, Jeffrey M.] Texas A&M Hlth Sci Ctr, Coll Med, Dallas, TX USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Columbia Univ, Div Cardiol, Dept Med, New York, NY USA. [Reilly, Muredach P.] Columbia Univ, Irving Inst Clin & Translat Res, New York, NY USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, NIH, 10 Ctr Dr, Bethesda, MD 20814 USA. EM nehal.mehta@nih.gov FU Baylor Heart and Vascular Institute Cardiovascular Research Review Committee; Jack and Jane Hamilton Cardiovascular Research Fund; Intramural Research Program at the National Institutes of Health [HL006193-002] FX This study was supported in part by the Baylor Heart and Vascular Institute Cardiovascular Research Review Committee and The Jack and Jane Hamilton Cardiovascular Research Fund and by grant HL006193-002 from the Intramural Research Program at the National Institutes of Health (Dr Mehta). NR 51 TC 1 Z9 1 U1 1 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 NOV PY 2016 VL 152 IS 11 BP 1244 EP 1253 DI 10.1001/jamadermatol.2016.2907 PG 10 WC Dermatology SC Dermatology GA EC6GO UT WOS:000388234700012 PM 27556410 ER PT J AU Hinkle, SN Mumford, SL Grantz, KL Silver, RM Mitchell, EM Sjaarda, LA Radin, RG Perkins, NJ Galai, N Schisterman, EF AF Hinkle, Stefanie N. Mumford, Sunni L. Grantz, Katherine L. Silver, Robert M. Mitchell, Emily M. Sjaarda, Lindsey A. Radin, Rose G. Perkins, Neil J. Galai, Noya Schisterman, Enrique F. TI Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss A Secondary Analysis of a Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID LOW-DOSE ASPIRIN; RISK-FACTORS; SYMPTOMS; TIME AB IMPORTANCE Nausea and vomiting during pregnancy have been associated with a reduced risk for pregnancy loss. However, most prior studies enrolled women with clinically recognized pregnancies, thereby missing early losses. OBJECTIVE To examine the association of nausea and vomiting during pregnancy with pregnancy loss. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial, Effects of Aspirin in Gestation and Reproduction, enrolled women with 1 or 2 prior pregnancy losses at 4 US clinical centers from June 15, 2007, to July 15, 2011. This secondary analysis was limited to women with a pregnancy confirmed by positive results of a human chorionic gonadotropin (hCG) test. Nausea symptoms were ascertained from daily preconception and pregnancy diaries for gestational weeks 2 to 8. From weeks 12 to 36, participants completed monthly questionnaires summarizing symptoms for the preceding 4 weeks. A week-level variable included nausea only, nausea with vomiting, or neither. MAIN OUTCOMES AND MEASURES Peri-implantation (hCG-detected pregnancy without ultrasonographic evidence) and clinically recognized pregnancy losses. RESULTS A total of 797 women (mean [SD] age, 28.7 [4.6] years) had an hCG-confirmed pregnancy. Of these, 188 pregnancies (23.6%) ended in loss. At gestational week 2, 73 of 409 women (17.8%) reported nausea without vomiting and 11 of 409 women (2.7%), nausea with vomiting. By week 8, the proportions increased to 254 of 443 women (57.3%) and 118 of 443 women (26.6%), respectively. Hazard ratios (HRs) for nausea (0.50; 95% CI, 0.32-0.80) and nausea with vomiting (0.25; 95% CI, 0.12-0.51) were inversely associated with pregnancy loss. The associations of nausea (HR, 0.59; 95% CI, 0.29-1.20) and nausea with vomiting (HR, 0.51; 95% CI, 0.11-2.25) were similar for peri-implantation losses but were not statistically significant. Nausea (HR, 0.44; 95% CI, 0.26-0.74) and nausea with vomiting (HR, 0.20; 95% CI, 0.09-0.44) were associated with a reduced risk for clinical pregnancy loss. CONCLUSIONS AND RELEVANCE Among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss. C1 [Hinkle, Stefanie N.; Mumford, Sunni L.; Grantz, Katherine L.; Mitchell, Emily M.; Sjaarda, Lindsey A.; Radin, Rose G.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20817 USA. [Silver, Robert M.] Univ Utah, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Mitchell, Emily M.] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA. [Galai, Noya] Univ Haifa, Dept Stat, Haifa, Israel. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20817 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603423, HHSN267200603424, HHSN267200603426] FX This study was supported by contracts HHSN267200603423, HHSN267200603424, and HHSN267200603426 from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 23 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2016 VL 176 IS 11 BP 1621 EP 1627 DI 10.1001/jamainternmed.2016.5641 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA EC4KK UT WOS:000388097700011 PM 27669539 ER PT J AU Chu, LC Porter, KK Corona-Villalobos, CP Gulsun, MA Shea, SM Markl, M Abraham, TP Bluemke, DA Kamel, IR Zimmerman, SL AF Chu, Linda C. Porter, Kristin K. Corona-Villalobos, Celia Pamela Gulsun, Mehmet Akif Shea, Steven M. Markl, Michael Abraham, Theodore P. Bluemke, David A. Kamel, Ihab R. Zimmerman, Stefan L. TI Evaluation of Left Ventricular Outflow Tract Obstruction With Four-Dimensional Phase Contrast Magnetic Resonance Imaging in Patients with Hypertrophic Cardiomyopathy-A Pilot Study SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE hypertrophic cardiomyopathy; cardiac magnetic resonance; four-dimensional phase contrast; left ventricular outflow tract obstruction ID FLOW PATTERNS; AORTIC FLOW; HEART AB Objective: This study aimed to validate 4-dimensional phase contrast (4D PC) cine magnetic resonance imaging (MRI) as a means of evaluating left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM). Methods: In this institutional review board-approved prospective study, 23 patients with suspected HCM from October 2012 to September 2013 underwent 4D PC MRI. Postprocessed 4D PC pathline cine data were reviewed by 2 blinded reviewers to determine presence or absence of LVOT obstruction. Sensitivity, specificity, and accuracy in 4D PC qualitative and quantitative assessment of LVOT obstruction were calculated using echo as reference standard. Results: Consensus interpretation of 4D PC showed 100.0% (7/7) sensitivity, 75.0% specificity (12/16), and 82.6% (19/23) accuracy in assessment of LVOT obstruction. The 4D PC quantitative estimates of LVOT gradient have 71.4% (5/7) sensitivity, 93.8% (15/16) specificity, and 87.0% (20/23) accuracy in evaluation of LVOT obstruction compared with echo. Conclusions: The 4D PC MRI can assess for LVOT obstruction in HCM patients. C1 [Chu, Linda C.; Porter, Kristin K.; Corona-Villalobos, Celia Pamela; Kamel, Ihab R.; Zimmerman, Stefan L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Halsted B168,600 N Wolfe St, Baltimore, MD 21287 USA. [Gulsun, Mehmet Akif; Shea, Steven M.] Siemens Corp, Corp Technol, Imaging & Comp Vis, Princeton, NJ USA. [Shea, Steven M.] Loyola Univ, Stritch Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Shea, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Abraham, Theodore P.] Johns Hopkins Univ, Sch Med, Dept Cardiol, Baltimore, MD USA. [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Chu, LC (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Halsted B168,600 N Wolfe St, Baltimore, MD 21287 USA. EM lindachu@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU RSNA Research Fellow Grant FX This study was supported by the 2012 RSNA Research Fellow Grant (L.C.). NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2016 VL 40 IS 6 BP 937 EP 940 DI 10.1097/RCT.0000000000000471 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EC9YA UT WOS:000388499000017 PM 27529682 ER PT J AU Pagani, FD Aaronson, KD Kormos, R Mann, DL Spino, C -Jeffries, N Taddei-Peters, WC Mancini, DM McNamara, DM Grady, KL Gorcsan, J Petrucci, R Anderson, AS Glick, HA Acker, MA Rame, JE Goldstein, DJ Pamboukian, SV Miller, MA Baldwin, JT AF Pagani, Francis D. Aaronson, Keith D. Kormos, Robert Mann, Douglas L. Spino, Cathie -Jeffries, Neal Taddei-Peters, Wendy C. Mancini, Donna M. McNamara, Dennis M. Grady, Kathleen L. Gorcsan, John Petrucci, Ralph Anderson, Allen S. Glick, Henry A. Acker, Michael A. Rame, J. Eduardo Goldstein, Daniel J. Pamboukian, Salpy V. Miller, Marissa A. Baldwin, J. Timothy CA Revive-IT Investigators TI The NHLBI REVIVE-IT study: Understanding its discontinuation in the context of current left ventricular assist device therapy SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE heart failure; ventricular assist device; mechanical circulatory support; clinical trials; assisted circulation ID ADVANCED HEART-FAILURE; MECHANICAL CIRCULATORY SUPPORT; DRUG ADMINISTRATION-APPROVAL; CONTINUOUS-FLOW; INTERAGENCY REGISTRY; DESTINATION THERAPY; TRANSPLANTATION; TRIAL; MULTICENTER; PROTOCOL AB The National Institutes of Health National Heart, Lung, and Blood Institute convened a working group in March 2008 to discuss how therapies for heart failure (HF) might be best advanced using clinical trials involving left ventricular assist devices (LVAD). This group opined that the field was ready for a trial to assess the use of long-term ventricular assist device therapy in patients who are less ill than patients currently eligible for destination therapy, which resulted in the Randomized Evaluation of VAD InterVEntion before Inotropic Therapy (REVIVE-IT) pilot study. The specific objective of REVIVE-IT was to compare LVAD therapy with optimal medical management in patients with less advanced HF than current LVAD indications to determine if wider application of permanent LVAD use to less ill patients would be associated with improved survival, quality of life, or functional capacity. REVIVE -IT represented an extraordinary effort to provide data from a randomized clinical trial to inform clinicians, scientists, industry, and regulatory agencies about the efficacy and safety of LVAD therapy in a population with less advanced HF. Despite significant support from the medical community, industry, and governmental agencies, REVIVE -IT failed to accomplish its goal. The reasons for its failure are instructive, and the lessons learned from the REVIVE -IT experience are likely to be relevant to any future study of LVAD therapy in a population with less advanced HF. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Pagani, Francis D.; Aaronson, Keith D.; Spino, Cathie] Univ Michigan, Ann Arbor, MI 48109 USA. [Kormos, Robert; McNamara, Dennis M.; Gorcsan, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Mann, Douglas L.] Washington Univ, St Louis, MO USA. [-Jeffries, Neal; Taddei-Peters, Wendy C.; Miller, Marissa A.; Baldwin, J. Timothy] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mancini, Donna M.] Columbia Univ, New York, NY USA. [Grady, Kathleen L.; Anderson, Allen S.] Northwestern Univ, Chicago, IL 60611 USA. [Petrucci, Ralph] Drexel Univ, Philadelphia, PA 19104 USA. [Glick, Henry A.; Acker, Michael A.; Rame, J. Eduardo] Univ Penn, Philadelphia, PA 19104 USA. [Goldstein, Daniel J.] Albert Einstein Coll Med, New York, NY USA. [Pamboukian, Salpy V.] Univ Alabama Birmingham, Birmingham, AL USA. RP Pagani, FD (reprint author), Univ Michigan, Med Ctr, 5144 Cardiovasc Ctr,SPC 5864,1500 East Med Ctr Dr, Ann Arbor, MI 48109 USA. EM fpagani@umich.edu FU National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100026C]; HeartWare, Inc.; Thoratec Corporation FX REVIVE-IT (ClinicalTrials.gov identifier: NCT01369407) was supported by funding from the National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI Contract Number: HHSN268201100026C). Additional funding in the early study period was provided by HeartWare, Inc., and in the later study period by Thoratec Corporation. NR 20 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2016 VL 35 IS 11 BP 1277 EP 1283 DI 10.1016/j.healun.2016.09.002 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA ED0OB UT WOS:000388540700001 PM 27836022 ER PT J AU Baker, MJ Goldstein, AM Gordon, PL Harbaugh, KS Mackley, HB Glantz, MJ Drabick, JJ AF Baker, Maria J. Goldstein, Alisa M. Gordon, Patricia L. Harbaugh, Kimberly S. Mackley, Heath B. Glantz, Michael J. Drabick, Joseph J. TI An interstitial deletion within 9p21.3 and extending beyond CDKN2A predisposes to melanoma, neural system tumours and possible haematological malignancies SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID GERM-LINE DELETION; FAMILIAL MELANOMA; PANCREATIC-CANCER; NERVOUS-SYSTEM; FAMMM SYNDROME; MUTATIONS; LOCUS; RISK; P16; NEUROFIBROMATOSIS AB Familial atypical multiple mole melanoma syndrome (FAMMM) is characterised by dysplastic naevi, malignant melanoma and pancreatic cancer. Given that large deletions involving CDKN2A (cyclin-dependent kinase inhibitor 2A) account for only 2% of cases, we describe a family that highlights the co-occurrence of both melanoma and neural system tumours to aid clinical recognition and propose a management strategy. A patient with multiple neurofibromas was referred with a provisional diagnosis of neurofibromatosis type 1 (NF1). Prior molecular testing, though, had failed to identify an NF1 mutation by sequencing and multiplex ligation-dependent probe amplification. His family history was significant for multiple in situ/malignant melanomas at young ages and several different cancers reminiscent of an underlying syndrome. A search of the Familial Cancer Database, FaCD Online, highlighted several families with cutaneous melanoma and nervous system tumours who were subsequently identified to have large deletions spanning CDKN2A. Although sequencing of CDKN2A and TP53 failed to identify a mutation, a heterozygous CDKN2A deletion was identified by targeted array comparative genomic hybridisation (CGH). Whole-genome oligonucleotide array CGH and SNP analysis identified an interstitial deletion of at least 1.5 Mb within 9p21.3 and spanning approximately 25 genes. Identification of the underlying molecular abnormality permits predictive testing for at-risk relatives. Given the young cancer diagnoses, a surveillance regimen was developed and a clinical team organised for ongoing management so that genetic testing could be offered to both adults and minor children. Surveillance recommendations addressed cancer risks associated with FAMMM, and other cancers exhibited by this family with a large contiguous gene deletion. C1 [Baker, Maria J.; Drabick, Joseph J.] Penn State Hershey Canc Inst, Penn State Milton S Hershey Med Ctr, Dept Med, 500 Univ Dr CH46, Hershey, PA 17033 USA. [Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. [Gordon, Patricia L.] Penn State Hershey Canc Inst, Penn State Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA. [Harbaugh, Kimberly S.; Glantz, Michael J.] Penn State Hershey Canc Inst, Penn State Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA. [Mackley, Heath B.] Penn State Hershey Canc Inst, Penn State Milton S Hershey Med Ctr, Dept Radiat Oncol, Hershey, PA USA. RP Baker, MJ (reprint author), Penn State Hershey Canc Inst, Penn State Milton S Hershey Med Ctr, Dept Med, 500 Univ Dr CH46, Hershey, PA 17033 USA. EM mbaker@hmc.psu.edu FU US National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG) FX This work was supported in part by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG). NR 44 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2016 VL 53 IS 11 BP 721 EP 727 DI 10.1136/jmedgenet-2015-103446 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA EC2TS UT WOS:000387977600001 ER PT J AU Jang, DS Ye, WJ Tian, GM Solomon, M Southall, N Hu, X Marugan, J Ferrer, M Maegawa, GHB AF Jang, Dae Song Ye, Wenjuan Tian Guimei Solomon, Melani Southall, Noel Hu, Xin Marugan, Juan Ferrer, Marc Maegawa, Gustavo H. B. TI Cell-Based High-Throughput Screening Identifies Galactocerebrosidase Enhancers as Potential Small-Molecule Therapies for Krabbe's Disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE beta-galactocerebrosidase; quantitative high-throughput screening; small molecules; Krabbe's disease ID PHARMACOLOGICAL CHAPERONES; BETA-HEXOSAMINIDASE; CHEMICAL LIBRARIES; GALC GENE; LEUKODYSTROPHY; GALACTOSIDASE; HETEROGENEITY; DISORDERS; MUTATIONS; HISTORY AB Krabbe's disease, also known as globoid cell leukodystrophy (GLD), is a lysosomal storage disease caused by the deficiency of the lysosomal enzyme beta-galactocerebrosidase (GALC), resulting in severe neurological manifestations related to demyelination secondary to elevated galactosylsphingosine (psychosine) with its subsequent cytotoxicity. The only available treatment is hematopoietic stem cell transplantation, which delays disease onset but does not prevent long-term neurological manifestations. This article describes the identification of small molecules that enhance mutant GALC activity, identified by quantitative cell-based high-throughput screening (qHTS). Using a specific neurologically relevant murine cell line (145M-Twi) modified to express common human hGALC-G270D mutant, we were able to detect GALC activity in a 1,536-well microplate format. The qHTS of approximately 46,000 compounds identified three small molecules that showed significant enhancements of residual mutant GALC activity in primary cell lines from GLD patients. These compounds were shown to increase the levels of GALCG270D mutant in the lysosomal compartment. In kinetic assessments, these small molecules failed to disturb the GALC kinetic profile under acidic conditions, which is highly desirable for folding-assisting molecules operating in the endoplasmic reticulum and not affecting GALC catalytic properties in the lysosomal compartment. In addition, these small molecules rescued the decreased GALC activity at neutral pH and partially stabilized GALC under heat-denaturating conditions. These drug-like compounds can be used as the starting point to develop novel small-molecule agents to treat the progressive neurodegenerative course of GLD. (C) 2016 Wiley Periodicals, Inc. C1 [Jang, Dae Song; Tian Guimei; Maegawa, Gustavo H. B.] Univ Florida, Dept Pediat, Gainesville, FL USA. [Ye, Wenjuan; Southall, Noel; Hu, Xin; Marugan, Juan; Ferrer, Marc] NIH, Ctr Adv Translat Sci, Rockville, MD USA. [Solomon, Melani] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA. [Maegawa, Gustavo H. B.] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. [Maegawa, Gustavo H. B.] Univ Florida, Dept Microbiol & Immunol, Gainesville, FL USA. RP Maegawa, GHB (reprint author), Univ Florida, Coll Med, Div Genet & Metab, Dept Pediat, Gainesville, FL 32610 USA.; Maegawa, GHB (reprint author), Univ Florida, Coll Med, Div Genet & Metab, Dept Neurosci, Gainesville, FL 32610 USA.; Maegawa, GHB (reprint author), Univ Florida, Coll Med, Div Genet & Metab, Dept Microbiol & Immunol, Gainesville, FL 32610 USA. EM gmaegawa@ufl.edu FU National Institute of Mental Health [5R03MH098689-02]; National Institutes of Health FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: 5R03MH098689-02; Contract grant sponsor: National Institutes of Health. NR 31 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV PY 2016 VL 94 IS 11 SI SI BP 1231 EP 1245 DI 10.1002/jnr.23875 PG 15 WC Neurosciences SC Neurosciences & Neurology GA EC9DE UT WOS:000388443500028 PM 27638606 ER PT J AU Sempos, CT Durazo-Arvizu, RA Binkley, N Jones, J Merkel, JM Carter, GD AF Sempos, C. T. Durazo-Arvizu, R. A. Binkley, N. Jones, J. Merkel, J. M. Carter, G. D. TI Developing vitamin D dietary guidelines and the lack of 25-hydroxyvitamin D assay standardization: The ever-present past SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 18th Workshop on Vitamin D CY APR 21-24, 2015 CL Delft, NETHERLANDS DE 25-Hydroxyvitamin D; CAP; DEQAS; NIST; PT/EQA; VDSP; Vitamin D ID TANDEM MASS-SPECTROMETRY; D-3 AB Unstandardized laboratory measurement of 25-hydroxyvitamin D (25(OH)D) confounds efforts to develop clinical and public health vitamin D guidelines. The Vitamin D Standardization Program (VDSP), an international collaborative effort, was founded in 2010 to correct this problem. Nearly all published vitamin D research is based on unstandardized laboratory 25(OH)D measurements. While it is impossible to standardize all old data, it may be possible to identify a small subset of prior studies critical to guidelines development. Once identified it may be possible to calibrate their 25(OH)D values to the NIST and Ghent University reference measurement procedures using VDSP methods thereby permitting future guidelines to be based on standardized results. We simulated the calibration of a small set of ten clinical trials of vitamin D supplementation on achieved 25(OH)D under minimal sun exposure. These studies were selected because they played a prominent role in setting the 2010 vitamin D dietary reference intakes (DR1). Using random-effects meta-regression analysis, Vitamin D External Quality Assessment (DEQAS) data on assay bias was used to simulate the potential bias due to the lack of assay standardization by calibrating the achieved 25(OH)D levels from those 10 studies to: (1) the largest negative, and (2) the largest positive bias from the DEQAS all laboratory trimmed mean (ALTM) for the appropriate assay and year of analysis. For a usual vitamin D intake of 600 IU/day the difference in mean achieved 25(OH)D values for those two options was 20 nmol/L. However, without re-calibration of 25 (OH)D values it is impossible to know the degree to which any of the current guidelines may have been biased. This approach may help stimulate the search for and standardization of that small subset of key studies and, in the cases where standardization is impossible, to identify areas of urgently needed vitamin D research. Published by Elsevier Ltd. C1 [Sempos, C. T.; Merkel, J. M.] NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01, Bethesda, MD 20892 USA. [Durazo-Arvizu, R. A.] Loyola Univ, Stritch Sch Med, Dept Publ Hlth Sci, 2160 S 1st Ave, Maywood, IL 60153 USA. [Binkley, N.] Univ Wisconsin, Osteoporosis Clin Res Program, Madison, WI USA. [Binkley, N.] Univ Wisconsin, Inst Aging, Madison, WI USA. [Jones, J.; Carter, G. D.] Charing Cross Hosp, Fulham Palace Rd, London W6 8RF, England. RP Sempos, CT (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01, Bethesda, MD 20892 USA. EM semposch@mail.nih.gov NR 15 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 2016 VL 164 SI SI BP 115 EP 119 DI 10.1016/j.jsbmb.2015.08.027 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA EC5EX UT WOS:000388157000020 PM 26321386 ER PT J AU Carter, GD Jones, JC Shannon, J Williams, EL Jones, G Kaufmann, M Sempos, C AF Carter, G. D. Jones, J. C. Shannon, J. Williams, E. L. Jones, G. Kaufmann, M. Sempos, C. TI 25-Hydroxyvitamin D assays: Potential interference from other circulating vitamin D metabolites SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 18th Workshop on Vitamin D CY APR 21-24, 2015 CL Delft, NETHERLANDS DE DEQAS; 25-Hydroxyvitamin D; 3-epi-25-Hydroxyvitamin D; 24,25-Dihydroxyvitamin D; Interference ID 24,25-DIHYDROXYVITAMIN D; SERUM; INFANTS AB The vitamin D External Quality Assessment Scheme (DEQAS) for 25-hydroxyvitamin D (25-OHD) has approximately 1100 participants in 53 countries using 26 different methods or variants of methods (October 2014). In April 2015, the scheme was extended to cover 24,25-dihydroxyvitamin D. (24,25 (OH)(2)D). Since 2013, the 25-OHD scheme has been accuracy-based with values assigned by the NIST reference measurement procedure (RMP). DEQAS is uniquely placed to assess the accuracy (bias) and specificity of 25-OHD methods in a routine laboratory setting. Other vitamin D metabolites are known to interfere in 25-OHD assays and DEQAS has distributed samples spiked with 3-epi-25-OHD3 (52.4 nmol/L), 24R,25(OH)(2)D-3 (14.4 nmol/L) and 245,25(OH)(2)D-3 (57.9 nmol/L). The 3-epimer showed a cross reactivity of 56% in a competitive protein binding assay but was not detected in any antibody-based methods. Not all HPLC/UV or LC-MS/MS methods were able to resolve 3-epi-25-OHD3 from 25-OHD3 and thus overestimated total 25-OHD:The cross reactivity of 24R,25(OH)(2)D-3 (245,25(OH)(2)D-3) ranged from <5% (<5%) to 548% (643%) in ligand binding assays. Both 24-hydroxylated metabolites were resolved by HPLC/UV and LC-MS/MS methods and thus caused no complications in the measurement of 25-OHD. Most antibodies to 25-OHD are known to cross-react with dihydroxylated metabolites but interference in some assays was far greater than expected. This may be related to the anomalous behaviour of exogenously added metabolites in these 25-OHD methods. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Carter, G. D.; Jones, J. C.; Shannon, J.; Williams, E. L.] Charing Cross Hosp, Fulham Palace Rd, London W6 8RF, England. [Jones, G.; Kaufmann, M.] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada. [Sempos, C.] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Carter, GD (reprint author), Charing Cross Hosp, Fulham Palace Rd, London W6 8RF, England. EM b.carter1@which.net NR 10 TC 2 Z9 2 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 2016 VL 164 SI SI BP 134 EP 138 DI 10.1016/j.jsbmb.2015.12.018 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA EC5EX UT WOS:000388157000023 PM 26718874 ER PT J AU Bavendam, TG Star, RA Rodgers, GP AF Bavendam, Tamara G. Star, Robert A. Rodgers, Griffin P. TI Research to Improve Urological Health for Women and Girls: Focus on Prevention SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 [Bavendam, Tamara G.] NIDDK, Womens Urol Hlth, NIH, 6707 Democracy Blvd,MSC 5458, Bethesda, MD 20892 USA. [Star, Robert A.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Rodgers, Griffin P.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Bavendam, TG (reprint author), NIDDK, Womens Urol Hlth, NIH, 6707 Democracy Blvd,MSC 5458, Bethesda, MD 20892 USA. EM tamara.bavendam@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2016 VL 25 IS 11 BP 1081 EP 1082 DI 10.1089/jwh.2016.5878 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA EC9SE UT WOS:000388483700001 PM 27182742 ER PT J AU Carr, GV Chen, J Yang, F Ren, M Yuan, P Tian, Q Bebensee, A Zhang, GY Du, J Glineburg, P Xun, R Akhile, O Akuma, D Pickel, J Barrow, JC Papaleo, F Weinberger, DR AF Carr, G. V. Chen, J. Yang, F. Ren, M. Yuan, P. Tian, Q. Bebensee, A. Zhang, G. Y. Du, J. Glineburg, P. Xun, R. Akhile, O. Akuma, D. Pickel, J. Barrow, J. C. Papaleo, F. Weinberger, D. R. TI KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article ID GENE POTASSIUM CHANNELS; PREFRONTAL CORTEX; MEMORY PERFORMANCE; RECOGNITION MEMORY; GAMMA OSCILLATIONS; PERIRHINAL CORTEX; SPATIAL MEMORY; BRAIN; DEFICITS; RECEPTORS AB Overexpression in humans of KCNH2-3.1, which encodes a primate-specific and brain-selective isoform of the human ether-a-go-gorelated potassium channel, is associated with impaired cognition, inefficient neural processing and schizophrenia. Here, we describe a new mouse model that incorporates the KCNH2-3.1 molecular phenotype. KCNH2-3.1 transgenic mice are viable and display normal sensorimotor behaviors. However, they show alterations in neuronal structure and microcircuit function in the hippocampus and prefrontal cortex, areas affected in schizophrenia. Specifically, in slice preparations from the CA1 region of the hippocampus, KCNH2-3.1 transgenic mice have fewer mature dendrites and impaired theta burst stimulation long-term potentiation. Abnormal neuronal firing patterns characteristic of the fast deactivation kinetics of the KCNH2-3.1 isoform were also observed in prefrontal cortex. Transgenic mice showed significant deficits in a hippocampal-dependent object location task and a prefrontal cortex-dependent T-maze working memory task. Interestingly, the hippocampal-dependent alterations were not present in juvenile transgenic mice, suggesting a developmental trajectory to the phenotype. Suppressing KCNH2-3.1 expression in adult mice rescues both the behavioral and physiological phenotypes. These data provide insight into the mechanism of association of KCNH2-3.1 with variation in human cognition and neuronal physiology and may explain its role in schizophrenia. C1 [Carr, G. V.; Yang, F.; Ren, M.; Yuan, P.; Tian, Q.; Xun, R.; Akuma, D.; Barrow, J. C.; Weinberger, D. R.] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA. [Chen, J.; Bebensee, A.; Zhang, G. Y.; Du, J.; Glineburg, P.; Xun, R.; Akhile, O.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Pickel, J.] NIMH, Transgen Core Facil, Bethesda, MD 20892 USA. [Barrow, J. C.] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA. [Papaleo, F.] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Genoa, Italy. [Weinberger, D. R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [Weinberger, D. R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Weinberger, D. R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA. [Weinberger, D. R.] Johns Hopkins Sch Med, McKusick Nathan Inst Genet Med, Baltimore, MD USA. RP Carr, GV; Weinberger, DR (reprint author), Johns Hopkins Med Campus, Lieber Inst Brain Dev, 855 North Wolfe St, Baltimore, MD 21205 USA. EM greg.carr@libd.org; drweinberger@libd.org OI Papaleo, Francesco/0000-0002-6326-0657 FU Intramural Research Program of the National Institute of Mental Health; US National Institute of Mental Health [R01MH101102]; Lieber Institute for Brain Development FX This work was funded by the Intramural Research Program of the National Institute of Mental Health to the Weinberger Lab, US National Institute of Mental Health grant R01MH101102 and the Lieber Institute for Brain Development. NR 49 TC 2 Z9 2 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2016 VL 21 IS 11 BP 1517 EP 1526 DI 10.1038/mp.2015.219 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ED2ZU UT WOS:000388719600006 PM 26857598 ER PT J AU De Bundel, D Zussy, C Espallergues, J Gerfen, CR Girault, JA Valjent, E AF De Bundel, D. Zussy, C. Espallergues, J. Gerfen, C. R. Girault, J-A Valjent, E. TI Dopamine D2 receptors gate generalization of conditioned threat responses through mTORC1 signaling in the extended amygdala SO MOLECULAR PSYCHIATRY LA English DT Article ID SIZED SPINY NEURONS; OVAL BED NUCLEUS; STRIA TERMINALIS; MAMMALIAN TARGET; FEAR MEMORY; SYSTEMIC INHIBITION; PREFRONTAL CORTEX; ANXIETY; CONSOLIDATION; RECONSOLIDATION AB Overgeneralization of conditioned threat responses is a robust clinical marker of anxiety disorders. In overgeneralization, responses that are appropriate to threat-predicting cues are evoked by perceptually similar safety-predicting cues. Inappropriate learning of conditioned threat responses may thus form an etiological basis for anxiety disorders. The role of dopamine (DA) in memory encoding is well established. Indeed by signaling salience and valence, DA is thought to facilitate discriminative learning between stimuli representing safety or threat. However, the neuroanatomical and biochemical substrates through which DA modulates overgeneralization of threat responses remain poorly understood. Here we report that the modulation of DA D2 receptor (D2R) signaling bidirectionally regulates the consolidation of fear responses. While the blockade of D2R induces generalized threat responses, its stimulation facilitates discriminative learning between stimuli representing safety or threat. Moreover, we show that controlled threat generalization requires the coordinated activation of D2R in the bed nucleus of the stria terminalis and the central amygdala. Finally, we identify the mTORC1 cascade activation as an important molecular event by which D2R mediates its effects. These data reveal that D2R signaling in the extended amygdala constitutes an important checkpoint through which DA participates in the control of threat processing and the emergence of overgeneralized threat responses. C1 [De Bundel, D.; Zussy, C.; Espallergues, J.; Valjent, E.] CNRS, UMR 5203, Inst Genom Fonct, Montpellier, France. [De Bundel, D.; Zussy, C.; Espallergues, J.; Valjent, E.] INSERM, U1191, Montpellier, France. [De Bundel, D.; Zussy, C.; Espallergues, J.; Valjent, E.] Univ Montpellier, UMR 5203, Montpellier, France. [Gerfen, C. R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Girault, J-A] INSERM, UMR S 839, Paris, France. [Girault, J-A] Inst Fer Moulin, Paris, France. [Girault, J-A] Univ Paris 06, UPMC, Sorbonne Univ, Paris, France. [De Bundel, D.] Vrije Univ Brussel, Ctr Neurosci, Dept Pharmaceut Chem & Drug Anal, 103 Laarbeeklaan, B-1090 Brussels, Belgium. RP De Bundel, D (reprint author), Vrije Univ Brussel, Ctr Neurosci, Dept Pharmaceut Chem & Drug Anal, 103 Laarbeeklaan, B-1090 Brussels, Belgium.; Valjent, E (reprint author), INSERM, CNRS UMR 5203, U1191, Inst Genom Fonct, 141 Rue Cardonille, F-34094 Montpellier 05, France. EM ddebunde@vub.ac.be; emmanuel.valjent@igf.cnrs.fr FU Inserm (ATIP-Avenir); Agence Nationale de la Recherche [ANR-2010-JCJC-1412]; Fondation pour la Recherche Medicale (FRM); ERC Advanced Grant FX We thank members of the Valjent laboratory for discussions. We also thank Bo Li for insightful and constructive comments. This work was supported by Inserm (ATIP-Avenir), and the Agence Nationale de la Recherche (ANR-2010-JCJC-1412) to EV. DDB was a recipient of a postdoctoral fellowship from the Fondation pour la Recherche Medicale (FRM). J-AG is supported by an ERC Advanced Grant and is affiliated with the Paris School of Neuroscience and the Bio-Psy Laboratory of excellence. NR 62 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2016 VL 21 IS 11 BP 1545 EP 1553 DI 10.1038/mp.2015.210 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ED2ZU UT WOS:000388719600009 PM 26782052 ER PT J AU Sapra, KJ Barr, DB Maisog, JM Sundaram, R Louis, GMB AF Sapra, Katherine J. Barr, Dana B. Maisog, Jose M. Sundaram, Rajeshwari Louis, Germaine M. Buck TI Time-to-Pregnancy Associated With Couples' Use of Tobacco Products SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID PERSISTENT ENVIRONMENTAL-POLLUTANTS; SEMEN QUALITY; CIGARETTE-SMOKING; INFERTILITY EVALUATION; SOCIAL DETERMINANTS; UNITED-STATES; WOMEN; FECUNDABILITY; CONSUMPTION; FERTILITY AB Previous studies suggest female smoking increases time-to-pregnancy (TTP), a couple-dependent reproductive outcome, while associations with male smoking are more ambiguous. Furthermore, despite small increases in smokeless tobacco use in the United States, no prior study has evaluated TTP among smokeless tobacco users. Using population-based sampling in 16 counties in Michigan and Texas, 501 couples discontinuing contraception to become pregnant were followed until positive pregnancy test or 12 months of trying. Participants were interviewed on lifetime and current cigarette, cigar, and chew/snuff (smokeless) use and provided blood samples for quantification of heavy metals and cotinine. Fecundability odds ratios (FORs) and 95% confidence intervals (95% CIs) were estimated, adjusted for demographics/lifestyle. FORs less than 1 reflect longer TTP. Eleven percentage of females and 15% of males smoked cigarettes. Among men, 14% smoked cigars, 9% used snuff, and 2% used chew. Compared with never tobacco users, male (FOR: 0.41, 95% CI: 0.24, 0.68) and female (FOR: 0.53, 95% CI: 0.33, 0.85) smoking were individually associated with longer TTP; males' smoking remained significant (FOR: 0.46, 95% CI: 0.27, 0.79) when modeling partners together. Cadmium levels were higher in smokers than smokeless tobacco and never users; adjusting for cadmium attenuated the cigarette-TTP association, particularly among women. TTP was shorter among smokeless tobacco users relative to smokers (FOR: 2.86, 95% CI: 1.47, 5.57). Compared with never users, smokeless tobacco did not alter TTP in our cohort; however, TTP was shorter compared with smokers. We observed longer TTP in male and female smokers; cadmium may partially contribute. Both partners' preconception smoking contributed to longer TTP, highlighting the importance of both partners' lifestyles in healthy reproduction and underscores the need for couple-based preconception guidance. The male's contribution is a new finding. Higher cadmium levels may partially contribute to longer TTP in smokers, particularly among females. Though we do not observe longer TTP among a small sample of smokeless tobacco users compared with never tobacco users, we observe shorter TTP compared with smokers. Further work is needed to more thoroughly delineate the relationship between smokeless tobacco use and TTP and possible mechanisms of tobacco use's effects on reproduction. C1 [Sapra, Katherine J.; Sundaram, Rajeshwari; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. [Barr, Dana B.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Maisog, Jose M.] Glotech Inc, Rockville, MD USA. RP Sapra, KJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. EM katherine.sapra@nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002; 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, HHSN27500001] 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, HHSN27500001). NR 46 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2016 VL 18 IS 11 BP 2154 EP 2161 DI 10.1093/ntr/ntw132 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA EC3IA UT WOS:000388018500015 PM 27190399 ER PT J AU Spong, CY AF Spong, Catherine Y. TI Study Explores Cost Benefits of Optimising Pregnancy Outcome SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material ID TERM; PRETERM; BIRTH C1 [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov NR 7 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2016 VL 30 IS 6 BP 529 EP 530 DI 10.1111/ppe.12314 PG 2 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA EC9IO UT WOS:000388458500001 PM 27870127 ER PT J AU Carcillo, JA Dean, JM Holubkov, R Berger, J Meert, KL Anand, KJS Zimmerman, J Newth, CJ Harrison, R Burr, J Willson, DF Nicholson, C Bell, MJ Berg, RA Shanley, TP Heidemann, SM Dalton, H Jenkins, TL Doctor, A Webster, A AF Carcillo, Joseph A. Dean, J. Michael Holubkov, Richard Berger, John Meert, Kathleen L. Anand, Kanwaljeet J. S. Zimmerman, Jerry Newth, Christopher J. Harrison, Rick Burr, Jeri Willson, Douglas F. Nicholson, Carol Bell, Michael J. Berg, Robert A. Shanley, Thomas P. Heidemann, Sabrina M. Dalton, Heidi Jenkins, Tammara L. Doctor, Allan Webster, Angie CA Eunice Kennedy Shriver Natl Inst TI Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise A Post Hoc Analysis of the CRISIS Trial SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE nosocomial infection; pediatric intensive care unit; immune competent host ID PEDIATRIC TRAUMA PATIENTS; HOSPITAL CARDIAC-ARREST; INTENSIVE-CARE-UNIT; ORGAN FAILURE; MORTALITY; LYMPHOPENIA; SURVIVORS; CYTOKINE; SEPSIS; INJURY AB Background: Nosocomial infection remains an important health problem in long stay (>3 days) pediatric intensive care unit (PICU) patients. Admission risk factors related to the development of nosocomial infection in long stay immune competent patients in particular are not known. Methods: Post-hoc analysis of the previously published Critical Illness Stress induced Immune Suppression (CRISIS) prevention trial database, to identify baseline risk factors for nosocomial infection. Because there was no difference between treatment arms of that study in nosocomial infection in the population without known baseline immunocompromise, both arms were combined and the cohort that developed nosocomial infection was compared with the cohort that did not. Results: There were 254 long stay PICU patients without known baseline immunocompromise. Ninety (35%) developed nosocomial infection, and 164 (65%) did not. Admission characteristics associated with increased nosocomial infection risk were increased age, higher Pediatric Risk of Mortality version III score, the diagnoses of trauma or cardiac arrest and lymphopenia (P < 0.05). The presence of sepsis or infection at admission was associated with reduced risk of developing nosocomial infection (P < 0.05). In multivariable analysis, only increasing age, cardiac arrest and existing lymphopenia remained significant admission risk factors (P < 0.05); whereas trauma tended to be related to nosocomial infection development (P < 0.07). Conclusions: These data suggest that increasing age, cardiac arrest and lymphopenia predispose long stay PICU patients without known baseline immunocompromise to nosocomial infection. These findings may inform pre-hoc stratification randomization strategies for prospective studies designed to prevent nosocomial infection in this population. C1 [Carcillo, Joseph A.; Bell, Michael J.] Univ Pittsburgh, Dept Crit Care Med & Pediat, Pittsburgh, PA USA. [Dean, J. Michael; Holubkov, Richard; Burr, Jeri; Webster, Angie] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Berger, John] George Washington Univ, Dept Pediat, Washington, DC 20052 USA. [Meert, Kathleen L.; Heidemann, Sabrina M.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Anand, Kanwaljeet J. S.] Univ Arkansas, Dept Pediat, Fayetteville, AR 72701 USA. [Zimmerman, Jerry] Univ Washington, Dept Pediat, Washington, DC USA. [Newth, Christopher J.] Univ Southern Calif, Dept Pediat, Los Angeles, CA USA. [Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA USA. [Willson, Douglas F.] Univ Virginia, Dept Pediat, Charlottesville, VA USA. [Nicholson, Carol; Jenkins, Tammara L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Rockville, MD USA. [Berg, Robert A.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Shanley, Thomas P.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Dalton, Heidi] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. [Doctor, Allan] Washington Univ, Dept Pediat, St Louis, MO 63130 USA. RP Carcillo, JA (reprint author), Childrens Hosp Pittsburgh, Suite 2000,Fac Pavil,4400 Penn Ave, Pittsburgh, PA 15214 USA. EM carcilloja@ccm.upmc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) [U10HD050096, U10HD049981, U10HD050009, U10HD049945, U10HD049983, U10HD050012, U10HD063106, U10HD063108, U10HD063114, U01HD049934] FX Angie Webster consulted with Pentara Corporation (statistical consultancy). There are no other conflicts of interest to report other than that this work was supported by the following cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS): U10HD050096, U10HD049981, U10HD050009, U10HD049945, U10HD049983, U10HD050012, U10HD063106, U10HD063108, U10HD063114 and U01HD049934. NR 21 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2016 VL 35 IS 11 BP 1182 EP 1186 DI 10.1097/INF.0000000000001286 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA EC5ZQ UT WOS:000388216200008 PM 27753764 ER PT J AU Shaikh, N Wald, ER Keren, R Gotman, N Ivanova, A Carpenter, MA Moxey-Mims, M Hoberman, A AF Shaikh, Nader Wald, Ellen R. Keren, Ron Gotman, Nathan Ivanova, Anastasia Carpenter, Myra A. Moxey-Mims, Marva Hoberman, Alejandro TI PREDICTORS OF NON-ESCHERICHIA COLI URINARY TRACT INFECTION SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE vesicoureteral reflux; Escherichia coli ID RESISTANCE PATTERNS; CHILDREN AB We aimed to determine which children are prone to non-Escherichia coli urinary tract infection (UTIs). We included 769 children with UTI. We found that circumcised males, Hispanic children, children without fever and children with grades 3 and 4 vesicoureteral reflux were more likely to have a UTI caused by organisms other than E. coli. This information may guide clinicians in their choice of antimicrobial therapy. C1 [Shaikh, Nader; Hoberman, Alejandro] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Div Gen Acad Pediat,UPMC, Pittsburgh, PA USA. [Wald, Ellen R.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA. [Keren, Ron] Childrens Hosp Philadelphia, Div Gen Pediat, Ctr Pediat Clin Effectiveness, Philadelphia, PA 19104 USA. [Gotman, Nathan; Ivanova, Anastasia; Carpenter, Myra A.] Univ North Carolina Chapel Hill, Collaborat Studies Coordinating Ctr, Dept Biostat, Chapel Hill, NC USA. [Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA. RP Shaikh, N (reprint author), UPMC, Childrens Hosp Pittsburgh, One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA. EM nader.shaikh@chp.edu FU NIDDK NIH HHS [U01 DK074053] NR 9 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2016 VL 35 IS 11 BP 1266 EP 1268 DI 10.1097/INF.0000000000001301 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA EC5ZQ UT WOS:000388216200024 PM 27434831 ER PT J AU Sproull, M Camphausen, K AF Sproull, Mary Camphausen, Kevin TI State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure SO RADIATION RESEARCH LA English DT Review ID TOTAL-BODY IRRADIATION; IN-VIVO EPR; GENE-EXPRESSION SIGNATURES; IONIZING-RADIATION; BIOLOGICAL DOSIMETRY; URINARY BIOMARKERS; MEDICAL-MANAGEMENT; RETROSPECTIVE DOSIMETRY; RADIOTHERAPY PATIENTS; NONHUMAN-PRIMATES AB With the possibility of large-scale terrorist attacks around the world, the need for modeling and development of new medical countermeasures for potential future chemical, biological, radiological and nuclear (CBRN) has been well established. Project Bioshield, initiated in 2004, provided a framework to develop and expedite research in the field of CBRN exposures. To respond to large-scale population exposures from a nuclear event or radiation dispersal device (RDD), new methods for determining received dose using biological modeling became necessary. The field of biodosimetry has advanced significantly beyond this original initiative, with expansion into the fields of genomics, proteomics, metabolomics and transcriptomics. Studies are ongoing to evaluate the use of lymphocyte kinetics for dose assessment, as well as the development of field-deployable EPR technology. In addition, expansion of traditional cytogenetic assessment methods through the use of automated platforms and the development of laboratory surge capacity networks have helped to advance our biodefense preparedness. In this review of the latest advances in the field of biodosimetry we evaluate our progress and identify areas that still need to be addressed to achieve true field-deployment readiness. (C) 2016 by Radiation Research Society C1 [Sproull, Mary; Camphausen, Kevin] NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov FU NIH [ZIDBC010990] FX The authors would like to thank Gregory Koblentz, Director of the Biodefense Graduate Program in the School of Policy Government and International Affairs at George Mason University, Fairfax, VA. This work has been funded by the NIH intramural division project ZIDBC010990. NR 118 TC 0 Z9 0 U1 3 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2016 VL 186 IS 5 BP 423 EP 435 DI 10.1667/RR14452.1 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA ED0KN UT WOS:000388531500001 PM 27710702 ER PT J AU Fargo, KN Carrillo, MC Weiner, MW Potter, WZ Khachaturian, Z Vradenburg, G Weiner, MW AF Fargo, Keith N. Carrillo, Maria C. Weiner, Michael W. Potter, William Z. Khachaturian, Zaven Vradenburg, George Weiner, Michael W. TI The crisis in recruitment for clinical trials in Alzheimer's and dementia: An action plan for solutions SO ALZHEIMERS & DEMENTIA LA English DT Editorial Material ID PREVENTION TRIALS; DRUG TRIALS; TASK-FORCE; DISEASE C1 [Fargo, Keith N.; Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Potter, William Z.] NIMH, Bethesda, MD USA. [Khachaturian, Zaven] Journal Alzheimers Assoc, Rockville, MD USA. RP Khachaturian, Z (reprint author), Journal Alzheimers Assoc, Rockville, MD USA. EM zaven@kra.net NR 15 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2016 VL 12 IS 11 BP 1113 EP 1115 DI 10.1016/j.jalz.2016.19.001 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA EC1AJ UT WOS:000387835600001 PM 27836052 ER PT J AU Snyder, HM Shineman, DW Friedman, LG Hendrix, JA Khachaturian, A Le Guillou, I Pickett, J Refolo, L Sancho, RM Ridley, SH AF Snyder, Heather M. Shineman, Diana W. Friedman, Lauren G. Hendrix, James A. Khachaturian, Ara Le Guillou, Ian Pickett, James Refolo, Lorenzo Sancho, Rosa M. Ridley, Simon H. TI Guidelines to improve animal study design and reproducibility for Alzheimer's disease and related dementias: For funders and researchers SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Reproducibility; Animal models; Preclinical; Drug development ID DRUG DISCOVERY; PRECLINICAL RESEARCH; MOUSE AB The reproducibility of laboratory experiments is fundamental to the scientific process. There have been increasing reports regarding challenges in reproducing and translating preclinical experiments in animal models. In Alzheimer's disease and related dementias, there have been similar reports and growing interest from funding organizations, researchers, and the broader scientific community to set parameters around experimental design, statistical power, and reporting requirements. A number of efforts in recent years have attempted to develop standard guidelines; however, these have not yet been widely implemented by researchers or by funding agencies. A workgroup of the International Alzheimer's disease Research Funder Consortium, a group of over 30 research funding agencies from around the world, worked to compile the best practices identified in these prior efforts for pre clinical biomedical research. This article represents a consensus of this work group's review and includes recommendations for researchers and funding agencies on designing, performing, reviewing, and funding preclinical research studies. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Snyder, Heather M.; Hendrix, James A.] Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL USA. [Shineman, Diana W.; Friedman, Lauren G.] Alzheimers Drug Discovery Fdn, Sci Affairs, New York, NY USA. [Khachaturian, Ara] Alzheimers & Dementia Journal Alzheimers Assoc, Editorial Off, Washington, DC USA. [Le Guillou, Ian; Pickett, James] Alzheimers Soc, Div Res, London, England. [Refolo, Lorenzo] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA. [Sancho, Rosa M.; Ridley, Simon H.] Alzheimers Res UK, Div Res, Cambridge, England. RP Snyder, HM (reprint author), Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL USA. EM hsnyder@alz.org NR 24 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2016 VL 12 IS 11 BP 1177 EP 1185 DI 10.1016/j.jalz.2016.07.001 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA EC1AJ UT WOS:000387835600008 PM 27836053 ER PT J AU Snyder, HM Asthana, S Bain, L Brinton, R Craft, S Dubal, DB Espeland, MA Gatz, M Mielke, MM Raber, J Rapp, PR Yaffe, K Carrillo, MC AF Snyder, Heather M. Asthana, Sanjay Bain, Lisa Brinton, Roberta Craft, Suzanne Dubal, Dena B. Espeland, Mark A. Gatz, Margaret Mielke, Michelle M. Raber, Jacob Rapp, Peter R. Yaffe, Kristine Carrillo, Maria C. TI Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative SO ALZHEIMERS & DEMENTIA LA English DT Review DE Alzheimer's disease; Neurodegeneration; Risk factors; Women; Sex biology; Estrogen; Hormones; APOE ID MILD COGNITIVE IMPAIRMENT; POSTMENOPAUSAL HORMONE-THERAPY; CONJUGATED EQUINE ESTROGENS; REGIONAL BRAIN VOLUMES; APOLIPOPROTEIN-E; AMYLOID-BETA; INTRANASAL INSULIN; OLDER-ADULTS; METABOLIC SYNDROME; RHESUS-MONKEYS AB More than 5 million Americans are living with Alzheimer's disease (AD) today, and nearly two-thirds of Americans with AD are women. This sex difference may be due to the higher longevity women generally experience; however, increasing evidence suggests that longevity alone is not a sufficient explanation and there may be other factors at play. The Alzheimer's Association convened an expert think tank to focus on the state of the science and level of evidence around gender and biological sex differences for AD, including the knowledge gaps and areas of science that need to be more fully addressed. This article summarizes the think tank discussion, moving forward a research agenda and funding program to better understand the biological underpinnings of sex- and gender-related disparities of risk for AD. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Snyder, Heather M.; Carrillo, Maria C.] Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL USA. [Asthana, Sanjay] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. [Brinton, Roberta] Univ Southern Calif, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA USA. [Brinton, Roberta] Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA USA. [Brinton, Roberta] Univ Southern Calif, Dept Neurol, Los Angeles, CA USA. [Craft, Suzanne] Wake Forest Sch Med, Dept Med, Winston Salem, NC USA. [Dubal, Dena B.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Espeland, Mark A.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Gatz, Margaret] Univ Southern Calif, Dept Psychol, Los Angeles, CA USA. [Mielke, Michelle M.] Mayo Clin, Dept Hlth Sci Res & Neurol, Div Epidemiol, Rochester, MN USA. [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Dept Neurol, Portland, OR 97201 USA. [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. [Raber, Jacob] Oregon Hlth & Sci Univ, ONPRC, Div Neurosci, Portland, OR 97201 USA. [Rapp, Peter R.] NIA, Lab Behav Neurosci, Neurocognit Aging Sect, Intramural Res Program, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Snyder, HM (reprint author), Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL USA. EM hsnyder@alz.org FU NIA NIH HHS [P50 AG044170] NR 125 TC 2 Z9 2 U1 11 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2016 VL 12 IS 11 BP 1186 EP 1196 DI 10.1016/j.jalz.2016.08.004 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA EC1AJ UT WOS:000387835600009 PM 27692800 ER PT J AU Cui, Y Li, SF Gu, H Hu, YZ Liang, X Lu, CQ Cai, Y Wang, CX Yang, Y Teng, GJ AF Cui, Y. Li, S. -F. Gu, H. Hu, Y. -Z. Liang, X. Lu, C. -Q. Cai, Y. Wang, C. -X. Yang, Y. Teng, G. -J. TI Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID STATE FUNCTIONAL CONNECTIVITY; ALZHEIMERS-DISEASE; NETWORK CENTRALITY; INSULIN-RESISTANCE; RATING-SCALE; COGNITION; MRI; GLUCOSE; FMRI; HUBS AB BACKGROUND AND PURPOSE: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS: Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS: This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline. C1 [Cui, Y.; Lu, C. -Q.; Cai, Y.; Wang, C. -X.; Teng, G. -J.] Southeast Univ, Jiangsu Key Lab Mol & Funct Imaging, Zhongda Hosp, Sch Med,Dept Radiol, Nanjing, Jiangsu, Peoples R China. [Cui, Y.; Li, S. -F.; Gu, H.; Hu, Y. -Z.; Liang, X.; Yang, Y.] NIDA, NIH, Neuroimaging Res Branch, Baltimore, MD USA. RP Teng, GJ (reprint author), Southeast Univ, Jiangsu Key Lab Mol & Funct Imaging, Zhongda Hosp, Sch Med,Dept Radiol, Nanjing, Jiangsu, Peoples R China.; Teng, GJ (reprint author), 87 Dingjiaqiao Rd, Nanjing 210009, Jiangsu, Peoples R China. EM gjteng@vip.sina.com FU Major State Basic Research Development Program of China (973 Program) [2013CB733800, 2013CB733803]; Key Project of Jiangsu Province Natural Science Foundation of China [BK20130057]; National Natural Science Foundation of China [81230034, 81271739]; Intramural Research Program of the National Institute on Drug Abuse, the National Institutes of Health FX This work was supported by grants from the Major State Basic Research Development Program of China (973 Program) (Nos. 2013CB733800, 2013CB733803), the Key Project of Jiangsu Province Natural Science Foundation of China (BK20130057), and the National Natural Science Foundation of China General Projects (Nos. 81230034, 81271739). S.-F.L., H.G., Y.-Z.H., X.L., and Y.Y. were supported by the Intramural Research Program of the National Institute on Drug Abuse, the National Institutes of Health. NR 32 TC 0 Z9 0 U1 6 U2 6 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 2016 VL 37 IS 11 BP 2115 EP 2122 DI 10.3174/ajnr.A4858 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EC2PI UT WOS:000387965400032 ER PT J AU Stateman, WA Knoppel, AB Flegel, WA Henkin, RI AF Stateman, William A. Knoeppel, Alexandra B. Flegel, Willy A. Henkin, Robert I. TI A genetic marker of the ACKR1 gene is present in patients with Type II congenital smell loss who have type I hyposmia and hypogeusia SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID MUTATIONS AB Purpose: Our previous study of Type II congenital smell loss patients revealed a statistically significant lower prevalence of an FY (ACKR1, formerly DARC) haplotype compared to controls. The present study correlates this genetic feature with subgroups of patients defined by specific smell and taste functions. Methods: Smell and taste function measurements were performed by use of olfactometry and gustometry to define degree of abnormality of smell and taste function. Smell loss was classified as anosmia or hyposmia (types I, II or III). Taste loss was similarly classified as ageusia or hypogeusia (types I, II or III). Based upon these results patient erythrocyte antigen expression frequencies were categorized by smell and taste loss with results compared between patients within the Type II group and published controls. Results: Comparison of antigen expression frequencies revealed a statistically significant decrease in incidence of an Fy(b) haplotype only among patients with type I hyposmia and any form of taste loss (hypogeusia). In all other patient groups erythrocyte antigens were expressed at normal frequencies. Conclusions: Data suggest that Type II congenital smell loss patients who exhibit both type I hyposmia and hypogeusia are genetically distinct from all other patients with Type II congenital smell loss. This distinction is based on decreased Fy(b) expression which correlated with abnormalities in two sensory modalities (hyposmia type I and hypogeusia). Only patients with these two specific sensory abnormalities expressed the Fy(b) antigen (encoded by the ACKR1 gene on the long arm of chromosome 1) at frequencies different from controls. (C) 2016 Elsevier Inc. All rights reserved. C1 [Stateman, William A.; Knoeppel, Alexandra B.; Henkin, Robert I.] Taste & Smell Clin, Ctr Mol Nutr & Sensory Disorders, 5125 MacArthur Blvd,NW 20, Washington, DC USA. [Flegel, Willy A.] NIH, Ctr Clin, Dept Transfus Med, 10 Ctr Dr MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. RP Henkin, RI (reprint author), Ctr Mol Nutr & Sensory Disorders, 5125 MacArthur Blvd,NW 20, Washington, DC 20016 USA. EM wstateman@gmail.com; abknoppel@gmail.com; flegelwa@cc.nih.gov; doc@tasteandsmell.com OI Knoppel, Alexandra/0000-0003-2504-7350 FU Intramural Research Program of the NIH Clinical Center FX Intramural Research Program of the NIH Clinical Center (partially). NR 18 TC 1 Z9 1 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2016 VL 37 IS 6 BP 484 EP 489 DI 10.1016/j.amjoto.2015.07.006 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA EB9SE UT WOS:000387736600002 PM 27968956 ER PT J AU Flanagan, CE Rhodus, NL Cole, KA Szabo, E Ondrey, FG AF Flanagan, Carrie E. Rhodus, Nelson L. Cole, Kate A. Szabo, Eva Ondrey, Frank G. TI Correlation analysis of oral lesion sizes by various standardized criteria SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID SOLID TUMORS; GUIDELINES; RECIST; LEUKOPLAKIA AB Objective: Requirements of an NCI contract examining a novel treatment for leukoplakia were to compare standard bi-dimensional measurement of oral lesions to examine for correlation with Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and to examine the feasibility of digital image analysis for automated measurements. Study design: Retrospective review. Methods: We examined 13 patients by bi-dimensional measurement and compared these measurements to 1) RECIST criteria, 2) scalar digital measurements using a standardized measuring device within the photograph, and 3) pixel number. Results: RECIST criteria correlated (r-squared = 0.8535, p < 0.0001) with bi-dimensional measurements. Digitized measures in photographs correlated with bi-dimensional measurements (r-squared = 0.6661, p = 0.0007), but were time consuming. There was minimal to no correlation between pixel number in Adobe Photoshop and the other measures. Conclusion: Bi-dimensional measurement of oral leukoplakia and RECIST criteria are highly correlated. Digital photography measurements, though highly correlative, are very cumbersome. We recommend bi-dimensional or longest length measurement and a simple photograph as standard of documentation for leukoplakia lesions. (C) 2016 Elsevier Inc. All rights reserved. C1 [Flanagan, Carrie E.; Cole, Kate A.; Ondrey, Frank G.] Univ Minnesota, Dept Otolaryngol, 420 Delaware St SE,MMC 396, Minneapolis, MN 55455 USA. [Rhodus, Nelson L.] Univ Minnesota, Div Oral Med & Diag, Sch Dent, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA. [Cole, Kate A.] Univ Minnesota, Ctr Canc, Clin Trials Off, Minneapolis, MN 55455 USA. [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Ondrey, FG (reprint author), Univ Minnesota, Dept Otolaryngol, 420 Delaware St SE,MMC 396, Minneapolis, MN 55455 USA. EM ondre002@umn.edu FU [NCI/NIHN-01-CN 15000]; [P30 CA77598-07NIH/NCI] FX NCI/NIHN-01-CN 15000; P30 CA77598-07NIH/NCI. NR 11 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2016 VL 37 IS 6 BP 502 EP 506 DI 10.1016/j.amjoto.2016.07.004 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA EB9SE UT WOS:000387736600006 PM 27968958 ER PT J AU Salas, AA Carlo, WA Ambalavanan, N Nolen, TL Stoll, BJ Das, A Higgins, RD AF Salas, Ariel A. Carlo, Waldemar A. Ambalavanan, Namasivayam Nolen, Tracy L. Stoll, Barbara J. Das, Abhik Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst Human Dev Neonatal Res Network TI Gestational age and birthweight for risk assessment of neurodevelopmental impairment or death in extremely preterm infants SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID OUTCOMES; PREDICTION; BIOMETRY; SCORES AB Background The risk of poor outcomes in preterm infants is primarily determined by birthweight (BW) and gestational age (GA). It is not known whether BW is a better outcome predictor than GA. Objective To test whether BW is better than GA (measured in days, rather than completed weeks) for prediction of neurodevelopmental impairment (NDI) and death. Design/methods Extremely preterm infants born at the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centres between 1998 and 2009 were studied. For the unadjusted analysis, the associations of GA (in days based on best obstetrical estimate) and BW (in grams) with NDI or death were compared using area under the curve (AUC). Adjusted analyses were performed using birth year, sex, race, antenatal steroids, singleton birth, pre-eclampsia, Apgar score at 5 min and small for GA as covariates. Results 10 652 preterm infants (89%) had outcome data at 18-22 months' corrected age. The mean BW was 678 g (SD: 155) and the mean GA was 173 days (SD: 10) or 245/7 weeks (SD: 13/7). The AUC for NDI or death was 80% with BW and 79% with GA (p=0.82). Unadjusted and adjusted analyses did not differ. NDI or death rates decreased with increasing GA through 26 weeks (estimated risk reduction with each additional day of gestation: 2.2%). Conclusion Both BW in grams and GA in days are good predictors of NDI and death in a preterm population selected on the basis of reliable GA. C1 [Salas, Ariel A.; Carlo, Waldemar A.; Ambalavanan, Namasivayam] Univ Alabama Birmingham, Birmingham, AL USA. [Nolen, Tracy L.; Das, Abhik] RTI Int, Res Triangle Pk, NC USA. [Stoll, Barbara J.] Emory Univ, Atlanta, GA 30322 USA. [Higgins, Rosemary D.] NICHD, GDB & FU Subcomm, Neonatal Res Network, Bethesda, MD USA. RP Carlo, WA (reprint author), Univ Alabama Birmingham, Dept Pediat, 1700 6th Ave South,Suite 9380 Women & Infants Ctr, Birmingham, AL 35249 USA. EM wcarlo@peds.uab.edu OI Ambalavanan, Namasivayam/0000-0003-0731-9092; Salas, Ariel/0000-0002-4676-7747 FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Child Health and Human Development; Department of Health and Human Services [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689]; National Institutes of Health [UL1 RR24139, UL1 RR24160, UL1 RR25008, M01 RR30, M01 RR32, M01 RR39, M01 RR44, M01 RR70, M01 RR80, M01 RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, M01 RR16587] FX The NIH and the Eunice Kennedy Shriver National Institute of Child Health and Human Development provided grant support for the Neonatal Research Network's Generic Database Study and Follow-up Study. The authors were supported by grants from the National Institute of Child Health and Human Development and the Department of Health and Human Services (U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521 and U10 HD40689) and from the National Institutes of Health (UL1 RR24139, UL1 RR24160, UL1 RR25008, M01 RR30, M01 RR32, M01 RR39, M01 RR44, M01 RR70, M01 RR80, M01 RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084 and M01 RR16587). NR 28 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 EI 1468-2052 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD NOV PY 2016 VL 101 IS 6 BP F494 EP F500 DI 10.1136/archdischild-2015-309670 PG 7 WC Pediatrics SC Pediatrics GA EB8IT UT WOS:000387635400004 ER PT J AU Stout, NL Silver, JK Raj, VS Rowland, J Gerber, L Cheville, A Ness, KK Radomski, M Nitkin, R Stubblefield, MD Morris, GS Acevedo, A Brandon, Z Braveman, B Cunningham, S Gilchrist, L Jones, L Padgett, L Wolf, T Winters-Stone, K Campbell, G Hendricks, J Perkin, K Chan, L AF Stout, Nicole L. Silver, Julie K. Raj, Vishwa S. Rowland, Julia Gerber, Lynn Cheville, Andrea Ness, Kirsten K. Radomski, Mary Nitkin, Ralph Stubblefield, Michael D. Morris, G. Stephen Acevedo, Ana Brandon, Zavera Braveman, Brent Cunningham, Schuyler Gilchrist, Laura Jones, Lee Padgett, Lynne Wolf, Timothy Winters-Stone, Kerri Campbell, Grace Hendricks, Jennifer Perkin, Karen Chan, Leighton TI Toward a National Initiative in Cancer Rehabilitation: Recommendations From a Subject Matter Expert Group SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Morbidity; Neoplasms; Recovery of function; Rehabilitation; Secondary prevention ID QUALITY-OF-LIFE; PROSPECTIVE SURVEILLANCE MODEL; RANDOMIZED CONTROLLED-TRIAL; PATIENT-REPORTED OUTCOMES; METASTATIC BREAST-CANCER; SHARED DECISION-MAKING; PHYSICAL FUNCTION; COGNITIVE IMPAIRMENT; INPATIENT REHABILITATION; GERIATRIC ASSESSMENT AB The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer survivors. These recommendations aim to enable future collaborations among a variety of stakeholders to improve the delivery of high-quality cancer care. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Stout, Nicole L.; Gerber, Lynn; Acevedo, Ana; Brandon, Zavera; Perkin, Karen; Chan, Leighton] NIH, Dept Rehabil Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Silver, Julie K.] Harvard Med Sch, Boston, MA USA. [Raj, Vishwa S.] Carolinas HealthCare Syst, Levine Canc Inst, Carolinas Rehabil, Charlotte, NC USA. [Rowland, Julia] NCI, Off Canc Survivorship, Rockville, MD USA. [Gerber, Lynn] George Mason Univ, Fairfax, VA 22030 USA. [Cheville, Andrea] Mayo Clin Rochester, Rochester, NY USA. [Ness, Kirsten K.] St Jude Childrens Res Hosp, Memphis, TN USA. [Radomski, Mary] Courage Kenny Rehabil Inst, Minneapolis, MN USA. [Nitkin, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Ctr Med Rehabil Res, NIH, Rockville, MD USA. [Stubblefield, Michael D.] Kessler Inst Rehabil Select Med, W Orange, NJ USA. [Morris, G. Stephen] Wingate Univ, Wingate, NC USA. [Braveman, Brent] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cunningham, Schuyler; Hendricks, Jennifer] NIH, Dept Social Work, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Gilchrist, Laura] St Catherine Univ, St Paul, MN USA. [Jones, Lee] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Padgett, Lynne] Amer Bar Assoc, Washington, DC 20013 USA. [Wolf, Timothy] Univ Missouri Columbia, Columbia, MO USA. [Winters-Stone, Kerri] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Campbell, Grace] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Stout, NL (reprint author), NIH, Off Strateg Res, Dept Rehabil Med, Ctr Clin, MSC 1604,10 Ctr Dr, Bethesda, MD 20892 USA. EM Nicole.stout@nih.gov FU Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health (NIH); National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research at the NIH FX Supported by the Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health (NIH), the National Cancer Institute, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research at the NIH. NR 128 TC 1 Z9 1 U1 7 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2016 VL 97 IS 11 BP 2006 EP 2015 DI 10.1016/j.apmr.2016.05.002 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA EB8IK UT WOS:000387634500023 PM 27237580 ER PT J AU Bleszynski, PA Luc, JGY Schade, P Phillips, SJ Tchantchaleishvili, V AF Bleszynski, Peter A. Luc, Jessica G. Y. Schade, Peter Phillips, Steven J. Tchantchaleishvili, Vakhtang TI Current State and Future Perspectives of Energy Sources for Totally Implantable Cardiac Devices SO ASAIO JOURNAL LA English DT Review DE pacemaker; total artificial heart; ventricular assist device; intracorporeal energy; implantable devices ID VENTRICULAR ASSIST DEVICE; MECHANICAL CIRCULATORY SUPPORT; TOTAL ARTIFICIAL-HEART; TRANSMISSION-SYSTEM; CLINICAL-EXPERIENCE; BIOFUEL CELLS; POWER SOURCE; BLOOD PUMPS; PACEMAKER; PERFORMANCE AB There is a large population of patients with end-stage congestive heart failure who cannot be treated by means of conventional cardiac surgery, cardiac transplantation, or chronic catecholamine infusions. Implantable cardiac devices, many designated as destination therapy, have revolutionized patient care and outcomes, although infection and complications related to external power sources or routine battery exchange remain a substantial risk. Complications from repeat battery replacement, power failure, and infections ultimately endanger the original objectives of implantable biomedical device therapy - eliminating the intended patient autonomy, affecting patient quality of life and survival. We sought to review the limitations of current cardiac biomedical device energy sources and discuss the current state and trends of future potential energy sources in pursuit of a lifelong fully implantable biomedical device. C1 [Bleszynski, Peter A.] Univ Rochester, Med Ctr, Dept Internal Med, Rochester, NY 14642 USA. [Luc, Jessica G. Y.] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Schade, Peter] Harvard Med Sch, Dept Neurobiol, Boston, MA USA. [Phillips, Steven J.] NIH, Natl Lib Med, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. [Tchantchaleishvili, Vakhtang] Univ Rochester, Med Ctr, Dept Surg, Div Cardiac Surg, Rochester, NY 14642 USA. RP Tchantchaleishvili, V (reprint author), Univ Rochester, Med Ctr, Div Cardiac Surg, Box Cardiac Surg,601 Elmwood Ave, Rochester, NY 14642 USA. EM tchantchaleishvili@gmail.com OI Schade, Peter/0000-0002-5449-4240; Luc, Jessica/0000-0002-3567-3796 NR 66 TC 1 Z9 1 U1 11 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1058-2916 EI 1538-943X J9 ASAIO J JI Asaio J. PD NOV-DEC PY 2016 VL 62 IS 6 BP 639 EP 645 DI 10.1097/MAT.0000000000000412 PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA EC1OX UT WOS:000387876500006 PM 27442857 ER PT J AU Miller, PE Houston, BA Schneider, ALC Bush, AL Whitman, GJ Stevens, GR Tedford, RJ Russell, SD AF Miller, P. Elliott Houston, Brian A. Schneider, Andrea L. C. Bush, Aaron L. Whitman, Glenn J. Stevens, Gerin R. Tedford, Ryan J. Russell, Stuart D. TI Associations of Preimplant Red Blood Cell Distribution Width with Clinical Outcomes Among Individuals with Left Ventricular Assist Devices SO ASAIO JOURNAL LA English DT Article DE left ventricular assist device; red blood cell distribution width; mortality; risk prediction ID FIBROBLAST GROWTH FACTOR-23; INTERMACS ANNUAL-REPORT; CHRONIC KIDNEY-DISEASE; HEART-FAILURE PATIENTS; CARDIOVASCULAR EVENTS; INTERAGENCY REGISTRY; DESTINATION THERAPY; CIRCULATORY SUPPORT; PROGNOSTIC VALUE; PREDICTORS AB Left ventricular assist devices (LVADs) are increasingly used for end-stage heart failure. However, post-LVAD complications are potentially devastating and remain unpredictable. The red blood cell distribution width (RDW) is a predictor of adverse events in patients with heart failure but has not been studied in the LVAD population. We reviewed laboratory results and clinical outcomes for all continuous flow LVADs implanted from 2004 to June 2014 (N = 188). Cox proportional hazards models adjusted for demographic, cardiovascular, and laboratory variables were used to assess association of preimplant RDW tertiles with mortality, gastrointestinal bleed, infection, pump thrombosis, and stroke more than 1 year of follow-up. Compared with the lowest tertile (RDW < 15.7%), the higher two tertiles (RDW 15.7-18% and RDW > 18.1%) had significantly higher risks of mortality (hazard ratio (HR) 6.95 [confidence interval: 2.67-18.10] and HR 4.61 [1.74-12.21], respectively) after full adjustment. Pre-implant RDW was not statistically associated with our secondary outcomes. In conclusion, higher preimplant RDW is independently associated with an increased risk of post-implant mortality and infection. Future studies are needed to understand the prognostic ability of RDW and to understand the biologic mechanism underlying this association. C1 [Miller, P. Elliott] NIH, Dept Crit Care Med, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. [Houston, Brian A.; Tedford, Ryan J.; Russell, Stuart D.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. [Schneider, Andrea L. C.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Bush, Aaron L.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Whitman, Glenn J.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA. RP Miller, PE (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. EM paul.miller@nih.gov FU NHLBI NIH HHS [T32 HL007227] NR 36 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1058-2916 EI 1538-943X J9 ASAIO J JI Asaio J. PD NOV-DEC PY 2016 VL 62 IS 6 BP 677 EP 683 DI 10.1097/MAT.0000000000000431 PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA EC1OX UT WOS:000387876500012 PM 27798492 ER PT J AU Wang, XQ Li, DF Wu, GY Bazer, FW AF Wang, Xiaoqiu Li, Defa Wu, Guoyao Bazer, Fuller W. TI Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells SO BIOLOGY OF REPRODUCTION LA English DT Article DE fructose; O-linked glycosylation; phosphorylation; trophoblast ID SECRETED PHOSPHOPROTEIN 1; ARGININE STIMULATES PROLIFERATION; SELECT NUTRIENTS; NITRIC-OXIDE; UTERINE HISTOTROPH; PLACENTAL TRANSFER; SKELETAL-MUSCLE; ANIMAL-MODELS; NEONATAL PIGS; METABOLISM AB During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose, which is the most abundant hexose sugar in fetal fluids and blood. However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored because it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. The phosphorylation for activation of this cascade is mediated by O-linked glycosylation with UDP-N-acetylglucosamine, a primary product of the hexosamine biosynthesis pathway. These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. C1 [Wang, Xiaoqiu; Wu, Guoyao; Bazer, Fuller W.] Texas A&M Univ, Ctr Anim Biotechnol & Gen, College Stn, TX 77843 USA. [Wang, Xiaoqiu; Wu, Guoyao; Bazer, Fuller W.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Li, Defa] China Agr Univ, State Key Lab Anim Nutr, Beijing, Peoples R China. [Wang, Xiaoqiu] NIEHS, Reprod & Dev Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RP Bazer, FW (reprint author), Texas A&M Univ, Ctr Anim Biotechnol & Gen, College Stn, TX 77843 USA.; Bazer, FW (reprint author), Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. EM fbazer@cvm.tamu.edu FU National Research Initiative Competitive Grants from the Animal Reproduction Program [2008-35203-19120, 2009-35206-05211, 2011-67015-20067, 2011-67015-20028, 2015-67015-23276]; Animal Growth & Nutrient Utilization Program of the USDA National Institute of Food and Agriculture [2008-35206-18764, 2014-67015-21770]; Texas A&M AgriLife Research [H-8200] FX This research was supported by National Research Initiative Competitive Grants from the Animal Reproduction Program (no. 2008-35203-19120, 2009-35206-05211, 2011-67015-20067, 2011-67015-20028, and 2015-67015-23276) and Animal Growth & Nutrient Utilization Program (2008-35206-18764 and 2014-67015-21770) of the USDA National Institute of Food and Agriculture, and Texas A&M AgriLife Research (H-8200). NR 55 TC 0 Z9 0 U1 4 U2 4 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 NOV 1 PY 2016 VL 95 IS 5 AR 102 DI 10.1095/biolreprod.116.142281 PG 17 WC Reproductive Biology SC Reproductive Biology GA EC1HU UT WOS:000387856300010 ER PT J AU Honda, K Srivastava, S AF Honda, Kazufumi Srivastava, Sudhir TI Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer SO BIOMARKERS IN MEDICINE LA English DT Review DE apolipoprotein A2 isoforms; early detection for pancreatic cancer; National Cancer Institute Early Detection Research Network; NCI EDRN; plasma/serum biomarker ID COHORT-CONSORTIUM PANSCAN; MONOCLONAL-ANTIBODY; POOLED-ANALYSIS; ADENOCARCINOMA; SERUM; BIOMARKER; DIAGNOSIS; PLASMA; GLYPICAN-1; POPULATION AB Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer. C1 [Honda, Kazufumi] Natl Canc Ctr, Res Inst, Div Chemotherapy & Clin Res, Tokyo 1040045, Japan. [Honda, Kazufumi] Japan Agcy Med Res & Dev AMED CREST, Tokyo 1000004, Japan. [Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD 20852 USA. RP Honda, K (reprint author), Natl Canc Ctr, Res Inst, Div Chemotherapy & Clin Res, Tokyo 1040045, Japan.; Honda, K (reprint author), Japan Agcy Med Res & Dev AMED CREST, Tokyo 1000004, Japan. EM khonda@ncc.go.jp FU Practical Research for Innovation Cancer Control from the Japan Agency for Medical Research and Development (AMED) [16ck0106101h0003]; Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED [16cm0106403h0001]; AMED CREST-AMED; Ministry of Education, Culture, Sports, Science and Technology (METX) of Japan FX This work was supported by Practical Research for Innovation Cancer Control from the Japan Agency for Medical Research and Development (AMED) (16ck0106101h0003 to K Honda), the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED (16cm0106403h0001 to K Honda), AMED CREST-AMED (K Honda), a Grant-in Aid for Scientific Research (B) and a Challenging Exploratory Research grant from the Ministry of Education, Culture, Sports, Science and Technology (METX) of Japan (K Honda). 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 63 TC 0 Z9 0 U1 0 U2 0 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. PD NOV PY 2016 VL 10 IS 11 BP 1197 EP 1207 DI 10.2217/bmm-2016-0209 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EA7EV UT WOS:000386793300009 PM 27673558 ER PT J AU Chrtkova, D AF Chrtkova, Dana TI Resolving mental illness stigma: should we seek recovery and equity instead of normalcy or solidarity? SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter ID SCHIZOPHRENIA; RELATIVES; INSIGHT C1 [Chrtkova, Dana] NIMH, Dept Social Psychiat, Bethesda, MD 20814 USA. RP Chrtkova, D (reprint author), NIMH, Dept Social Psychiat, Bethesda, MD 20814 USA. EM Dana.Chrtkova@nudz.cz NR 5 TC 0 Z9 0 U1 4 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD NOV PY 2016 VL 209 IS 5 BP 435 EP 435 DI 10.1192/bjp.209.5.433 PG 1 WC Psychiatry SC Psychiatry GA EC2ID UT WOS:000387934500014 ER PT J AU Loftfield, E Freedman, ND Lai, GY Weinstein, SJ McGlynn, KA Taylor, PR Mannisto, S Albanes, D Stolzenberg-Solomon, RZ AF Loftfield, Erikka Freedman, Neal D. Lai, Gabriel Y. Weinstein, Stephanie J. McGlynn, Katherine A. Taylor, Philip R. Mannisto, Satu Albanes, Demetrius Stolzenberg-Solomon, Rachael Z. TI Higher Glucose and Insulin Levels Are Associated with Risk of Liver Cancer and Chronic Liver Disease Mortality among Men without a History of Diabetes SO CANCER PREVENTION RESEARCH LA English DT Article ID NUTRITION EXAMINATION SURVEY; HEPATITIS-C INFECTION; BILIARY-TRACT CANCER; 3RD NATIONAL-HEALTH; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; MOLECULAR-MECHANISMS; FIBROSIS PROGRESSION; METABOLIC SYNDROME; SERUM-INSULIN AB Insulin resistance likely increases the risk of chronic liver disease (CLD) and liver cancer, but long-term prospective studies with measured fasting glucose and insulin are lacking. We evaluated the associations of prediagnostic fasting glucose, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) with liver cancer and CLD mortality in a prospective study of Finnish male smokers with extended follow-up time (<= 22 years) and information on known risk factors using data from 138 incident primary liver cancer cases, 216CLD deaths, and 681 matched controls. Fasting glucose and insulin were measured in baseline serum. We used unconditional logistic regression to estimate ORs and 95% confidence intervals adjusted for age, alcohol, education, smoking, body mass index, and hepatitis B and C viral status. Among those without self-reported diabetes, glucose was positively associated with liver cancer [quartile 3 vs. quartile 1 (Q3/Q1): OR = 1.88; 1.03-3.49; Q4/Q1: OR = 2.40; 1.33-4.35; P-trend = 0.002], and undiagnosed, biochemically defined, diabetes was associated with higher risk of liver cancer (OR = 2.95; 1.46-5.96) and CLD mortality (OR = 1.88; 1.00-3.56). Serum insulin and HOMA-IR were also positively associated with liver cancer (Q4/Q1: OR = 3.41; 1.74-6.66; P-trend < 0.0001; OR = 3.72; 1.89-7.32, P-trend < 0.0001, respectively) and CLD (OR = 2.51; 1.44-4.37; P-trend = 0.0002; OR = 2.31; 1.343.97; P-trend = 0.001, respectively), with stronger associations observed for liver cancer diagnosed > 10 years after baseline. In conclusion, elevated fasting glucose and insulin and insulin resistance were independently associated with risk of liver cancer and CLD mortality, suggesting a potentially important etiologic role for insulin and glucose dysregulation even in the absence of diagnosed diabetes. (C) 2016 AACR. C1 [Loftfield, Erikka; Freedman, Neal D.; Lai, Gabriel Y.; Weinstein, Stephanie J.; McGlynn, Katherine A.; Taylor, Philip R.; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Mannisto, Satu] Natl Inst Hlth andWelfare, Helsinki, Finland. RP Loftfield, E (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM erikka.loftfield@nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 47 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2016 VL 9 IS 11 BP 866 EP 874 DI 10.1158/1940-6207.CAPR-16-0141 PG 9 WC Oncology SC Oncology GA EB8ZZ UT WOS:000387682200006 PM 27574287 ER PT J AU Iyer, S Wang, Y Xiong, W Tang, DL Jedrychowski, W Chanock, S Wang, S Stigter, L Mroz, E Perera, F AF Iyer, Shoba Wang, Ya Xiong, Wei Tang, Deliang Jedrychowski, Wieslaw Chanock, Stephen Wang, Shuang Stigter, Laura Mroz, Elzbieta Perera, Frederica TI Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[a]P-DNA adducts in a cohort of non-smoking Polish mothers and newborns SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA ADDUCTS; AFRICAN-AMERICAN; CAUCASIAN MOTHERS; EPITHELIAL-CELLS; CORD BLOOD; INDUCTION; DOMINICAN; CANCER; DAMAGE AB Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women (n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[a]P metabolism, detoxification, and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM1, GSTT2, NQO1, and XRCC1. We observed significant interactions between maternal PAH exposure and SNPs on cord B[a]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2, and newborn CYP1A1 and CYP1B1. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. C1 [Iyer, Shoba; Tang, Deliang; Stigter, Laura; Perera, Frederica] Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA. [Wang, Ya; Xiong, Wei; Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Jedrychowski, Wieslaw] Jagiellonian Univ, Epidemiol & Prevent Med, Coll Med, PL-31007 Krakow, Poland. [Chanock, Stephen] NCI, Gaithersburg, MD 20877 USA. [Mroz, Elzbieta] Jagiellonian Univ, Coll Med, Chair Epidemiol & Prevent Med, PL-31007 Krakow, Poland. RP Perera, F (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA. EM fpp1@columbia.edu FU National Institute for Environmental Health Sciences (NIEHS); U.S. Environmental Protection Agency (US EPA) [NIEHS/EPA P01ES09600/R82702701, NIEHS/EPA P01ES09600/RD832141, NIEHS/EPA P01ES09600/RD834509]; NIEHS [R01ES10165, R01ES015282, R01ES08977, T32CA009529]; Herbert Irving Comprehensive Cancer Center [5P30CA3696]; Anonymous Foundation FX The study received funding from the National Institute for Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (US EPA): NIEHS/EPA P01ES09600/R82702701, NIEHS/EPA P01ES09600/RD832141, NIEHS/EPA P01ES09600/ RD834509, NIEHS R01ES10165, NIEHS R01ES015282, NIEHS R01ES08977, NIEHS training grant T32CA009529, the Herbert Irving Comprehensive Cancer Center Core grant (5P30CA3696), and an Anonymous Foundation. NR 25 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2016 VL 37 IS 11 BP 1110 EP 1115 DI 10.1093/carcin/bgw090 PG 6 WC Oncology SC Oncology GA EC2WH UT WOS:000387984500009 ER PT J AU Meguro, A Horita, N Takeuchi, M Ohno, S Mizuki, N AF Meguro, A. Horita, N. Takeuchi, M. Ohno, S. Mizuki, N. TI ASSOCIATION STUDY OF TRAF5 AND TRAF3IP2 GENE POLYMORPHISMS WITH SUSCEPTIBILITY TO BEHCET'S DISEASE AND VOGT-KOYANAGI-HARADA DISEASE IN A JAPANESE POPULATION SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Meguro, A.; Horita, N.; Mizuki, N.] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa, Japan. [Takeuchi, M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Ohno, S.] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido 060, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV-DEC PY 2016 VL 34 IS 6 SU 102 MA P26 BP S156 EP S156 PG 1 WC Rheumatology SC Rheumatology GA EC3ZP UT WOS:000388065900076 ER PT J AU Remmers, EF Takeuchi, M Ombrello, MJ Kirino, Y Erer, B Tugal-Tutkun, I Seyahi, E Ozyazgan, Y Watts, NR Gul, A Katner, DL AF Remmers, E. F. Takeuchi, M. Ombrello, M. J. Kirino, Y. Erer, B. Tugal-Tutkun, I Seyahi, E. Ozyazgan, Y. Watts, N. R. Gul, A. Katner, D. L. TI HOMOZYGOSITY FOR A SINGLE ERAP1 ALLOTYPE GREATLY INCREASES BEHCET'S DISEASE RISK IN HLA-B*51 CARRIERS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Remmers, E. F.; Takeuchi, M.; Katner, D. L.] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Ombrello, M. J.; Watts, N. R.] NIAMSD, Bethesda, MD 20892 USA. [Kirino, Y.] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa, Japan. [Erer, B.; Tugal-Tutkun, I; Gul, A.] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey. [Seyahi, E.; Ozyazgan, Y.] Istanbul Univ, Cerrahpasa Fac Med, Istanbul, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV-DEC PY 2016 VL 34 IS 6 SU 102 MA O6 BP S141 EP S142 PG 2 WC Rheumatology SC Rheumatology GA EC3ZP UT WOS:000388065900030 ER PT J AU Takeuchi, M Mizuki, N Meguro, A Ombrello, M Kirino, Y Satorius, C Le, J Erer, B Kawagoe, T Ustek, D Tugal-Tutkun, I Seyahi, E Ozyazgan, Y Sousa, I Davatchi, F Francisco, V Shahram, F Abdollahi, B Nadji, A Shafiee, N Ghaderibarmi, F Ohno, S Ueda, A Ishigatsubo, Y Oliveira, S Gul, A Kastner, D Remmers, E AF Takeuchi, M. Mizuki, N. Meguro, A. Ombrello, M. Kirino, Y. Satorius, C. Le, J. Erer, B. Kawagoe, T. Ustek, D. Tugal-Tutkun, I Seyahi, E. Ozyazgan, Y. Sousa, I Davatchi, F. Francisco, V Shahram, F. Abdollahi, B. Nadji, A. Shafiee, N. Ghaderibarmi, F. Ohno, S. Ueda, A. Ishigatsubo, Y. Oliveira, S. Gul, A. Kastner, D. Remmers, E. TI DENSE GENOTYPING OF IMMUNE-RELATED LOCI IMPLICATES HOST RESPONSES TO MICROBIAL EXPOSURE IN BEHCET'S DISEASE SUSCEPTIBILITY SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Takeuchi, M.; Satorius, C.; Le, J.] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Mizuki, N.; Meguro, A.; Kirino, Y.; Kawagoe, T.; Ueda, A.; Ishigatsubo, Y.] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa, Japan. [Ombrello, M.] NIAMSD, Bethesda, MD 20892 USA. [Erer, B.; Tugal-Tutkun, I; Gul, A.] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey. [Ustek, D.] Istanbul Univ, Inst Inst Expt Med, Istanbul, Turkey. [Seyahi, E.; Ozyazgan, Y.] Istanbul Univ, Cerrahpasa Fac Med, Istanbul, Turkey. [Sousa, I; Francisco, V; Oliveira, S.] Univ Lisbon, Fac Med, Lisbon, Portugal. [Davatchi, F.; Abdollahi, B.; Nadji, A.; Shafiee, N.; Ghaderibarmi, F.] Univ Tehran Med Sci, Tehran, Iran. [Ohno, S.] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. [Kastner, D.; Remmers, E.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV-DEC PY 2016 VL 34 IS 6 SU 102 MA O4 BP S141 EP S141 PG 1 WC Rheumatology SC Rheumatology GA EC3ZP UT WOS:000388065900028 ER PT J AU Wallace, G Candia, J Morton, L Biancotta, A Murray, P Nussenblatt, R AF Wallace, G. Candia, J. Morton, L. Biancotta, A. Murray, P. Nussenblatt, R. TI OCULAR DISEASE PHENOTYPING FROM MULTIPARAMETER CELL ANALYSIS BY MACHINE LEARNING ALGORITHMS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Wallace, G.; Morton, L.; Murray, P.] Univ Birmingham, Inst Inflammat & Ageing, Birmingham, W Midlands, England. [Candia, J.; Biancotta, A.; Nussenblatt, R.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 7 U2 7 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 NOV-DEC PY 2016 VL 34 IS 6 SU 102 MA O2 BP S140 EP S140 PG 1 WC Rheumatology SC Rheumatology GA EC3ZP UT WOS:000388065900026 ER PT J AU Yamane, T Meguro, A Takeuchi, M Ohno, S Mizuki, N AF Yamane, T. Meguro, A. Takeuchi, M. Ohno, S. Mizuki, N. TI GENOME-WIDE SCREENING OF LOCI ASSOCIATED WITH CLINICAL MANIFESTATIONS OF BEHCET'S DISEASE SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Yamane, T.; Meguro, A.; Mizuki, N.] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa, Japan. [Takeuchi, M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Ohno, S.] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV-DEC PY 2016 VL 34 IS 6 SU 102 MA O5 BP S141 EP S141 PG 1 WC Rheumatology SC Rheumatology GA EC3ZP UT WOS:000388065900029 ER PT J AU Vatsalya, V Pandey, A Schwandt, ML Cave, MC Barve, SS Ramchandani, VA McClain, CJ AF Vatsalya, Vatsalya Pandey, Akash Schwandt, Melanie L. Cave, Matthew C. Barve, Shirish S. Ramchandani, Vijay A. McClain, Craig J. TI Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients SO CLINICAL DRUG INVESTIGATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ATYPICAL ANTIPSYCHOTIC-DRUGS; DOUBLE-BLIND; MEDICAL PROGRESS; BIPOLAR-I; EFFICACY; DEPRESSION; SCHIZOPHRENIA; DISORDER; HEPATOTOXICITY AB Studies have reported liver injury as a consequence of antipsychotic treatment. Very heavy alcohol drinking (ten or more drinks/day for men and eight for women) also causes liver injury. This study aims to evaluate liver injury with quetiapine extended release (XR) in very heavy drinking alcohol-dependent (AD) patients. Two hundred and eighteen AD patients, 18-65 years of age, received 12 weeks of quetiapine XR or placebo treatment in a dose-escalated manner reaching the full dose of 400 mg/day during week 4. Blood chemistry and hematology were assessed at baseline (W0), post-titration at the end of week 3 (W4), week 8 (W8), and end of week 12 (W13). Patients were further grouped as GR.1 (no liver injury, ALT aecurrency sign40) and GR.2 (pre-existing liver injury, ALT > 40) within each treatment. Drinking history, fasting blood glucose concentration (FBG), and lipid panel were used as covariates in the analyses. Liver injury and total drinks and average drinking measures from the Timeline follow-back questionnaire (TLFB) were highly associated. No significant exacerbation in liver injury was observed in patients treated with quetiapine XR in GR.2. Liver injury as determined by elevated alanine aminotransaminase (ALT) was reported in a few patients in GR.1 who received quetiapine XR; however, the occurrence was low, and the level of liver injury was not significant. FBG and lipid measures showed some elevation, but did not show any significant association with liver injury. Quetiapine XR did not show any significant exacerbation of liver injury in very heavy drinking alcohol-dependent patients with pre-existing liver injury. Frequency and severity of new liver injury cases in quetiapine XR-treated patients without any pre-existing liver injury was also low. Study findings support medical management of AD patients with heavy drinking profile using quetiapine XR formulation. C1 [Vatsalya, Vatsalya; Cave, Matthew C.; Barve, Shirish S.; McClain, Craig J.] Univ Louisville, Sch Med, Dept Med, 505 S Hancock St,Ctr Room 521A, Louisville, KY 40202 USA. [Pandey, Akash] Maria Fareri Childrens Hosp, Westchester Med Ctr, Dept Pediat Gastroenterol, Valhalla, NY USA. [Schwandt, Melanie L.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [Barve, Shirish S.; McClain, Craig J.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Vatsalya, Vatsalya; Ramchandani, Vijay A.] NIAAA, Lab Clin & Translat Studies, Sect Human Psychopharmacol, Bethesda, MD 20892 USA. [McClain, Craig J.] Robley Rex VA Med Ctr, Louisville, KY USA. RP Vatsalya, V (reprint author), Univ Louisville, Sch Med, Dept Med, 505 S Hancock St,Ctr Room 521A, Louisville, KY 40202 USA.; Vatsalya, V (reprint author), NIAAA, Lab Clin & Translat Studies, Sect Human Psychopharmacol, Bethesda, MD 20892 USA. EM v0vats01@exchange.louisville.edu OI Vatsalya, Vatsalya/0000-0001-6764-6891 FU NIH - National Institute of Alcohol Abuse and Alcoholism [CSP-1027, Z99-AA999999, P50-AA024337-01, U01-AA021901, R37-AA010762, ZIA AA000466] FX This study was supported by the NIH - National Institute of Alcohol Abuse and Alcoholism: CSP-1027 (VV) and Z99-AA999999 (VV); P50-AA024337-01, U01-AA021901 and R37-AA010762 (CJM); and ZIA AA000466 (VAR). NR 43 TC 0 Z9 0 U1 2 U2 2 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1173-2563 EI 1179-1918 J9 CLIN DRUG INVEST JI Clin. Drug Invest. PD NOV PY 2016 VL 36 IS 11 BP 935 EP 944 DI 10.1007/s40261-016-0439-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EA6PB UT WOS:000386750000007 PM 27503091 ER PT J AU Elmore, JG Cook, AJ Bogart, A Carney, PA Geller, BM Taplin, SH Buist, DSM Onega, T Lee, CI Miglioretti, DL AF Elmore, Joann G. Cook, Andrea J. Bogart, Andy Carney, Patricia A. Geller, Berta M. Taplin, Stephen H. Buist, Diana S. M. Onega, Tracy Lee, Christoph I. Miglioretti, Diana L. TI Radiologists' interpretive skills in screening vs. diagnostic mammography: are they related? SO CLINICAL IMAGING LA English DT Article DE Screening mammography; Diagnostic mammography; Interpretive performance; Sensitivity; Specificity ID FALSE-POSITIVE RATES; PERFORMANCE BENCHMARKS; ACCURACY; VARIABILITY; VOLUME AB Purpose: This study aims to determine whether radiologists who perform well in screening also perform well in interpreting diagnostic mammography. Materials and methods: We evaluated the accuracy of 468 radiologists interpreting 2,234,947 screening and 196,164 diagnostic mammograms. Adjusting for site, radiologist, and patient characteristics, we identified radiologists with performance in the highest tertile and compared to those with lower performance. Results: A moderate correlation was noted for radiologists' accuracy when interpreting screening versus their accuracy on diagnostic examinations: sensitivity (rspeannan=0.51, 95% CI: 0.22, 0.80; P=.0006) and specificity (rspearman=0.40, 95% CI: 0.30, 0.49; P<.0001). Conclusion: Different educational approaches to screening and diagnostic imaging should be considered. (C) 2016 Elsevier Inc. All rights reserved. C1 [Elmore, Joann G.] Univ Washington, Div Gen Internal Med, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. [Cook, Andrea J.; Buist, Diana S. M.; Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. [Bogart, Andy] RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. [Geller, Berta M.] Univ Vermont, UHC, 1 South Prospect St, Burlington, VT 05401 USA. [Taplin, Stephen H.] NCI, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA. [Onega, Tracy] Dartmouth Med Sch, One Med Ctr Dr,HB7937, Lebanon, NH 03756 USA. [Lee, Christoph I.] Univ Washington, Dept Radiol, Sch Med, 825 Eastlake Ave E,G3-200, Seattle, WA 98109 USA. [Lee, Christoph I.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, 1959 NE Pacific St,Box 357660, Seattle, WA 98195 USA. [Miglioretti, Diana L.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Biostat,Med Sci 1C, One Shields Ave,Room 144, Davis, CA 95616 USA. RP Elmore, JG (reprint author), Univ Washington, Div Gen Internal Med, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. EM jelmore@u.washington.edu FU public health service grant from the Agency for Healthcare Research and Quality, National Cancer Institute (NCI) [R01 HS-010591, R01 CA-107623, K05 CA-104699]; NCI [HHSN261201100031C] FX This study is supported by public health service grant R01 HS-010591 from the Agency for Healthcare Research and Quality, National Cancer Institute (NCI) grants R01 CA-107623 and K05 CA-104699. Data collection and statistical analysis for this work were supported by the NCI-funded BCSC (HHSN261201100031C). NR 32 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 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD NOV-DEC PY 2016 VL 40 IS 6 BP 1096 EP 1103 DI 10.1016/j.clinimag.2016.06.014 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EB6XW UT WOS:000387529900007 PM 27438069 ER PT J AU Gumbo, T Makhene, MK Seddon, JA AF Gumbo, Tawanda Makhene, Mamodikoe K. Seddon, James A. TI Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; children; future; investment; PK; PD; hollow fiber ID HOLLOW-FIBER MODEL; MYCOBACTERIUM-TUBERCULOSIS; RESISTANT TUBERCULOSIS; PHARMACOKINETICS-PHARMACODYNAMICS; ANTITUBERCULOSIS DRUGS; SYSTEM MODEL; EFFLUX-PUMP; CHILDREN; PYRAZINAMIDE; MICE AB There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. C1 [Gumbo, Tawanda] Baylor Univ, Med Ctr, Baylor Res Inst, Ctr Infect Dis Res & Expt Therapeut, Dallas, TX USA. [Gumbo, Tawanda] Univ Cape Town, Dept Med, Observatory, South Africa. [Makhene, Mamodikoe K.] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Seddon, James A.] Imperial Coll London, Dept Paediat, Ctr Int Child Hlth, Norfolk Pl, London W2 1PG, England. RP Seddon, JA (reprint author), Imperial Coll London, Dept Paediat, Ctr Int Child Hlth, Norfolk Pl, London W2 1PG, England. EM james.seddon@imperial.ac.uk FU Academy of Medical Sciences [AMS-SGCL11-Seddon] FX T. G. is employed by the Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute. M. K. M. is employed by the NIAID, part of the US NIH. J. A. S. is employed as a National Institute of Health Research Academic Clinical Lecturer. He is also supported by a grant from the Academy of Medical Sciences (AMS-SGCL11-Seddon). NR 54 TC 2 Z9 2 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 NOV 1 PY 2016 VL 63 SU 3 BP S110 EP S115 DI 10.1093/cid/ciw484 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EC2XA UT WOS:000387986500008 PM 27742642 ER PT J AU Seddon, JA Makhene, MK AF Seddon, James A. Makhene, Mamodikoe K. TI Harnessing Novel Quantitative Pharmacology Approaches to Optimize the Treatment of Children With Tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; children; resistant; hollow fiber; pharmacokinetics C1 [Seddon, James A.] Imperial Coll London, Dept Paediat, Ctr Int Child Hlth, Norfolk Pl, London W2 1PG, England. [Makhene, Mamodikoe K.] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Seddon, JA (reprint author), Imperial Coll London, Dept Paediat, Ctr Int Child Hlth, Norfolk Pl, London W2 1PG, England. EM james.seddon@imperial.ac.uk FU Academy of Medical Sciences FX J. A. S. is employed as a National Institute of Health Research Academic Clinical Lecturer and is also supported by a grant from the Academy of Medical Sciences. M. K. M. is employed by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 11 TC 2 Z9 2 U1 2 U2 2 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 NOV 1 PY 2016 VL 63 SU 3 BP S61 EP S62 DI 10.1093/cid/ciw481 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EC2XA UT WOS:000387986500001 PM 27742635 ER PT J AU Meisel, C Plenz, D Schulze-Bonhage, A Reichmann, H AF Meisel, Christian Plenz, Dietmar Schulze-Bonhage, Andreas Reichmann, Heinz TI Quantifying antiepileptic drug effects using intrinsic excitability measures SO EPILEPSIA LA English DT Article DE Epilepsy; Antiepileptic drug; Biomarker; Excitability ID EPILEPSY; POLYTHERAPY; LOAD AB Pathologic increases in excitability levels of cortical tissue commonly underlie the initiation and spread of seizure activity in patients with epilepsy. By reducing the excitability levels in neural tissue, antiepileptic drug (AED) pharmacotherapy aims to reduce seizure severity and frequency. However, AEDs may also bring about adverse effects, which have been reported to increase with higher AED load. Measures that monitor the dose-dependent effects of AEDs on cortical tissue and quantify its excitability level are therefore of prime importance for efficient clinical care and treatment but have been difficult to identify. Here, we systematically analyze continuous multiday electrocorticography (ECoG) data from 10 patients under different levels of AED load and derive the recently proposed intrinsic excitability measures (IEMs) from different brain regions and across different frequency bands. We find that IEMs are significantly negatively correlated with AED load (prescribed daily dose/defined daily dose). Furthermore, we demonstrate that IEMs derived from different brain regions can robustly capture global changes in the degree of excitability. These results provide a step toward the ultimate goal of developing a reliable quantitative measure of central physiologic effects of AEDs in patients with epilepsy. C1 [Meisel, Christian; Plenz, Dietmar] NIMH, 35 Convent Dr, Bethesda, MD 20892 USA. [Meisel, Christian; Reichmann, Heinz] Univ Clin Carl Gustav Carus, Dept Neurol, Dresden, Germany. [Schulze-Bonhage, Andreas] Univ Med Ctr Freiburg, Epilepsy Ctr, Neuroctr, Freiburg, Germany. RP Meisel, C (reprint author), NIMH, 35 Convent Dr, Bethesda, MD 20892 USA. EM christian@meisel.de FU Intramural Research Program of the National Institute of Mental Health (NIMH) FX This study was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (NIH), Bethesda, MD (http://biowulf.nih.gov). NR 16 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD NOV PY 2016 VL 57 IS 11 BP E210 EP E215 DI 10.1111/epi.13517 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA EB8PC UT WOS:000387652200001 PM 27562603 ER PT J AU Kadmiel, M Janoshazi, A Xu, XJ Cidlowski, JA AF Kadmiel, Mahita Janoshazi, Agnes Xu, Xiaojiang Cidlowski, John A. TI Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Cornea; Glucocorticoids; Gene expression; Wound healing; Migration; Cytoskeleton; Epithelial integrity ID GENE-EXPRESSION; DEXAMETHASONE; MIGRATION; NEOVASCULARIZATION; OSTEOPROTEGERIN; INFLAMMATION; EPIREGULIN; RECEPTORS; DISEASE; INJURY AB Glucocorticoids play diverse roles in almost all physiological systems of the body, including both anti-inflammatory and immunosuppressive roles. Synthetic glucocorticoids are one of the most widely prescribed drugs and are used in the treatment of conditions such as autoimmune diseases, allergies, ocular disorders and certain types of cancers. In the interest of investigating glucocorticoid actions in the cornea of the eye, we established that multiple cell types in mouse corneas express functional glucocorticoid receptor (GR) with corneal epithelial cells having robust expression. To define glucocorticoid actions in a cell type-specific manner, we employed immortalized human corneal epithelial (HCE) cell line to define the glucocorticoid transcriptome and elucidated its functions in corneal epithelial cells. Over 4000 genes were significantly regulated within 6 h of dexamethasone treatment, and genes associated with cell movement, cytoskeletal remodeling and permeability were highly regulated. Real-time in vitro wound healing assays revealed that glucocorticoids delay wound healing by attenuating cell migration. These functional alterations were associated with cytoskeletal remodeling at the wounded edge of a scratch wounded monolayer. However, glucocorticoid treatment improved the organization of tight-junction proteins and enhanced the epithelial barrier function. Our results demonstrate that glucocorticoids profoundly alter corneal epithelial gene expression and many of these changes likely impact both wound healing and epithelial cell barrier function. Published by Elsevier Ltd. C1 [Kadmiel, Mahita; Janoshazi, Agnes; Cidlowski, John A.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. [Xu, Xiaojiang] NIEHS, Integrat Bioinformat, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27713 USA. EM cidlows1@niehs.nih.gov FU NIEHS Intramural Research Program FX We thank Jeff Tucker from the NIEHS Fluorescence Microscopy and Imaging Center for his assistance in the real-time wound healing studies. We also thank the NIEHS Flow Cytometry Center. We thank Drs. Robert Oakley, Xiaoling Li and Harriet Kinyamu for their critical reading of the manuscript. This work was funded by the NIEHS Intramural Research Program. NR 47 TC 1 Z9 1 U1 3 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2016 VL 152 BP 10 EP 33 DI 10.1016/j.exer.2016.08.020 PG 24 WC Ophthalmology SC Ophthalmology GA EC1AL UT WOS:000387835800002 PM 27600171 ER PT J AU Low, LA Tagle, DA AF Low, Lucie A. Tagle, Danilo A. TI Tissue chips to aid drug development and modeling for rare diseases SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE Clinical trials; drug development; induced pluripotent stem cells (iPSCs); microphysiological systems; platforms; rare diseases; tissue chips; toxicity screening ID PLURIPOTENT STEM-CELL; ORGANS-ON-CHIPS; IN-VITRO; HUMAN LIVER; MICROPHYSIOLOGICAL SYSTEMS; CULTURE ANALOG; METABOLISM; TOXICOLOGY; PDMS; ABSORPTION AB Introduction: The technologies used to design, create and use microphysiological systems (MPS, tissue chips' or organs-on-chips') have progressed rapidly in the last 5years, and validation studies of the functional relevance of these platforms to human physiology, and response to drugs for individual model organ systems, are well underway. These studies are paving the way for integrated multi-organ systems that can model diseases and predict drug efficacy and toxicology of multiple organs in real-time, improving the potential for diagnostics and development of novel treatments of rare diseases in the future.Areas covered: This review will briefly summarize the current state of tissue chip research and highlight model systems where these microfabricated (or bioengineered) devices are already being used to screen therapeutics, model disease states, and provide potential treatments in addition to helping elucidate the basic molecular and cellular phenotypes of rare diseases.Expert opinion: Microphysiological systems hold great promise and potential for modeling rare disorders, as well as for their potential use to enhance the predictive power of new drug therapeutics, plus potentially increase the statistical power of clinical trials while removing the inherent risks of these trials in rare disease populations. C1 [Low, Lucie A.; Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Low, Lucie A.] NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA. RP Tagle, DA (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. EM danilo.tagle@nih.gov FU National Center for Advancing Translational Services (NCATS) FX This paper was funded by National Center for Advancing Translational Services (NCATS). NR 57 TC 0 Z9 0 U1 6 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD NOV PY 2016 VL 4 IS 11 BP 1113 EP 1121 DI 10.1080/21678707.2016.1244479 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EA7KM UT WOS:000386809800004 ER PT J AU Lecchi, A Femia, EA Paoletta, S Dupuis, A Ohlmann, P Gachet, C Jacobson, KA Machura, K Podda, GM Zieger, B Cattaneo, M AF Lecchi, Anna Femia, Eti A. Paoletta, Silvia Dupuis, Arnaud Ohlmann, Philippe Gachet, Christian Jacobson, Kenneth A. Machura, Katharina Podda, Gian M. Zieger, Barbara Cattaneo, Marco TI Inherited dysfunctional platelet P2Y(12) receptor mutations associated with bleeding disorders SO HAMOSTASEOLOGIE LA English DT Article DE Platelets; mutation; P2Y(12) receptor ID ADENOSINE-DIPHOSPHATE; ANTITHROMBOTIC DRUGS; ADP RECEPTORS; IDENTIFICATION; PATIENT; AGGREGATION; DEFECTS; ACTIVATION; RESISTANCE; DIATHESIS AB The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) (P2Y(12)R) plays a critical role in platelet aggregation. The present report illustrates an update of dysfunctional platelet P2Y(12)R mutations diagnosed with congenital lifelong bleeding problems. Described patients with heterozygous or homozygous substitution in the P2Y(12)R gene and qualitative abnormalities of the platelet P2Y(12)R are summarized. Recently, a further dysfunctional variant of P2Y(12)R has been identified in two brothers who presented with a lifelong severe bleeding disorder. During in vitro aggregation studies, the patient's platelets show a markedly reduced and rapid reversible ADP-promoted aggregation. A homozygous c.561T>A substitution that changes the codon for Nisi 87 to Gln (p.His187GIn) in the P2Y(12)R gene has been identified. This mutation causes no change in receptor expression but decreases the affinity of the ligand for the receptor, even at high concentrations. Structure modelling studies indicated that the p.His187GIn mutation, located in the fifth transmembrane spanning domain (TM5), impairs conformational changes of the receptor. Structural integrity of the TM5 region is necessary for agonist and antagonist binding and for correct receptor function. C1 [Lecchi, Anna; Cattaneo, Marco] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy. [Femia, Eti A.; Podda, Gian M.] Univ Milan, Dipartimento Sci Salute, ASST Santi Paolo & Carlo, Div Med 3, Milan, Italy. [Paoletta, Silvia; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Dupuis, Arnaud; Ohlmann, Philippe; Gachet, Christian] Univ Strasbourg, Etab Francais Sang Alsace Lorraine Champagne Arde, INSERM, Unite Mixte Rech S949, Strasbourg, France. [Machura, Katharina; Zieger, Barbara] Univ Freiburg, Med Ctr, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med,Fac Med, Freiburg, Germany. RP Machura, K (reprint author), Univ Med Ctr, Freiburg Dept Pediat & Adolescent Med, Breisacher Str 66, D-79106 Freiburg, Germany. EM katharina.machura@uniklinik-freiburg.de RI Gachet, Christian/H-9156-2016 FU Intramural NIH HHS [ZIA DK031116-28] NR 32 TC 1 Z9 1 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0720-9355 J9 HAMOSTASEOLOGIE JI Hamostaseologie PD NOV PY 2016 VL 36 IS 4 BP 279 EP 283 DI 10.5482/HAMO-16-03-0010 PG 5 WC Hematology SC Hematology GA EC2IE UT WOS:000387934600006 PM 27487748 ER PT J AU Schoenfeld, TJ McCausland, HC Sonti, AN Cameron, HA AF Schoenfeld, Timothy J. McCausland, Hayley C. Sonti, Anup N. Cameron, Heather A. TI Anxiolytic Actions of Exercise in Absence of New Neurons SO HIPPOCAMPUS LA English DT Article DE adult neurogenesis; anxiety; exercise; immediate early genes ID ADULT HIPPOCAMPAL NEUROGENESIS; LONG-TERM POTENTIATION; DENTATE GYRUS; ANXIETY; MICE; BEHAVIOR; ANTIDEPRESSANT; ACTIVATION; DEPRESSION; LESIONS AB Physical exercise reduces anxiety-like behavior in adult mice. The specific mechanisms that mediate this anxiolytic effect are unclear, but adult neurogenesis in the dentate gyrus has been implicated because it is robustly increased by running and has been linked to anxiodepressive-like behavior. We therefore tested the effects of long-term wheel running on anxiety-like behavior in GFAP-TK (TK) mice, a transgenic strain with complete ablation of adult neurogenesis. Five weeks of running reduced anxiety-like behavior equally in both TK mice and wild type (WT) control mice on two tests, elevated plus-maze and novelty-suppressed feeding. WT and TK mice also had similar patterns of c-fos expression in the hippocampus following anxiety testing. Following testing on the elevated plus-maze, running reduced c-fos expression in the dorsal dentate gyrus and CA3 in both WT and TK mice. Following testing on novelty-suppressed feeding, running reduced c-fos expression throughout the dentate gyrus and CA3 in both WT and TK mice. Interestingly, following testing on a less anxiogenic version of novelty-suppressed feeding, running reduced c-fos expression only in the dorsal dentate gyrus in both WT and TK mice, supporting earlier suggestions that the dorsal hippocampus is less involved in emotional behavior than the ventral region. These results suggest that although running increases adult neurogenesis, new neurons are not involved in the decreased anxiety-like behavior or hippocampal activation produced by running. (C) 2016 Wiley Periodicals, Inc. C1 [Schoenfeld, Timothy J.; McCausland, Hayley C.; Sonti, Anup N.; Cameron, Heather A.] NIMH, NIH, Bethesda, MD 20892 USA. RP Schoenfeld, TJ (reprint author), NIMH, Sect Neuroplast, Porter Neurosci Res Ctr, Bldg 35,Room 3C-911,35 Lincoln Dr,MSC 3718, Bethesda, MD 20892 USA. EM schoenfeldt@mail.nih.gov RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 FU Intramural Program of the NIH, National Institute of Mental Health [ZIAMH002784] FX Grant sponsor: Intramural Program of the NIH, National Institute of Mental Health; Grant number: ZIAMH002784. NR 33 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD NOV PY 2016 VL 26 IS 11 BP 1373 EP 1378 DI 10.1002/hipo.22649 PG 6 WC Neurosciences SC Neurosciences & Neurology GA EB7SJ UT WOS:000387590300001 PM 27571506 ER PT J AU Wang, DD Eng, M Greenbaum, A Myers, E Forbes, M Pantelic, M Song, T Nelson, C Divine, G Taylor, A Wyman, J Guerrero, M Lederman, RJ Paone, G O'Neill, W AF Wang, Dee Dee Eng, Marvin Greenbaum, Adam Myers, Eric Forbes, Michael Pantelic, Milan Song, Thomas Nelson, Christina Divine, George Taylor, Andrew Wyman, Janet Guerrero, Mayra Lederman, Robert J. Paone, Gaetano O'Neill, William TI Predicting LVOT Obstruction After TMVR SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE 3D print; computer aided design; LVOT obstruction; transcatheter mitral valve replacement C1 [Wang, Dee Dee; Eng, Marvin; Greenbaum, Adam; Divine, George; Taylor, Andrew; Wyman, Janet; Guerrero, Mayra; Paone, Gaetano; O'Neill, William] Henry Ford Hlth Syst, Ctr Struct Heart Dis, Div Cardiol, Detroit, MI USA. [Myers, Eric; Forbes, Michael] Henry Ford Hlth Syst, Henry Ford Innovat Inst, Detroit, MI USA. [Pantelic, Milan; Song, Thomas; Nelson, Christina] Henry Ford Hlth Syst, Div Radiol, Detroit, MI USA. [Guerrero, Mayra] NorthShore Univ Hlth Syst, Evanston Hosp, Div Cardiol, Evanston, IL USA. [Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Wang, DD (reprint author), Henry Ford Hlth Syst, Inst Struct Heart Dis, 2799 West Grand Blvd,K14, Detroit, MI 48202 USA. EM dwang2@hfhs.org FU Intramural NIH HHS [ZIA HL006040-06] NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2016 VL 9 IS 11 BP 1349 EP 1352 DI 10.1016/j.jcmg.2016.01.017 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA EC1GE UT WOS:000387852100015 PM 27209112 ER PT J AU Qin, XY Feng, JC Cao, C Wu, HT Loh, YP Cheng, Y AF Qin, Xiao-Yan Feng, Jin-Chao Cao, Chang Wu, Huan-Tong Loh, Y. Peng Cheng, Yong TI Association of Peripheral Blood Levels of Brain-Derived Neurotrophic Factor With Autism Spectrum Disorder in Children A Systematic Review and Meta-analysis SO JAMA PEDIATRICS LA English DT Article ID BDNF LEVELS; ALZHEIMERS-DISEASE; MENTAL-RETARDATION; NEONATAL BLOOD; SERUM-LEVELS; PROTEIN; GENE; EPILEPSY; SCHIZOPHRENIA; NEUROPEPTIDES AB IMPORTANCE Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) may be implicated in the developmental outcomes of children with autism spectrum disorder (ASD). OBJECTIVE To use meta-analysis to determine whether children with ASD have altered peripheral blood levels of BDNF. DATA SOURCE A systematic search of PubMed, PsycINFO, and Web of Science was performed for English-language literature through February 7, 2016. The search terms included brain-derived neurotrophic factor or BDNF in combination with autism, without year restriction. Two additional records were retrieved after a review of the reference lists of selected articles. STUDY SELECTION Studies were included if they provided data on peripheral blood levels of BDNF in children with ASD and healthy control children. Studies that included adults or with overlapping samples were excluded. DATA EXTRACTION AND SYNTHESIS Data were extracted by 2 independent observers from 19 included studies. Data were pooled using a random-effects model with Comprehensive Meta-analysis software. MAIN OUTCOMES AND MEASURES Blood levels of BDNF in children with ASD compared with healthy controls. Altered levels of BDNF were hypothesized to be related to ASD. RESULTS This meta-analysis included 19 studies with 2896 unique participants. Random-effects meta-analysis of all 19 studies showed that children with ASD had significantly increased peripheral blood levels of BDNF compared with healthy controls (Hedges g, 0.490; 95% CI, 0.185-0.794; P = .002). Subgroup analyses in 4 studies revealed that neonates diagnosed with ASD later in life had no association with blood levels of BDNF (Hedges g, 0.384; 95% CI, -0.244 to 1.011; P = .23), whereas children in the nonneonate ASD group (15 studies) demonstrated significantly increased BDNF levels compared with healthy controls (Hedges g, 0.524; 95% CI, 0.206 to 0.842; P = .001). Further analysis showed that children in the nonneonate ASD group had increased BDNF levels in serum (10 studies) (Hedges g, 0.564; 95% CI, 0.168 to 0.960; P = .005) but not in plasma (5 studies) (Hedges g, 0.436; 95% CI, -0.176 to 1.048; P = .16). Meta-regression analyses revealed that sample size had a moderating effect on the outcome of the meta-analysis in the nonneonate group. In addition, no publication bias was found in the meta-analysis. CONCLUSIONS AND RELEVANCE Children with ASD have increased peripheral blood levels of BDNF, strengthening the clinical evidence of an abnormal neurotrophic factor profile in this population. C1 [Qin, Xiao-Yan; Feng, Jin-Chao; Cao, Chang; Wu, Huan-Tong] Minzu Univ China, Ctr Translat Neurosci, Coll Life & Environm Sci, Beijing, Peoples R China. [Qin, Xiao-Yan] Minzu Univ China, Beijing Engn Res Ctr Food Environm & Hlth, Beijing, Peoples R China. [Loh, Y. Peng; Cheng, Yong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Room 6C80, Bethesda, MD 20892 USA. RP Cheng, Y (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Room 6C80, Bethesda, MD 20892 USA. EM chengy4@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Minzu University 985 Academic Team-building Fund [YLDX01013, 2015MDTD13C]; 111 Project of China [B08044] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; grants YLDX01013 and 2015MDTD13C from the Minzu University 985 Academic Team-building Fund; and grant B08044 from the 111 Project of China. NR 67 TC 1 Z9 1 U1 10 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD NOV PY 2016 VL 170 IS 11 BP 1079 EP 1086 DI 10.1001/jamapediatrics.2016.1626 PG 8 WC Pediatrics SC Pediatrics GA EC4KM UT WOS:000388097900015 PM 27654278 ER PT J AU Yuan, C Gaskins, AJ Blaine, AI Zhang, CL Gillman, MW Missmer, SA Field, AE Chavarro, JE AF Yuan, Changzheng Gaskins, Audrey J. Blaine, Arianna I. Zhang, Cuilin Gillman, Matthew W. Missmer, Stacey A. Field, Alison E. Chavarro, Jorge E. TI Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood SO JAMA PEDIATRICS LA English DT Article ID BODY-MASS INDEX; GUT MICROBIOTA; WEIGHT-GAIN; HYGIENE HYPOTHESIS; VAGINAL DELIVERY; SCHOOL-CHILDREN; LIFE-STYLE; SECTION; COHORT; OVERWEIGHT AB IMPORTANCE Cesarean birth has been associated with higher risk of obesity in offspring, but previous studies have focused primarily on childhood obesity and have been hampered by limited control for confounders. OBJECTIVE To investigate the association between cesarean birth and risk of obesity in offspring. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from September 1, 1996, to December 31, 2012, among participants of the Growing Up Today Study, including 22 068 offspring born to 15 271 women, followed up via questionnaire from ages 9 to 14 through ages 20 to 28 years. Data analysis was conducted from October 10, 2015, to June 14, 2016. EXPOSURE Birth by cesarean delivery. MAIN OUTCOMES AND MEASURES Risk of obesity based on International Obesity Task Force or World Health Organization body mass index cutoffs, depending on age. Secondary outcomes included risks of obesity associated with changes in mode of delivery and differences in risk between siblings whose modes of birth were discordant. RESULTS Of the 22 068 offspring (20 950 white; 9359 male and 12 709 female), 4921 individuals (22.3%) were born by cesarean delivery. The cumulative risk of obesity through the end of follow-up was 13% among all participants. The adjusted risk ratio for obesity among offspring delivered via cesarean birth vs those delivered via vaginal birth was 1.15 (95% CI, 1.06-1.26; P =.002). This association was stronger among women without known indications for cesarean delivery (adjusted risk ratio, 1.30; 95% CI, 1.09-1.54; P =.004). Offspring delivered via vaginal birth among women who had undergone a previous cesarean delivery had a 31% (95% CI, 17%-47%) lower risk of obesity compared with those born to women with repeated cesarean deliveries. In within-family analysis, individuals born by cesarean delivery had 64%(8%-148%) higher odds of obesity than did their siblings born via vaginal delivery. CONCLUSIONS AND RELEVANCE Cesarean birth was associated with offspring obesity after accounting for major confounding factors. Although additional research is needed to clarify the mechanisms underlying this association, clinicians and patients should weigh this risk when considering cesarean delivery in the absence of a clear indication. C1 [Yuan, Changzheng; Gaskins, Audrey J.; Gillman, Matthew W.; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Bldg 2 3rd Floor,655 Huntington Ave, Boston, MA 02115 USA. [Yuan, Changzheng; Gaskins, Audrey J.; Missmer, Stacey A.; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Blaine, Arianna I.] Dartmouth Coll, Dartmouth Inst Hlth Policy & Clin Practice, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. [Gillman, Matthew W.] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Missmer, Stacey A.; Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Missmer, Stacey A.; Chavarro, Jorge E.] Harvard Med Sch, Boston, MA USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. [Missmer, Stacey A.] Boston Childrens Hosp, Dept Med, Div Adolescent Young Adult Med, Boston, MA USA. [Field, Alison E.] Brown Univ, Dept Epidemiol, Sch Publ Hlth, Providence, RI 02912 USA. RP Chavarro, JE (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, Bldg 2 3rd Floor,655 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu FU National Institutes of Health [UM1-CA176726, P30-DK046200, U54-CA155626, T32-DK007703-16, HD066963, HL096905, DK084001, MH087786]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This study was supported by grants UM1-CA176726, P30-DK046200, U54-CA155626, T32-DK007703-16, HD066963, HL096905, DK084001, and MH087786 from the National Institutes of Health. Dr Zhang is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 56 TC 0 Z9 0 U1 10 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD NOV PY 2016 VL 170 IS 11 AR e162385 DI 10.1001/jamapediatrics.2016.2385 PG 8 WC Pediatrics SC Pediatrics GA EC4KM UT WOS:000388097900001 PM 27599167 ER PT J AU Li, X Venniro, M Shaham, Y AF Li, Xuan Venniro, Marco Shaham, Yavin TI Translational Research on Incubation of Cocaine Craving SO JAMA PSYCHIATRY LA English DT Editorial Material ID ABSTINENCE; WITHDRAWAL; SEEKING; RATS C1 [Li, Xuan; Venniro, Marco; Shaham, Yavin] NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM yavin.shaham@nih.gov FU Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health FX The authors reported having received research funding from the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. No other disclosures were reported. NR 15 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 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD NOV PY 2016 VL 73 IS 11 BP 1115 EP 1116 DI 10.1001/jamapsychiatry.2016.2110 PG 2 WC Psychiatry SC Psychiatry GA EC2GJ UT WOS:000387927400004 PM 27604057 ER PT J AU Olfson, M Melanie, W Wang, S Crystal, S Liu, SM Gerhard, T Blanco, C AF Olfson, Mark Wall, Melanie Wang, Shuai Crystal, Stephen Liu, Shang-Min Gerhard, Tobias Blanco, Carlos TI Short-term Suicide Risk After Psychiatric Hospital Discharge SO JAMA PSYCHIATRY LA English DT Article ID FOLLOW-UP; HEALTH-SERVICES; DISORDERS; CARE; PREVALENCE; STRATEGIES; MORTALITY; CONTACT; AUTOPSY; FINLAND AB IMPORTANCE Although psychiatric inpatients are recognized to be at increased risk for suicide immediately after hospital discharge, little is known about the extent to which their short-term suicide risk varies across groups with major psychiatric disorders. OBJECTIVE To describe the risk for suicide during the 90 days after hospital discharge for adults with first-listed diagnoses of depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorders in relation to inpatients with diagnoses of nonmental disorders and the general population. DESIGN, SETTING, AND PARTICIPANTS This national retrospective longitudinal cohort included inpatients aged 18 to 64 years in the Medicaid program who were discharged with a first-listed diagnosis of a mental disorder (depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorder) and a 10% random sample of inpatients with diagnoses of nonmental disorders. The cohort included 770 643 adults in the mental disorder cohort, 1 090 551 adults in the nonmental disorder cohort, and 370 deaths from suicide from January 1, 2001, to December 31, 2007. Data were analyzed from March 5, 2015, to June 6, 2016. MAIN OUTCOMES AND MEASURES Suicide rates per 100 000 person-years were determined for each study group during the 90 days after hospital discharge and the demographically matched US general population. Adjusted hazard ratios (ARHs) of short-term suicide after hospital discharge were also estimated by Cox proportional hazards regression models. Information on suicide as a cause of death was obtained from the National Death Index. RESULTS In the overall population of 1861194 adults (27% men; 73% women; mean [SD] age, 35.4 [13.1] years), suicide rates for the cohorts with depressive disorder (235.1 per 100 000 person-years), bipolar disorder (216.0 per 100 000 person-years), schizophrenia (168.3 per 100 000 person-years), substance use disorder (116.5 per 100 000 person-years), and other mental disorders (160.4 per 100 000 person-years) were substantially higher than corresponding rates for the cohort with nonmental disorders (11.6 per 100 000 person-years) or the US general population (14.2 per 100 000 person-years). Among the cohort with mental disorders, AHRs of suicide were associated with inpatient diagnosis of depressive disorder (AHR, 2.0; 95% CI, 1.4-2.8; reference cohort, substance use disorder), an outpatient diagnosis of schizophrenia (AHR, 1.6; 95% CI, 1.1-2.2), an outpatient diagnosis of bipolar disorder (AHR, 1.6; 95% CI, 1.2-2.1), and an absence of any outpatient health care in the 6 months preceding hospital admission (AHR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS AND RELEVANCE After psychiatric hospital discharge, adults with complex psychopathologic disorders with prominent depressive features, especially patients who are not tied into a system of health care, appear to have a particularly high short-term risk for suicide. C1 [Olfson, Mark; Wall, Melanie; Wang, Shuai; Liu, Shang-Min] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. [Crystal, Stephen] Rutgers State Univ, Ctr Hlth Serv Res Pharmacotherapy Chron Dis Manag, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ USA. [Gerhard, Tobias] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharm Practice & Adm, Piscataway, NJ USA. [Blanco, Carlos] NIDA, Div Epidemiol Serv & Prevent Res, Rockville, MD USA. RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@cumc.columbia.edu FU Agency for Healthcare Research and Quality [U19 HS021112]; New York State Psychiatric Institute FX This research was supported by grant U19 HS021112 from the Agency for Healthcare Research and Quality and by the New York State Psychiatric Institute. NR 42 TC 2 Z9 2 U1 7 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD NOV PY 2016 VL 73 IS 11 BP 1119 EP 1126 DI 10.1001/jamapsychiatry.2016.2035 PG 8 WC Psychiatry SC Psychiatry GA EC2GJ UT WOS:000387927400006 PM 27654151 ER PT J AU Watson, MJ Sidana, A Diaz, AW Siddiqui, MM Hankins, RA Bratslavsky, G Linehan, WM Metwalli, AR AF Watson, Matthew J. Sidana, Abhinav Diaz, Annerleim Walton Siddiqui, M. Minhaj Hankins, Ryan A. Bratslavsky, Gennady Linehan, W. Marston Metwalli, Adam R. TI Repeat Robotic Partial Nephrectomy: Characteristics, Complications, and Renal Functional Outcomes SO JOURNAL OF ENDOUROLOGY LA English DT Article DE laparoscopy approach; renal cancer; robotics ID NEPHRON-SPARING SURGERY; ASSISTED PARTIAL NEPHRECTOMY; CELL CARCINOMA; FEASIBILITY; KIDNEY; CANCER; TUMORS; EXPERIENCE; RECURRENCE; MORBIDITY AB Introduction: Multifocal and hereditary kidney cancers often require repeated ipsilateral nephron sparing procedures with higher blood loss and complication rates compared to first time renal surgery. Consequently, many surgeons avoid minimally invasive techniques in the setting. We present the characteristics, complications, and short-term renal functional outcomes of patients who underwent a repeat robotic partial nephrectomy (rRPNx). Materials and Methods: A database was retrospectively reviewed to identify patients who underwent robotic partial nephrectomies between January 2007 and December 2013. Selection criteria for the rRPNx cohort included patients who had undergone at least two ipsilateral renal surgeries, with the second procedure being an rRPNx. All other patients comprised the initial robotic partial nephrectomy (iRPNx) group. Results: One hundred twenty-four patients who underwent robotic partial nephrectomy during the study period were identified. rRPNx constituted 26 (21%) of the total cases. Age of the rRPNx cohort was similar (p = 0.56), but number of tumors resected was two-fold greater in the rRPNx group (p = 0.44). Neither surgery time nor renal clamp time was significantly longer in either group (p = 0.18 and p = 0.65, respectively). Importantly, estimated blood loss (EBL) was significantly larger than in the iRPNx group (p = 0.01). Both groups had similar intravenous pain medication administration durations (p = 0.32), but postsurgical length of stay was greater for the rRPNx patients (p = 0.011). There were no significant differences in clavian complication rates (p = 0.17-0.39), with the exception of urine leak which occurred more frequently in the rRPNx group (p = 0.01). There was no difference in percent change in serum creatinine or estimated glomerular filtration rate (p = 0.89 and p = 0.67, respectively). Conclusions: rRPNx is safe and feasible in select patients. EBL, postoperative lengths of stay, and urine leak were the only factors significantly associated with rRPNx compared to iRPNx. Patient 3-month follow-up revealed excellent and comparable outcomes between the two groups. C1 [Watson, Matthew J.; Sidana, Abhinav; Diaz, Annerleim Walton; Linehan, W. Marston; Metwalli, Adam R.] NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10 CRC, Bethesda, MD 20892 USA. [Siddiqui, M. Minhaj] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA. [Hankins, Ryan A.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. RP Metwalli, AR (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10 CRC, Bethesda, MD 20892 USA. EM adam.metwalli@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. NR 24 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 EI 1557-900X J9 J ENDOUROL JI J. Endourol. PD NOV PY 2016 VL 30 IS 11 BP 1219 EP 1226 DI 10.1089/end.2016.0517 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA EC4QA UT WOS:000388116900013 PM 27650937 ER PT J AU Hakim, FT Memon, S Jin, P Imanguli, MM Wang, H Rehman, N Yan, XY Rose, J Mays, JW Dhamala, S Kapoor, V Telford, W Dickinson, J Davis, S Halverson, D Naik, HB Baird, K Fowler, D Stroncek, D Cowen, EW Pavletic, SZ Gress, RE AF Hakim, Frances T. Memon, Sarfraz Jin, Ping Imanguli, Matin M. Wang, Huan Rehman, Najibah Yan, Xiao-Yi Rose, Jeremy Mays, Jacqueline W. Dhamala, Susan Kapoor, Veena Telford, William Dickinson, John Davis, Sean Halverson, David Naik, Haley B. Baird, Kristin Fowler, Daniel Stroncek, David Cowen, Edward W. Pavletic, Steven Z. Gress, Ronald E. TI Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; STEM-CELL TRANSPLANTATION; GENE-EXPRESSION; CHRONIC GVHD; MONOCLONAL-ANTIBODY; ACTIVATING FACTOR; RISK-FACTORS; T-CELLS; B-CELLS; PHASE-I AB Although chronic graft-versus-host disease (CGVHD) is the primary nonrelapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: 1) IFN-inducible genes, and 2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation, and Ag presentation) were concurrently upregulated in CGVHD monocytes compared with normal subjects and non-CGVHD control patients. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and were linked to CXCR3(+) lymphocyte trafficking. Furthermore, the levels of the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) were correlated at both the gene and the plasma levels, implicating IFN induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, damage-/pathogen-associated molecular pattern receptor genes capable of inducing type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa, and glands, and expression of TLR7 and DDX58 receptor genes correlated with upregulation of type I IFN-inducible genes in monocytes. Finally, in serial analyses after transplant, IFNinducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes, and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD. The Journal of Immunology, 2016, 197: 3490-3503. C1 [Hakim, Frances T.; Memon, Sarfraz; Imanguli, Matin M.; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy; Dhamala, Susan; Kapoor, Veena; Telford, William; Dickinson, John; Halverson, David; Fowler, Daniel; Pavletic, Steven Z.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, CRC 3330,10 Ctr Dr,MSC 1203, Bethesda, MD 20892 USA. [Jin, Ping; Wang, Huan; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Jin, Ping; Wang, Huan; Stroncek, David] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD 20892 USA. [Davis, Sean] NCI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Naik, Haley B.; Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hakim, FT (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, CRC 3330,10 Ctr Dr,MSC 1203, Bethesda, MD 20892 USA. EM hakimf@mail.nih.gov OI rehman, najibah/0000-0003-2718-6784; Wang, Huan/0000-0003-3100-6141 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The Nano-String assays were supported by a National Cancer Institute Director's Intramural Innovation Award (to F.T.H.). NR 65 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2016 VL 197 IS 9 BP 3490 EP 3503 DI 10.4049/jimmunol.1601054 PG 14 WC Immunology SC Immunology GA EC2PN UT WOS:000387965900009 PM 27694491 ER PT J AU Kannanganat, S Wyatt, LS Gangadhara, S Chamcha, V Chea, LS Kozlowski, PA LaBranche, CC Chennareddi, L Lawson, B Reddy, PBJ Styles, TM Vanderford, TH Montefiori, DC Moss, B Robinson, HL Amara, RR AF Kannanganat, Sunil Wyatt, Linda S. Gangadhara, Sailaja Chamcha, Venkatesarlu Chea, Lynette S. Kozlowski, Pamela A. LaBranche, Celia C. Chennareddi, Lakshmi Lawson, Benton Reddy, Pradeep B. J. Styles, Tiffany M. Vanderford, Thomas H. Montefiori, David C. Moss, Bernard Robinson, Harriet L. Amara, Rama Rao TI High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5 alpha-Restrictive Macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MYELOID SUPPRESSOR-CELLS; IMMUNE-RESPONSES; DENDRITIC CELLS; DNA VACCINE; RHESUS-MONKEYS; CELLULAR-IMMUNITY; SIV CHALLENGE; INFECTION; HIV-1 AB We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor alpha 4 beta 7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5 alpha (TRIM5 alpha) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5 alpha-restrictive animals receiving no or the lowest dose (1 x 10(5) PFU) of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5 alpha-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5 alpha-restrictive animals, but not in the TRIM5 alpha-permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of TRIM5 alpha restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5 alpha-restrictive animals, and 3) high doses of codelivered MVA/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus-like particles. C1 [Kannanganat, Sunil; Gangadhara, Sailaja; Chamcha, Venkatesarlu; Chea, Lynette S.; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B. J.; Styles, Tiffany M.; Vanderford, Thomas H.; Amara, Rama Rao] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Kannanganat, Sunil; Gangadhara, Sailaja; Chamcha, Venkatesarlu; Chea, Lynette S.; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B. J.; Styles, Tiffany M.; Vanderford, Thomas H.; Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Wyatt, Linda S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA. [LaBranche, Celia C.; Montefiori, David C.] Duke Univ, Dept Surg, Med Ctr, Durham, NC 27705 USA. [Robinson, Harriet L.] GeoVax Inc, 1900 Lake Pk Dr,Suite 380, Smyma, GA 30080 USA. RP Robinson, HL (reprint author), GeoVax Inc, 1900 Lake Pk Dr,Suite 380, Smyma, GA 30080 USA.; Amara, RR (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM hrobinson@geovax.com; ramara@emory.edu FU NCRR NIH HHS [P51 RR000168, K26 RR000168, P51 RR000165]; NIAID NIH HHS [P30 AI050409, U19 AI109633, HHSN272201100016C, P01 AI088575, U19 AI074073, U19 AI096187] NR 51 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2016 VL 197 IS 9 BP 3586 EP 3596 DI 10.4049/jimmunol.1600629 PG 11 WC Immunology SC Immunology GA EC2PN UT WOS:000387965900018 PM 27683750 ER PT J AU Filley, CM Fields, RD AF Filley, Christopher M. Fields, R. Douglas TI White matter and cognition: making the connection SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review DE cognition; dementia; glial cells; myelin; white matter ID CENTRAL-NERVOUS-SYSTEM; CHRONIC TRAUMATIC ENCEPHALOPATHY; SOLVENT VAPOR ABUSE; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; ACTION-POTENTIALS; OLIGODENDROCYTE DIFFERENTIATION; TOLUENE ABUSE; DISCONNEXION SYNDROMES; SUBCORTICAL DEMENTIA AB Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. C1 [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Aurora, CO USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Filley, Christopher M.] Vet Affairs Med Ctr, Denver Dept, Denver, CO USA. [Fields, R. Douglas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Filley, CM (reprint author), Behav Neurol Sect, 12631 East 17th Ave,B-185, Aurora, CO 80045 USA. EM christopher.filley@ucdenver.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by funds for intramural research from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 145 TC 0 Z9 0 U1 11 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2016 VL 116 IS 5 BP 2093 EP 2104 DI 10.1152/jn.00221.2016 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA EC2VV UT WOS:000387983300009 PM 27512019 ER PT J AU Belter, CW AF Belter, Christopher W. TI Citation analysis as a literature search method for systematic reviews SO JOURNAL OF THE ASSOCIATION FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Review DE bibliometrics; information retrieval ID NETWORK ANALYSIS SEBRINA; INFORMATION-RETRIEVAL; SCIENTIFIC FIELDS; SCIENCE; COCITATION; SCIENTOMETRICS; BIBLIOMETRICS; IR; INTRAPARTUM; DIMENSION AB Systematic reviews are essential for evaluating biomedical treatment options, but the growing size and complexity of the available biomedical literature combined with the rigor of the systematic review method mean that systematic reviews are extremely difficult and labor-intensive to perform. In this article, I propose a method of searching the literature by systematically mining the various types of citation relationships between articles. I then test the method by comparing its precision and recall to that of 14 published systematic reviews. The method successfully retrieved 74% of the studies included in these reviews and 90% of the studies it could reasonably be expected to retrieve. The method also retrieved fewer than half of the total number of publications retrieved by these reviews and can be performed in substantially less time. This suggests that the proposed method offers a promising complement to traditional text-based methods of literature identification and retrieval for systematic reviews. C1 [Belter, Christopher W.] NIH, NIH Lib, Bethesda, MD 20892 USA. RP Belter, CW (reprint author), NIH, NIH Lib, Bethesda, MD 20892 USA. EM Christopher.Belter@nih.gov RI Belter, Christopher/L-6487-2013 OI Belter, Christopher/0000-0001-5221-6880 NR 86 TC 1 Z9 1 U1 22 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2330-1635 EI 2330-1643 J9 J ASSOC INF SCI TECH PD NOV PY 2016 VL 67 IS 11 BP 2766 EP 2777 DI 10.1002/asi.23605 PG 12 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA DZ3VK UT WOS:000385777500014 ER PT J AU Sierra, F AF Sierra, Felipe TI Special Issue: Moving Geroscience Into Uncharted Waters: Guest Editorial Moving Geroscience Into Uncharted Waters SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 [Sierra, Felipe] NIA, Div Aging Biol, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. RP Sierra, F (reprint author), NIA, Div Aging Biol, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2016 VL 71 IS 11 BP 1385 EP 1387 DI 10.1093/gerona/glw087 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EC3AG UT WOS:000387995800001 PM 27535965 ER PT J AU Kirkland, JL Stout, MB Sierra, F AF Kirkland, James L. Stout, Michael B. Sierra, Felipe TI Resilience in Aging Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Resilience; Health Span ID COLD STRESS; FRAILTY INDEX; OLDER-ADULTS; COGNITIVE IMPAIRMENT; OXIDATIVE STRESS; CANCER-TREATMENT; C57BL/6J MICE; INJURY MODEL; DWARF MICE; LIFE-SPAN AB Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context. The preliminary set of tests ranked by the participants is discussed here, recognizing that this is a first attempt. C1 [Kirkland, James L.; Stout, Michael B.] Mayo Clin, Mayo Clin Kogod Ctr Aging, Rochester, MN USA. [Sierra, Felipe] NIA, Div Aging Biol, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. RP Sierra, F (reprint author), NIA, Div Aging Biol, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov FU NIA NIH HHS [K99 AG051661] NR 80 TC 0 Z9 0 U1 2 U2 2 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 NOV PY 2016 VL 71 IS 11 BP 1407 EP 1414 DI 10.1093/gerona/glw086 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EC3AG UT WOS:000387995800004 PM 27535963 ER PT J AU Varma, VR Hausdorff, JM Studenski, SA Rosano, C Camicioli, R Alexander, NB Chen, WG Lipsitz, LA Carlson, MC AF Varma, Vijay R. Hausdorff, Jeffrey M. Studenski, Stephanie A. Rosano, Caterina Camicioli, Richard Alexander, Neil B. Chen, Wen G. Lipsitz, Lewis A. Carlson, Michelle C. TI Aging, the Central Nervous System, and Mobility in Older Adults: Interventions SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE CNS; Cognition; Disability ID RANDOMIZED CONTROLLED-TRIAL; MOTORIC COGNITIVE RISK; IMPROVES GAIT PERFORMANCE; PHYSICAL-ACTIVITY; FALL RISK; ALZHEIMERS-DISEASE; HEARING IMPAIRMENT; ELDERLY-PEOPLE; CLINICAL-TRIAL; PARKINSONS-DISEASE AB Research suggests that the central nervous system (CNS) and mobility are closely linked. CNS-mediated mobility impairment may represent a potentially new and prevalent syndrome within the older adult populations. Interventions targeting this group may have the potential to improve mobility and cognition and prevent disability. In 2012, the Gerontological Society of America (GSA) and the National Institute on Aging (NIA) sponsored a 3-year conference workshop series, "Aging, the CNS, and Mobility." The goal of this third and final conference was to (i) report on the state of the science of interventions targeting CNS-mediated mobility impairment among community-dwelling older adults and (ii) partnering with the NIA, explore the future of research and intervention design focused on a potentially novel aging syndrome. Evidence was presented in five main intervention areas: (i) pharmacology and diet; (ii) exercise; (iii) electrical stimulation; (iv) sensory stimulation/deprivation; and (v) a combined category of multimodal interventions. Workshop participants identified important gaps in knowledge and key recommendations for future interventions related to recruitment and sample selection, intervention design, and methods to measure effectiveness. In order to develop effective preventive interventions for this prevalent syndrome, multidisciplinary teams are essential particularly because of the complex nature of the syndrome. Additionally, integrating innovative methods into the design of interventions may help researchers better measure complex mechanisms, and finally, the value of understanding the link between the CNS and mobility should be conveyed to researchers across disciplines in order to incorporate cognitive and mobility measurements into study protocols. C1 [Varma, Vijay R.; Carlson, Michelle C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 805 Hampton House,624 N Broadway St, Baltimore, MD 21205 USA. [Varma, Vijay R.; Carlson, Michelle C.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Varma, Vijay R.] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Hausdorff, Jeffrey M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Ctr Study Movement Cognit & Mobil, Neurol Inst, Tel Aviv, Israel. [Hausdorff, Jeffrey M.] Tel Aviv Univ, Dept Phys Therapy, Sackler Fac Med, Tel Aviv, Israel. [Hausdorff, Jeffrey M.] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel. [Studenski, Stephanie A.] NIA, Longitudinal Studies Sect, Bethesda, MD 20892 USA. [Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Camicioli, Richard] Univ Alberta, Dept Med, Div Neurol, Edmonton, AB, Canada. [Alexander, Neil B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Chen, Wen G.] NIA, Div Neurosci, Bethesda, MD 20892 USA. [Lipsitz, Lewis A.] Harvard Med Sch, Hebrew Senior Life, Res, Inst Aging Res, Boston, MA USA. RP Carlson, MC (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 805 Hampton House,624 N Broadway St, Baltimore, MD 21205 USA. EM mcarlso2@jhu.edu OI Camicioli, Richard/0000-0003-2977-8660 FU National Institute on Aging [U13-AG-041613-01, 5T32AG000247] FX This work was supported by a cooperative conference grant (National Institute on Aging, U13-AG-041613-01) and a postdoctoral training grant (National Institute on Aging, 5T32AG000247). NR 80 TC 2 Z9 2 U1 8 U2 8 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 NOV PY 2016 VL 71 IS 11 BP 1451 EP 1458 DI 10.1093/gerona/glw080 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EC3AG UT WOS:000387995800009 PM 27154905 ER PT J AU Leaderbrand, K Chen, HJ Corcoran, KA Guedea, AL Jovasevic, V Wess, J Radulovic, J AF Leaderbrand, Katherine Chen, Helen J. Corcoran, Kevin A. Guedea, Anita L. Jovasevic, Vladimir Wess, Jurgen Radulovic, Jelena TI Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; DOPAMINE 1-CLASS RECEPTORS; HIPPOCAMPAL THETA-RHYTHM; CHOLINERGIC MODULATION; FEAR MEMORY; RETROSPLENIAL CORTEX; NEUROTRANSMITTER RECEPTORS; SYNAPTIC-TRANSMISSION; PASSIVE-AVOIDANCE; RAT HIPPOCAMPUS AB Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on which mAChR subtypes are critical for memory processing. Using pharmacological and genetic approaches, we found that (1) encoding and retrieval of contextual memory requires mAChR in the dorsal hippocampus (DH) and retrosplenial cortex (RSC), (2) memory formation requires hippocampal M-3 and cooperative activity of RSC M-1 and M-3, and (3) memory retrieval is more impaired by inactivation of multiple M-1-M-4 mAChR in DH or RSC than inactivation of individual receptor subtypes. Contrary to the view that acetylcholine supports learning but is detrimental to memory retrieval, we found that coactivation of multiple mAChR is required for retrieval of both recently and remotely acquired context memories. Manipulations with higher receptor specificity were generally less potent than manipulations targeting multiple receptor subtypes, suggesting that mAChR act in synergy to regulate memory processes. These findings provide unique insight into the development of therapies for amnestic symptoms, suggesting that broadly acting, rather than receptor-specific, mAchR agonists and positive allosteric modulators may be the most effective therapeutic approach. C1 [Leaderbrand, Katherine; Chen, Helen J.; Corcoran, Kevin A.; Guedea, Anita L.; Jovasevic, Vladimir; Radulovic, Jelena] Northwestern Univ, Feinberg Sch Med, Asher Ctr Study & Treatment Depress Disorders, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Wess, Jurgen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. RP Radulovic, J (reprint author), Northwestern Univ, Feinberg Sch Med, Asher Ctr Study & Treatment Depress Disorders, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. EM j-radulovic@northwestern.edu FU NIMH [MH078064, MH108837, T32MH067564]; Northwestern University's Presidential Fellowship; Intramural Research Program, NIDDK, NIH FX NIMH (MH078064 and MH108837 to J.R., T32MH067564), Northwestern University's Presidential Fellowship (K.L.), and the Intramural Research Program, NIDDK, NIH (J.W.). NR 79 TC 0 Z9 0 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 EI 1549-5485 J9 LEARN MEMORY JI Learn. Mem. PD NOV PY 2016 VL 23 IS 11 BP 631 EP 638 DI 10.1101/lm.043133.116 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA EC2PA UT WOS:000387964300005 PM 27918283 ER PT J AU Wittig, JH Morgan, B Masseau, E Richmond, BJ AF Wittig, John H., Jr. Morgan, Barak Masseau, Evan Richmond, Barry J. TI Humans and monkeys use different strategies to solve the same short-term memory tasks SO LEARNING & MEMORY LA English DT Article ID WORKING-MEMORY; RHESUS-MONKEYS; PREFRONTAL CORTEX; MECHANISMS; RECENCY AB The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory. C1 [Wittig, John H., Jr.; Masseau, Evan; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Morgan, Barak] Univ Cape Town, Dept Publ Law, Global Risk Governance Program, ZA-7701 Rondebosch, South Africa. [Morgan, Barak] Univ Witwatersrand, DVC Res Off, DST NRF Ctr Excellence Human Dev, ZA-2050 Johannesburg, South Africa. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU Intramural Research Program of the National Institute of Mental Health FX We thank Adin Horovitz, Kate Kempen, and Michelle Henry for assisting with data collection, and Benjamin Basile and Brian Scott for their critical comments that helped improve the manuscript. The views expressed in this article do not necessarily represent the views of the University of Cape Town, NIMH, NIH, or the U.S. Government. This study was supported by the Intramural Research Program of the National Institute of Mental Health. NR 21 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 EI 1549-5485 J9 LEARN MEMORY JI Learn. Mem. PD NOV PY 2016 VL 23 IS 11 BP 644 EP 647 DI 10.1101/lm.041764.116 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA EC2PA UT WOS:000387964300007 PM 27918285 ER PT J AU Jones, L Carol, H Evans, K Richmond, J Houghton, PJ Smith, MA Lock, RB AF Jones, L. Carol, H. Evans, K. Richmond, J. Houghton, P. J. Smith, M. A. Lock, R. B. TI A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program SO LEUKEMIA LA English DT Review ID ACUTE MYELOID-LEUKEMIA; PROTEASOME INHIBITOR BORTEZOMIB; HISTONE DEACETYLASE INHIBITOR; PHASE-I CONSORTIUM; STAGE 1; KINASE INHIBITOR; ONCOLOGY-GROUP; THERAPEUTIC ADVANCES; CHILDHOOD LEUKEMIA; XENOGRAFT MODELS AB Acute lymphoblastic leukemia (ALL) in children exemplifies how multi-agent chemotherapy has improved the outcome for patients. Refinements in treatment protocols and improvements in supportive care for this most common pediatric malignancy have led to a cure rate that now approaches 90%. However, certain pediatric ALL subgroups remain relatively intractable to treatment and many patients who relapse face a similarly dismal outcome. Moreover, survivors of pediatric ALL suffer the long-term sequelae of their intensive treatment throughout their lives. Therefore, the development of drugs to treat relapsed/refractory pediatric ALL, as well as those that more specifically target leukemia cells, remains a high priority. As pediatric malignancies represent a minority of the overall cancer burden, it is not surprising that they are generally underrepresented in drug development efforts. The identification of novel therapies relies largely on the reappropriation of drugs developed for adult malignancies. However, despite the large number of experimental agents available, clinical evaluation of novel drugs for pediatric ALL is hindered by limited patient numbers and the availability of effective established drugs. The Pediatric Preclinical Testing Program (PPTP) was established in 2005 to provide a mechanism by which novel therapeutics could be evaluated against xenograft and cell line models of the most common childhood malignancies, including ALL, to prioritize those with the greatest activity for clinical evaluation. In this article, we review the results of >50 novel agents and combinations tested against the PPTP ALL xenografts, highlighting comparisons between PPTP results and clinical data where possible. C1 [Jones, L.; Carol, H.; Evans, K.; Richmond, J.; Lock, R. B.] UNSW, Lowy Canc Res Ctr, Childrens Canc Inst, Leukaemia Biol Program, POB 81, Sydney, NSW 2031, Australia. [Houghton, P. J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Mol Med, San Antonio, TX 78229 USA. [Smith, M. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Lock, RB (reprint author), UNSW, Lowy Canc Res Ctr, Childrens Canc Inst, Leukaemia Biol Program, POB 81, Sydney, NSW 2031, Australia. EM rlock@ccia.unsw.edu.au RI Lock, Richard/G-4253-2013 FU National Cancer Institute [NOI-CM-42216, NOI-CM-91001-03] FX This research was funded by grants from the National Cancer Institute (NOI-CM-42216 and NOI-CM-91001-03). We acknowledge the numerous researchers who provided technical assistance and data analysis over the course of this project. Children's Cancer Institute is affiliated with the University of New South Wales and The Sydney Children's Hospitals Network. NR 109 TC 1 Z9 1 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD NOV PY 2016 VL 30 IS 11 BP 2133 EP 2141 DI 10.1038/leu.2016.192 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA EC0PM UT WOS:000387803100003 PM 27416986 ER PT J AU Nicolae, A Xi, L Pham, TH Pham, TA Navarro, W Meeker, HG Pittaluga, S Jaffe, ES Raffeld, M AF Nicolae, A. Xi, L. Pham, T. H. Pham, T-A Navarro, W. Meeker, H. G. Pittaluga, S. Jaffe, E. S. Raffeld, M. TI Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas SO LEUKEMIA LA English DT Letter ID GAMMA-DELTA-T; STAT3 MUTATIONS; NK CELLS; LEUKEMIA C1 [Nicolae, A.; Pittaluga, S.; Jaffe, E. S.] NCI, Pathol Lab, Hematopathol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Xi, L.; Pham, T. H.; Pham, T-A; Navarro, W.; Meeker, H. G.; Raffeld, M.] NCI, Pathol Lab, Mol Diagnost Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Pathol Lab, Mol Diagnost Sect, Ctr Canc Res, Bethesda, MD 20892 USA. EM mraff@mail.nih.gov FU Intramural NIH HHS [Z01 BC011079-01] NR 13 TC 1 Z9 1 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD NOV PY 2016 VL 30 IS 11 BP 2245 EP 2247 DI 10.1038/leu.2016.178 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA EC0PM UT WOS:000387803100018 PM 27389054 ER PT J AU Kasper, N Peterson, KE Zhang, ZZ Ferguson, KK Sanchez, BN Cantoral, A Meeker, JD Tellez-Rojo, MM Pawlowski, CM Ettinger, AS AF Kasper, Nicole Peterson, Karen E. Zhang, Zhenzhen Ferguson, Kelly K. Sanchez, Brisa N. Cantoral, Alejandra Meeker, John D. Tellez-Rojo, Maria M. Pawlowski, Carolyn M. Ettinger, Adrienne S. TI Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women (vol 20, pg 1713, 2016) SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Correction C1 [Kasper, Nicole; Peterson, Karen E.; Zhang, Zhenzhen; Ettinger, Adrienne S.] Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Kasper, Nicole] Univ Colorado Anschutz Med Campus, Sect Nutr, Dept Pediat, 13123 E 16th Ave, Aurora, CO 80045 USA. [Peterson, Karen E.] Harvard Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. [Peterson, Karen E.] Univ Michigan, Ctr Human Growth & Dev, 300 N Ingalls St, Ann Arbor, MI 48104 USA. [Zhang, Zhenzhen; Sanchez, Brisa N.] Univ Michigan, Sch Publ Hlth, Dept Biostat, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Ferguson, Kelly K.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Ferguson, Kelly K.] NIEHS, Epidemiol Branch, US Dept HHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Cantoral, Alejandra; Tellez-Rojo, Maria M.] Natl Inst Publ Hlth, Ctr Res Nutr & Hlth, Univ 655 Colonia Santa Maria Ahuacatitlan, Cuernavaca 62100, Morelos, Mexico. [Pawlowski, Carolyn M.] CS Mott Childrens Hosp, Brandon Newborn Intens Care Unit, 1540 E Hosp Dr, Ann Arbor, MI 48109 USA. RP Peterson, KE (reprint author), Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA.; Peterson, KE (reprint author), Harvard Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.; Peterson, KE (reprint author), Univ Michigan, Ctr Human Growth & Dev, 300 N Ingalls St, Ann Arbor, MI 48104 USA. EM karenep@umich.edu NR 1 TC 0 Z9 0 U1 5 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD NOV PY 2016 VL 20 IS 11 BP 2411 EP 2411 DI 10.1007/s10995-016-2026-9 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EB8VV UT WOS:000387670300023 PM 27370266 ER PT J AU Aniweh, Y Gao, XH Gunalan, K Preiser, PR AF Aniweh, Yaw Gao, Xiaohong Gunalan, Karthigayan Preiser, Peter R. TI PfRH2b specific monoclonal antibodies inhibit merozoite invasion SO MOLECULAR MICROBIOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM MEROZOITES; ERYTHROCYTE-BINDING LIGAND; MALARIA PARASITE INVASION; YOELII ADHESIVE PROTEINS; COMPLEMENT RECEPTOR 1; HOST-CELL SELECTION; PHENOTYPIC VARIATION; GLYCOPHORIN-B; HOMOLOG; MECHANISM AB Erythrocyte invasion by merozoite is a multistep process involving multiple ligand-receptor interactions. The Plasmodium falciparum reticulocyte binding protein homologues (PfRHs) consists of five functional members. The differential expression of PfRHs has been linked to the utilization of different invasion pathways by the merozoites as well as a mechanism of immune evasion. PfRHs are expressed at the apical end of merozoite and form interactions with distinct red blood cell (RBC) surface receptors that are important for successful invasion. Here we show that PfRH2b undergoes processing before and during merozoite invasion. The different processed fragments bind to chymotrypsin sensitive RBC surface receptors. We also show that PfRH2b follows the merozoite tight junction during invasion. Monoclonal antibodies (mAbs) inhibit merozoites invasion by blocking tight junction formation. mAbs binding to PfRH2b block merozoites intracellular Ca2+ signal necessary for EBA175 surface expression. The data suggests that a conserved function of PfRHs, where their interaction with RBC surface receptors facilitated recruitment of EBA175 and other tight junction proteins necessary for merozoite invasion by modulating merozoite intracellular Ca2+ signals. C1 [Aniweh, Yaw; Gao, Xiaohong; Gunalan, Karthigayan; Preiser, Peter R.] Nanyang Technol Univ, Sch Biol Sci, Div Mol Genet & Cell Biol, Singapore 637551, Singapore. [Aniweh, Yaw] Univ Ghana, Coll Basic & Appl Sci, WACCBIP, POB LG 54, Legon, Ghana. [Gunalan, Karthigayan] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Preiser, PR (reprint author), Nanyang Technol Univ, Sch Biol Sci, Div Mol Genet & Cell Biol, Singapore 637551, Singapore. EM PRPreiser@ntu.edu.sg FU Singapore Ministry of Health's National Medical Research Council [NMRC/1308/2011]; Ministry of Education [RG 152-14] FX This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Individual Research Grant (NMRC/1308/2011) and Ministry of Education Tier 1 grant (RG 152-14). NR 76 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2016 VL 102 IS 3 BP 386 EP 404 DI 10.1111/mmi.13468 PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA EB9ZJ UT WOS:000387756800002 PM 27438226 ER PT J AU Serpeloni, M Jimenez-Ruiz, E Vidal, NM Kroeber, C Andenmatten, N Lemgruber, L Morking, P Pall, GS Meissner, M Avila, AR AF Serpeloni, Mariana Jimenez-Ruiz, Elena Vidal, Newton Medeiros Kroeber, Constanze Andenmatten, Nicole Lemgruber, Leandro Morking, Patricia Pall, Gurman S. Meissner, Markus Avila, Andrea R. TI UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii SO MOLECULAR MICROBIOLOGY LA English DT Article ID NUCLEAR EXPORT; TREX COMPLEX; BINDING PROTEIN; GENE-EXPRESSION; TRANSCRIPTION; RECRUITMENT; YEAST; MACHINERY; CELLS; TRYPANOSOMES AB Nucleo-cytoplasmic RNA export is an essential post-transcriptional step to control gene expression in eukaryotic cells and is poorly understood in apicomplexan parasites. With the exception of UAP56, a component of TREX (Transcription Export) complex, other components of mRNA export machinery are not well conserved in divergent supergroups. Here, we use Toxoplasma gondii as a model system to functionally characterize TgUAP56 and its potential interaction factors. We demonstrate that TgUAP56 is crucial for mRNA export and that functional interference leads to significant accumulation of mRNA in the nucleus. It was necessary to employ bioinformatics and phylogenetic analysis to identify orthologs related to mRNA export, which show a remarkable low level of conservation in T. gondii. We adapted a conditional Cas9/CRISPR system to carry out a genetic screen to verify if these factors were involved in mRNA export in T. gondii. Only the disruption of TgRRM_1330 caused accumulation of mRNA in the nucleus as found with TgUAP56. This protein is potentially a divergent partner of TgUAP56, and provides insight into a divergent mRNA export pathway in apicomplexans. C1 [Serpeloni, Mariana; Morking, Patricia; Avila, Andrea R.] Fiocruz MS, Inst Carlos Chagas, Curitiba, Parana, Brazil. [Serpeloni, Mariana] Univ Fed Parana, Dept Biol Celular & Mol, Curitiba, Parana, Brazil. [Serpeloni, Mariana; Jimenez-Ruiz, Elena; Kroeber, Constanze; Andenmatten, Nicole; Lemgruber, Leandro; Pall, Gurman S.; Meissner, Markus] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Wellcome Trust Ctr Mol Parasitol, Glasgow, Lanark, Scotland. [Vidal, Newton Medeiros] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Avila, AR (reprint author), Fiocruz MS, Inst Carlos Chagas, Curitiba, Parana, Brazil.; Meissner, M (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Wellcome Trust Ctr Mol Parasitol, Glasgow, Lanark, Scotland. EM markus.meissner@glasgow.ac.uk; aravila@fiocruz.br FU Programa Estrategico de Apoio a Pesquisa em Saude (PAPES/FIOCRUZ, Brazil) [407775/2012-9 - CNPq]; Fundacao Araucaria [145/2015]; CAPES Foundation, Ministry of Education of Brazil (CAPES, Brazil) [PDSE Fellowship] [9445-12-9]; National Counsel of Technological and Scientific Development (CNPq, Brazil) [PDE Fellowship] [249741/2013-0]; ERC-Starting grant [ERC-2012-StG309255-EndoTox]; Wellcome Trust [087582/Z/08/Z, 085349]; Intramural Research Program of the National Library of Medicine, National Institutes of Health; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; National Institutes of Health FX This work was supported by the Programa Estrategico de Apoio a Pesquisa em Saude (PAPES/FIOCRUZ, Brazil) [407775/2012-9 - CNPq]; Fundacao Araucaria [145/2015]; CAPES Foundation, Ministry of Education of Brazil (CAPES, Brazil) [PDSE Fellowship 9445-12-9]; National Counsel of Technological and Scientific Development (CNPq, Brazil) [PDE Fellowship 249741/2013-0]; This work was supported by an ERC-Starting grant (ERC-2012-StG309255-EndoTox) and the Wellcome Trust 087582/Z/08/Z Senior Fellowship for MM. The Wellcome Trust Centre for Molecular Parasitology is supported by core funding from the Wellcome Trust (085349)). This research was partially supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health. NMV's postdoctoral fellowship is funded by a partnership between Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and the National Institutes of Health. NR 76 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2016 VL 102 IS 4 BP 672 EP 689 DI 10.1111/mmi.13485 PG 18 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA EB9ZM UT WOS:000387757100008 PM 27542978 ER PT J AU Boeve, BF Dickson, DW Duda, JE Ferman, TJ Galasko, DR Galvin, JE Goldman, JG Growdon, JH Hurtig, HI Kaufer, DI Kantarci, K Leverenz, JB Lippa, CF Lopez, OL McKeith, IG Singleton, AB Taylor, A Tsuang, D Weintraub, D Zabetian, CP AF Boeve, Bradley F. Dickson, Dennis W. Duda, John E. Ferman, Tanis J. Galasko, Douglas R. Galvin, James E. Goldman, Jennifer G. Growdon, John H. Hurtig, Howard I. Kaufer, Daniel I. Kantarci, Kejal Leverenz, James B. Lippa, Carol F. Lopez, Oscar L. McKeith, Ian G. Singleton, Andrew B. Taylor, Angela Tsuang, Debby Weintraub, Daniel Zabetian, Cyrus P. TI Arguing against the proposed definition changes of PD SO MOVEMENT DISORDERS LA English DT Article DE Dementia with Lewy bodies; dementia; Parkinson's disease; parkinsonism ID PARKINSON-DISEASE DEMENTIA; LEWY BODIES; DIAGNOSIS; RISK; DLB; CONSORTIUM; APOE AB As members of the Lewy Body Dementia Association Scientific Advisory Council, we aim to address some of the issues raised in the article titled Time to Redefine PD? Introductory Statement of the MDS Task Force on the Definition of Parkinson's Disease. In particular, we suggest that the 1-year rule distinguishing Parkinson's disease dementia from dementia with Lewy bodies is worth maintaining because it serves an important purpose in clinical practice and clinical and basic science research and when helping the lay community understand the complexity of these different clinical phenotypes. Furthermore, we believe that adding an additional diagnostic label, PD (dementia with Lewy bodies subtype), will confuse rather than clarify the distinction between dementia with Lewy bodies and PD or PD dementia, and will not improve management or expedite therapeutic development. We present arguments supporting our contentions. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. C1 [Boeve, Bradley F.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55895 USA. [Dickson, Dennis W.] Mayo Clin, Jacksonville, FL 32224 USA. [Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Duda, John E.; Hurtig, Howard I.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Ferman, Tanis J.] Mayo Clin, Coll Med, Dept Psychiat & Psychol, Jacksonville, FL 32224 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Galvin, James E.] Florida Atlantic Univ, Marcus Neurosci Inst, Boca Raton, FL 33431 USA. [Goldman, Jennifer G.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Growdon, John H.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Kaufer, Daniel I.] Univ North Carolina Chapel Hill, Dept Neurol, Chapel Hill, NC USA. [Kantarci, Kejal] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN 55895 USA. [Leverenz, James B.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. [Lippa, Carol F.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [McKeith, Ian G.] Newcastle Univ, Inst Ageing, Newcastle Upon Tyne, Tyne & Wear, England. [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Taylor, Angela] Lewy Body Dementia Assoc, Lilburn, GA USA. [Tsuang, Debby] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Boeve, BF (reprint author), Mayo Clin, Dept Neurol, Rochester, MN 55895 USA. EM bboeve@mayo.edu FU Intramural NIH HHS [Z01 AG000932-01]; NIA NIH HHS [P50 AG005131, P50 AG005136] NR 24 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2016 VL 31 IS 11 BP 1619 EP 1622 DI 10.1002/mds.26721 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA EB5LK UT WOS:000387415700004 PM 27492190 ER PT J AU Albanese, A Bhatia, K DeLong, MR Fahn, S Fung, VSC Hallett, M Jankovic, J Jinnah, HA Mink, JW Teller, JK AF Albanese, Alberto Bhatia, Kailash DeLong, Mahlon R. Fahn, Stanley Fung, Victor S. C. Hallett, Mark Jankovic, Joseph Jinnah, H. A. Mink, Jonathan W. Teller, Jan K. TI "Complex" dystonia is not a category in the new 2013 consensus classification SO MOVEMENT DISORDERS LA English DT Letter C1 [Albanese, Alberto] Humanitas Res Hosp, Dept Neurol, Milan, Italy. [Bhatia, Kailash] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England. [DeLong, Mahlon R.; Jinnah, H. A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Fahn, Stanley] Columbia Univ, Dept Neurol, New York, NY USA. [Fung, Victor S. C.] Univ Sydney, Westmead Hosp, Dept Neurol, Movement Disorders Unit, Sydney, NSW, Australia. [Fung, Victor S. C.] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia. [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. [Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Jinnah, H. A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Jinnah, H. A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Mink, Jonathan W.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Teller, Jan K.] Dystonia Med Res Fdn, Chicago, IL USA. RP Albanese, A (reprint author), Humanitas Res Hosp, Dept Neurol, Milan, Italy. NR 2 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2016 VL 31 IS 11 BP 1758 EP 1759 DI 10.1002/mds.26764 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA EB5LK UT WOS:000387415700030 PM 27612445 ER PT J AU Khan, I Arany, PR AF Khan, Imran Arany, Praveen R. TI Photobiomodulation Therapy Promotes Expansion of Epithelial Colony Forming Units SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article DE colony forming units; laser; photobiomodulation; stem cells ID LEVEL LASER THERAPY; STEM-CELLS; PHOTOTHERAPY; MEDICINE AB Objective: This preliminary study examines the effects of low-dose light therapy, also called Photobiomodulation (PBM) therapy, on epithelial colony forming units (eCFUs) in epithelial cells from skin and mucosa to assess their potential to contribute to tissue regeneration. Also, preliminary comparison of basic PBM parameters such as wavelengths, light sources, and dose were evaluated in promoting eCFUs. Background Data: Regenerative medicine is at the brink of exploiting the tremendous potential offered by advances in stem cell biology. The two distinct aspects for utilization of stem cells, either resident (endogenous) or transplanted (exogenous), rely on cells amenable to expansion and being directed toward mature, functional tissues. Despite major progress in fundamental understanding of stem cell pluripotency, there remain fundamental challenges in applying these insights into clinical practice. Methods: PBM treatments with various devices, wavelengths, and doses were used on two epithelial cell lines and colony forming assays were performed. Results: This study noted a dose-dependent effect of 810 nm laser on increasing eCFUs, either in terms of size or numbers. Comparisons of different wavelengths and light sources noted better efficacy of collimated and coherent lasers compared to LEDs and broad-band light. Conclusions: PBM therapy promotes expansion of eCFUs that represent progenitors and stem cell populations capable of contributing to tissue repair and regeneration. Further exploration of the precise mechanisms would allow optimization of PBM clinical protocols to harness the regenerative potential of stem cells for wound healing and other clinical regenerative applications. C1 [Khan, Imran; Arany, Praveen R.] NIDCR, Cell Regulat & Control Unit, NIH, Bethesda, MD USA. [Arany, Praveen R.] SUNY Buffalo, Sch Dent Med, Oral Biol, 3435 Main St,B36A Foster Hall, Buffalo, NY 14214 USA. [Khan, Imran] NCI, NIH, Bethesda, MD 20892 USA. RP Arany, PR (reprint author), SUNY Buffalo, Sch Dent Med, Oral Biol, 3435 Main St,B36A Foster Hall, Buffalo, NY 14214 USA. EM prarany@buffalo.edu FU National Institutes of Health FX We thank Mr. Mel Boldt, QBMI, Inc., and Mr. Allan Gardiner, Photomed Tech, Inc., for providing the devices and the Gutkind laboratory, NIDCR, for providing NOKSI cells. This work was supported, in part, by the intramural research program of the National Institutes of Health. NR 17 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 EI 1557-8550 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD NOV PY 2016 VL 34 IS 11 SI SI BP 550 EP 555 DI 10.1089/pho.2015.4054 PG 6 WC Surgery SC Surgery GA EC4NW UT WOS:000388110300009 PM 27841965 ER PT J AU Doernberg, SN Peteet, JR Kim, SYH AF Doernberg, Samuel N. Peteet, John R. Kim, Scott Y. H. TI Capacity Evaluations of Psychiatric Patients Requesting Assisted Death in the Netherlands SO PSYCHOSOMATICS LA English DT Article DE assisted suicide; euthanasia; decision-making capacity; mental health; Netherlands ID MILD COGNITIVE IMPAIRMENT; DECISION-MAKING CAPACITY; MENTAL-RETARDATION; EUTHANASIA; CONSULTATION; COMPETENCE; DEMENTIA; CONSENT; DISEASE AB Background: Euthanasia or physician-assisted suicide (EAS) of psychiatric patients is legal in some countries but remains controversial. Objective: This study examined a frequently raised concern about the practice: how physicians address the issue of decision making capacity of persons requesting psychiatric EAS. Methods: A review of psychiatric EAS case summaries published by the Dutch Regional Euthanasia Review Committees. Directed content analysis using a capacity-specific 4 abilities model (understanding of facts, applying those facts to self, weighing/reasoning, and evidencing choice) was used to code texts discussing capacity. A total of 66 cases from 2011-2014 were reviewed. Results: In 55% (36 of 66) of cases, the capacity-speck discussion consisted of only global judgments of patients' capacity, even in patients with psychotic disorders. Further, 32% (21 of 66) of cases included evidentiary statements regarding capacity specific abilities; only 5 cases (8%) mentioned all 4 abilities. Physicians frequently stated that psychosis or depression did or did not affect capacity but provided little explanation regarding their judgments. Physicians in 8 cases (12%) disagreed about capacity; even when no explanation was given for the disagreement, the review committees generally accepted the judgment of the physician performing EAS. In one case, the physicians noted that not all capacity-specific abilities were intact but deemed the patient capable. Conclusion: Case summaries of psychiatric EAS in the Netherlands do not show that a high threshold of capacity is required for granting EAS. Although this may reflect limitations in documentation, it likely represents a practice that reflects the normative position of the review committees. C1 [Doernberg, Samuel N.; Kim, Scott Y. H.] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. [Peteet, John R.] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA. EM scott.kim@nih.gov FU Intramural Research Program of the National Institutes of Health Clinical Center FX This research was supported in part by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 37 TC 1 Z9 1 U1 10 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2016 VL 57 IS 6 BP 556 EP 565 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA EC3YY UT WOS:000388064200002 PM 27590345 ER PT J AU Epstein, SA Maurer, CW LaFaver, K Ameli, R Sinclair, S Hallett, M AF Epstein, Steven A. Maurer, Carine W. LaFaver, Kathrin Ameli, Rezvan Sinclair, Stephen Hallett, Mark TI Insights into Chronic Functional Movement Disorders: The Value of Qualitative Psychiatric Interviews SO PSYCHOSOMATICS LA English DT Article DE functional movement disorder; psychogenic movement disorder; conversion disorder; qualitative; interview ID PSYCHOGENIC NONEPILEPTIC SEIZURES; RANDOMIZED CLINICAL-TRIAL; CONVERSION DISORDER; SYMPTOMS; PSYCHOPATHOLOGY; PSYCHOTHERAPY; PROFILES; LIFE AB Background: Patients with functional movement disorders (FMDs) are commonly seen by neurologists and psychosomatic medicine psychiatrists. Research literature provides scant information about the subjective experiences of individuals with this often chronic problem. Objective: To enhance our understanding of psychologic aspects of FMDs by conducting qualitative interviews of research subjects. Methods: In total, 36 patients with FMDs were recruited from the Human Motor Control clinic at the National Institutes of Health. Each subject participated in a qualitative psychiatric interview and a structured diagnostic psychiatric interview. Results: Of our 36 subjects, 28 had current or lifetime psychiatric disorders in addition to conversion disorder and 22 had current disorders. Qualitative interviews provided rich information on patients' understanding of their illnesses and impaired cognitive processing of emotions. Conclusion: Our study supports the addition of open-ended qualitative interviews to delineate emotional dynamics and conceptual frameworks among such patients. Exploratory interviews generate enhanced understanding of such complex patients, above and beyond that gained by assessing DSM diagnostic comorbidities. C1 [Epstein, Steven A.] Georgetown Univ, Sch Med & MedStar Hlth, Dept Psychiat, Washington, DC USA. [Maurer, Carine W.; LaFaver, Kathrin; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [LaFaver, Kathrin] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA. [Ameli, Rezvan] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Sinclair, Stephen] NIMH, Sect Affect Cognit Neurosci, NIH, Bethesda, MD 20892 USA. RP Epstein, SA (reprint author), Georgetown Univ, Dept Psychiat, Sch Med, 2115 Wisconsin Ave NW, Washington, DC 20007 USA. EM epsteins@gunet.georgetown.edu FU Neurotoxin Institute; NIH, United States (from Brainsway); NIH Intramural Program; BCN Peptides, S.A.; Medtronics, Inc.; Parkinson Alliance; UniQure; Merz; Allergan FX Dr. Hallett serves as Chair of the Medical Advisory Board and may receive honoraria and funding for travel from the Neurotoxin Institute. He is involved in the development of Neuroglyphics for tremor assessment and has a collaboration with Portland State University to develop sensors to measure tremor. He may accrue revenue on US Patent #6,780,413 B2 (Issued: August 24, 2004): Immunotoxin (MAB-Ricin) for the treatment of focal movement disorders, and US Patent #7,407,478 (Issued: August 5, 2008): Coil for Magnetic Stimulation and methods for using the same (H-coil); in relation to the latter, he has received license fee payments from the NIH, United States (from Brainsway) for licensing of this patent. He is on the Editorial Board of 20 journals, and received royalties and honoraria from publishing from Cambridge University Press, Oxford University Press, John Wiley & Sons, Wolters Kluwer, Springer, and Elsevier. He has received honoraria for lecturing from Columbia University. Dr. Hallett's research at the NIH is largely supported by the NIH Intramural Program. Supplemental research funds have been granted by BCN Peptides, S.A. for treatment studies of blepharospasm; Medtronics, Inc., for studies of deep brain stimulation; Parkinson Alliance for studies of eye movements in Parkinson's disease; UniQure for a clinical trial of AAV2-GDNF for Parkinson Disease; Merz for treatment studies of focal hand dystonia; and Allergan for studies of methods to inject botulinum toxins. NR 27 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2016 VL 57 IS 6 BP 566 EP 575 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA EC3YY UT WOS:000388064200003 PM 27377316 ER PT J AU Shaw, RJ Pao, M Holland, JE DeMaso, DR AF Shaw, Richard J. Pao, Maryland Holland, Jennifer E. DeMaso, David R. TI Practice Patterns Revisited in Pediatric Psychosomatic Medicine SO PSYCHOSOMATICS LA English DT Article DE practice patterns; psychosomatic medicine; delivery of healthcare; children ID CONSULTATION-LIAISON PSYCHIATRY; SERVICES; SATISFACTION; CHILD AB Background: Given the heightened focus on the implementation of integrated care and population health management strategies,. there is a critical need for an analysis of pediatric psychosomatic medicine (PPM) programs. Objective: The goal was to survey current practice patterns in academic PPM programs in North America regarding their service composition, clinical consultation services, changes in service demand, funding, and major challenges so as to inform and support advocacy efforts on behalf of children in their need for responsive and effective PPM services. Results: With a 52.5% survey response rate from 122 child and adolescent psychiatry programs in North America, the demand for PPM services was reported to have significantly increased over the past decade as seen in the described expansion in clinical consultation services and the reported higher patient acuity, as well as new responsibilities in the care of youth with psychiatric illnesses who require boarding on medical inpatient services. Although an increased willingness by hospital administrators to fund PPM services was apparent, adequate funding remained a core issue. Although the value of research is well recognized, few programs are engaged in systematic PPM investigation. Conclusion: This survey provides evidence that the current field of PPM appears to be in an increasingly stronger position within academic medical centers. It is just as apparent today, as it has been in the past, that there is a need to communicate at local, regional, and national levels that PPM is an essential behavioral health service. C1 [Shaw, Richard J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA. [Holland, Jennifer E.; DeMaso, David R.] Boston Childrens Hosp, Dept Psychiat, 300 Longwood Ave, Boston, MA 02115 USA. RP DeMaso, DR (reprint author), Boston Childrens Hosp, Dept Psychiat, 300 Longwood Ave, Boston, MA 02115 USA. EM david.demaso@childrens.harvard.edu NR 25 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2016 VL 57 IS 6 BP 576 EP 585 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA EC3YY UT WOS:000388064200004 PM 27393387 ER PT J AU Ford, CL Mesfin, MS Gaines, TL Godette, DC AF Ford, Chandra L. Mesfin, Mulatu S. Gaines, Tommi L. Godette, Dionne C. TI How Underestimates of Need Contribute to Biased Conclusions SO SEXUALLY TRANSMITTED DISEASES LA English DT Letter ID COST-EFFECTIVENESS; HIV; OLDER; AGE; COMORBIDITIES; DISPARITIES; PREVALENCE; ADULTS; STATES C1 [Ford, Chandra L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Mesfin, Mulatu S.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Gaines, Tommi L.] Univ Calif San Diego, Dept Med, Div Global Publ Hlth, San Diego, CA 92103 USA. [Godette, Dionne C.] NIAAA, Div Epidemiol & Prevent Res, NIH, Rockville, MD 20852 USA. RP Ford, CL (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. FU NICHD NIH HHS [P2C HD041022]; NINR NIH HHS [R01 NR014789] NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV PY 2016 VL 43 IS 11 BP 696 EP 697 DI 10.1097/OLQ.0000000000000526 PG 2 WC Infectious Diseases SC Infectious Diseases GA EA6FS UT WOS:000386722600007 PM 27893599 ER PT J AU Phillips, LA Chamberland, PE Hekler, EB Abrams, J Eisenberg, MH AF Phillips, L. Alison Chamberland, Pier-Eric Hekler, Eric B. Abrams, Jessica Eisenberg, Miriam H. TI Intrinsic Rewards Predict Exercise via Behavioral Intentions for Initiators but via Habit Strength for Maintainers SO SPORT EXERCISE AND PERFORMANCE PSYCHOLOGY LA English DT Article DE intrinsic motivation; physical activity; habit; behavioral automaticity; behavioral maintenance ID SELF-DETERMINATION THEORY; PHYSICAL-ACTIVITY; SEDENTARY BEHAVIOR; HEALTH BEHAVIOR; PAST BEHAVIOR; OLDER-ADULTS; AUTOMATICITY; ADHERENCE; MAINTENANCE; MOTIVATION AB Regular exercise is thought to involve both reflective (e.g., intention) and automatic (e.g., habit) mechanisms. Intrinsic motivation is a reflective factor in exercise initiation; we propose that the experience of intrinsic exercise rewards (enjoyment; stress reduction) may come to function as a factor in exercise automaticity, or habit, and therefore of exercise maintenance. The current studies evaluate whether the relationship between intrinsic exercise rewards and exercise is mediated by behavioral intention for those newer to exercise (initiators) but mediated by behavioral habit strength for longer term exercisers (maintainers). In 2 studies, self-reported exercise stage (initiation vs. maintenance), intrinsic exercise rewards, intentions, and habit strength were measured at baseline. For outcomes, Study 1 concurrently assessed self-reported exercise in a large sample of U.S. college students (n = 463), and Study 2 prospectively assessed objective activity using accelerometers for 1 month in a U.S. college student and staff population (n = 114). Moderated mediation analyses resulted in support of the hypotheses: Habit strength significantly mediated the relationship between intrinsic rewards and exercise for maintainers in Studies 1 and 2 (unstandardized indirect effect = 7.66 and 0.04, respectively; p < .05) but less strongly for initiators in Study 1 and not at all for initiators in Study 2. Intentions mediated the relationship for initiators (unstandardized indirect effect = 0.94 and 0.02, respectively; p < .05) but not for maintainers, as expected. We concluded that intrinsic rewards may promote exercise repetition via intentional or reflective means in initiation but via habit strength in maintenance. Interventions that foster intrinsic exercise rewards may promote exercise maintenance through habitual action. C1 [Phillips, L. Alison] Iowa State Univ, Dept Psychol, W112 Lagomarcino Hall, Ames, IA 50011 USA. [Chamberland, Pier-Eric] Univ Quebec Trois Rivieres, Dept Psychol, Trois Rivieres, PQ, Canada. [Hekler, Eric B.] Arizona State Univ, Sch Nutr & Hlth Promot, Tempe, AZ 85287 USA. [Abrams, Jessica] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Eisenberg, Miriam H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Phillips, LA (reprint author), Iowa State Univ, Dept Psychol, W112 Lagomarcino Hall, Ames, IA 50011 USA. EM alisonp@iastate.edu OI Eisenberg, Miriam/0000-0002-7133-8805 FU Fondation Desjardins; Quebec Fund for Research on Society and Culture [FRQS: 176459] FX Participation of the second author was facilitated by doctoral awards from the Fondation Desjardins (2012-2013), the Quebec Fund for Research on Society and Culture (2013-2014) [FRQS: 176459] and the Social Sciences and Humanities Research Council of Canada (2014-2016) [CRSH: 752-2014-2291]. NR 73 TC 1 Z9 1 U1 13 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 2157-3905 EI 2157-3913 J9 SPORT EXERC PERFORM JI Sport Exerc. Perform. Psychol. PD NOV PY 2016 VL 5 IS 4 BP 352 EP 364 DI 10.1037/spy0000071 PG 13 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied SC Social Sciences - Other Topics; Psychology GA EC2PV UT WOS:000387966800006 ER PT J AU Feasel, MG Wohlfarth, A Nilles, JM Pang, SK Kristovich, RL Huestis, MA AF Feasel, Michael G. Wohlfarth, Ariane Nilles, John M. Pang, Shaokun Kristovich, Robert L. Huestis, Marilyn A. TI Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass Spectrometry SO AAPS JOURNAL LA English DT Article DE carfentanil; metabolism; norcarfentanil; opioid ID MAJOR METABOLITES; HUMAN URINE; FENTANYL; SUFENTANIL; ALFENTANIL; REMIFENTANIL; RECEPTORS; REVEALS; BINDING; PLASMA AB Carfentanil is an ultra-potent synthetic opioid. No human carfentanil metabolism data are available. Reportedly, Russian police forces used carfentanil and remifentanil to resolve a hostage situation in Moscow in 2002. This alleged use prompted interest in the pharmacology and toxicology of carfentanil in humans. Our study was conducted to identify human carfentanil metabolites and to assess carfentanil's metabolic clearance, which could contribute to its acute toxicity in humans. We used Simulations Plus's ADMET Predictor (TM) and Molecular Discovery's MetaSite (TM) to predict possible metabolite formation. Both programs gave similar results that were generally good but did not capture all metabolites seen in vitro. We incubated carfentanil with human hepatocytes for up to 1 h and analyzed samples on a Sciex 3200 QTRAP mass spectrometer to measure parent compound depletion and extrapolated that to represent intrinsic clearance. Pooled primary human hepatocytes were then incubated with carfentanil up to 6 h and analyzed for metabolite identification on a Sciex 5600+ TripleTOF (QTOF) high-resolution mass spectrometer. MS and MS/MS analyses elucidated the structures of the most abundant metabolites. Twelve metabolites were identified in total. N-Dealkylation and monohydroxylation of the piperidine ring were the dominant metabolic pathways. Two N-oxide metabolites and one glucuronide metabolite were observed. Surprisingly, ester hydrolysis was not a major metabolic pathway for carfentanil. While the human liver microsomal system demonstrated rapid clearance by CYP enzymes, the hepatocyte incubations showed much slower clearance, possibly providing some insight into the long duration of carfentanil's effects. C1 [Feasel, Michael G.; Kristovich, Robert L.] US Army, Edgewood Chem Biol Ctr, Res Dev & Engn Command, 5183 Blackhawk Rd, Gunpowder, MD 21010 USA. [Wohlfarth, Ariane; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Wohlfarth, Ariane] Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden. [Wohlfarth, Ariane] Linkoping Univ, Div Drug Res, Dept Med Hlth Sci, S-58185 Linkoping, Sweden. [Nilles, John M.] Excet Inc, Springfield, VA 22150 USA. [Pang, Shaokun] SCIEX Ltd, Foster City, CA 94404 USA. RP Feasel, MG (reprint author), US Army, Edgewood Chem Biol Ctr, Res Dev & Engn Command, 5183 Blackhawk Rd, Gunpowder, MD 21010 USA. EM michael.g.feasel.civ@mail.mil FU Defense Threat Reduction Agency (DTRA) [CB3281] FX This work was funded by the Defense Threat Reduction Agency (DTRA) under project number CB3281. NR 33 TC 0 Z9 0 U1 8 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD NOV PY 2016 VL 18 IS 6 BP 1489 EP 1499 DI 10.1208/s12248-016-9963-5 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EB7DU UT WOS:000387547000015 PM 27495118 ER PT J AU Venkatesh, KK Cantonwine, DE Ferguson, K Arjona, M Meeker, JD McElrath, TF AF Venkatesh, Kartik K. Cantonwine, David E. Ferguson, Kelly Arjona, Melanie Meeker, John D. McElrath, Thomas F. TI Inflammatory and oxidative stress markers associated with decreased cervical length in pregnancy SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE cervical length; cervix; inflammation; oxidative stress; pregnancy ID SPONTANEOUS PRETERM BIRTH; PLASMA-LEVELS; BIOMARKERS; CYTOKINES; DELIVERY; WOMEN; RISK; MIDGESTATION; MECHANISMS; INFECTION AB Problem: We assess whether inflammatory and oxidative stress markers early in pregnancy are associated with decreasing cervical length in the second trimester. Method of study: This is a secondary analysis of a nested case-control study of preterm birth conducted at a tertiary care center from 2006 to 2008. Plasma inflammatory markers included the following: interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP); and urine oxidative stress markers included the following: 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane, measured at two study visits (median 10 and 18 weeks of gestation). The primary outcome was cervical length<10th percentile measured between 16 and 24 weeks of gestation. Logistic regression models were used, adjusting for body mass index, age, race, parity, tobacco use, education, and gestational age at cervical length measurement. Results: Among 384 observed women, the 10th percentile cervical length was 3.0 cm. IL-10 levels were significantly higher among women with a cervical length<10th percentile compared to women with a longer cervix (mean IL-10: 95.5 vs 25.8 pg/mL, P < .01). Similarly, IL-6 levels were significantly higher among women with a cervical length <10th percentile (mean IL-6: 25.2 vs 4.3 pg/mL, P < .01). After controlling for potential confounders, an increase in IL-10 was significantly associated with a cervical length<10th percentile at both 10 and 18 weeks (adjusted odd ratio [AOR]: 1.74; 95% CI: 1.18-2.58; P = .005). At 18 weeks, only IL-6 was also significantly associated with a cervical length <10th percentile (AOR: 1.54; 95% CI: 1.11-2.13; P = .009). Other inflammatory biomarkers, including CRP, IL-1 beta, TNF-alpha, and oxidative stress biomarkers, 8-OHdG and 8-isoprostane, were not associated with cervical length. Conclusion: There was a significant association between the cytokines IL-6 and IL-10 early in pregnancy and decreased cervical length, suggesting an imbalance of immune regulation could impact cervical length. C1 [Venkatesh, Kartik K.] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. [Cantonwine, David E.; Arjona, Melanie; McElrath, Thomas F.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 75 Francis St, Boston, MA 02115 USA. [Ferguson, Kelly] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Venkatesh, KK (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM kvenkatesh@partners.org OI Ferguson, Kelly/0000-0001-8467-3250 FU National Institutes of Health (NIH/NIEHS) [R01ES018872] FX This study was funded by the following grant from the National Institutes of Health (R01ES018872 NIH/NIEHS). NR 38 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD NOV PY 2016 VL 76 IS 5 BP 376 EP 382 DI 10.1111/aji.12545 PG 7 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA EB4LG UT WOS:000387342700005 PM 27476489 ER PT J AU Gomez-Lopez, N Romero, R Arenas-Hernandez, M Ahn, H Panaitescu, B Vadillo-Ortega, F Sanchez-Torres, C Salisbury, KS Hassan, SS AF Gomez-Lopez, Nardhy Romero, Roberto Arenas-Hernandez, Marcia Ahn, Hyunyoung Panaitescu, Bogdan Vadillo-Ortega, Felipe Sanchez-Torres, Carmen Salisbury, Katherine S. Hassan, Sonia S. TI In vivo T-cell activation by a monoclonal alpha CD3 epsilon antibody induces preterm labor and birth SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE adaptive immunity; cytokines; maternal-fetal rejection; mouse; parturition; pregnancy; T cells ID MATERNAL-FETAL INTERFACE; CHRONIC CHORIOAMNIONITIS; PREGNANCY COMPLICATIONS; CLINICAL-SIGNIFICANCE; UNKNOWN ETIOLOGY; LYMPHOCYTES-T; INFLAMMATION; TERM; PARTURITION; REJECTION AB Problem: Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T--cell activation by a monoclonal alpha CD3 epsilon antibody induces preterm labor and birth. Method of study: Pregnant B6 mice were intraperitoneally injected with a monoclonal alpha CD3 epsilon antibody or its isotype control. The gestational age, the rates of preterm birth and pup mortality at birth as well as the fetal heart rate and umbilical artery pulsatility index were determined. Results: Injection of a monoclonal aCD3e antibody led to preterm labor/birth (alpha CD3 epsilon 83 +/- 16.97% [10/12] vs isotype 0% [0/8]) and increased the rate of pup mortality at birth (alpha CD3 epsilon 87.30 +/- 8.95% [77/85] vs isotype 4.91 +/- 4.34% [3/59]). In addition, injection of a monoclonal alpha CD3 epsilon antibody decreased the fetal heart rate and increased the umbilical artery pulsatility index when compared to the isotype control. Conclusion: In vivo T-cell activation by a monoclonal alpha CD3 epsilon antibody in late gestation induces preterm labor and birth. C1 [Gomez-Lopez, Nardhy; Romero, Roberto; Arenas-Hernandez, Marcia; Ahn, Hyunyoung; Panaitescu, Bogdan; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Gomez-Lopez, Nardhy; Romero, Roberto; Arenas-Hernandez, Marcia; Ahn, Hyunyoung; Panaitescu, Bogdan; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Gomez-Lopez, Nardhy; Arenas-Hernandez, Marcia; Ahn, Hyunyoung; Panaitescu, Bogdan; Salisbury, Katherine S.; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Gomez-Lopez, Nardhy] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, 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. [Romero, Roberto] Wayne State Univ, Ctr Mol Obstet & Genet, Detroit, MI USA. [Arenas-Hernandez, Marcia; Sanchez-Torres, Carmen] CINVESTAV, Dept Mol Biomed, Mexico City, DF, Mexico. [Vadillo-Ortega, Felipe] Univ Nacl Autonoma Mexico, Fac Med, Unit Vinculat, Inst Nacl Med Genom, Mexico City, DF, Mexico. RP Gomez-Lopez, N; Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA.; Gomez-Lopez, N (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.; Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Detroit, MI 48202 USA. EM nardhy.gomez-lopez@wayne.edu; romeror@mail.nih.gov RI Sanchez-Torres, Carmen/K-4713-2014 OI Sanchez-Torres, Carmen/0000-0003-0045-8233 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services (NICHD/NIH/DHHS); NICHD/NIH/DHHS [HHSN275201300006C]; Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health 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, U. S. Department of Health and Human Services (NICHD/NIH/DHHS), and, in part, with federal funds from the NICHD/NIH/DHHS under Contract No. HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health. We thank Tara N. Mial for her critical readings of the manuscript. NR 48 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD NOV PY 2016 VL 76 IS 5 BP 386 EP 390 DI 10.1111/aji.12562 PG 5 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA EB4LG UT WOS:000387342700007 PM 27658719 ER PT J AU Otani, T Al-Issa, A Pourmorteza, A McVeigh, ER Wada, S Ashikaga, H AF Otani, Tomohiro Al-Issa, Abdullah Pourmorteza, Amir McVeigh, Elliot R. Wada, Shigeo Ashikaga, Hiroshi TI A Computational Framework for Personalized Blood Flow Analysis in the Human Left Atrium SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Image-based simulation; Computed tomography; Computational fluid dynamics; Cardiac mechanics; Left atrium ID TEMPORAL RELATIONSHIP; APPENDAGE MORPHOLOGY; ISCHEMIC-STROKE; SINUS RHYTHM; FIBRILLATION; HEART; RISK; EVENTS; DIAMETER; DISEASE AB Atrial fibrillation (AF), the most common human arrhythmia, is a marker of an increased risk of embolic stroke. However, recent studies suggest that AF may not be mechanistically responsible for the stroke events. An alternative explanation for the mechanism of intracardiac thrombosis and stroke in patients with AF is structural remodeling of the left atrium (LA). Nevertheless, a mechanistic link between LA structural remodeling and intracardiac thrombosis is unclear, because there is no clinically feasible methodology to evaluate the complex relationship between these two phenomena in individual patients. Computational fluid dynamics (CFD) is a powerful tool that could potentially link LA structural remodeling and intracardiac thrombosis in individual patients by evaluating the patient-specific LA blood flow characteristics. However, the lack of knowledge of the material and mechanical properties of the heart wall in specific patients makes it challenging to solve the complexity of fluid-structure interaction. In this study, our aim was to develop a clinically feasible methodology to perform personalized blood flow analysis within the heart. We propose an alternative computational approach to perform personalized blood flow analysis by providing the three-dimensional LA endocardial surface motion estimated from patient-specific cardiac CT images. In two patients (case 1 and 2), a four-dimensional displacement vector field was estimated using nonrigid registration. The LA blood outflow across the mitral valve (MV) was calculated from the LV volume, and the flow field within the LA was derived from the incompressible Navier-Stokes equation. The CFD results successfully captured characteristic features of LA blood flow observed clinically by transesophageal echocardiogram. The LA global flow characteristics and vortex structures also agreed well with previous reports. The time course of LAA emptying was similar in both cases, despite the substantial difference in the LA structure and function. We conclude that our CT-based, personalized LA blood flow analysis is a clinically feasible methodology that can be used to improve our understanding of the mechanism of intracardiac thrombosis and stroke in individual patients with LA structural remodeling. C1 [Otani, Tomohiro; Al-Issa, Abdullah; Ashikaga, Hiroshi] Johns Hopkins Univ, Div Cardiol, Sch Med, Cardiac Arrhythmia Serv, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. [Pourmorteza, Amir; McVeigh, Elliot R.; Ashikaga, Hiroshi] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Otani, Tomohiro; Wada, Shigeo] Osaka Univ, Dept Mech Sci & Bioengn, Grad Sch Engn Sci, Osaka, Japan. [Pourmorteza, Amir] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA. [McVeigh, Elliot R.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [McVeigh, Elliot R.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [McVeigh, Elliot R.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Ashikaga, H (reprint author), Johns Hopkins Univ, Div Cardiol, Sch Med, Cardiac Arrhythmia Serv, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. EM hashika1@jhmi.edu FU Japan Society for the Promotion of Science (JSPS) [A2616220]; Magic That Matters Fund for Cardiovascular Research; Zegar Family Foundation FX The authors thank Satoshi Ii for valuable input as to the CFD methodology. The authors also thank Yuko Inoue and Susumu Tao for clinical input. This work was supported by research grants from the Japan Society for the Promotion of Science (JSPS) (Research Fellowship for Young Scientist A2616220, to Otani), Magic That Matters Fund for Cardiovascular Research (to Ashikaga) and Zegar Family Foundation (to Ashikaga). NR 34 TC 0 Z9 0 U1 9 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2016 VL 44 IS 11 BP 3284 EP 3294 DI 10.1007/s10439-016-1590-x PG 11 WC Engineering, Biomedical SC Engineering GA EB4OQ UT WOS:000387352000011 PM 26968855 ER PT J AU Sabayan, B van Buchem, MA Sigurdsson, S Zhang, Q Meirelles, O Harris, TB Gudnason, V Arai, AE Launer, LJ AF Sabayan, Behnam van Buchem, Mark A. Sigurdsson, Sigurdur Zhang, Qian Meirelles, Osorio Harris, Tamara B. Gudnason, Vilmundur Arai, Andrew E. Launer, Lenore J. TI Cardiac and Carotid Markers Link With Accelerated Brain Atrophy The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik) SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE brain; brain natriuretic peptide; carotid stenosis; gray matter; white matter ID VASCULAR COGNITIVE IMPAIRMENT; CARDIOVASCULAR RISK-FACTORS; CEREBRAL AUTOREGULATION; ALZHEIMERS-DISEASE; BLOOD-FLOW; FOLLOW-UP; PROGRESSION; HEART; ATHEROSCLEROSIS; DECLINE AB Objective-Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. Approach and Results-In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [ CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Conclusions-Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. C1 [Sabayan, Behnam; van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RA Leiden, Netherlands. [Sabayan, Behnam] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands. [van Buchem, Mark A.] Leiden Univ, Leiden Inst Brain & Cognit, NL-2300 RA Leiden, Netherlands. [Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland. [Zhang, Qian; Meirelles, Osorio; Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, LEPS, IRP, NIH, 7201 Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU National Heart, Lung, and Blood Institute Intramural Research Program [Z01 HL004607-08]; National Institute on Aging Intramural Research Program [N01-AG-12100]; Icelandic Heart Association; Icelandic Parliament; Medstar Research Institute [2003-145]; Internationale Stichting Alzheimer Onderzoek FX This study was funded by the National Heart, Lung, and Blood Institute Intramural Research Program (Z01 HL004607-08 CE), the National Institute on Aging Intramural Research Program (N01-AG-12100), Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study was approved by the Icelandic National Bioethics Committee (VSN: 00-063) and the Medstar Research Institute (project 2003-145). Behnam Sabayan is partly supported by a grant from Internationale Stichting Alzheimer Onderzoek. NR 34 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2016 VL 36 IS 11 BP 2246 EP + DI 10.1161/ATVBAHA.116.308018 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA EB0RC UT WOS:000387051500020 PM 27609370 ER PT J AU Tooze, JA Freedman, LS Carroll, RJ Midthune, D Kipnis, V AF Tooze, Janet A. Freedman, Laurence S. Carroll, Raymond J. Midthune, Douglas Kipnis, Victor TI The impact of stratification by implausible energy reporting status on estimates of diet-health relationships SO BIOMETRICAL JOURNAL LA English DT Article DE Attenuation; Bias (epidemiology); Food frequency questionnaire; Models; Statistical; Underreporting ID FUNDAMENTAL PRINCIPLES; RECOVERY BIOMARKERS; MEASUREMENT ERROR; WEIGHT STATUS; CHILDREN; ADULTS; ASSOCIATIONS; INSTRUMENTS; PHYSIOLOGY; CUTOFF AB The food frequency questionnaire (FFQ) is known to be prone to measurement error. Researchers have suggested excluding implausible energy reporters (IERs) of FFQ total energy when examining the relationship between a health outcome and FFQ-reported intake to obtain less biased estimates of the effect of the error-prone measure of exposure; however, the statistical properties of stratifying by IER status have not been studied. Under certain assumptions, including nondifferential error, we show that when stratifying by IER status, the attenuation of the estimated relative risk in the stratified models will be either greater or less in both strata (implausible and plausible reporters) than for the nonstratified model, contrary to the common belief that the attenuation will be less among plausible reporters and greater among IERs. Whether there is more or less attenuation depends on the pairwise correlations between true exposure, observed exposure, and the stratification variable. Thus exclusion of IERs is inadvisable but stratification by IER status can sometimes help. We also address the case of differential error. Examples from the Observing Protein and Energy Nutrition Study and simulations illustrate these results. C1 [Tooze, Janet A.] Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. [Freedman, Laurence S.] Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Midthune, Douglas; Kipnis, Victor] NCI, Bethesda, MD 20892 USA. RP Tooze, JA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jtooze@wakehealth.edu FU National Cancer Institute at the National Institutes of Health [P30 CA012197, U01 CA057030] FX This work was supported by the National Cancer Institute at the National Institutes of Health (P30 CA012197 for J.A.T. and U01 CA057030 for R.J.C.). NR 31 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD NOV PY 2016 VL 58 IS 6 BP 1538 EP 1551 DI 10.1002/bimj.201500201 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA EB1WX UT WOS:000387148100015 PM 27550787 ER PT J AU Applebaum, AJ Bevans, M Son, T Evans, K Hernandez, M Giralt, S DuHamel, K AF Applebaum, A. J. Bevans, M. Son, T. Evans, K. Hernandez, M. Giralt, S. DuHamel, K. TI A scoping review of caregiver burden during allogeneic HSCT: lessons learned and future directions SO BONE MARROW TRANSPLANTATION LA English DT Review ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; QUALITY-OF-LIFE; FAMILY CAREGIVERS; CANCER-PATIENTS; INFORMAL CAREGIVERS; PANCYTOPENIC PHASE; BLOOD; EXPERIENCE; NEEDS AB The extant literature documents burden among caregivers of patients undergoing a hematopoietic stem cell transplantation (HSCT), but little is known about the burden of caregivers of patients receiving outpatient and homebound HSCTs. This scoping study sought to evaluate what is known about the burden of the increasing number of adult caregivers of patients receiving outpatient HSCTs and to create practice guidelines for how to best support this vulnerable group. Online databases were searched for studies that evaluated caregiver burden in adult caregivers of HSCT patients since 2010 (the publication date of the most recent systematic review on HSCT caregiver burden). Of the 1271 articles retrieved, 12 met the inclusion criteria, though none specifically examined outpatient or homebound caregivers. Overall, studies corroborated existing literature on the experience of significant burden among HSCT caregivers across the HSCT trajectory, and highlighted the emotional costs of outpatient transplants on caregivers and the need to identify caregivers at high risk for burden early in the transplant process. Future studies of outpatient caregivers should include a comprehensive assessment of burden and seek to identify points along the transplant trajectory at which caregivers are at particular risk for negative outcomes and when intervention is most appropriate. C1 [Applebaum, A. J.; Son, T.; Evans, K.; Hernandez, M.; Giralt, S.; DuHamel, K.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Bevans, M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Applebaum, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Caregivers Clin, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM applebaa@mskcc.org NR 49 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2016 VL 51 IS 11 BP 1416 EP 1422 DI 10.1038/bmt.2016.164 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA EB3DW UT WOS:000387243700003 PM 27295270 ER PT J AU Bilic, E Delimar, V Desnica, L Pulanic, D Bilic, E Bakovic, M Curtis, LM Seiwerth, RS Stipetic, MM Ceovic, R Pulanic, TK Aleric, I Milos, O Vrhovac, R Nemet, D Pavletic, SZ AF Bilic, E. Delimar, V. Desnica, L. Pulanic, D. Bilic, E. Bakovic, M. Curtis, L. M. Seiwerth, R. S. Stipetic, M. M. Ceovic, R. Pulanic, T. K. Aleric, I. Milos, O. Vrhovac, R. Nemet, D. Pavletic, S. Z. TI High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD SO BONE MARROW TRANSPLANTATION LA English DT Letter ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; INDUCED PERIPHERAL NEUROPATHY; STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; CLINICAL-TRIALS; DIAGNOSIS; CRITERIA C1 [Bilic, E.; Delimar, V.; Milos, O.] Univ Hosp Ctr Zagreb, Dept Neurol, Zagreb, Croatia. [Bilic, E.; Pulanic, D.; Bilic, E.; Ceovic, R.; Vrhovac, R.; Nemet, D.] Univ Zagreb, Sch Med, Zagreb, Croatia. [Desnica, L.; Pulanic, D.; Seiwerth, R. S.; Vrhovac, R.; Nemet, D.] Univ Hosp Ctr Zagreb, Div Haematol, Dept Internal Med, Zagreb, Croatia. [Pulanic, D.; Aleric, I.; Nemet, D.] JJ Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia. [Bilic, E.] Univ Hosp Ctr Zagreb, Dept Pediat Haematol & Oncol, Zagreb, Croatia. [Bakovic, M.] Univ Zagreb, Sch Med, Inst Forens Med & Criminalist, Zagreb, Croatia. [Curtis, L. M.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stipetic, M. M.] Univ Zagreb, Sch Dent Med, Zagreb, Croatia. [Stipetic, M. M.] Univ Hosp Ctr Zagreb, Univ Dent Clin, Clin Dept Oral Med, Zagreb, Croatia. [Ceovic, R.] Univ Hosp Ctr Zagreb, Dept Dermatol & Venerol, Zagreb, Croatia. [Pulanic, T. K.] Community Hlth Ctr Zagreb East, Gynecol Dept, Zagreb, Croatia. [Aleric, I.] Univ Hosp Ctr Zagreb, Dept Pulmol, Zagreb, Croatia. RP Bilic, E (reprint author), Univ Hosp Ctr Zagreb, Dept Neurol, Zagreb, Croatia.; Bilic, E (reprint author), Univ Zagreb, Sch Med, Zagreb, Croatia. EM ervina.bilic@mef.hr NR 15 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2016 VL 51 IS 11 BP 1513 EP 1517 DI 10.1038/bmt.2016.158 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA EB3DW UT WOS:000387243700020 PM 27272447 ER PT J AU Karamzadeh, N Amyot, F Kenney, K Anderson, A Chowdhry, F Dashtestani, H Wassermann, EM Chernomordik, V Boccara, C Wegman, E Diaz-Arrastia, R Gandjbakhche, AH AF Karamzadeh, Nader Amyot, Franck Kenney, Kimbra Anderson, Afrouz Chowdhry, Fatima Dashtestani, Hadis Wassermann, Eric M. Chernomordik, Victor Boccara, Claude Wegman, Edward Diaz-Arrastia, Ramon Gandjbakhche, Amir H. TI A machine learning approach to identify functional biomarkers in human prefrontal cortex for individuals with traumatic brain injury using functional near-infrared spectroscopy SO BRAIN AND BEHAVIOR LA English DT Article DE classification; feature selection; machine learning; near-infrared spectroscopy; traumatic brain injury; time series feature extraction; wrapper method ID WORKING-MEMORY; COMPUTER-INTERFACE; MOTOR IMAGERY; CEREBRAL HEMODYNAMICS; BLOOD-VOLUME; CLASSIFICATION; COMPLEXITY; OSCILLATIONS; FREQUENCY; FMRI AB BackgroundWe have explored the potential prefrontal hemodynamic biomarkers to characterize subjects with Traumatic Brain Injury (TBI) by employing the multivariate machine learning approach and introducing a novel task-related hemodynamic response detection followed by a heuristic search for optimum set of hemodynamic features. To achieve this goal, the hemodynamic response from a group of 31 healthy controls and 30 chronic TBI subjects were recorded as they performed a complexity task. MethodsTo determine the optimum hemodynamic features, we considered 11 features and their combinations in characterizing TBI subjects. We investigated the significance of the features by utilizing a machine learning classification algorithm to score all the possible combinations of features according to their predictive power. Results and ConclusionsThe identified optimum feature elements resulted in classification accuracy, sensitivity, and specificity of 85%, 85%, and 84%, respectively. Classification improvement was achieved for TBI subject classification through feature combination. It signified the major advantage of the multivariate analysis over the commonly used univariate analysis suggesting that the features that are individually irrelevant in characterizing the data may become relevant when used in combination. We also conducted a spatio-temporal classification to identify regions within the prefrontal cortex (PFC) that contribute in distinguishing between TBI and healthy subjects. As expected, Brodmann areas (BA) 10 within the PFC were isolated as the region that healthy subjects (unlike subjects with TBI), showed major hemodynamic activity in response to the High Complexity task. Overall, our results indicate that identified temporal and spatio-temporal features from PFC's hemodynamic activity are promising biomarkers in classifying subjects with TBI. C1 [Karamzadeh, Nader; Wegman, Edward] George Mason Univ, Dept Computat & Data Sci, Fairfax, VA 22030 USA. [Karamzadeh, Nader; Anderson, Afrouz; Chowdhry, Fatima; Dashtestani, Hadis; Chernomordik, Victor; Gandjbakhche, Amir H.] NICHHD, NIH, Bethesda, MD 20892 USA. [Amyot, Franck; Kenney, Kimbra; Diaz-Arrastia, Ramon] Uniformed Serv, Dept Neurol, Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Wassermann, Eric M.] NIMH, NIH, Bethesda, MD 20892 USA. [Boccara, Claude] Inst Langevin ESPCI ParisTech, Paris, France. RP Gandjbakhche, AH (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM amir@helix.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorder and Stroke; Department of Defense in Center for Neuroscience and Regenerative Medicine FX We acknowledge the funding of the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorder and Stroke, and Department of Defense in Center for Neuroscience and Regenerative Medicine. NR 59 TC 0 Z9 0 U1 10 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD NOV PY 2016 VL 6 IS 11 DI 10.1002/brb3.541 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA EB7RJ UT WOS:000387587500004 ER PT J AU Marcus, PM Pashayan, N Church, TR Doria-Rose, VP Gould, MK Hubbard, RA Marrone, M Miglioretti, DL Pharoah, PD Pinsky, PF Rendle, KA Robbins, HA Roberts, MC Rolland, B Schiffman, M Tiro, JA Zauber, AG Winn, DM Khoury, MJ AF Marcus, Pamela M. Pashayan, Nora Church, Timothy R. Doria-Rose, V. Paul Gould, Michael K. Hubbard, Rebecca A. Marrone, Michael Miglioretti, Diana L. Pharoah, Paul D. Pinsky, Paul F. Rendle, Katherine A. Robbins, Hilary A. Roberts, Megan C. Rolland, Betsy Schiffman, Mark Tiro, Jasmin A. Zauber, Ann G. Winn, Deborah M. Khoury, Muin J. TI Population-Based Precision Cancer Screening: A Symposium on Evidence, Epidemiology, and Next Steps SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID PROSTATE-CANCER; COLORECTAL-CANCER; LUNG-CANCER; SUSCEPTIBILITY LOCI; CERVICAL-CANCER; BREAST-CANCER; HUMAN-PAPILLOMAVIRUS; COST-EFFECTIVENESS; UNITED-STATES; TASK-FORCE AB Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled "Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps". The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial. (C) 2016 AACR C1 [Marcus, Pamela M.; Doria-Rose, V. Paul; Rendle, Katherine A.; Roberts, Megan C.; Winn, Deborah M.; Khoury, Muin J.] NCI, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA. [Pashayan, Nora] UCL, Dept Appl Hlth Res, London, England. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [Gould, Michael K.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Hubbard, Rebecca A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Marrone, Michael; Robbins, Hilary A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Miglioretti, Diana L.] Univ Calif Davis, Dept Publ Hlth Sci, Sacramento, CA 95817 USA. [Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Pharoah, Paul D.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pinsky, Paul F.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Rolland, Betsy] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Tiro, Jasmin A.] UT Southwestern Med Ctr, Dept Clin Sci, Dallas, TX USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Marcus, PM (reprint author), NCI, 9609 Med Ctr Dr,Room 4E-608, Bethesda, MD 20892 USA. EM marcusp@mail.nih.gov FU Cancer Research UK [10119, 10124]; Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA008748, P01 CA154292, T32 CA009314] NR 46 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2016 VL 25 IS 11 BP 1449 EP 1455 DI 10.1158/1055-9965.EPI-16-0555 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EB7AI UT WOS:000387537000001 PM 27507769 ER PT J AU Loftfield, E Vogtmann, E Sampson, JN Moore, SC Nelson, H Knight, R Chia, N Sinha, R AF Loftfield, Erikka Vogtmann, Emily Sampson, Joshua N. Moore, Steven C. Nelson, Heidi Knight, Rob Chia, Nicholas Sinha, Rashmi TI Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER RISK; SERUM METABOLITES; PROSPECTIVE COHORT; GUT MICROBIOME; DISEASE; PROFILES; FECES; DIET; ASSOCIATION; PERFORMANCE AB Background: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures. Methods: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated (i) technical reproducibility within sample replicates, (ii) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and (iii) concordance of metabolite measures with the putative "goldstandard," day 0 samples without solution. Results: Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC > 0.87) but not FIT (median ICC = 0.52). Similarly, Spearman correlation coefficients (r(s)) estimating metabolite concordance with the "gold standard" were higher for 95% ethanol (median r(s) = 0.82) and FOBT (median r(s) = 0.70) than for FIT (median r(s) = 0.40). Conclusions: Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the "gold standard" is highest with 95% ethanol and acceptable with FOBT. Impact: Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics. (C) 2016 AACR. C1 [Loftfield, Erikka; Vogtmann, Emily; Moore, Steven C.; Sinha, Rashmi] NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Sampson, Joshua N.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Nelson, Heidi; Chia, Nicholas] Mayo Clin, Ctr Individualized Med, Microbiome Program, Rochester, MN USA. [Nelson, Heidi; Chia, Nicholas] Mayo Clin, Dept Surg, Rochester, MN USA. [Knight, Rob] Mayo Clin, Hlth Sci Res, Rochester, MN USA. [Knight, Rob] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Chia, Nicholas] Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92103 USA. RP Loftfield, E (reprint author), NCI, 9609 Med Ctr Dr MSC 9768, Bethesda, MD 20892 USA. EM erikka.loftfield@nih.gov RI Moore, Steven/D-8760-2016 OI Moore, Steven/0000-0002-8169-1661 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA179243] NR 44 TC 0 Z9 0 U1 13 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2016 VL 25 IS 11 BP 1483 EP 1490 DI 10.1158/1055-9965.EPI-16-0409 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EB7AI UT WOS:000387537000005 PM 27543620 ER PT J AU Sim, GC Liu, CW Wang, E Liu, H Creasy, C Dai, ZM Overwijk, W Roszik, J Marincola, F Hwu, P Grimm, E Radvanyi, L AF Sim, Geok Choo Liu, Chengwen Wang, Ena Liu, Hui Creasy, Caitlin Dai, Zhimin Overwijk, WillemW. Roszik, Jason Marincola, Francesco Hwu, Patrick Grimm, Elizabeth Radvanyi, Laszlo TI IL2 Variant Circumvents ICOS+ Regulatory T-cell Expansion and Promotes NK Cell Activation SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; METASTATIC MELANOMA; NATURAL-KILLER; CYTOKINE SECRETION; IMMUNE SUPPRESSION; MONONUCLEAR-CELLS; CANCER-PATIENTS; PLASMID DNA; HUMAN IL-2; RECEPTOR AB Clinical responses to high-dose IL2 therapy are limited due to selective expansion of CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Treg), especially ICOS+ Tregs, rather than natural killer (NK) cells and effector T cells. These ICOS+ Tregs are highly suppressive and constitutively express high levels of IL2Ra (CD25) and CD39. Here, we characterized the effect of a mutant form of IL2 (F42K), which preferentially binds to the lower affinity IL2Rb gamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets. Unlike wild-type (WT) IL2, F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs in peripheral blood mononuclear cells (PBMC) from healthy controls and melanoma patients. Instead, it promoted the expansion of CD16(+)CD56(+) NK cells and CD56(hi)CD16(-) NK cell subsets in both short-and long-term cultures, with enhanced Bcl-2 expression. Stimulation of PBMCs with F42K induced expression of more NK cell activation molecules, such as NK-p30, NKp44, DNAM-1, NKG2D, 4-1BB/ CD137, and Tim-3, than WT IL2. F42K induced greater upregulation of TRAIL, and NK-mediated cytolytic activity was increased against both autologous and HLA-mismatched melanoma cells compared with WT IL2. Gene expression analysis revealed distinct gene expression profiles stimulated by F42K, WT IL2, and IL15. F42K therapy in vivo also induced a dramatic reduction in the expansion of ICOS(+)Tregs, promoted NK cell expansion, and inhibited melanoma tumor growth more efficiently than WT IL2 and more effectively than anti-CTLA-4. Our findings suggest that F42K could be a potential substitute for WT IL2 as a cytokine therapy for cancer. (C) 2016 AACR. C1 [Sim, Geok Choo; Liu, Chengwen; Creasy, Caitlin; Dai, Zhimin; Overwijk, WillemW.; Roszik, Jason; Hwu, Patrick; Grimm, Elizabeth; Radvanyi, Laszlo] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Sim, Geok Choo; Radvanyi, Laszlo] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA. [Wang, Ena; Marincola, Francesco] Sidra Med & Res Ctr, Div Translat Med, Doha, Qatar. [Liu, Hui] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Dai, Zhimin] EMD Serono, 45A Middlesex Turnpike, Billerica, MA 01821 USA. [Sim, Geok Choo] MerckKGaA, Frankfurter Str 250, D-64293 Darmstadt, Germany. RP Sim, GC (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA.; Radvanyi, L (reprint author), EMD Serono, 45A Middlesex Turnpike, Rockland, MA 02370 USA. EM gcsim1@yahoo.co.uk; laszlo.radvanyi@emdserono.com FU NCI NIH HHS [P30 CA016672] NR 48 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD NOV PY 2016 VL 4 IS 11 BP 983 EP 994 DI 10.1158/2326-6066.CIR-15-0195 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA EB6ZH UT WOS:000387533800010 PM 27697858 ER PT J AU Zhang, P Zhuang, RQ Guo, ZD Su, XH Chen, XY Zhang, XZ AF Zhang, Pu Zhuang, Rongqiang Guo, Zhide Su, Xinhui Chen, Xiaoyuan Zhang, Xianzhong TI A Highly Efficient Copper-Mediated Radioiodination Approach Using Aryl Boronic Acids SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE copper catalysts; molecular imaging; radiochemistry; radioiodination; radiopharmaceuticals ID CHLORAMINE-T; PHENYLBORONIC ACIDS; CUPRIC ACETATE; PHARMACOKINETICS; ORGANOBORANES; IODINATION; ARYLATION; THERAPY; OXIDANT AB A convenient and quantitative radioiodination method by copper-mediated cross-coupling of aryl boronic acids was developed. The mild labeling conditions, ready availability of the boronic acid substrate, simple operation, broad functional group tolerance and excellent radiochemical yield (RCY) make this a practical strategy for radioiodine labeling without further purification. C1 [Zhang, Pu; Zhuang, Rongqiang; Guo, Zhide; Zhang, Xianzhong] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Su, Xinhui] Xiamen Univ, Zhongshan Hosp, Xiamen 361004, Peoples R China. RP Zhang, XZ (reprint author), Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; zhangxzh@xmu.edu.cn RI Zhang, Xianzhong/A-7754-2012 OI Zhang, Xianzhong/0000-0002-1001-1884 FU National Key Basic Research Program of China [2014CB744503]; National Natural Science Foundation of China [21271030, 81471707]; Fundamental Research Funds for the Central Universities [20720150063, 2013SH009] FX This study was financially supported by the National Key Basic Research Program of China (2014CB744503) and the National Natural Science Foundation of China (21271030, 81471707) and partially by the Fundamental Research Funds for the Central Universities (20720150063, 2013SH009). NR 36 TC 1 Z9 1 U1 6 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PD NOV PY 2016 VL 22 IS 47 BP 16782 EP 16785 DI 10.1002/chem.201604105 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA EB1UF UT WOS:000387140200010 PM 27730680 ER PT J AU Schantz, MM Powers, CD Schleicher, RL Betz, JM Wise, SA AF Schantz, Michele M. Powers, Carissa D. Schleicher, Rosemary L. Betz, Joseph M. Wise, Stephen A. TI Interlaboratory analytical comparison of fatty acid concentrations in serum or plasma SO CLINICA CHIMICA ACTA LA English DT Article DE Fatty acids; Serum; Plasma; Interlaboratory study; SRM 2378; SRM 1950 ID QUALITY-ASSURANCE PROGRAM; MEASUREMENT PERFORMANCE; ASSOCIATION; ADULTS; TIME AB Background: There are a large number of clinical studies focusing on the measurement of individual fatty acids in serum or plasma; however, few studies have focused on the interlaboratory comparisons of these measurements. The National Institutes of Standards and Technology (NIST), in collaboration with the National Institutes of Health Office of Dietary Supplements (NIH-ODS) and the Centers for Disease Control and Prevention (CDC), has initiated a quality assurance program for assessing and improving the comparability of individual fatty acid measurements in serum and plasma. Methods: This is a performance-based study so participants are encouraged to use their laboratory's methods for the quantification of the individual fatty acids that they typically measure in the unknown serum or plasma samples along with a control material. The control materials used to date are SRM 1950 Metabolites in Human Plasma and SRM 2378 Fatty Acids in Frozen Human Serum. Results: To date, two studies of the Fatty Acid Quality Assurance Program (FAQAP) have been completed with 11 and 14 participants, respectively. The agreement among the laboratories for individual fatty acids was within 20% for 70% of the data submitted. Laboratories were also requested to run triplicate analyses for each unknown sample. The precision of the individual laboratory data was generally good, with relative standard deviations <20%. Conclusions: The results from the first two exercises indicate the need for additional assessment of the comparability among laboratories doing these measurements. Future studies will be conducted with the goals of increasing the number of participating laboratories, increasing awareness of the need to use control materials, and improving the comparability among laboratories. Published by Elsevier B.V. C1 [Schantz, Michele M.; Wise, Stephen A.] NIST, Div Chem Sci, Gaithersburg, MD 20899 USA. [Powers, Carissa D.; Schleicher, Rosemary L.] Ctr Dis Control & Prevent, Nutr Biomarkers Branch, Div Lab Sci, Atlanta, GA 30341 USA. [Betz, Joseph M.; Wise, Stephen A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Schantz, MM (reprint author), NIST, Div Chem Sci, Gaithersburg, MD 20899 USA. EM Michele.schantz@nist.gov FU National Institutes of Health (NIH), Office of Dietary Supplements (ODS) [AOD 14043-001] FX The financial support for these intercomparison exercises was provided by the National Institutes of Health (NIH) (grant number AOD 14043-001), Office of Dietary Supplements (ODS). The time and effort of the analysts and management of the participating laboratories are gratefully acknowledged. Certain commercial equipment, instruments, or materials are identified in this report to specify adequately the experimental procedure. 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 the best available for the purpose. The findings and conclusions in this article are those of the authors and do not necessarily represent the official views or positions of the CDC/Agency for Toxic Substance and Disease Registry or the Department of Health and Human Services. NR 19 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD NOV 1 PY 2016 VL 462 BP 148 EP 152 DI 10.1016/j.cca.2016.09.013 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA EB2MB UT WOS:000387195400026 PM 27662814 ER PT J AU Del Prete, GQ Lifson, JD Keele, BF AF Del Prete, Gregory Q. Lifson, Jeffrey D. Keele, Brandon F. TI Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE macaque; simian-human immunodeficiency virus; simian immunodeficiency virus; vaccine challenge ID SIMIAN IMMUNODEFICIENCY VIRUS; MAURITIAN CYNOMOLGUS MACAQUES; RHESUS MACAQUES; MENSTRUAL-CYCLE; PIGTAIL MACAQUES; NEUTRALIZATION SENSITIVITY; DISEASE PROGRESSION; PARTIAL PROTECTION; MACACA-NEMESTRINA; SIV CHALLENGES AB Purpose of reviewNonhuman primate (NHP) models of AIDS are powerful systems for evaluating HIV vaccine approaches in vivo. Authentic features of HIV-1 transmission, dissemination, target cell tropism, and pathogenesis, and aspects of anti-HIV-1 immune responses, can be recapitulated in NHPs provided the appropriate, specific model parameters are considered. Here, we discuss key model parameter options and their implications for HIV-1 vaccine evaluation.Recent findingsWith the availability of several different NHP host species/subspecies, different challenge viruses and challenge stock production methods, and various challenge routes and schemata, multiple NHP models of AIDS exist for HIV vaccine evaluation. The recent development of multiple new challenge viruses, including chimeric simian-human immunodeficiency viruses and simian immunodeficiency virus clones, improved characterization of challenge stocks and production methods, and increased insight into specific challenge parameters have resulted in an increase in the number of available models and a better understanding of the implications of specific study design choices.SummaryRecent progress and technical developments promise new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission. C1 [Del Prete, Gregory Q.; Lifson, Jeffrey D.; Keele, Brandon F.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, Frederick, MD USA. RP Del Prete, GQ (reprint author), Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, POB B, Frederick, MD 21702 USA. EM delpretegq@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This study was supported with federal funds from the National Cancer Institute, National Institutes of Health under contract HHSN261200800001E. 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 US Government. NR 95 TC 0 Z9 0 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2016 VL 11 IS 6 BP 546 EP 554 DI 10.1097/COH.0000000000000311 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA EA1JP UT WOS:000386348700002 PM 27559710 ER PT J AU Russell, ND Marovich, MA AF Russell, Nina D. Marovich, Mary A. TI Pox-Protein Public Private Partnership program and upcoming HIV vaccine efficacy trials SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE HIV vaccine efficacy trials; HIV Vaccine Trials Network 702; Pox-Protein Public Private Partnership program ID RHESUS-MONKEYS; PROTECTIVE EFFICACY; SIV CHALLENGES; ACQUISITION; SIGNATURES; AIDSVAX; ALVAC; RISK AB Purpose of reviewThe purpose of review is to provide an overview of the Pox-Protein Public Private Partnership (P5) and highlight the progress of the P5 program, including an upcoming HIV vaccine efficacy trial in South Africa.Recent findingsThe RV144 Thai vaccine efficacy trial was the first to demonstrate that an HIV-1 vaccine can prevent HIV acquisition. The P5 vaccine regimen uses an ALVAC prime and protein boost modeled after the RV144 vaccine and adapted for the subtype C virus predominant in the southern African region. This regimen was recently tested in the HIV Vaccine Trials Network 100 phase 1/2a study in South Africa. Based on prospectively defined immunogenicity thresholds, criteria were met to support the launch of an efficacy study in late 2016. The aim of this phase 2b/3 trial will be to improve upon the results of RV144, with increased and more durable vaccine efficacy, to accelerate the potential licensure of a preventive vaccine in southern Africa.SummaryThe planned P5 efficacy trial, HIV Vaccine Trials Network 702, is designed to test and prospectively define correlates of protection, if efficacious. A vaccine with modest efficacy, vaccine efficacy at least 50%, could have substantial public health impact and significantly decrease the incidence of new infections in heavily burdened areas of the world. C1 [Russell, Nina D.; Marovich, Mary A.] Bill & Melinda Gates Fdn, 440 5th Ave N, Seattle, WA 98109 USA. RP Russell, ND (reprint author), NIAID, NIH, 5601 Fishers Lane,RM 9D21, Rockville, MD 20852 USA. EM mary.marovich@nih.gov NR 17 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2016 VL 11 IS 6 BP 614 EP 619 DI 10.1097/COH.0000000000000322 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA EA1JP UT WOS:000386348700011 PM 27636503 ER PT J AU Massart, R Nemoda, Z Suderman, MJ Sutti, S Ruggiero, AM Dettmer, AM Suomi, SJ Szyf, M AF Massart, Renaud Nemoda, Zsofia Suderman, Matthew J. Sutti, Sheila Ruggiero, Angela M. Dettmer, Amanda M. Suomi, Stephen J. Szyf, Moshe TI Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CHILDHOOD TRAUMA; BRAIN STRUCTURE; RHESUS-MONKEYS; MATERNAL-CARE; X-CHROMOSOME; STRESS; GENE; BEHAVIOR; EXPERIENCE; DISORDER AB Studies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex. C1 [Massart, Renaud; Nemoda, Zsofia; Suderman, Matthew J.; Szyf, Moshe] McGill Univ, Montreal, PQ, Canada. [Sutti, Sheila; Ruggiero, Angela M.; Dettmer, Amanda M.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Suomi, SJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.; Szyf, M (reprint author), McGill Univ, Dept Pharmacol & Therapeut, 3655 Promonade Sir William Osler, Montreal, PQ H3G Y6, Canada. EM suomis@lce.nichd.nih.gov; moshe.szyf@mcgill.ca FU Canadian Institutes of Health Research [MOP-42411]; European Research ERAnet-Neuron Network; Division of Intramural Research at the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health; Marie Curie International Outgoing Fellowship within the European Community Framework Programme FX This study was supported by grants from the Canadian Institutes of Health Research (MOP-42411) and the European Research ERAnet-Neuron Network (to M.S.) and by funds from the Division of Intramural Research at the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health. Stephen J. Suomi is a Fellow of the Canadian Institute for Advanced Research. Zsofia Nemoda was supported by a Marie Curie International Outgoing Fellowship within the European Community Framework Programme. NR 52 TC 0 Z9 0 U1 5 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 EI 1469-2198 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD NOV PY 2016 VL 28 IS 4 BP 1259 EP 1272 DI 10.1017/S0954579416000833 PN 2 PG 14 WC Psychology, Developmental SC Psychology GA EB6OP UT WOS:000387504400005 PM 27687908 ER PT J AU Colasanto, MP Eyal, S Mohassel, P Bamshad, M Bonnemann, CG Zelzer, E Moon, AM Kardon, G AF Colasanto, Mary P. Eyal, Shai Mohassel, Payam Bamshad, Michael Bonnemann, Carsten G. Zelzer, Elazar Moon, Anne M. Kardon, Gabrielle TI Development of a subset of forelimb muscles and their attachment sites requires the ulnar-mammary syndrome gene Tbx3 SO DISEASE MODELS & MECHANISMS LA English DT Article DE Ulnar-mammary syndrome; UMS; Tbx3; Limb; Muscle; Bone ID VERTEBRATE LIMB MUSCLE; CONNECTIVE-TISSUE; TENDON PROGENITORS; MYOGENIC CELLS; BONE; MORPHOGENESIS; DISTINCT; CRE; INTEGRATION; EXPRESSION AB In the vertebrate limb over 40 muscles are arranged in a precise pattern of attachment via muscle connective tissue and tendon to bone and provide an extensive range of motion. How the development of somite-derived muscle is coordinated with the development of lateral plate-derived muscle connective tissue, tendon and bone to assemble a functional limb musculoskeletal system is a long-standing question. Mutations in the T-box transcription factor, TBX3, have previously been identified as the genetic cause of ulnar-mammary syndrome (UMS), characterized by distinctive defects in posterior forelimb bones. Using conditional mutagenesis in mice, we now show that TBX3 has a broader role in limb musculoskeletal development. TBX3 is not only required for development of posterior forelimb bones (ulna and digits 4 and 5), but also for a subset of posterior muscles (lateral triceps and brachialis) and their bone eminence attachment sites. TBX3 specification of origin and insertion sites appears to be tightly linked with whether these particular muscles develop and may represent a newly discovered mechanism for specification of anatomical muscles. Re-examination of an individual with UMS reveals similar previously unrecognized muscle and bone eminence defects and indicates a conserved role for TBX3 in regulating musculoskeletal development. C1 [Colasanto, Mary P.; Kardon, Gabrielle] Univ Utah, Dept Human Genet, 15 North 2030 East, Salt Lake City, UT 84112 USA. [Eyal, Shai; Zelzer, Elazar] Weizmann Inst Sci, Dept Mol Genet, 234 Herzl St, IL-76100 Rehovot, Israel. [Mohassel, Payam; Bonnemann, Carsten G.] NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bldg 35,Room 2A-116,MSC 3705,35 Convent Dr, Bethesda, MD 20892 USA. [Bamshad, Michael] Univ Washington, Sch Med, Dept Pediat, Div Med Genet, 1959 NE Pacific St HSB I 607-F, Seattle, WA 98195 USA. [Moon, Anne M.] Weis Ctr Res, Geisinger Clin, 100 North Acad Ave, Danville, PA 17822 USA. RP Kardon, G (reprint author), Univ Utah, Dept Human Genet, 15 North 2030 East, Salt Lake City, UT 84112 USA. EM gkardon@genetics.utah.edu FU National Institutes of Health Developmental Biology Training Grant [5T32 HD07491]; European Research Council [310098]; National Institutes of Health [R01HD053728] FX M.P.C. was supported by National Institutes of Health Developmental Biology Training Grant [grant number 5T32 HD07491]. S.E. and E.Z. were supported by European Research Council [grant number 310098]. This work was supported by the National Institutes of Health [grant number R01HD053728 to G.K.]. NR 47 TC 0 Z9 0 U1 2 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD NOV 1 PY 2016 VL 9 IS 11 BP 1257 EP 1269 DI 10.1242/dmm.025874 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA EB7PL UT WOS:000387581000003 PM 27491074 ER PT J AU McGinnis, KA Tate, JP Williams, EC Skanderson, M Bryant, KJ Gordon, AJ Kraemer, KL Maisto, SA Crystal, S Fiellin, DA Justice, AC AF McGinnis, Kathleen A. Tate, Janet P. Williams, Emily C. Skanderson, Melissa Bryant, Kendall J. Gordon, Adam J. Kraemer, Kevin L. Maisto, Stephen A. Crystal, Steven Fiellin, David A. Justice, Amy C. TI Comparison of AUDIT-C collected via electronic medical record and self-administered research survey in HIV infected and uninfected patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol consumption; Population-based screening; AUDIT-C; Electronic health record; Veterans; HIV ID RANDOMIZED CONTROLLED-TRIAL; ALCOHOL-USE; PRIMARY-CARE; HEAVY DRINKING; BRIEF INTERVENTION; UNHEALTHY ALCOHOL; SCREENING-TEST; DRUG-USE; VETERANS; QUALITY AB Background: Using electronic medical record (EMR) data for clinical decisions, quality improvement, and research is common. While unhealthy alcohol use is particularly risky among HIV infected individuals (HIV+), the validity of EMR data for identifying unhealthy alcohol use among HIV+ is unclear. Among HIV+ and uninfected, we: (1) assess agreement of EMR and research AUDIT-C at validated cutoffs for unhealthy alcohol use; (2) explore EMR cutoffs that maximize agreement; and (3) assess subpopulation variation in agreement. Methods: Using data from the Veterans Aging Cohort Study (VACS), EMR AUDIT-C cutoffs of 2+, 3+, and 4+ for men (2+ and 3+ for women) were compared to research AUDIT-C 4+ for men (3+ for women). Agreement was compared by demographics, HIV, hepatitis C infection, and alcohol related diagnosis. Results: Among 1082 HIV+ and 1160 uninfected men, 14% and 22% had an EMR and research AUDIT-C 4+, respectively. Among 32 HIV+ and 115 uninfected women, 9% and 14% had an EMR and research AUDIT-C 3+. For men, EMR agreement with the research AUDIT-C 4+ was highest at a cutoff of 3+ (kappa = 0.49). For women, EMR agreement with AUDIT-C 3+ was highest at a cutoff of 2+ (kappa =0.46). Moderate agreement was consistent across subgroups. Conclusions: EMR AUDIT-C underestimates unhealthy alcohol use compared to research AUDIT-C in both HIV+ and uninfected individuals. Methods for improving quality of clinical screening may be in need of investigation. Researchers and clinicians may consider alternative EMR cutoffs that maximize agreement given limitations of clinical screening. Published by Elsevier Ireland Ltd. C1 [McGinnis, Kathleen A.; Tate, Janet P.; Skanderson, Melissa; Fiellin, David A.; Justice, Amy C.] VA CT Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. [Tate, Janet P.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, Div Gen Internal Med, New Haven, CT USA. [Williams, Emily C.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Williams, Emily C.] VA Hlth Serv Res & Dev, Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Seattle, WA USA. [Bryant, Kendall J.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Gordon, Adam J.; Kraemer, Kevin L.] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Maisto, Stephen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Crystal, Steven] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Fiellin, David A.; Justice, Amy C.] Rutgers State Univ, Hlth Serv Res, New Brunswick, NJ USA. RP McGinnis, KA (reprint author), VA CT Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. EM kathleen.mcginnis3@va.gov OI Fiellin, David/0000-0002-4006-010X FU National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism [U24-AA020794, U01-AA020790, U01-AA020795, U01-AA020799, U10 AA013566]; Career Development Award from VA Health Services Research Development [CDA 12-276] FX The views are not those of the Department of Veterans Affairs or the United States Government. COMpAAAS/Veterans Aging Cohort Study, a CHAART Cooperative Agreement, is supported by the National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism (U24-AA020794, U01-AA020790, U01-AA020795, U01-AA020799; U10 AA013566-completed) and in kind by the US Department of Veterans Affairs. Dr. Williams is supported by a Career Development Award from VA Health Services Research & Development (CDA 12-276). NR 39 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2016 VL 168 BP 196 EP 202 DI 10.1016/j.drugalcdep.2016.09.015 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA EB6VN UT WOS:000387523800028 PM 27694059 ER PT J AU Antonny, B Burd, C De Camilli, P Chen, E Daumke, O Faelber, K Ford, M Frolov, VA Frost, A Hinshaw, JE Kirchhausen, T Kozlov, MM Lenz, M Low, HH McMahon, H Merrifield, C Pollard, TD Robinson, PJ Roux, A Schmid, S AF Antonny, Bruno Burd, Christopher De Camilli, Pietro Chen, Elizabeth Daumke, Oliver Faelber, Katja Ford, Marijn Frolov, Vadim A. Frost, Adam Hinshaw, Jenny E. Kirchhausen, Tom Kozlov, Michael M. Lenz, Martin Low, Harry H. McMahon, Harvey Merrifield, Christien Pollard, Thomas D. Robinson, Phillip J. Roux, Aurelien Schmid, Sandra TI Membrane fission by dynamin: what we know and what we need to know SO EMBO JOURNAL LA English DT Review DE dynamin; membrane fission; endocytosis; GTPase; molecular motor ID CLATHRIN-MEDIATED ENDOCYTOSIS; SYNAPTIC VESICLE ENDOCYTOSIS; DEPENDENT CONFORMATIONAL-CHANGES; DOMAIN-CONTAINING PROTEINS; MITOCHONDRIAL FISSION; CRYSTAL-STRUCTURE; GTP HYDROLYSIS; BAR DOMAINS; COATED-PIT; MECHANOCHEMICAL ENZYME AB The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion. C1 [Antonny, Bruno] Univ Nice Sophia Antipolis, CNRS, Inst Pharmacol Mol & Cellulaire, Valbonne, France. [Burd, Christopher] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. [De Camilli, Pietro] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Neurosci, New Haven, CT 06510 USA. [De Camilli, Pietro] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol, New Haven, CT 06510 USA. [De Camilli, Pietro] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT USA. [Chen, Elizabeth] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Daumke, Oliver; Faelber, Katja] Max Delbruck Ctr Mol Med, Dept Crystallog, Berlin, Germany. [Ford, Marijn] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA USA. [Frolov, Vadim A.] Univ Basque Country, CSIC, Biofis Inst, Leioa, Spain. [Frolov, Vadim A.] Univ Basque Country, Dept Biochem & Mol Biol, Leioa, Spain. [Frolov, Vadim A.] Basque Fdn Sci, Ikerbasque, Bilbao, Spain. [Frost, Adam] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Hinshaw, Jenny E.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Kirchhausen, Tom] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Kirchhausen, Tom] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Kozlov, Michael M.] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, Tel Aviv, Israel. [Lenz, Martin] Univ Paris Saclay, Univ Paris Sud, CNRS, LPTMS, Orsay, France. [Low, Harry H.] Imperial Coll, Dept Life Sci, London, England. [McMahon, Harvey] MRC Lab Mol Biol, Cambridge, England. [Merrifield, Christien] Inst Integrat Biol Cell, Gif Sur Yvette, France. [Pollard, Thomas D.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Robinson, Phillip J.] Univ Sydney, Childrens Med Res Inst, Cell Signalling Unit, Westmead, NSW, Australia. [Roux, Aurelien] Univ Geneva, Dept Biochem, Geneva 4, Switzerland. [Roux, Aurelien] Univ Geneva, Swiss NCCR Chem Biol, Geneva 4, Switzerland. [Schmid, Sandra] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. RP Roux, A (reprint author), Univ Geneva, Dept Biochem, Geneva 4, Switzerland.; Roux, A (reprint author), Univ Geneva, Swiss NCCR Chem Biol, Geneva 4, Switzerland. EM aurelien.roux@unige.ch OI Robinson, Phillip J./0000-0002-7878-0313; Lenz, Martin/0000-0002-2307-1106 FU Medical Research Council [MC_U105178795] NR 114 TC 3 Z9 3 U1 24 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD NOV PY 2016 VL 35 IS 21 BP 2270 EP 2284 DI 10.15252/embj.201694613 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA EB1VA UT WOS:000387142500003 PM 27670760 ER PT J AU Sengupta, A Chaffiol, A Mace, E Caplette, R Desrosiers, M Lampic, M Forster, V Marre, O Lin, JY Sahel, JA Picaud, S Dalkara, D Duebel, J AF Sengupta, Abhishek Chaffiol, Antoine Mace, Emilie Caplette, Romain Desrosiers, Melissa Lampic, Marusa Forster, Valerie Marre, Olivier Lin, John Y. Sahel, Jose-Alain Picaud, Serge Dalkara, Deniz Duebel, Jens TI Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina SO EMBO MOLECULAR MEDICINE LA English DT Article DE channelrhodopsin; optogenetics; primate; retina; vision restoration ID MIDGET GANGLION-CELLS; VISUAL FUNCTION; ECTOPIC EXPRESSION; BIPOLAR CELLS; PHOTORECEPTOR DEGENERATION; OPTOGENETIC EXCITATION; PHOTOCHEMICAL DAMAGE; CONE PHOTORECEPTORS; RESTORATION; TRANSDUCTION AB Targeting the photosensitive ion channel channelrhodopsin-2 (ChR2) to the retinal circuitry downstream of photoreceptors holds promise in treating vision loss caused by retinal degeneration. However, the high intensity of blue light necessary to activate channelrhodopsin-2 exceeds the safety threshold of retinal illumination because of its strong potential to induce photochemical damage. In contrast, the damage potential of red-shifted light is vastly lower than that of blue light. Here, we show that a red-shifted channelrhodopsin (ReaChR), delivered by AAV injections in blind rd1 mice, enables restoration of light responses at the retinal, cortical, and behavioral levels, using orange light at intensities below the safety threshold for the human retina. We further show that postmortem macaque retinae infected with AAV-ReaChR can respond with spike trains to orange light at safe intensities. Finally, to directly address the question of translatability to human subjects, we demonstrate for the first time, AAV- and lentivirus-mediated optogenetic spike responses in ganglion cells of the postmortem human retina. C1 [Sengupta, Abhishek; Chaffiol, Antoine; Mace, Emilie; Caplette, Romain; Desrosiers, Melissa; Lampic, Marusa; Forster, Valerie; Marre, Olivier; Sahel, Jose-Alain; Picaud, Serge; Dalkara, Deniz; Duebel, Jens] INSERM, U968, Paris, France. [Sengupta, Abhishek; Chaffiol, Antoine; Mace, Emilie; Caplette, Romain; Desrosiers, Melissa; Lampic, Marusa; Forster, Valerie; Marre, Olivier; Sahel, Jose-Alain; Picaud, Serge; Dalkara, Deniz; Duebel, Jens] UPMC Univ Paris 06, Sorbonne Univ, Inst Vis, UMR S 968, Paris, France. [Sengupta, Abhishek; Chaffiol, Antoine; Mace, Emilie; Caplette, Romain; Desrosiers, Melissa; Lampic, Marusa; Forster, Valerie; Marre, Olivier; Sahel, Jose-Alain; Picaud, Serge; Dalkara, Deniz; Duebel, Jens] CNRS, UMR 7210, Paris, France. [Lin, John Y.] Univ Tasmania, Sch Med, Hobart, Tas, Australia. [Sahel, Jose-Alain] Hop Quinze Vingts, Paris, France. [Sengupta, Abhishek] NEI, Unit Retinal Neurophysiol, Bethesda, MD 20892 USA. [Sengupta, Abhishek] NIH, Grad Partnerships Program, Bldg 10, Bethesda, MD 20892 USA. RP Dalkara, D; Duebel, J (reprint author), INSERM, U968, Paris, France.; Dalkara, D; Duebel, J (reprint author), UPMC Univ Paris 06, Sorbonne Univ, Inst Vis, UMR S 968, Paris, France.; Dalkara, D; Duebel, J (reprint author), CNRS, UMR 7210, Paris, France. EM deniz.dalkara@gmail.com; jens.duebel@inserm.fr RI Dalkara, Deniz/D-5057-2017; Picaud, Serge/H-4012-2014; Marre, Olivier/F-2751-2017; Sahel, Jose-Alain/F-3172-2017; Sengupta, Abhishek/I-5938-2013; OI Sengupta, Abhishek/0000-0002-9105-3743; Marre, Olivier/0000-0002-0090-6190 FU Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (INSERM); Pierre et Marie Curie University (UPMC); Agence Nationale de la Recherche [LIFESENSES: ANR-10-LABX-65]; ERC Starting Grant (OPTOGENRET) [309776] FX We thank Roger Y. Tsien for providing the ReaChR plasmids. We thank Benjamin Taklifi and Celine Winckler for technical support and Elric Esposito and Stephane Deny for helpful discussions. We are thankful to Noga Vardi for critical feedback. We thank Manuel Simonutti in the Plateforme Animalerie at the Institut de la Vision for performing intravitreal AAV injections. We are grateful to Kate Grieve for organizing the human donor eyes. This study was supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Sante et de la Recherche Medicale (INSERM), Pierre et Marie Curie University (UPMC), an Agence Nationale de la Recherche Grant (LIFESENSES: ANR-10-LABX-65) and an ERC Starting Grant (OPTOGENRET, Grant No 309776). NR 54 TC 2 Z9 2 U1 10 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD NOV PY 2016 VL 8 IS 11 BP 1248 EP 1264 DI 10.15252/emmm.201505699 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EB1LA UT WOS:000387111900003 PM 27679671 ER PT J AU Li, MX Cole, F Patel, DS Misenko, SM Her, J Malhowski, A Alhamza, A Zheng, HY Baer, R Ludwig, T Jasin, M Nussenzweig, A Serrano, L Bunting, SF AF Li, Minxing Cole, Francesca Patel, Dharm S. Misenko, Sarah M. Her, Joonyoung Malhowski, Amy Alhamza, Ali Zheng, Haiyan Baer, Richard Ludwig, Thomas Jasin, Maria Nussenzweig, Andre Serrano, Lourdes Bunting, Samuel F. TI 53BP1 ablation rescues genomic instability in mice expressing "RING-less' BRCA1 SO EMBO REPORTS LA English DT Article DE cancer; DNA repair; genomic integrity; mouse models; RAD51 ID E3 LIGASE ACTIVITY; TUMOR SUPPRESSION; HOMOLOGOUS RECOMBINATION; UBIQUITIN-LIGASE; THERAPY RESISTANCE; DEFICIENT CELLS; HISTONE H2AX; DNA-REPAIR; IDENTIFICATION; BINDING AB BRCA1 mutations strongly predispose affected individuals to breast and ovarian cancer, but the mechanism by which BRCA1 acts as a tumor suppressor is not fully understood. Homozygous deletion of exon 2 of the mouse Brca1 gene normally causes embryonic lethality, but we show that exon 2-deleted alleles of Brca1 are expressed as a mutant isoform that lacks the N-terminal RING domain. This RING-less BRCA1 protein is stable and efficiently recruited to the sites of DNA damage. Surprisingly, robust RAD51 foci form in cells expressing RING-less BRCA1 in response to DNA damage, but the cells nonetheless display the substantial genomic instability. Genomic instability can be rescued by the deletion of Trp53bp1, which encodes the DNA damage response factor 53BP1, and mice expressing RING-less BRCA1 do not show an increased susceptibility to tumors in the absence of 53BP1. Genomic instability in cells expressing RING-less BRCA1 correlates with the loss of BARD1 and a defect in restart of replication forks after hydroxyurea treatment, suggesting a role of BRCA1-BARD1 in genomic integrity that is independent of RAD51 loading. C1 [Li, Minxing; Patel, Dharm S.; Misenko, Sarah M.; Her, Joonyoung; Alhamza, Ali; Bunting, Samuel F.] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Cole, Francesca; Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10021 USA. [Cole, Francesca] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX USA. [Malhowski, Amy; Nussenzweig, Andre] NCI, Lab Genome Integr, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zheng, Haiyan] Rutgers State Univ, Biol Mass Spectrometry Facil, Piscataway, NJ USA. [Baer, Richard] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, Inst Canc Genet, New York, NY USA. [Ludwig, Thomas] Ohio State Univ, Dept Canc Biol & Genet, Columbus, OH 43210 USA. [Serrano, Lourdes] Rutgers State Univ, Human Genet Inst New Jersey, Dept Genet, Piscataway, NJ USA. RP Bunting, SF (reprint author), Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. EM bunting@cabm.rutgers.edu FU NCI [R00CA160574]; Rutgers Biotech Training Program [T32 GM008339]; New Jersey Commission on Cancer Research; NIH [DP2HD087943, S10OD016400] FX Thanks to Dr. Peter Lobel for advice on MS and Jake Altshuler for assistance with data analysis. This work was supported by NCI R00CA160574. DP and SM were supported by the Rutgers Biotech Training Program (T32 GM008339) and by predoctoral awards from the New Jersey Commission on Cancer Research. FC was supported by NIH grant DP2HD087943. The Rutgers Biological Mass Spectrometry Facility was supported by NIH S10OD016400. NR 40 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD NOV PY 2016 VL 17 IS 11 BP 1532 EP 1541 DI 10.15252/embr.201642497 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA EB1XD UT WOS:000387148700006 PM 27670884 ER PT J AU de Figueiredo, FAT Ramos, J Kawakita, ERH Bilal, AS de Sousa, FB Swaim, WD Issa, JPM Gerlach, RF AF Tocchini de Figueiredo, Fellipe Augusto Ramos, Junia Hashimoto Kawakita, Erika R. Bilal, Alina S. de Sousa, Frederico B. Swaim, William D. Mardegan Issa, Joao P. Gerlach, Raquel F. TI Lead line in rodents: an old sign of lead intoxication turned into a new method for environmental surveillance SO ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH LA English DT Article DE Lead line; Sentinels; Dental enamel; Lead; Tooth; Environmental monitoring ID SURFACE ENAMEL; IN-VIVO; CHILDREN; CADMIUM; TISSUES; BLOOD; TEETH; BIOMARKERS; DENTIN; BONE AB The "lead line" was described by Henry Burton in 1840. Rodents are used as sentinels to monitor environmental pollution, but their teeth have not been used to determine lead. To determine whether lead deposits can be observed in the teeth of lead-exposed animals, since the gingival deposits known as "lead line" would likely have a correlate in the calcified tissue to which the gums are opposed during life. Male Wistar rats were exposed to lead in the drinking water (30 mg/L) since birth until 60 days-old. Molars and the incisors of each hemimandible were analyzed by scanning electron microscopy (SEM) on regular and backscattered electrons (BSE) mode. Elements were determined using electron dispersive spectroscopy (EDS). Clean cervical margins were observed on control teeth, as opposed to the findings of extensive deposits on lead-exposed animals, even in hemimandibles that had been exhumed after being buried for 90 days. BSE/EDS indicated that those deposits were an exogenous material compatible with lead sulfite. Presence of calcium, phosphorus, magnesium, carbon, lead, and oxygen is presented. Lead-exposed animals presented marked root resorption. The lead deposits characterized here for the first time show that the "lead line" seen in gums has a calcified tissue counterpart, that is detectable post-mortem even in animals exposed to a low dose of lead. This is likely a good method to detect undue lead exposure and will likely have wide application for pollution surveillance using sentinels. C1 [Tocchini de Figueiredo, Fellipe Augusto; Ramos, Junia; Hashimoto Kawakita, Erika R.; Bilal, Alina S.; Mardegan Issa, Joao P.; Gerlach, Raquel F.] Univ Sao Paulo, Sch Dent Ribeirao Preto FORP, Dept Morphol Physiol & Basic Pathol, Ave Cafe S-N, BR-14040904 Sao Paulo, Brazil. [de Sousa, Frederico B.] Fed Univ Paraiba UFPB, Dept Morphol, Hlth Sci Ctr, Joao Pessoa, Paraiba, Brazil. [Swaim, William D.] NIDCR, NIH, Bethesda, MD USA. [Gerlach, Raquel F.] Univ Sao Paulo, FMRP, Grad Program Pharmacol & Toxicol, Ave Bandeirantes 3400, BR-14049900 Sao Paulo, Brazil. RP de Figueiredo, FAT (reprint author), Univ Sao Paulo, Sch Dent Ribeirao Preto FORP, Dept Morphol Physiol & Basic Pathol, Ave Cafe S-N, BR-14040904 Sao Paulo, Brazil. EM fellipe.figueiredo@usp.br; Juniaramos@forp.usp.br; erika.kawakita@usp.br; asusanab@gmail.com; fredericosousa@hotmail.com; bswaim@dir.nidcr.nih.gov; jpmissa@forp.usp.br; rfgerlach@forp.usp.br FU Conselho Nacional de Pesquisa; CNPq; (Brazilian) National Research Council FX This study was supported by the Conselho Nacional de Pesquisa, CNPq, and the (Brazilian) National Research Council. NR 29 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0944-1344 EI 1614-7499 J9 ENVIRON SCI POLLUT R JI Environ. Sci. Pollut. Res. PD NOV PY 2016 VL 23 IS 21 BP 21475 EP 21484 DI 10.1007/s11356-016-7336-3 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA EB7VQ UT WOS:000387599600033 PM 27510160 ER PT J AU Aas, S AF Aas, Sean TI Disabled - therefore, Unhealthy? SO ETHICAL THEORY AND MORAL PRACTICE LA English DT Article DE Disability; Conceptual ethics; Health; Impairment ID HEALTH AB This paper argues that disabled people can be healthy. I argue, first, following the well-known 'social model of disability', that we should prefer a usage of 'disabled' which does not imply any kind of impairment that is essentially inconsistent with health. This is because (a) one can be disabled only because limited by false social perception of impairment and (b) one can be, if impaired, disabled not because of the impairment but rather only because of the social response to it. Second, I argue that it is often wrong to use the term 'healthy' in a way that makes health inconsistent with any degree whatsoever of health-relevant bodily dysfunction. Whether someone is 'healthy' properly-so-called depends on standards of health presupposed in conversational context. Sometimes, I argue, these standards are or ought to be lax enough to allow some people with some health deficits still to count as 'healthy' per se. Taking inspiration from David Lewis and Mary Kate Mcgowan, I go on to argue that denying that someone is 'healthy' in a context typically succeeds in shifting going presuppositions to require standards strict enough to make that denial acceptable. And this, I conclude by arguing, often constitutes an abuse of conversational power. C1 [Aas, Sean] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. RP Aas, S (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM Sean.aas@gmail.com NR 21 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-2820 EI 1572-8447 J9 ETHICAL THEORY MORAL JI Ethical Theory Moral Pract. PD NOV PY 2016 VL 19 IS 5 BP 1259 EP 1274 DI 10.1007/s10677-016-9735-4 PG 16 WC Philosophy SC Philosophy GA EB2ZK UT WOS:000387230900013 ER PT J AU Koretzky, M Bonham, VL Berkman, BE Kruszka, P Adeyemo, A Muenke, M Hull, SC AF Koretzky, Maya Bonham, Vence L. Berkman, Benjamin E. Kruszka, Paul Adeyemo, Adebowale Muenke, Maximilian Hull, Sara Chandros TI Towards a more representative morphology: clinical and ethical considerations for including diverse populations in diagnostic genetic atlases SO GENETICS IN MEDICINE LA English DT Review DE ethics; dysmorphology; genetics; global health; diverse populations ID PARTICIPATORY RESEARCH; CYSTIC-FIBROSIS; RACE; HEALTH; CATEGORIES; SCIENCE; MATTER AB An important gap exists in textbooks (or atlases) of dysmorphology used by health-care professionals to help diagnose genetic syndromes. The lack of varied phenotypic images in available atlases limits the utility of these atlases as diagnostic tools in globally diverse populations, causing geneticists difficulty in diagnosing conditions in individuals of different ancestral backgrounds who may present with variable morphological features. Proposals to address the underinclusion of images from diverse populations in existing atlases can take advantage of the Internet and digital photography to create new resources that take into account the broad global diversity of populations affected by genetic disease. Creating atlases that are more representative of the global population will expand resources available to care for diverse patients with these conditions, many of whom have been historically underserved by the medical system. However, such projects also raise ethical questions that are grounded in the complex intersection of imagery, medicine, history, and race and ethnicity. We consider here the benefits of producing such a resource while also considering ethical and practical concerns, and we offer recommendations for the ethical creation, structure, equitable use, and maintenance of a diverse morphological atlas for clinical diagnosis. C1 [Koretzky, Maya; Berkman, Benjamin E.; Hull, Sara Chandros] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Bonham, Vence L.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Berkman, Benjamin E.; Hull, Sara Chandros] NHGRI, Bioeth Core, NIH, Bethesda, MD 20892 USA. [Kruszka, Paul; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Hull, SC (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.; Hull, SC (reprint author), NHGRI, Bioeth Core, NIH, Bethesda, MD 20892 USA. EM shull@mail.nih.gov OI Berkman, Benjamin/0000-0002-9098-0799; Adeyemo, Adebowale/0000-0002-3105-3231; Hull, Sara/0000-0001-8742-4997 FU intramural research program of the National Human Genome Research Institute FX This work was funded in part by the intramural research program of the National Human Genome Research Institute. The authors acknowledge the helpful feedback of Donald Hadley, Manjit Kaur, and participants at the Mid-Atlantic Bioethics Fellows' Colloquium for earlier versions of this work. Written parental consent was obtained to publish the photographs of children with Down syndrome that are included in Figure 1. NR 36 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD NOV PY 2016 VL 18 IS 11 BP 1069 EP 1074 DI 10.1038/gim.2016.7 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA EA8DR UT WOS:000386866000001 PM 26963283 ER PT J AU Bowdin, S Gilbert, A Bedoukian, E Carew, C Adam, MP Belmont, J Bernhardt, B Biesecker, L Bjornsson, HT Blitzer, M D'Alessandro, LCA Deardorff, MA Demmer, L Elliott, A Feldman, GL Glass, IA Herman, G Hindorff, L Hisama, F Hudgins, L Innes, AM Jackson, L Jarvik, G Kim, R Korf, B Ledbetter, DH Li, M Liston, E Marshall, C Medne, L Meyn, MS Monfared, N Morton, C Mulvihill, JJ Plon, SE Rehm, H Roberts, A Shuman, C Spinner, NB Stavropoulos, DJ Valverde, K Waggoner, DJ Wilkens, A Cohn, RD Krantz, ID AF Bowdin, Sarah Gilbert, Adel Bedoukian, Emma Carew, Christopher Adam, Margaret P. Belmont, John Bernhardt, Barbara Biesecker, Leslie Bjornsson, Hans T. Blitzer, Miriam D'Alessandro, Lisa C. A. Deardorff, Matthew A. Demmer, Laurie Elliott, Alison Feldman, Gerald L. Glass, Ian A. Herman, Gail Hindorff, Lucia Hisama, Fuki Hudgins, Louanne Innes, A. Micheil Jackson, Laird Jarvik, Gail Kim, Raymond Korf, Bruce Ledbetter, David H. Li, Mindy Liston, Eriskay Marshall, Christian Medne, Livija Meyn, M. Stephen Monfared, Nasim Morton, Cynthia Mulvihill, John J. Plon, Sharon E. Rehm, Heidi Roberts, Amy Shuman, Cheryl Spinner, Nancy B. Stavropoulos, D. James Valverde, Kathleen Waggoner, Darrel J. Wilkens, Alisha Cohn, Ronald D. Krantz, Ian D. TI Recommendations for the integration of genomics into clinical practice SO GENETICS IN MEDICINE LA English DT Review DE clinical genetics; genomics; genetics counseling; phenotyping; precision medicine ID MORPHOLOGY STANDARD TERMINOLOGY; HUMAN PHENOTYPE ONTOLOGY; INFORMED-CONSENT; INCIDENTAL FINDINGS; INSITU HYBRIDIZATION; SEQUENCE VARIANTS; MEDICAL-GENETICS; ELEMENTS; RETURN; DISEASE AB The introduction of diagnostic clinical genome and exome sequencing (CGES) is changing the scope of practice for clinical geneticists. Many large institutions are making a significant investment in infrastructure and technology, allowing clinicians to access CGES, especially as health-care coverage begins to extend to clinically indicated genomic sequencing-based tests. Translating and realizing the comprehensive clinical benefits of genomic medicine remain a key challenge for the current and future care of patients. With the increasing application of CGES, it is necessary for geneticists and other health-care providers to understand its benefits and limitations in order to interpret the clinical relevance of genomic variants identified in the context of health and disease. New, collaborative working relationships with specialists across diverse disciplines (e.g., clinicians, laboratorians, bioinformaticians) will undoubtedly be key attributes of the future practice of clinical genetics and may serve as an example for other specialties in medicine. These new skills and relationships will also inform the development of the future model of clinical genetics training curricula. To address the evolving role of the clinical geneticist in the rapidly changing climate of genomic medicine, two Clinical Genetics Think Tank meetings were held that brought together physicians, laboratorians, scientists, genetic counselors, trainees, and patients with experience in clinical genetics, genetic diagnostics, and genetics education. This article provides recommendations that will guide the integration of genomics into clinical practice. C1 [Bowdin, Sarah; Gilbert, Adel; Carew, Christopher; Meyn, M. Stephen; Shuman, Cheryl; Cohn, Ronald D.] Univ Toronto, Hosp Sick Children, Dept Pediat, Ctr Genet Med, Toronto, ON, Canada. [Bowdin, Sarah; Medne, Livija] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON, Canada. [Bedoukian, Emma; Deardorff, Matthew A.; Medne, Livija; Wilkens, Alisha; Krantz, Ian D.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Individualized Med Genet Ctr, Philadelphia, PA 19104 USA. [Bedoukian, Emma; Deardorff, Matthew A.; Wilkens, Alisha] Childrens Hosp Philadelphia, Dept Pathol, Div Human Genet, Individualized Med Genet Ctr, Philadelphia, PA USA. [Adam, Margaret P.; Glass, Ian A.] Univ Washington, Sch Med, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [Adam, Margaret P.; Glass, Ian A.] Seattle Childrens Hosp, Seattle, WA USA. [Belmont, John] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA. [Bernhardt, Barbara] Hosp Univ Penn, Div Translat Med & Human Genet, 3400 Spruce St, Philadelphia, PA 19104 USA. [Biesecker, Leslie] NIH, Med Genom & Metab Genet Branch, Natl Human Genome Res Inst, Bldg 10, Bethesda, MD 20892 USA. [Bjornsson, Hans T.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Bjornsson, Hans T.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Blitzer, Miriam] Univ Maryland, Sch Med, Dept Pediat, Div Human Genet, Baltimore, MD 21201 USA. [D'Alessandro, Lisa C. A.] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Cardiol, Toronto, ON, Canada. [Deardorff, Matthew A.; Krantz, Ian D.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Deardorff, Matthew A.; Li, Mindy; Spinner, Nancy B.; Krantz, Ian D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Demmer, Laurie] Carolinas Med Ctr, Dept Pediat, Charlotte, NC 28203 USA. [Elliott, Alison] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Feldman, Gerald L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Feldman, Gerald L.] Wayne State Univ, Sch Med, Dept Pediat & Pathol, Detroit, MI USA. [Herman, Gail] Ohio State Univ, Nationwide Childrens Hosp, Ctr Mol & Human Genet, Columbus, OH 43210 USA. [Hindorff, Lucia; Jarvik, Gail] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA. [Hisama, Fuki] Univ Washington, Dept Med, Div Med Genet, Seattle, WA USA. [Hudgins, Louanne] Stanford Univ, Sch Med, Dept Pediat, Div Med Genet, Stanford, CA 94305 USA. [Innes, A. Micheil] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada. [Innes, A. Micheil] Univ Calgary, Cumming Sch Med, Alberta Childrens Hosp Res Inst, Calgary, AB, Canada. [Jackson, Laird; Kim, Raymond; Liston, Eriskay; Meyn, M. Stephen; Monfared, Nasim; Shuman, Cheryl; Cohn, Ronald D.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Korf, Bruce] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Ledbetter, David H.] Geisinger Hlth Syst, Danville, PA USA. [Li, Mindy; Spinner, Nancy B.] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol, Div Genom Diagnost, Philadelphia, PA 19104 USA. [Marshall, Christian; Stavropoulos, D. James] Univ Toronto, Hosp Sick Children, Dept Paediat Lab Med, Genome Diagnost, Toronto, ON, Canada. [Morton, Cynthia; Rehm, Heidi] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Med, Boston, MA USA. [Morton, Cynthia; Rehm, Heidi; Roberts, Amy] Harvard Univ, Sch Med, Boston, MA USA. [Mulvihill, John J.] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Roberts, Amy] Boston Childrens Hosp, Dept Med, Dept Cardiol, Boston, MA USA. [Roberts, Amy] Boston Childrens Hosp, Dept Med, Div Genet, Boston, MA USA. [Valverde, Kathleen] Arcadia Univ, Coll Hlth Sci, Glenside, PA USA. [Waggoner, Darrel J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. RP Cohn, RD (reprint author), Univ Toronto, Hosp Sick Children, Dept Pediat, Ctr Genet Med, Toronto, ON, Canada.; Krantz, ID (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Individualized Med Genet Ctr, Philadelphia, PA 19104 USA.; Krantz, ID (reprint author), Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA.; Krantz, ID (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.; Cohn, RD (reprint author), Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. EM Ronald.cohn@sickkids.ca; ian2@mail.med.upenn.edu RI innes, allan micheil/A-9955-2017 FU Hospital for Sick Children; Departments of Pediatrics and Pathology at the Children's Hospital of Philadelphia; National Human Genome Research Institute [5UO1HG006546]; Intramural Research Program of the National Human Genome Research Institute; Centre for Genetic Medicine, Hospital for Sick Children, Toronto, Canada; Departments of Pediatrics and Pathology at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Centre for Genetic Medicine FX The Clinical Genetics Think Tank was funded by the Centre for Genetic Medicine, Hospital for Sick Children, and the Departments of Pediatrics and Pathology at the Children's Hospital of Philadelphia, with additional funding from the National Human Genome Research Institute (5UO1HG006546 to I.D.K. and N.B.S.). The authors acknowledge the parent and patient members of the CGTT, M. Hardy, B. Kovalski, H. Kovalski, D. Siciliano, J. Strautnieks, and T. Stoppa, and the support of Joe St. Geme and Bob Doms at the Children's Hospital of Philadelphia. L.G.B. was supported by the Intramural Research Program of the National Human Genome Research Institute. Funding to cover attendance and accommodation for all participants at both meetings was provided by the Centre for Genetic Medicine, Hospital for Sick Children, Toronto, Canada, and the Departments of Pediatrics and Pathology at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. NR 67 TC 1 Z9 1 U1 12 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD NOV PY 2016 VL 18 IS 11 BP 1075 EP 1084 DI 10.1038/gim.2016.17 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA EA8DR UT WOS:000386866000002 PM 27171546 ER PT J AU Muenke, M Adeyemo, A Kruszka, P AF Muenke, Maximilian Adeyemo, Adebowale Kruszka, Paul TI An electronic atlas of human malformation syndromes in diverse populations SO GENETICS IN MEDICINE LA English DT Editorial Material C1 [Muenke, Maximilian; Kruszka, Paul] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD NOV PY 2016 VL 18 IS 11 BP 1085 EP 1087 DI 10.1038/gim.2016.3 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA EA8DR UT WOS:000386866000003 PM 26938780 ER PT J AU Duffy, AG Makarova-Rusher, OV Greten, TF AF Duffy, Austin G. Makarova-Rusher, Oxana V. Greten, Tim F. TI The case for immune-based approaches in biliary tract carcinoma SO HEPATOLOGY LA English DT Review ID HLA CLASS-I; GASTROINTESTINAL CANCERS; HEPATOCELLULAR-CARCINOMA; PEPTIDE VACCINATION; COLORECTAL-CANCER; T-CELLS; CHOLANGIOCARCINOMA; IMMUNOTHERAPY; EXPRESSION; SURVIVAL AB Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches has yet to be seen. However, the etiological background of BTCoverlapping in almost every known causative or associated factor with inflammationprovides a strong clue that these approaches may have an impact in this group of diseases. This review covers what we currently know about the role of the immune system in the etiology of BTC, highlighting differences by subtype, and pointing to the therapeutic opportunities currently entering the clinic or about to do so. (Hepatology 2016;64:1785-1791) C1 [Duffy, Austin G.; Makarova-Rusher, Oxana V.; Greten, Tim F.] NCI, Gastrointestinal Malignancies Sect, Thoracic GI Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Duffy, AG (reprint author), NCI, 9000 Rockville Pike,10-12N224, Bethesda, MD 20892 USA. EM duffya@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, 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 49 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD NOV PY 2016 VL 64 IS 5 BP 1785 EP 1791 DI 10.1002/hep.28635 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EB6AX UT WOS:000387464200038 PM 27177447 ER PT J AU Kattakuzhy, S Levy, R Rosenthal, E Tang, L Wilson, E Kottilil, S AF Kattakuzhy, Sarah Levy, Rachel Rosenthal, Elana Tang, Lydia Wilson, Eleanor Kottilil, Shyam TI Hepatitis C genotype 3 disease SO HEPATOLOGY INTERNATIONAL LA English DT Review DE Hepatitis C; Genotype-3; Treatment review ID TREATMENT-EXPERIENCED PATIENTS; DACLATASVIR PLUS SOFOSBUVIR; PEGINTERFERON ALPHA-2A; PEGYLATED INTERFERON; VIRUS-INFECTION; CORE PROTEIN; RIBAVIRIN; HCV; COMBINATION; STEATOSIS AB Hepatitis C genotype 3 (GT-3) infection comprises up to 30 % of all HCV infections worldwide, with roughly 54.3 million cases concentrated in South and Southeast Asia. Longitudinal studies have demonstrated significantly increased rates of steatosis, fibrosis, and hepatocellular carcinoma in GT-3 disease, thus distinguishing this genotype as both the most difficult and urgent to treat. However, novel direct-acting antiviral agents currently approved have not demonstrated the uniform potency seen in GT-1 disease for GT-3. This review outlines (1) the epidemiology and natural history, (2) phase II and III clinical trials demonstrating effective treatment options, and (3) current and future therapeutic issues in the quest to eradicate hepatitis C genotype 3 disease. C1 [Kattakuzhy, Sarah; Rosenthal, Elana; Tang, Lydia; Wilson, Eleanor; Kottilil, Shyam] Univ Maryland, Inst Human Virol, Div Clin Care & Res, 5415 W,Cedar Lane Suite 203b, Bethesda, MD 20814 USA. [Levy, Rachel] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Kattakuzhy, S (reprint author), Univ Maryland, Inst Human Virol, Div Clin Care & Res, 5415 W,Cedar Lane Suite 203b, Bethesda, MD 20814 USA. EM skattakuzhy@ihv.umaryland.edu OI Rosenthal, Elana/0000-0001-7234-4871; Wilson, Eleanor/0000-0002-4855-514X NR 45 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-0533 EI 1936-0541 J9 HEPATOL INT JI Hepatol. Int. PD NOV PY 2016 VL 10 IS 6 BP 861 EP 870 DI 10.1007/s12072-016-9748-z PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EB3BG UT WOS:000387235900004 PM 27328848 ER PT J AU Shrivastava, S Meissner, EG Funk, E Poonia, S Shokeen, V Thakur, A Poonia, B Sarin, SK Trehanpati, N Kottilil, S AF Shrivastava, Shikha Meissner, Eric G. Funk, Emily Poonia, Seerat Shokeen, Virender Thakur, Arun Poonia, Bhawna Sarin, Shiv Kumar Trehanpati, Nirupma Kottilil, Shyamasundaran TI Elevated hepatic lipid and interferon stimulated gene expression in HCV GT3 patients relative to non-alcoholic steatohepatitis SO HEPATOLOGY INTERNATIONAL LA English DT Article DE ISG (interferon stimulated genes); Hepatitis C virus genotype 3; NASH (non-alcoholic steatohepatitis) ID C VIRUS-INFECTION; GENOTYPE 3; LIVER-DISEASE; FATTY LIVER; FOLLOW-UP; STEATOSIS; IMMUNITY; THERAPY AB HCV GT-3 has a more pronounced effect on hepatic steatosis and host lipids than other HCV genotypes and is proving less responsive to all oral interferon-free treatment with direct acting antiviral agents. As both HCV GT3 infection and NASH can result in steatosis and cirrhosis, we asked whether hepatic transcriptional profiles reflective of the host response to inflammation differed based on the etiology of injury. Hepatic gene expression was determined for 48 pre-selected genes known to be associated with hepatic interferon signaling and lipid metabolic pathways in treatment-na < ve HCV GT-3 (n = 9) and NASH (n = 14) patients. Genes with significantly higher expression in HCV included chemokines CXCL10, CXCL11 interferon IFNA2, interferon receptors IFNAR1, IL10RB negative regulators of interferon signaling SOCS3, USP18, JAK/STAT and IRF family members STAT1, STAT2, and IRF, and TGFB family members TGFB1, TGFBR1, and TGFBR2 and other ISGs like OAS2, IF127, IF144 and ISG15. HCV infection was also associated with higher expression of genes associated with lipid metabolism APOE, APOL3, SREBF1 and HMBS. Furthermore, our results suggest that, in HCV GT3-infected patients, IL28B (CC) genotype is associated with lower baseline ISG expression such as IRF9, ISG15, MX1, STAT1, CXCL10, CXCL11, and IFI27 compared to CT/TT genotype. HCV GT-3 and NASH both induce hepatic steatosis and inflammation, while HCV GT-3 infection is uniquely associated with elevated transcription of hepatic ISGs and genes associated with lipid metabolism. These changes likely reflect the unique host response to HCV replication distinct from the inflammatory response induced by NASH. C1 [Shrivastava, Shikha; Poonia, Bhawna; Kottilil, Shyamasundaran] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Meissner, Eric G.] Med Univ South Carolina, Div Infect Dis, Dept Microbiol & Immunol, Charleston, SC USA. [Funk, Emily; Poonia, Seerat] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Shokeen, Virender; Thakur, Arun; Sarin, Shiv Kumar; Trehanpati, Nirupma] Inst Liver & Biliary Sci, New Delhi, India. RP Kottilil, S (reprint author), Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.; Trehanpati, N (reprint author), Inst Liver & Biliary Sci, New Delhi, India. EM trehanpati@gmail.com; SKottilil@ihv.umaryland.edu FU National Institute of Allergy and Infectious Diseases (NIH), Bethesda, United States; Institute of Liver and biliary Sciences, New Delhi, India FX National Institute of Allergy and Infectious Diseases (NIH), Bethesda, United States and Institute of Liver and biliary Sciences, New Delhi, India, supported this study. NR 24 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-0533 EI 1936-0541 J9 HEPATOL INT JI Hepatol. Int. PD NOV PY 2016 VL 10 IS 6 BP 937 EP 946 DI 10.1007/s12072-016-9733-6 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EB3BG UT WOS:000387235900012 PM 27193023 ER PT J AU Thacker, SG Zarzour, A Chen, Y Alcicek, MS Freeman, LA Sviridov, DO Demosky, SJ Remaley, AT AF Thacker, Seth G. Zarzour, Abdalrahman Chen, Ye Alcicek, Mustafa S. Freeman, Lita A. Sviridov, Dennis O. Demosky, Stephen J., Jr. Remaley, Alan T. TI High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation SO IMMUNOLOGY LA English DT Article DE apolipoprotein A I; high-density lipoprotein; inflammasome; interleukin-1 beta ID MULTIPLE SIGNALING PATHWAYS; NALP3 INFLAMMASOME; EFFLUX CAPACITY; T-LYMPHOCYTES; APOA-I; HDL; INTERLEUKIN-1-BETA; RECEPTORS; DISEASE; ATHEROSCLEROSIS AB Interleukin-1 beta (IL-1 beta), a potent pro-inflammatory cytokine, has been implicated in many diseases, including atherosclerosis. Activation of IL-1 beta is controlled by a multi-protein complex, the inflammasome. The exact initiating event in atherosclerosis is unknown, but recent work has demonstrated that cholesterol crystals (CC) may promote atherosclerosis development by activation of the inflammasome. High-density lipoprotein (HDL) has consistently been shown to be anti-atherogenic and to have anti-inflammatory effects, but its mechanism of action is unclear. We demonstrate here that HDL is able to suppress IL-1 beta secretion in response to cholesterol crystals in THP-1 cells and in human-monocytederived macrophages. HDL is able to blunt inflammatory monocyte cell recruitment in vivo following intraperitoneal CC injection in mice. HDL appears to modulate inflammasome activation in several ways. It reduces the loss of lysosomal membrane integrity following the phagocytosis of CC, but the major mechanism for the suppression of inflammasome activation by HDL is decreased expression of pro-IL-1 beta and NLRP3, and reducing caspase-1 activation. In summary, we have described a novel anti-inflammatory effect of HDL, namely its ability to suppress inflammasome activation by CC by modulating the expression of several key components of the inflammasome. C1 [Thacker, Seth G.; Zarzour, Abdalrahman; Alcicek, Mustafa S.; Freeman, Lita A.; Sviridov, Dennis O.; Demosky, Stephen J., Jr.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Chen, Ye] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NHLBI, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley1@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX This project has been funded from intramural research funds from the National Heart, Lung, and Blood Institute. 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 US Government. We thank the Flow Cytometry Core of NHLBI (Bldg 10, Room 8C104, 10 Center Drive, Bethesda 20892, MD, USA) and Light Microscopy Core of NHLBI (Bldg 10, Room 6N-309, 10 Center Drive Bethesda, MD 20892) for their assistance and the Department of Transfusion Medicine at the NIH Clinical Center for providing plasma and monocytes. NR 49 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD NOV PY 2016 VL 149 IS 3 BP 306 EP 319 DI 10.1111/imm.12638 PG 14 WC Immunology SC Immunology GA EB4RH UT WOS:000387360300006 PM 27329564 ER PT J AU Strich, JR Jerussi, TD Wiestner, A Holland, SM AF Strich, Jeffrey R. Jerussi, Theresa D. Wiestner, Adrian Holland, Steven M. TI Pneumocystis jirovecii Pneumonia in a Treatment-Naive Patient With Chronic Lymphocytic Leukemia SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article DE Pneumocystis jiroveci pneumonia; chronic lymphocytic leukemia; opportunistic infection ID CARINII-PNEUMONIA; INFECTION; DIAGNOSIS AB Pneumocystis jirovecii pneumonia is a known complication in patients with chronic lymphocytic leukemia who are treated with fludarabine-based chemotherapy; however, it is extremely uncommon in treatment-naive patients. Here, we report a case of Pneumocystis jirovecii pneumonia in a patient with untreated chronic lymphocytic leukemia. C1 [Strich, Jeffrey R.] NIAID, Div Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Jerussi, Theresa D.] NIH, Off Patient Safety & Clin Qual, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Lab Lymphoid Malignancies, Bldg 10, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Strich, JR (reprint author), NIAID, NIH, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20814 USA. EM jeffrey.strich@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1056-9103 EI 1536-9943 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD NOV PY 2016 VL 24 IS 6 BP E86 EP E87 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA EB6CJ UT WOS:000387468200014 PM 27917032 ER PT J AU Gaffney, D Small, B Kitchener, H Ryu, SY Viswanathan, A Trimble, T Covens, A Wilailak, S Lertkhachonsuk, AA Sitathanee, C Mahantshetty, U Fisher, B Springer, S Pollatz, T Spiller, A Bacon, M Jhingran, A AF Gaffney, David Small, Bill Kitchener, Henry Ryu, Sang Young Viswanathan, Akila Trimble, Ted Covens, Al Wilailak, Sarikapan Lertkhachonsuk, Arb-aroon Sitathanee, Chomporn Mahantshetty, Umesh Fisher, Brandon Springer, Susan Pollatz, Thomas Spiller, Antonius Bacon, Monica Jhingran, Anuja TI Cervix Cancer Research Network (CCRN) Improving Access to Cervix Cancer Trials on a Global Scale SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Cervix cancer; Cervical cancer; Brachytherapy; Radiotherapy; CCRN ID RADIATION-THERAPY; RADIOTHERAPY; BRACHYTHERAPY; CHEMOTHERAPY AB Eighty-seven percent of cervix cancer occurs in less-developed regions of the world, and there is up to an 18-fold difference in mortality rate for cervix cancer depending on the region of the world. The Cervix Cancer Research Network (CCRN) was founded through the Gynecologic Cancer InterGroup with the aim of improving access to clinical trials in cervix cancer worldwide, and in so doing improving standards of care. The CCRN recently held its first international educational symposium in Bangkok. Sixty-two participants attended from 16 different countries including Pakistan, India, Bangladesh, Thailand, Malaysia, Singapore, Philippines, Taiwan, China, Vietnam, Korea, Japan, Columbia, Brazil, Canada, and the United States. The focus of this symposium was to evaluate progress, to promote new clinical trials for the CCRN, and to provide education regarding the role of brachytherapy in the treatment of cervical cancer. C1 [Gaffney, David] Univ Utah, Dept Radiat Oncol, Salt Lake City, UT USA. [Small, Bill] Loyola Univ, Dept Surg, Chicago, IL 60611 USA. [Kitchener, Henry] Univ Manchester, Inst Canc Sci, Manchester, Lancs, England. [Ryu, Sang Young] Korea Inst Radiol & Med Sci, Korea Canc Ctr Hosp, Dept Obstet & Gynecol, Seoul, South Korea. [Viswanathan, Akila] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA. [Trimble, Ted] NCI, Washington, DC USA. [Covens, Al] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Wilailak, Sarikapan; Lertkhachonsuk, Arb-aroon; Sitathanee, Chomporn] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok, Thailand. [Mahantshetty, Umesh] Tata Mem Hosp, Mumbai, Maharashtra, India. [Fisher, Brandon] Radiating Hope, Salt Lake City, UT USA. [Springer, Susan] Elekta, Veenendaal, Netherlands. [Pollatz, Thomas] Varian Med Syst, Palo Alto, CA USA. [Spiller, Antonius] BEBIG, Lubeck Area, Lubeck, Germany. [Bacon, Monica] Gynecol Canc InterGrp, Kingston, ON, Canada. [Jhingran, Anuja] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Jhingran, A (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM ajhingra@mdanderson.org FU NCI NIH HHS [P30 CA008748] NR 11 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2016 VL 26 IS 9 BP 1690 EP 1693 DI 10.1097/IGC.0000000000000823 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA EB1JG UT WOS:000387106200022 PM 27779548 ER PT J AU Valverde, EE DiNenno, EA Schulden, JD Oster, A Painter, T AF Valverde, Eduardo E. DiNenno, Elizabeth A. Schulden, Jeffrey D. Oster, Alexandra Painter, Thomas TI Sexually transmitted infection diagnoses among Hispanic immigrant and migrant men who have sex with men in the United States SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE Bacterial disease; sexually transmitted infection; high-risk behaviour; MSM; men; Hispanic immigrant ID RISK BEHAVIORS; COMMERCIAL SEX; NORTH-CAROLINA; DAY LABORERS; SELF-REPORT; HIV RISK; CALIFORNIA; MIGRATION; SYPHILIS; FARMWORKERS AB Hispanic immigrant/migrant men who have sex with men (MSM) should be at higher risk for sexually transmitted infections/human immunodeficiency virus (STIs/HIV) given individual-level factors associated with the migration process that have been theorised to increase susceptibility to STIs/HIV among migrant populations. However, relatively little is known if these individual level factors are actually associated with the STI prevalence among this population. During 2005-2007, 2576 men and women foreign-born Hispanics were surveyed at three community-based organisations offering services to immigrant/migrant communities in the US. We analysed demographic characteristics, sexual risk behaviours, migration patterns, and factors associated with STI diagnoses (syphilis, chlamydia, and gonorrhoea) in the past 12 months among Hispanic immigrant/migrant MSM. Of 1482 Hispanic immigrant/migrant men surveyed who reported having sex in the past 12 months, 353 (24%) reported sex with a man, and of these, 302 answered questions regarding whether or not they had been diagnosed with a bacterial STI in the past year. Of these 302 men, 25% reported being married; 42% self-identified as being heterosexual and 20% as bisexual. Twenty-nine (9.6%) men reported that they had received an STI diagnosis in the past year. In the multivariate logistic regression model, men who reported receiving money or goods for sex had increased odds of a self-reported STI diagnosis. The prevalence of bacterial STIs among Hispanic immigrant/migrant MSM is lower than the prevalence of bacterial STIs among other MSM in the United States. Nevertheless, receiving money or goods for sex was significantly associated with a self-reported STI diagnosis among Hispanic immigrant/migrant MSM. It is important to understand factors contributing to participation in exchange sex among this population. HIV/STI prevention interventions tailored to non-gay identifying MSM are important for Hispanic immigrant/migrant MSM. C1 [Valverde, Eduardo E.; DiNenno, Elizabeth A.; Oster, Alexandra; Painter, Thomas] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Schulden, Jeffrey D.] NIDA, NIH, Neurosci Ctr, Bethesda, MD 20892 USA. RP Valverde, EE (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS E-47, Atlanta, GA 30329 USA. EM evalverde@cdc.gov NR 28 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PD NOV PY 2016 VL 27 IS 13 BP 1162 EP 1169 DI 10.1177/0956462415610679 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA EA9XX UT WOS:000386999100003 PM 26464501 ER PT J AU Watts, B Norton, WE AF Watts, Brook Norton, Wynne E. TI Learning from the Virtual Breakthrough Series Collaboratives in the Veterans Health Administration SO JOINT COMMISSION JOURNAL ON QUALITY AND PATIENT SAFETY LA English DT Editorial Material C1 [Watts, Brook] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Watts, Brook] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Watts, Brook] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH 44106 USA. [Norton, Wynne E.] NCI, Implementat Sci Team, Off Director, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Watts, B (reprint author), Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.; Watts, B (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.; Watts, B (reprint author), Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH 44106 USA. EM brook.watts@va.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU JOINT COMMISSION RESOURCES INC PI OAK BROOK PA 1515 W 22 ST, STE 1300W, OAK BROOK, IL 60523 USA SN 1553-7250 EI 1938-131X J9 JT COMM J QUAL PATIE JI Jt. Comm. J. Qual. Patient Saf. PD NOV PY 2016 VL 42 IS 11 BP 483 EP 484 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EB7GM UT WOS:000387554700001 PM 28266916 ER PT J AU Pergamin-Hight, L Pine, DS Fox, NA Bar-Haim, Y AF Pergamin-Hight, Lee Pine, Daniel S. Fox, Nathan A. Bar-Haim, Yair TI Attention bias modification for youth with social anxiety disorder SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Adolescence; anxiety; attention; treatment trials ID RANDOMIZED CONTROLLED-TRIAL; CHILDRENS DEPRESSION INVENTORY; PEDIATRIC ANXIETY; COGNITIVE PERFORMANCE; LONGITUDINAL DATA; MODIFICATION ABM; CLINICAL-TRIALS; THREAT; PHOBIA; CHILDHOOD AB BackgroundAttention bias modification treatment (ABMT) targets threat-related attention biases in anxiety disorders. Most clinical trials of ABMT have focused on adults or small samples of youth. The current randomized controlled trial (RCT) examines ABMT efficacy in youth with social anxiety disorder (SAD) and tests possible moderators of treatment outcomes. MethodSixty-seven youth with SAD were randomly assigned to ABMT or attention control training (ACT) conditions. Anxiety severity was measured at baseline, posttreatment, and 3-month follow-up. ClinicalTrials.gov name and identifier: Attention bias modification treatment for children with social anxiety, NCT01397032; . ResultsBoth ABMT and ACT induced significant reductions in clinician and self-rated social anxiety (ps<.001). An additional reduction was observed at the 3-month follow-up in clinician-rated anxiety symptoms (p=.03). Moderation effects were nonsignificant for the clinician-rated anxiety outcome, but age moderated self-reported anxiety. Older but not younger children, showed significant reduction in anxiety following ABMT relative to ACT (p<.001). Individual differences in attention control also moderated ABMT's effect on self-reported anxiety (p=.05). Children rated by their parents as lower on attention control benefited more from ABMT than those rated higher on attention control. Baseline attention bias did not moderate anxiety (p=.17). ConclusionsDespite significant reductions in social anxiety, no specific evidence for ABMT was found relative to a control condition. Age and attention control moderated ABMT effects on self-reported SAD symptoms, with clinical effects for older relative to younger children and for those with lower attention control. These results highlight the need to consider developmental influences in the implementation of ABMT protocols. C1 [Pergamin-Hight, Lee; Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Pine, Daniel S.] NIMH, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel. RP Pergamin-Hight, L (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. EM leepe@post.tau.ac.il FU United States-Israel Binational Science Foundation (BSF) [2009340] FX This work was partially supported by the United States-Israel Binational Science Foundation (BSF, Grant # 2009340). The authors have declared that they have no competing or potential conflicts of interest. NR 56 TC 0 Z9 0 U1 7 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2016 VL 57 IS 11 BP 1317 EP 1325 DI 10.1111/jcpp.12599 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA EB1PL UT WOS:000387125800014 PM 27435286 ER PT J AU LeMoult, J Joormann, J Kircanski, K Gotlib, IH AF LeMoult, Joelle Joormann, Jutta Kircanski, Katharina Gotlib, Ian H. TI Attentional bias training in girls at risk for depression SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Attention bias modification; depression; adolescents ID COGNITIVE VULNERABILITY; MAJOR DEPRESSION; EMOTIONAL FACES; CHILDREN; STRESS; DISORDERS; METAANALYSIS; ADOLESCENCE; PERSPECTIVE; PREVALENCE AB BackgroundThis study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression. MethodsThe final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self-reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments. ResultsAs expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor. ConclusionsThe current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents. C1 [LeMoult, Joelle; Gotlib, Ian H.] Stanford Univ, Dept Psychol, Bldg 420,Jordan Hall, Stanford, CA 94305 USA. [Joormann, Jutta] Yale Univ, Dept Psychol, New Haven, CT USA. [Kircanski, Katharina] NIMH, Dept Hlth & Human Serv, Emot & Dev Branch, NIH, Bethesda, MD 20892 USA. RP LeMoult, J (reprint author), Stanford Univ, Dept Psychol, Bldg 420,Jordan Hall, Stanford, CA 94305 USA. EM jlemoult@stanford.edu FU National Institute of Mental Health (NIMH) [F32-MH102013, F32-MH096385, MH74849]; Brain & Behavior Research Foundation [22337] FX This research was supported by the National Institute of Mental Health (NIMH) grants F32-MH102013 (JL), F32-MH096385 (KK), and MH74849 (IHG), the Brain & Behavior Research Foundation (formerly NARSAD; Young Investigator Award 22337 to JL and Distinguished Investigator Award to IHG). The authors declare that they have no competing or potential conflicts of interest. The authors thank Hannah Burley, Maria Lemus, and Talia Kori for their assistance with data collection and management. NR 38 TC 0 Z9 0 U1 12 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2016 VL 57 IS 11 BP 1326 EP 1333 DI 10.1111/jcpp.12587 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA EB1PL UT WOS:000387125800015 PM 27390111 ER PT J AU Milligan, KL Schirm, K Leonard, S Hussey, AA Agharahimi, A Kleiner, DE Fuss, I Lingala, S Heller, T Rosenzweig, SD AF Milligan, Ki L. Schirm, Karen Leonard, Stephanie Hussey, Ashleigh A. Agharahimi, Anahita Kleiner, David E. Fuss, Ivan Lingala, Shilpa Heller, Theo Rosenzweig, Sergio D. TI Ataxia telangiectasia associated with nodular regenerative hyperplasia SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Letter ID COMMON VARIABLE IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; PORTAL-HYPERTENSION; ALPHA-FETOPROTEIN; HEPATIC ABNORMALITIES; LIVER-DISEASE; DISORDERS; GENE C1 [Milligan, Ki L.; Schirm, Karen] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Milligan, Ki L.; Hussey, Ashleigh A.; Agharahimi, Anahita; Rosenzweig, Sergio D.] NIAID, Primary Immunodeficiency Clin, NIH, Bldg 10,Room 2C410,10 Ctr Dr, Bethesda, MD 20892 USA. [Leonard, Stephanie] Univ Calif San Diego, Rady Childrens Hosp, Div Allergy & Immunol, San Diego, CA 92103 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Fuss, Ivan] NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. [Lingala, Shilpa; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Rosenzweig, Sergio D.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C410,10 Ctr Dr, Bethesda, MD 20892 USA. RP Rosenzweig, SD (reprint author), NIAID, Primary Immunodeficiency Clin, NIH, Bldg 10,Room 2C410,10 Ctr Dr, Bethesda, MD 20892 USA.; Rosenzweig, SD (reprint author), NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C410,10 Ctr Dr, Bethesda, MD 20892 USA. EM srosenzweig@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2016 VL 36 IS 8 BP 739 EP 742 DI 10.1007/s10875-016-0334-x PG 4 WC Immunology SC Immunology GA EB5RD UT WOS:000387437100001 PM 27671921 ER PT J AU Bedsaul, JR Zaritsky, LA Zoon, KC AF Bedsaul, Jacquelyn R. Zaritsky, Luna A. Zoon, Kathryn C. TI Type I Interferon-Mediated Induction of Antiviral Genes and Proteins Fails to Protect Cells from the Cytopathic Effects of Sendai Virus Infection SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article DE interferon; Sendai virus; antiviral state; signaling ID HUMAN LYMPHOBLASTOID INTERFERON; PHOSPHATIDYLINOSITOL 3-KINASE; POSITIVE FEEDBACK; DENDRITIC CELLS; IFN RESPONSES; INFLUENZA-A; C-PROTEIN; ALPHA; ACTIVATION; APOPTOSIS AB Sendai virus (SeV), a murine paramyxovirus, has been used to study the induction of type I interferon (IFN) subtypes in robust quantities. Few studies have measured whether the IFN that SeV induces actually fulfills its intended purpose of interfering with virus-mediated effects in the cells in which it is produced. We determined the effects of IFN on SeV-mediated cytopathic effects (CPE) and the ability of IFN to protect against virus infection. SeV-induced biologically active IFN resulted in Jak/STAT activation and the production of a number of interferon-stimulated genes (ISGs). However, these responses did not inhibit SeV replication or CPE. This observation was not due to SeV effects on canonical IFN signaling. Furthermore, pretreating cells with type I IFN and establishing an antiviral state before infection did not mediate SeV effects. Therefore, the induction of canonical IFN signaling pathways and ISGs does not always confer protection against the IFN-inducing virus. Because type I IFNs are approved to treat various infections, our findings suggest that typical markers of IFN activity may not be indicative of a protective antiviral response and should not be used alone to determine whether an antiviral state against a particular virus is achieved. C1 [Bedsaul, Jacquelyn R.; Zaritsky, Luna A.; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, Div Intramural Res, NIH, Bldg 50 Room 5515,50 South Dr, Bethesda, MD 20892 USA. RP Zoon, KC (reprint author), NIAID, Cytokine Biol Sect, Div Intramural Res, NIH, Bldg 50 Room 5515,50 South Dr, Bethesda, MD 20892 USA. EM kzoon@niaid.nih.gov FU Intramural Research Training Award (IRTA) Program; Division of Intramural Research (DIR) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) FX This work was supported by the Intramural Research Training Award (IRTA) Program and the Division of Intramural Research (DIR) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). NR 50 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2016 VL 36 IS 11 BP 652 EP 665 DI 10.1089/jir.2016.0051 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA EB5XM UT WOS:000387454100005 PM 27508859 ER PT J AU Gorjifard, S Goldszmid, RS AF Gorjifard, Sayeh Goldszmid, Romina S. TI Microbiota-myeloid cell crosstalk beyond the gut SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE systemic immunity; host-microbial interactions; cancer; infection; mononuclear phagocytes ID HEMATOPOIETIC STEM-CELLS; GERM-FREE-MICE; TISSUE-RESIDENT MACROPHAGES; COLONY-STIMULATING FACTOR; TOLL-LIKE RECEPTORS; NOD-LIKE RECEPTOR; COMMENSAL BACTERIA; IMMUNE-RESPONSE; BONE-MARROW; PROGENITOR CELLS AB The gut microbiota is a complex and dynamic microbial ecosystem that plays a fundamental role in host physiology. Locally, the gut commensal microbes/host symbiotic relationship is vital for barrier fortification, nutrient absorption, resistance against intestinal pathogens, and the development and maintenance of the mucosal immune system. It is now clear that the effects of the indigenous intestinal flora extend beyond the gut, ranging from shaping systemic immune responses to metabolic and behavioral functions. However, the underlying mechanisms of the gut microbiota/systemic immune system interactions remain largely unknown. Myeloid cells respond to microbial signals, including those derived from commensals, and initiate innate and adaptive immune responses. In this review, we focus on the impact of the gut microbiota on myeloid cells at extraintestinal sites. In particular, we discuss how commensal-derived signals affect steady-state myelopoiesis and cellular function and how that influences the response to infection and cancer therapy. C1 [Gorjifard, Sayeh; Goldszmid, Romina S.] NCI, Inflammatory Cell Dynam Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Bldg 37 Rm 4134C,37 Convent Dr, Bethesda, MD 20892 USA. RP Goldszmid, RS (reprint author), NCI, Inflammatory Cell Dynam Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Bldg 37 Rm 4134C,37 Convent Dr, Bethesda, MD 20892 USA. EM rgoldszmid@mail.nih.gov FU Intramural Research Program of the U.S. National Institutes of Health National Cancer Institute FX This work was supported by the Intramural Research Program of the U.S. National Institutes of Health National Cancer Institute. The authors are grateful to Dr. Amiran Dzutsev for helpful discussion and critical reading of the manuscript. The authors regret omission of important articles as a result of scope and space limitations. NR 136 TC 0 Z9 0 U1 13 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2016 VL 100 IS 5 BP 865 EP 879 DI 10.1189/jlb.3RI0516-222R PG 15 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA DZ6YA UT WOS:000386007500005 PM 27605211 ER PT J AU Rosenberg, HF Masterson, JC Furuta, GT AF Rosenberg, Helene F. Masterson, Joanne C. Furuta, Glenn T. TI Eosinophils, probiotics, and the microbiome SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE Lactobacillus; Bifidobacterium; inflammation; cytokines; mucosal ID CLOSTRIDIUM-DIFFICILE INFECTION; OBSTRUCTIVE PULMONARY-DISEASE; LETHAL PNEUMOVIRUS INFECTION; ANTIGEN-PRESENTING CELLS; TEICHOIC-ACIDS; GASTROINTESTINAL-TRACT; BEIGE FAT; PREVENTION; METAANALYSIS; ASTHMA AB There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile. Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. C1 [Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike,MSC 1883,Bldg 10,Room 11C215, Bethesda, MD 20892 USA. [Masterson, Joanne C.; Furuta, Glenn T.] Childrens Hosp Colorado, Dept Pediat, Gastrointestinal Eosinophil Dis Program, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Masterson, Joanne C.; Furuta, Glenn T.] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO USA. [Masterson, Joanne C.; Furuta, Glenn T.] Univ Colorado, Sch Med, Dept Med, Mucosal Inflammat Program, Aurora, CO USA. RP Rosenberg, HF (reprint author), NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike,MSC 1883,Bldg 10,Room 11C215, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU U.S. National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [AI000941]; NIH [1K24DK100303]; Consortium for Gastrointestinal Eosinophilic Researchers (CEGIR); CEGIR is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR) [U54 AI117804]; NIAID; NIH National Institute of Diabetes and Digestive Kidney Disease; NCATS FX Supported by U.S. National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) intramural funding (AI000941 to H.F.R.), by NIH (1K24DK100303 to G.T.F.), and by the Consortium for Gastrointestinal Eosinophilic Researchers (CEGIR). CEGIR (Grant U54 AI117804) is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between NIAID, the NIH National Institute of Diabetes and Digestive Kidney Disease, and NCATS (to G.T.F.). The authors thank Dr. James J. Lee and Dr. Nancy A. Lee (Mayo Clinic, Scottsdale, AZ, USA) for the generous gift of anti-hEPX and anti-mMBP used for the immunohistochemical staining images. NR 88 TC 0 Z9 0 U1 11 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2016 VL 100 IS 5 BP 881 EP 888 DI 10.1189/jlb.3RI0416-202R PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA DZ6YA UT WOS:000386007500006 PM 27549754 ER PT J AU Shaikh, SR Fessler, MB Gowdy, KM AF Shaikh, Saame Raza Fessler, Michael B. Gowdy, Kymberly M. TI Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE respiratory infections; immunity; oxidized phospholipids; n-3 PUFAs ID POLYUNSATURATED FATTY-ACIDS; NATURAL-KILLER-CELLS; ACUTE LUNG INJURY; NF-KAPPA-B; INFLUENZA-VIRUS INFECTION; POLARIZATION IN-VIVO; NIEMANN-PICK C1; MEMORY T-CELLS; DENDRITIC CELLS; OXIDIZED PHOSPHOLIPIDS AB Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection. C1 [Shaikh, Saame Raza] East Carolina Heart Inst, East Carolina Diabet & Obes Inst, Dept Biochem & Mol Biol, Greenville, NC USA. [Gowdy, Kymberly M.] ECU, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. [Fessler, Michael B.] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Gowdy, KM (reprint author), East Carolina Univ, 600 Moye Blvd,6S-10, Greenville, NC 27834 USA. EM gowdyk14@ecu.edu FU U.S. National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIH/NIEHS) [Z01 ES102005]; NIH, National Institute of Complementary and Integrative Health [R01AT008375]; Health Effects Institute Walter Rosenblith Award FX This work was supported in part by the U.S. National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIH/NIEHS) Grant Z01 ES102005 (to MBF), and NIH, National Institute of Complementary and Integrative Health Grant R01AT008375 (to SRS), and a Health Effects Institute Walter Rosenblith Award (to KMG). The authors thank Dr. William Guesdon (ECU) for help with literature searches and Lois Wyrick (NIH/NIEHS) for assistance with drafting the figures. NR 173 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2016 VL 100 IS 5 BP 985 EP 997 DI 10.1189/jlb.4VMR0316-103R PG 13 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA DZ6YA UT WOS:000386007500017 PM 27286794 ER PT J AU Landrum, M Lee, JM Benson, M Brown, G Chen, C Chitipiralla, S Gu, B Hart, J Hoffman, D Jang, W Katz, K Ovetsky, M Riley, G Sethi, A Tully, R Rubinstein, W Maglott, D AF Landrum, M. Lee, J. M. Benson, M. Brown, G. Chen, C. Chitipiralla, S. Gu, B. Hart, J. Hoffman, D. Jang, W. Katz, K. Ovetsky, M. Riley, G. Sethi, A. Tully, R. Rubinstein, W. Maglott, D. TI ClinVar: A Centralized Database for Interpretations of Both Germline and Somatic Variants SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Meeting of the Association-for-Molecular-Pathology CY NOV 10-12, 2016 CL Charlotte, NC SP Assoc Mol Pathol C1 [Landrum, M.; Lee, J. M.; Benson, M.; Brown, G.; Chen, C.; Chitipiralla, S.; Gu, B.; Hart, J.; Hoffman, D.; Jang, W.; Katz, K.; Ovetsky, M.; Riley, G.; Sethi, A.; Tully, R.; Rubinstein, W.; Maglott, D.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2016 VL 18 IS 6 MA G02 BP 937 EP 937 PG 1 WC Pathology SC Pathology GA EB2OF UT WOS:000387201000020 ER PT J AU Lee, LC Han, M Luo, J Turner, S AF Lee, L. C. Han, M. Luo, J. Turner, S. TI CRISPR-Based Genome-Wide Knockout and Overexpression Screens Identify Novel and Putative Acquired Resistance Mechanisms to Pharmacological Inhibition of ALK in Human Neuroblastoma Cell Lines SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Meeting of the Association-for-Molecular-Pathology CY NOV 10-12, 2016 CL Charlotte, NC SP Assoc Mol Pathol C1 [Lee, L. C.; Han, M.; Turner, S.] Univ Cambridge, Cambridge, England. [Luo, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2016 VL 18 IS 6 MA S22 BP 1003 EP 1003 PG 1 WC Pathology SC Pathology GA EB2OF UT WOS:000387201000290 ER PT J AU Deharvengt, SJ de Abreu, FB Peterson, JD Daber, R Ananda, G Sarsani, V Spotlow, V Sims, DJ Harrington, RD Lih, C Williams, PM Harper, KN Bouk, CH Datta, V Konigshofer, Y Huang, C Dickens, J Tsongalis, GJ AF Deharvengt, S. J. de Abreu, F. B. Peterson, J. D. Daber, R. Ananda, G. Sarsani, V. Spotlow, V. Sims, D. J. Harrington, R. D. Lih, C. Williams, P. M. Harper, K. N. Bouk, C. H. Datta, V. Konigshofer, Y. Huang, C. Dickens, J. Tsongalis, G. J. TI The Use of Biosynthetic Controls as Performance Standards for NGS Assays of Somatic Tumors: A Multi-laboratory Study SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Meeting of the Association-for-Molecular-Pathology CY NOV 10-12, 2016 CL Charlotte, NC SP Assoc Mol Pathol C1 [Deharvengt, S. J.; de Abreu, F. B.; Peterson, J. D.; Tsongalis, G. J.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. [Deharvengt, S. J.; de Abreu, F. B.; Peterson, J. D.; Tsongalis, G. J.] Dartmouth Hitchcock Med Ctr, Geisel Sch Med, Lebanon, NH 03766 USA. [Daber, R.] Bioreference Labs, Emwood Pk, NJ USA. [Ananda, G.; Sarsani, V.; Spotlow, V.] Jackson Lab Genom Med, Farmington, CT USA. [Sims, D. J.; Harrington, R. D.; Lih, C.; Williams, P. M.; Harper, K. N.; Bouk, C. H.; Datta, V.] Leidos Biomed Res Inc, Frederick, MD USA. [Sims, D. J.; Harrington, R. D.; Lih, C.; Williams, P. M.; Harper, K. N.; Bouk, C. H.; Datta, V.] Frederick Natl Lab Canc Res, Frederick, MD USA. [Konigshofer, Y.; Huang, C.; Dickens, J.] SeraCare Life Sci Inc, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2016 VL 18 IS 6 MA TT06 BP 1031 EP 1032 PG 2 WC Pathology SC Pathology GA EB2OF UT WOS:000387201000406 ER PT J AU Taieb, D Hicks, RJ Pacak, K AF Taieb, David Hicks, Rodney J. Pacak, Karel TI Nuclear Medicine in Cancer Theranostics: Beyond the Target SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID EXPERIENCE; THERAPY C1 [Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, CERIMED, Marseille, France. [Hicks, Rodney J.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Peter MacCallum Canc Ctr, Canc Imaging & Neuroendocrine Tumour Serv, Melbourne, Vic, Australia. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD USA. RP Taieb, D (reprint author), Aix Marseille Univ, Dept Nucl Med, La Timone Univ Hosp, European Ctr Res Med Imaging, 264 Rue St Pierre, F-13385 Marseille, France. EM david.taieb@ap-hm.fr NR 11 TC 0 Z9 0 U1 4 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2016 VL 57 IS 11 BP 1659 EP 1660 DI 10.2967/jnumed.116.178343 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EB1GG UT WOS:000387097000006 PM 27445288 ER PT J AU Fisher, C Feigenbaum, K Cusack, G Wallen, GR Cox, K AF Fisher, Cheryl Feigenbaum, Kathryn Cusack, Georgie Wallen, Gwenyth R. Cox, Kim TI Developing Competency to Sustain Evidence-Based Practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PROGRAM; CARE AB Organizations must ensure that nursing care delivery is based on best evidence. This article describes how a clinical research hospital used a competency-based approach to structure the development and execution of a strategic plan and integrated evidence-based practice concepts into the activities of nurses at all levels. The article will also describe the process for developing and implementing the competency across our department including outcomes achieved. C1 [Fisher, Cheryl] NHLBI, Dept Nursing, Bldg 10, Bethesda, MD 20892 USA. [Cusack, Georgie] NHLBI, Educ & Outcomes, Bldg 10, Bethesda, MD 20892 USA. [Cox, Kim] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Feigenbaum, Kathryn; Wallen, Gwenyth R.] NIH, Ctr Clin, Dept Nursing, Bldg 10,Room 6-3525,9000 Rockville Pike, Bethesda, MD 20892 USA. RP Fisher, C (reprint author), NIH, Ctr Clin, Dept Nursing, Bldg 10,Room 6-3525,9000 Rockville Pike, Bethesda, MD 20892 USA. EM cfisher@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2016 VL 46 IS 11 BP 581 EP 585 DI 10.1097/NNA.0000000000000408 PG 5 WC Nursing SC Nursing GA EB3ER UT WOS:000387246300008 PM 27779538 ER PT J AU Sellers, SL Moss, ME Calzone, K Abdallah, KE Jenkins, JF Bonham, VL AF Sellers, Sherrill L. Moss, Melissa E. Calzone, Kathleen Abdallah, Khadijah E. Jenkins, Jean F. Bonham, Vence L. TI Nurses' Use of Race in Clinical Decision Making SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE RACE (Racial Attributes in Clinical Evaluation) Measure; clinical use of race; clinical decision making; nurses ID HEALTH-CARE; NURSING PRACTICE; VIRTUAL HUMAN; GENOMICS; KNOWLEDGE; ATTITUDES; DISPARITIES; GENETICS; IMPLICIT; ASSOCIATION AB PurposeTo examine nurses' self-reported use of race in clinical evaluation. DesignThis cross-sectional study analyzed data collected from three separate studies using the Genetics and Genomics in Nursing Practice Survey, which includes items about use of race and genomic information in nursing practice. The Racial Attributes in Clinical Evaluation (RACE) scale was used to measure explicit clinical use of race among nurses from across the United States. MethodsMultivariate regression analysis was used to examine associations between RACE score and individual-level characteristics and beliefs in 5,733 registered nurses. FindingsAnalysis revealed significant relationships between RACE score and nurses' race and ethnicity, educational level, and views on the clinical importance of patient demographic characteristics. Asian nurses reported RACE scores 1.41 points higher than White nurses (p < .001), and Black nurses reported RACE scores 0.55 points higher than White nurses (p < .05). Compared to diploma-level nurses, the baccalaureate-level nurses reported 0.69 points higher RACE scores (p < .05), master's-level nurses reported 1.63 points higher RACE scores (p < .001), and doctorate-level nurses reported 1.77 points higher RACE scores (p < .01). In terms of clinical importance of patient characteristics, patient race and ethnicity corresponded to a 0.54-point increase in RACE score (p < .001), patient genes to a 0.21-point increase in RACE score (p < .001), patient family history to a 0.15-point increase in RACE score (p < .01), and patient age to a 0.19-point increase in RACE score (p < .001). ConclusionsHigher reported use of race among minority nurses may be due, in part, to differential levels of racial self-awareness. A relatively linear positive relationship between level of nursing degree nursing education and use of race suggests that a stronger foundation of knowledge about genetic ancestry, population genetics and the concept race and genetic ancestry may increase in clinical decision making could allow nurses to more appropriately use of race in clinical care. Integrating patient demographic characteristics into clinical decisions is an important component of nursing practice. Clinical RelevanceRegistered nurses provide care for diverse racial and ethnic patient populations and stand on the front line of clinical care, making them essential for reducing racial and ethnic disparities in healthcare delivery. Exploring registered nurses' individual-level characteristics and clinical use of race may provide a more comprehensive understanding of specific training needs and inform nursing education and practice. C1 [Sellers, Sherrill L.] Miami Univ, Undergrad Educ, Oxford, OH 45056 USA. [Sellers, Sherrill L.] Miami Univ, Dept Family Studies & Social Work, Oxford, OH 45056 USA. [Moss, Melissa E.; Abdallah, Khadijah E.; Bonham, Vence L.] NHGRI, Hlth Dispar Unit, Social & Behav Res Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Calzone, Kathleen] NCI, Res, Ctr Canc Res, Genet Branch,NIH, Bethesda, MD 20892 USA. [Jenkins, Jean F.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Sellers, SL (reprint author), Miami Univ, Dept Family Studies & Social Work, 207 McGuffey Hall, Oxford, OH 45056 USA. EM sellersl@miamioh.edu FU Intramural Research Programs of the NIH National Human Genome Research Institute; National Cancer Institute; West Virginia University; National Council of State Boards of Nursing FX The authors would like to thank the Magnet (R) designated hospitals that participated in the MINC study and the nursing associations (NCEMNA and ANA) that collaborated on this project. Most importantly, the authors would like to thank the thousands of RNs who participated in the study. This research was supported in part by the Intramural Research Programs of the NIH National Human Genome Research Institute, National Cancer Institute, and the West Virginia University, and the MINC project was funded by the National Council of State Boards of Nursing. NR 50 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD NOV PY 2016 VL 48 IS 6 BP 577 EP 586 DI 10.1111/jnu.12251 PG 10 WC Nursing SC Nursing GA EB2DB UT WOS:000387166400007 PM 27676232 ER PT J AU Bigert, C Gustavsson, P Straif, K Taeger, D Pesch, B Kendzia, B Schuz, J Stucker, I Guida, F Bruske, I Wichmann, HE Pesatori, AC Landi, MT Caporaso, N Tse, LA Yu, ITS Siemiatycki, J Lavoue, J Richiardi, L Mirabelli, D Simonato, L Jockel, KH Ahrens, W Pohlabeln, H Tardon, A Zaridze, D Field, JK 't Mannetje, A Pearce, N McLaughlin, J Demers, P Szeszenia-Dabrowska, N Lissowska, J Rudnai, P Fabianova, E Dumitru, RS Bencko, V Foretova, L Janout, V Boffetta, P Peters, S Vermeulen, R Kromhout, H Bruning, T Olsson, AC AF Bigert, Carolina Gustavsson, Per Straif, Kurt Taeger, Dirk Pesch, Beate Kendzia, Benjamin Schuz, Joachim Stucker, Isabelle Guida, Florence Brueske, Irene Wichmann, Heinz-Erich Pesatori, Angela C. Landi, Maria Teresa Caporaso, Neil Tse, Lap Ah Yu, Ignatius Tak-sun Siemiatycki, Jack Lavoue, Jerome Richiardi, Lorenzo Mirabelli, Dario Simonato, Lorenzo Joeckel, Karl-Heinz Ahrens, Wolfgang Pohlabeln, Hermann Tardon, Adonina Zaridze, David Field, John K. 't Mannetje, Andrea Pearce, Neil McLaughlin, John Demers, Paul Szeszenia-Dabrowska, Neonila Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Dumitru, Rodica Stanescu Bencko, Vladimir Foretova, Lenka Janout, Vladimir Boffetta, Paolo Peters, Susan Vermeulen, Roel Kromhout, Hans Bruening, Thomas Olsson, Ann C. TI Lung Cancer Among Firefighters: Smoking-Adjusted Risk Estimates in a Pooled Analysis of Case-Control Studies SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FLORIDA PROFESSIONAL FIREFIGHTERS; PHILADELPHIA 1950-2009; OCCUPATIONAL-EXPOSURE; COHORT MORTALITY; US FIREFIGHTERS; FIRE FIGHTERS; SAN-FRANCISCO; CASE-REFERENT; NEW-ZEALAND; POPULATION AB Objectives:The aim of this study was to explore lung cancer risk among firefighters, with adjustment for smoking.Methods:We used pooled information from the SYNERGY project including 14 case-control studies conducted in Europe, Canada, New Zealand, and China, with lifetime work histories and smoking habits for 14,748 cases of lung cancer and 17,543 controls. We estimated odds ratios by unconditional logistic regression with adjustment for smoking and having ever been employed in a job known to present an excess risk of lung cancer.Results:There was no increased lung cancer risk overall or by specific cell type among firefighters (n=190), neither before nor after smoking adjustment. We observed no significant exposure-response relationship in terms of work duration.Conclusions:We found no evidence of an excess lung cancer risk related to occupational exposure as a firefighter. C1 [Bigert, Carolina; Gustavsson, Per] Karolinska Inst, Inst Environm Med, Solnavagen 4,10th Floor, SE-11365 Stockholm, Sweden. [Straif, Kurt; Schuz, Joachim; Olsson, Ann C.] Int Agcy Res Canc, Lyon, France. [Taeger, Dirk; Pesch, Beate; Kendzia, Benjamin; Bruening, Thomas] Ruhr Univ Bochum IPA, German Social Accid Insurance Inst, Inst Prevent & Occupat Med, Bochum, Germany. [Stucker, Isabelle; Guida, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Team, Villejuif, France. [Stucker, Isabelle; Guida, Florence] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France. [Brueske, Irene] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol 1, Neuherberg, Germany. [Wichmann, Heinz-Erich] Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, Heinz-Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Munich, Germany. [Wichmann, Heinz-Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany. [Pesatori, Angela C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Pesatori, Angela C.] IRCCS Ca Granda Fdn, Milan, Italy. [Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA. [Tse, Lap Ah; Yu, Ignatius Tak-sun] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Div Occupat & Environm Hlth, Hong Kong, Hong Kong, Peoples R China. [Siemiatycki, Jack; Lavoue, Jerome] Univ Montreal, Univ Montreal Hosp Ctr, Res Ctr, Montreal, PQ, Canada. [Richiardi, Lorenzo; Mirabelli, Dario] Univ Turin, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy. [Simonato, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy. [Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Ahrens, Wolfgang; Pohlabeln, Hermann] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany. [Tardon, Adonina] Univ Oviedo, CIBERESP, Oviedo, Spain. [Zaridze, David] Russian Canc Res Ctr, Moscow, Russia. [Field, John K.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool, Merseyside, England. ['t Mannetje, Andrea; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [McLaughlin, John] Publ Hlth Ontario, Toronto, ON, Canada. [Demers, Paul] Canc Care Ontario, Occupat Canc Res Ctr, Toronto, ON, Canada. [Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Rudnai, Peter] Natl Publ Hlth Ctr, Budapest, Hungary. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania. [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, Olomouc, Czech Republic. [Janout, Vladimir] Univ Ostrava, Fac Med, Ostrava, Czech Republic. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Peters, Susan; Vermeulen, Roel; Kromhout, Hans] Inst Risk Assessment Sci, Utrecht, Netherlands. [Peters, Susan] Univ Western Australia, Sch Populat Hlth, Occupat Resp Epidemiol, Perth, WA, Australia. RP Bigert, C (reprint author), Karolinska Inst, Inst Environm Med, Solnavagen 4,10th Floor, SE-11365 Stockholm, Sweden. EM carolina.bigert@ki.se RI Bruning, Thomas/G-8120-2015; Vermeulen, Roel/F-8037-2011; Yu, Ignatius Tak Sun/A-9936-2008; OI Bruning, Thomas/0000-0001-9560-5464; Vermeulen, Roel/0000-0003-4082-8163; pesatori, angela/0000-0002-0261-3252 FU AFA Insurance in Sweden [130104]; German Social Accident Insurance (DGUV); Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer; National Cancer Institute of Canada; Canadian Cancer Society; Cancer Care Ontario; French agency of health security (ANSES); Fondation de France; French National Research Agency (ANR); National Institute of Cancer (INCA); Fondation for Medical Research (FRM); French Institute for Public Health Surveillance (InVS); Health Ministry (DGS); Organization for the Research on Cancer (ARC); French Ministry of work, solidarity and public function (DGT); Federal Ministry of Education, Science, Research, and Technology [01 HK 173/0]; Federal Ministry of Science and the Ministry of Labour and Social Affairs; European Commission's INCO-COPERNICUS program; Polish State Committee for Scientific Research; Roy Castle Foundation as part of the Liverpool Lung Project; MH CZ - DRO (MMCI)in the INCO part [00209805]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD; Environmental Epidemiology Program of the Lombardy Region, Italy; Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy; Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo; Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias; Fondo de Investigacion Sanitaria (FIS),; Ciber de Epidemiologia y Salud Publica (CIBER-ESP), Spain; Research Grants Council of the Hong Kong Special Administrative Region, China; Health Research Council of New Zealand; New Zealand Department of Labour; Lottery Health Research; Cancer Society of New Zealand; Swedish Council for Work Life Research; Swedish EPA FX This study was funded by AFA Insurance in Sweden (grant no. 130104). AFA Insurance is owned by Sweden's labor market parties: the Confederation of Swedish Enterprise, the Swedish Trade Union Confederation and The Council for Negotiation and Co-operation. The SYNERGY project is funded by the German Social Accident Insurance (DGUV). The original studies were funded by a list of agencies, including the Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer, the National Cancer Institute of Canada with funds provided by the Canadian Cancer Society and Cancer Care Ontario; the French agency of health security (ANSES), the Fondation de France, the French National Research Agency (ANR), the National Institute of Cancer (INCA), the Fondation for Medical Research (FRM), the French Institute for Public Health Surveillance (InVS), the Health Ministry (DGS), the Organization for the Research on Cancer (ARC), and the French Ministry of work, solidarity and public function (DGT). In Germany, the studies were funded by the Federal Ministry of Education, Science, Research, and Technology grant no. 01 HK 173/0 and the Federal Ministry of Science and the Ministry of Labour and Social Affairs. The INCO study was supported by a grant from the European Commission's INCO-COPERNICUS program, a grant from the Polish State Committee for Scientific Research, and the Roy Castle Foundation as part of the Liverpool Lung Project. In Brno, Czech Republic, the study was supported by MH CZ - DRO (MMCI, 00209805) in the INCO part. The EAGLE study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD; the Environmental Epidemiology Program of the Lombardy Region, Italy; and the Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy. The TURIN study was supported by the Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo. The CAPUA study was supported by the Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, the Fondo de Investigacion Sanitaria (FIS), and the Ciber de Epidemiologia y Salud Publica (CIBER-ESP), Spain. The Hong Kong study was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China. The OCANZ study was funded by the Health Research Council of New Zealand, the New Zealand Department of Labour, Lottery Health Research, and by the Cancer Society of New Zealand. The Swedish study LUCAS was supported by the Swedish Council for Work Life Research and the Swedish EPA. NR 45 TC 0 Z9 0 U1 16 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 2016 VL 58 IS 11 BP 1137 EP 1143 DI 10.1097/JOM.0000000000000878 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EB3OD UT WOS:000387273800018 PM 27820764 ER PT J AU Clark, SM Pocivavsek, A Nicholson, JD Notarangelo, FM Langenberg, P McMahon, RP Kleinman, JE Hyde, TM Stiller, J Postolache, TT Schwarcz, R Tonelli, LH AF Clark, Sarah M. Pocivavsek, Ana Nicholson, James D. Notarangelo, Francesca M. Langenberg, Patricia McMahon, Robert P. Kleinman, Joel E. Hyde, Thomas M. Stiller, John Postolache, Teodor T. Schwarcz, Robert Tonelli, Leonardo H. TI Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID ACUTE TRYPTOPHAN DEPLETION; NECROSIS-FACTOR-ALPHA; REAL-TIME PCR; INTERFERON-ALPHA; QUINOLINIC ACID; ADOLESCENT DEPRESSION; ORBITOFRONTAL CORTEX; MAJOR DEPRESSION; BIPOLAR DISORDER; SUICIDE VICTIMS AB Background Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. Methods We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide. Results We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon- and tumour necrosis factor-. Notably, quinolinic acid levels were also lower in depressed individuals than controls. Limitations Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons. Conclusion Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC. C1 [Clark, Sarah M.; Nicholson, James D.; Tonelli, Leonardo H.] Univ Maryland, Sch Med, Dept Psychiat, Lab Behav Neuroimmunol, 655 W Baltimore St, Baltimore, MD 21201 USA. [Pocivavsek, Ana; Notarangelo, Francesca M.; McMahon, Robert P.; Schwarcz, Robert] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, 655 W Baltimore St, Baltimore, MD 21201 USA. [Langenberg, Patricia] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 655 W Baltimore St, Baltimore, MD 21201 USA. [Kleinman, Joel E.; Hyde, Thomas M.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. [Kleinman, Joel E.; Hyde, Thomas M.] Lieber Inst Brain Dev, Johns Hopkins Med Campus, Baltimore, MD USA. [Stiller, John; Postolache, Teodor T.] Univ Maryland, Sch Med, Dept Psychiat, Mood & Anxiety Program, 655 W Baltimore St, Baltimore, MD 21201 USA. RP Tonelli, LH (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Lab Behav Neuroimmunol, 655 W Baltimore St, Baltimore, MD 21201 USA. EM ltonelli@psych.umaryland.edu FU National Institute of Mental Health [MH097676, MH083729] FX This study was supported in part by grants from the National Institute of Mental Health (MH097676 to L.H.T. and MH083729 to R.S.). Ryan Mulford and Partam Manalai are acknowledged for their technical assistance with tissue processing and mRNA purification. NR 61 TC 0 Z9 0 U1 5 U2 5 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 EI 1488-2434 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD NOV PY 2016 VL 41 IS 6 BP 386 EP 394 DI 10.1503/jpn.150226 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EB1OD UT WOS:000387121400007 PM 27070351 ER PT J AU Nansel, TR Lipsky, LM Eisenberg, MH Liu, AY Mehta, SN Laffel, LMB AF Nansel, Tonja R. Lipsky, Leah M. Eisenberg, Miriam H. Liu, Aiyi Mehta, Sanjeev N. Laffel, Lon M. B. TI Can Families Eat Better Without Spending More? Improving Diet Quality Does Not Increase Diet Cost in a Randomized Clinical Trial among Youth with Type 1 Diabetes and Their Parents SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Diet quality; Diet cost; Type 1 diabetes; Intervention; Families ID ENERGY-DENSITY; LOW-INCOME; SOCIOECONOMIC-STATUS; HEALTHFUL DIET; UNITED-STATES; FOOD COSTS; US ADULTS; FAT DIETS; NUTRITION; WOMEN AB Background Although cost is a frequently cited barrier to healthful eating, limited prospective data exist. Objective To examine the association of diet cost with diet quality change. Design An 18-month randomized clinical trial evaluated a dietary intervention. Participants and setting Youth with type 1 diabetes duration >= 1 year, age 8.0 to 16.9 years, receiving care at an outpatient tertiary diabetes center in Boston, MA, participated along with a parent from 2010 to 2013 (N=136). Eighty-two percent of participants were from middle- to upper-income households. Intervention The family-based behavioral intervention targeted intake of whole plant foods. Main outcome measures Diet quality as indicated by the Healthy Eating Index 2005 (HEI-2005) (which measures conformance to the 2005 Dietary Guidelines for Americans) and whole plant food density (cup or ounce equivalents per 1,000 kcal target food groups) were calculated from 3-day food records of youth and parent dietary intake at six and four time points, respectively. Food prices were obtained from two online supermarkets common to the study location. Daily diet cost was calculated by summing prices of reported foods. Statistical analyses performed Random effects models estimated treatment group differences in time-varying diet cost. Separate models for youth and parent adjusted for covariates examined associations of time-varying change in diet quality with change in diet cost. Results There was no treatment effect on time-varying diet cost for either youth (0.49, 95% CI -1.07 to 0.08; P=0.10) or parents (beta .24, 95% CI -1.61 to 2.08; P=0.80). In addition, time-varying change in diet quality indicators was not associated with time varying change in diet cost for youth. Among parents, a 1-cup or 1-oz equivalent increase in whole plant food density was associated with a $0.63/day lower diet cost (0.63, 95% CI -1.20 to 0.05; P=0.03). Conclusions Improved diet quality was not accompanied by greater cost for youth with type 1 diabetes and their parents participating in a randomized clinical trial. Findings challenge the prevailing assumption that improving diet quality necessitates greater cost. C1 [Nansel, Tonja R.; Lipsky, Leah M.; Eisenberg, Miriam H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20892 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Mehta, Sanjeev N.; Laffel, Lon M. B.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Laffel, Lon M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20892 USA.; Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, Bethesda, MD USA. EM nanselt@mail.nih.gov OI Eisenberg, Miriam/0000-0002-7133-8805; Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082; Lipsky, Leah/0000-0003-2645-4388 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C, HHSN2752008000031/HHSN275002] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract nos. HHSN267200703434C and HHSN2752008000031/HHSN275002. NR 60 TC 0 Z9 0 U1 15 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2016 VL 116 IS 11 BP 1751 EP 1759 DI 10.1016/j.jand.2016.07.005 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EB2OZ UT WOS:000387203000004 PM 27597745 ER PT J AU Costello, RB Dwyer, JT Saldanha, L Bailey, RL Merkel, J Wambogo, E AF Costello, Rebecca B. Dwyer, Johanna T. Saldanha, Leila Bailey, Regan L. Merkel, Joyce Wambogo, Edwina TI Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes? A Narrative Review SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Review DE Cinnamon; Fasting plasma glucose; Hemoglobin A1c; Type 2 diabetes mellitus ID FASTING BLOOD-GLUCOSE; 3T3-L1 ADIPOCYTES; CLINICAL-TRIAL; EXTRACT; INSULIN; METAANALYSIS; HEMOGLOBIN; SAFETY; METABOLISM; COUMARIN AB Cinnamon (Cinnamomum sp) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control, although conclusions from meta analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven randomized controlled trials were identified that met our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies, participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blind. Cinnamon doses ranged from 120 to 6,000 mg/day. The species of cinnamon used varied: seven used Cinnamomum cassia or Cinnamomum aromaticum, one used Cinnamomum zeylanicum, and three did not disclose the species. Because of the heterogeneity of the studies, a meta-analysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, whereas changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L [130 mg/dL] and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, registered dietitian nutritionists and other health care professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs. C1 [Costello, Rebecca B.; Dwyer, Johanna T.; Saldanha, Leila; Bailey, Regan L.; Merkel, Joyce; Wambogo, Edwina] NIH, Off Dietary Supplements, 6100 Execut Blvd,Suite 3B01, Bethesda, MD 20892 USA. [Dwyer, Johanna T.] Tufts Univ, Sch Med, Nutr, Boston, MA 02111 USA. [Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Dwyer, Johanna T.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Ctr Aging, Boston, MA 02111 USA. [Bailey, Regan L.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. RP Costello, RB (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Suite 3B01, Bethesda, MD 20892 USA. EM costellb@od.nih.gov FU Office of Dietary Supplements of the National Institutes of Health, Department of Health and Human Services; US Department of Agriculture, Agricultural Research Service [58-1950-0-014] FX This work was supported by the Office of Dietary Supplements of the National Institutes of Health, Department of Health and Human Services. Partial support was also provided by the US Department of Agriculture, Agricultural Research Service, under agreement no. 58-1950-0-014. NR 50 TC 1 Z9 1 U1 13 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2016 VL 116 IS 11 BP 1794 EP 1802 DI 10.1016/j.jand.2016.07.015 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EB2OZ UT WOS:000387203000009 PM 27618575 ER PT J AU de Jesus, JM Kahan, S Eckel, RH AF de Jesus, Janet M. Kahan, Scott Eckel, Robert H. TI Nutrition Interventions for Cardiovascular Disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Physician counseling; Nutrition therapy; Cardiovascular disease; Risk factor; Treatment; Prevention; Blood pressure; Lipids ID CORONARY-HEART-DISEASE; MODERATE ALCOHOL-CONSUMPTION; RANDOMIZED CONTROLLED-TRIAL; DIETARY FATTY-ACIDS; LOW-GLYCEMIC-INDEX; BLOOD-PRESSURE; MEDITERRANEAN DIET; RISK-FACTORS; CLINICAL-TRIAL; SODIUM-INTAKE AB Nutrition therapy is effective at controlling cardiovascular disease risk factors and therefore reducing cardiovascular disease risk. Physicians should play an active role in providing nutrition interventions for patients who would benefit from cardiovascular disease risk reduction or refer them to other professionals as needed. The evidence on nutrition interventions for blood pressure and lipid control, including overall dietary patterns, dietary fat and macronutrients, dietary cholesterol, sodium, and alcohol intake, is discussed. C1 [de Jesus, Janet M.] NHLBI, CTRIS, NIH, Rockledge 1 Bldg,Room 6189,MSC 7960, Bethesda, MD 20817 USA. [Kahan, Scott] George Washington Univ, Sch Med & Hlth Sci, Dept Hlth Policy, 1020 19th St NW,Suite 450, Washington, DC 20036 USA. [Eckel, Robert H.] Univ Colorado Denver Anschutz Med Campus, Div Endocrinol Metab & Diabet, Res Complex 1 South, Aurora, CO 80045 USA. RP de Jesus, JM (reprint author), NHLBI, CTRIS, NIH, Rockledge 1 Bldg,Room 6189,MSC 7960, Bethesda, MD 20817 USA. EM dejesusjm@mail.nih.gov NR 83 TC 0 Z9 0 U1 9 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2016 VL 100 IS 6 BP 1251 EP + DI 10.1016/j.mcna.2016.06.007 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA EB8JO UT WOS:000387637500009 PM 27745593 ER PT J AU Ko, SU Simonsick, EM Deshpande, N Studenski, S Ferrucci, L AF Ko, Seung-uk Simonsick, Eleanor M. Deshpande, Nandini Studenski, Stephanie Ferrucci, Luigi TI Ankle Proprioception-Associated Gait Patterns in Older Adults: Results from the Baltimore Longitudinal Study of Aging SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ANKLE PROPRIOCEPTION; MECHANICAL WORK EXPENDITURE; BLSA GAIT LAB; IMPAIRED BALANCE IN GAIT ID NARROW-BASE WALKING; AGE; FALLS; STABILITY; PROPULSION; ABILITY; BALANCE; SPEED; RISK AB Introduction Ankle proprioception training has been found to improve balance-related gait disorders; however, the relationship between ankle proprioception and specific gait patterns in older adults with and without impaired balance has not been systematically examined. Methods This study characterizes gait patterns of 230 older adults age 60-95 yr evaluated in the Baltimore Longitudinal Study of Aging gait laboratory with (n = 82) and without impaired balance (inability to successfully complete a narrow walk) and examines ankle proprioception performance. Results Participants with impaired balance had a higher angle threshold for perceiving ankle movement than those without impaired balance even after controlling for the substantial age difference between groups (P = 0.017). Gait speed, stride length, hip and ankle range of motion, and mechanical work expenditure from the knee and ankle were associated with ankle proprioception performance (P < 0.050 for all) in the full sample, but these associations were evident only in participants with impaired balance in stratified analysis. Conclusion Ankle proprioception in older persons with balance impairment may play a role in balance-related gait disorders and should be targeted for intervention. C1 [Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, South Korea. [Simonsick, Eleanor M.; Studenski, Stephanie; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Deshpande, Nandini] Queens Univ, Sch Rehabil Therapy, Kingston, ON, Canada. RP Ko, SU (reprint author), Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, South Korea. EM seunguk.ko@gmail.com FU Intramural Research Program of the National Institutes of Health; National Institute on Aging; Chonnam National University FX This article was supported by the Intramural Research Program of the National Institutes of Health, the National Institute on Aging, and the Chonnam National University. Data for these analyses were obtained from the BLSA, a study performed by the National Institute on Aging. The results of the present study do not constitute endorsement by the American College of Sports Medicine. NR 22 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2016 VL 48 IS 11 BP 2190 EP 2194 DI 10.1249/MSS.0000000000001017 PG 5 WC Sport Sciences SC Sport Sciences GA EA4OU UT WOS:000386593200015 PM 27327030 ER PT J AU Gallicchio, L Flaws, JA Smith, RL AF Gallicchio, Lisa Flaws, Jodi A. Smith, Rebecca L. TI Age at menarche, androgen concentrations, and midlife obesity: findings from the Midlife Women's Health Study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Androgens; Menarche; Menopause; Obesity ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; ADULT OBESITY; HOT FLASHES; GIRLS; RISK; PUBERTY; EARLIER; ONSET; HORMONES AB Objective: Studies have shown that earlier age at menarche is associated with a higher risk of midlife obesity; however, the mechanism underlying this association is not known. The purpose of this study was to examine whether the association between age at menarche and midlife obesity is due to variation in circulating androgen concentrations. Methods: Baseline data were analyzed from 748 women aged 45 to 54 years enrolled in the Midlife Women's Health Study, a prospective cohort study conducted in the Baltimore, MD region. Information on age at menarche was collected through a self-administered questionnaire. Body mass index (BMI) was calculated using height and weight measured at a clinic visit. Obesity was defined as a BMI between 30 and 34.9 kg/m(2); super obesity was defined as a BMI greater than 35 kg/m(2). Testosterone, estradiol, and sex hormone-binding globulin were measured in blood samples using enzyme-linked immunosorbent assays. The free androgen index (FAI) was calculated using the formula: (testosterone x 3.467)/sex hormone-binding globulin x 100. Results: After adjustment for covariates, for each year increase in age at menarche, the odds of obesity and super obesity decreased by 31% (odds ratio (OR) 0.69; 95% confidence limits (CL) 0.59, 0.81) and 34% (OR 0.66; 95% CL 0.52, 0.83), respectively. Addition of the FAI into the models did not attenuate the observed estimates. Conclusions: The results of this study indicate that age at menarche is associated with midlife obesity independent of free testosterone concentrations measured in adulthood. C1 [Gallicchio, Lisa] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Flaws, Jodi A.] Univ Illinois, Coll Vet Med, Dept Comparat Biosci, Urbana, IL 61801 USA. [Smith, Rebecca L.] Univ Illinois, Coll Vet Med, Dept Pathobiol, 2001 S Lincoln Ave, Urbana, IL 61802 USA. RP Smith, RL (reprint author), Univ Illinois, Coll Vet Med, Dept Pathobiol, 2001 S Lincoln Ave, Urbana, IL 61802 USA. EM rlsdvm@illinois.edu FU NIH [R01 AG018400] FX NIH R01 AG018400. NR 38 TC 1 Z9 1 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV PY 2016 VL 23 IS 11 BP 1182 EP 1188 DI 10.1097/GME.0000000000000691 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EB3GR UT WOS:000387252300006 PM 27433862 ER PT J AU Gordon, JL Rubinow, DR Thurston, RC Paulson, J Schmidt, PJ Girdler, SS AF Gordon, Jennifer L. Rubinow, David R. Thurston, Rebecca C. Paulson, Julia Schmidt, Peter J. Girdler, Susan S. TI Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Catecholamines; Cortisol; Hemodynamics; Hot flashes; Hot flushes; Inflammation; Night sweats; Stress reactivity; Trier Social Stress Test; Vasomotor symptoms ID INTIMA-MEDIA THICKNESS; CORONARY-ARTERY CALCIFICATION; LEFT-VENTRICULAR HYPERTROPHY; HEART-RATE-VARIABILITY; CARDIAC VAGAL CONTROL; HOT FLASHES; POSTMENOPAUSAL WOMEN; MENTAL STRESS; PSYCHOLOGICAL STRESS; MENOPAUSAL SYMPTOMS AB Objective: Vasomotor symptoms (VMS) may be associated with an increased risk of cardiovascular disease. One candidate mechanism may involve alterations in physiological responses to stress. The current study therefore examined the relationship between self-reported VMS bother and cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses to an acute psychosocial stress protocol. Methods: One hundred eighty-six women in the menopausal transition or early postmenopausal stage (age 45-60 y) provided the data for this article. Subjective hot flash and night sweat bother were assessed using the Greene Climacteric Scale. Women also underwent a stressor battery involving a speech and a mental arithmetic task while cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses were assessed. Repeated measures regression analyses were used to examine the relationship between self-reported VMS and physiologic responses to the stressor. Results: In multivariate analyses adjusting for potential confounders, self-reported hot flash bother was associated with lower overall cardiac index and stroke volume index and higher overall vascular resistance index and levels of the inflammatory cytokine interleukin-6. Hot flash bother also tended to be associated with higher overall cortisol levels and higher baseline levels of plasma norepinephrine. Night sweat bother, on the other hand, was associated with higher overall cortisol levels and tended to be associated with higher interleukin-6. Conclusions: Self-reported VMS bother is associated with an unfavorable hemodynamic and neuroendocrine profile characterized by increased hypothalamic-pituitary-adrenal axis and central sympathetic activation, inflammation, and vasoconstriction. Further research investigating this profile in relation to VMS, and the potential health implications of this association, is warranted. C1 [Gordon, Jennifer L.; Rubinow, David R.; Paulson, Julia; Girdler, Susan S.] Univ North Carolina Chapel Hill, Dept Psychiat, Chapel Hill, NC USA. [Thurston, Rebecca C.] Univ Pittsburgh, Dept Psychiat Epidemiol & Psychol, Pittsburgh, PA 15260 USA. [Schmidt, Peter J.] NIMH, Sect Behav Endocrinol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Girdler, SS (reprint author), Univ North Carolina Chapel Hill, Sch Med, Dept Psychiat, CB 7160,101 Manning Dr, Chapel Hill, NC 27599 USA. EM Susan_Girdler@med.unc.edu FU NIH [RO1-MH087619] FX This research was supported by NIH grant RO1-MH087619. NR 56 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV PY 2016 VL 23 IS 11 BP 1189 EP 1198 DI 10.1097/GME.0000000000000689 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EB3GR UT WOS:000387252300007 PM 27465715 ER PT J AU Hibler, EA Kauderer, J Greene, MH Rodriguez, GC Alberts, DS AF Hibler, Elizabeth A. Kauderer, James Greene, Mark H. Rodriguez, Gustavo C. Alberts, David S. TI Bone loss after oophorectomy among high-risk women: an NRG oncology/gynecologic oncology group study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Bone mineral density; Oophorectomy; Premenopausal ID REDUCING SALPINGO-OOPHORECTOMY; HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; BISPHOSPHONATE THERAPY; MUTATION CARRIERS; ZOLEDRONIC ACID; EARLY MENOPAUSE; OVARIAN-CANCER; FRACTURE RISK; OSTEOPOROSIS AB Objective: Women undergoing premenopausal oophorectomy for a variety of reasons, including to reduce ovarian or breast cancer risk were evaluated for accelerated bone loss. Methods: The Gynecologic Oncology Group (GOG)-0215 randomized phase-II trial of zoledronic acid was initiated to determine if postoophorectomy bisphosphonate therapy could prevent this bone loss. The study was closed after slow accrual prevented evaluation of the primary study endpoint. We analyzed changes in bone mineral density (BMD) among the 80 women randomized to the observation arm of this study, as measured 3, 9, and 18 months postenrollment. Results: The mean change in BMD from baseline to 18 months was -0.09 (95% CI, -0.12 to -0.07), -0.05 (95% CI, -0.07 to -0.03), and -0.06 (95% CI, -0.07 to -0.05) g/cm(2) across the lumbar spine, right hip, and left hip, respectively. This represents a BMD decrease of -8.5% for the lumbar spine and -5.7% for both the right and left hips from baseline to 18 months' observation. Conclusions: These results demonstrate that premenopausal women undergoing oophorectomy clearly experience bone loss, an adverse effect of oophorectomy, which requires attention and active management. BMD should be monitored postoophorectomy, and treated per standard practice guidelines. Future studies will be required to determine if early treatment can mitigate fracture risk, and to test promising therapeutic interventions and novel prevention strategies, such as increased physical activity or alternative medications, in randomized trials. C1 [Hibler, Elizabeth A.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA. [Hibler, Elizabeth A.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Kauderer, James] Roswell Pk Canc Inst, Stat & Data Ctr, NRG Oncol Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Greene, Mark H.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA. [Rodriguez, Gustavo C.] Northshore Univ Hlth, Kellogg Canc Ctr, Evanston, IL USA. [Alberts, David S.] Univ Arizona, Ctr Canc, Tucson, AZ USA. RP Hibler, EA (reprint author), Northwest Univ, Chicago, IL 60611 USA. EM elizabeth.hibler@northwestern.edu FU National Cancer Institute [CA 27469, CA 37517, 1 U10 CA180822, U10CA180868, U10CA101165]; Novartis Pharmaceuticals [GOG-0215]; National Cancer Institute; NCI [R25 CA-160056] FX This study was supported by the National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the GOG Statistical and Data Center (CA 37517), NRG Oncology (1 U10 CA180822), NRG Operations (U10CA180868), and GOG CCOP RB (U10CA101165). Funding for the present study (GOG-0215) was provided by Novartis Pharmaceuticals, which was not involved in the data collection, analysis, interpretation, or writing of manuscripts related to this study. The research of M.H.G. was supported by the Intramural Research Program of the National Cancer Institute. E.A.H. was supported by the NCI R25 CA-160056 awarded to Vanderbilt University. The GOG owns the data from the study and the authors had the full responsibility for the decision to submit the results for publication. The following GOG member institutions participated in this protocol: Roswell Park Cancer Institute, Walter Reed National Military Medical Center, University of Minnesota Medical Center-Fairview, University of Colorado Cancer Center-Anschutz Cancer Pavilion, University of California at Los Angeles Health System, University of Cincinnati, University of North Carolina at Chapel Hill, University of California Medical Center at Irvine, The University of New Mexico Cancer Center, Ohio State University Comprehensive Cancer Center, Fox Chase Cancer Center, Women's Cancer Center of Nevada, University of Oklahoma Health Sciences Center, University of Virginia, Mayo Clinic, Case Western Reserve University, Yale University, Women & Infants Hospital, and Community Clinical Oncology Program. NR 38 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV PY 2016 VL 23 IS 11 BP 1228 EP 1232 DI 10.1097/GME.0000000000000692 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EB3GR UT WOS:000387252300012 PM 27433858 ER PT J AU Amin, ND Zheng, YL Binukumar, BK Shukla, V Skuntz, S Grant, P Steiner, J Bhaskar, M Pant, HC AF Amin, Niranjana D. Zheng, Yali Binukumar, B. K. Shukla, Varsha Skuntz, Susan Grant, Philip Steiner, Joseph Bhaskar, Manju Pant, Harish C. TI The interaction of Munc 18 (p67) with the p10 domain of p35 protects in vivo Cdk5/p35 activity from inhibition by TFP5, a peptide derived from p35 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; ACTIVATOR P25; TAU HYPERPHOSPHORYLATION; PROTEOLYTIC CLEAVAGE; NEURONAL CELLS; BOVINE BRAIN; NEUROFILAMENT; PROTEINS; NEURODEGENERATION AB In a series of studies, we have identified TFP5, a truncated fragment of p35, the Cdk5 kinase regulatory protein, which inhibits Cdk5/p35 and the hyperactive Cdk5/p25 activities in test tube experiments. In cortical neurons, however, and in vivo in Alzheimer's disease (AD) model mice, the peptide specifically inhibits the Cdk5/p25 complex and not the endogenous Cdk5/p35. To account for the selective inhibition of Cdk5/p25 activity, we propose that the "p10" N-terminal domain of p35, absent in p25, spares Cdk5/p35 because p10 binds to macromolecules (e.g., tubulin and actin) as a membrane-bound multimeric complex that favors p35 binding to Cdk5 and catalysis. To test this hypothesis, we focused on Munc 18, a key synapse-associated neuronal protein, one of many proteins copurifying with Cdk5/p35 in membrane-bound multimeric complexes. Here we show that, in vitro, the addition of p67 protects Cdk5/p35 and has no effect on Cdk5/p25 activity in the presence of TFP5. In cortical neurons transfected with p67siRNA, we also show that TFP5 inhibits Cdk5/p35 activity, whereas in the presence of p67 the activity is protected. It does so without affecting any other kinases of the Cdk family of cyclin kinases. This difference may be of significant therapeutic value because the accumulation of the deregulated, hyperactive Cdk5/p25 complex in human brains has been implicated in pathology of AD and other neurodegenerative disorders. C1 [Amin, Niranjana D.; Zheng, Yali; Binukumar, B. K.; Shukla, Varsha; Skuntz, Susan; Grant, Philip; Steiner, Joseph; Bhaskar, Manju; Pant, Harish C.] NINDS, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU Intramural Research Programs of the National Institutes of Health, National Institute of Neurological Disorders and Stroke FX We acknowledge Christine Winters (National Institutes of Health, National Institute of Neurological Disorders and Stroke) for providing cortices for the cortical neuron preparations. This research was supported by the Intramural Research Programs of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 57 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV 1 PY 2016 VL 27 IS 21 BP 3221 EP 3232 DI 10.1091/mbc.E15-12-0857 PG 12 WC Cell Biology SC Cell Biology GA EB5BV UT WOS:000387389000012 PM 27630261 ER PT J AU Smith, RC King, JG Tao, DY Zeleznik, OA Brando, C Thallinger, GG Dinglasan, RR AF Smith, Ryan C. King, Jonas G. Tao, Dingyin Zeleznik, Oana A. Brando, Clara Thallinger, Gerhard G. Dinglasan, Rhoel R. TI Molecular Profiling of Phagocytic Immune Cells in Anopheles gambiae Reveals Integral Roles for Hemocytes in Mosquito Innate Immunity SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PLASMODIUM-FALCIPARUM INFECTION; MALARIA PARASITES; ANTIPLASMODIAL IMMUNITY; DROSOPHILA-MELANOGASTER; ACTIN CYTOSKELETON; AEDES-AEGYPTI; RESPONSES; GENES; PROPHENOLOXIDASE; MELANIZATION AB The innate immune response is highly conserved across all eukaryotes and has been studied in great detail in several model organisms. Hemocytes, the primary immune cell population in mosquitoes, are important components of the mosquito innate immune response, yet critical aspects of their biology have remained uncharacterized. Using a novel method of enrichment, we isolated phagocytic granulocytes and quantified their proteomes by mass spectrometry. The data demonstrate that phagocytosis, blood-feeding, and Plasmodium falciparum infection promote dramatic shifts in the proteomic profiles of An. gambiae granulocyte populations. Of interest, large numbers of immune proteins were induced in response to blood feeding alone, suggesting that granulocytes have an integral role in priming the mosquito immune system for pathogen challenge. In addition, we identify several granulocyte proteins with putative roles as membrane receptors, cell signaling, or immune components that when silenced, have either positive or negative effects on malaria parasite survival. Integrating existing hemocyte transcriptional profiles, we also compare differences in hemocyte transcript and protein expression to provide new insight into hemocyte gene regulation and discuss the potential that post-transcriptional regulation may be an important component of hemocyte gene expression. These data represent a significant advancement in mosquito hemocyte biology, providing the first comprehensive proteomic profiling of mosquito phagocytic granulocytes during homeostasis blood-feeding, and pathogen challenge. Together, these findings extend current knowledge to further illustrate the importance of hemocytes in shaping mosquito innate immunity and their principal role in defining malaria parasite survival in the mosquito host. C1 [Smith, Ryan C.; King, Jonas G.; Tao, Dingyin; Brando, Clara; Dinglasan, Rhoel R.] Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, 615 North Wolfe St, Baltimore, MD 21205 USA. [Smith, Ryan C.; King, Jonas G.; Tao, Dingyin; Brando, Clara; Dinglasan, Rhoel R.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, 615 North Wolfe St, Baltimore, MD 21205 USA. [Zeleznik, Oana A.; Thallinger, Gerhard G.] Graz Univ Technol, Inst Knowledge Discovery, Bioinformat, A-8010 Graz, Austria. [Zeleznik, Oana A.; Thallinger, Gerhard G.] BioTechMed OM Ctr Graz, A-8010 Graz, Austria. [Smith, Ryan C.] Iowa State Univ, Dept Entomol, Ames, IA 50011 USA. [King, Jonas G.] Mississippi State Univ, Dept Biochem Mol Biol Entomol & Plant Pathol, Starkville, MS 39762 USA. [Tao, Dingyin] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Dinglasan, Rhoel R.] Univ Florida, Dept Infect Dis & Immunol, Emerging Pathogens Inst, 2055Mowry Rd,Room 375, Gainesville, FL 32611 USA. RP Dinglasan, RR (reprint author), Univ Florida, Dept Infect Dis & Immunol, Emerging Pathogens Inst, 2055Mowry Rd,Room 375, Gainesville, FL 32611 USA. EM rdinglasan@epi.ufl.edu FU Bloomberg Family Foundation through the Johns Hopkins Malaria Research Institute; Austrian BMWFJ; BMVIT; SFG; Standortagentur Tirol; ZIT through the Austrian FFG-COMET-Funding Program FFG [824186]; JHMRI FX The work was supported in part by the Bloomberg Family Foundation through the Johns Hopkins Malaria Research Institute (to RRD) and the Austrian BMWFJ, BMVIT, SFG, Standortagentur Tirol, and ZIT through the Austrian FFG-COMET-Funding Program FFG grant #824186 (to GGT). Additional support was provided by a JHMRI Postdoctoral fellowship (to RCS). NR 64 TC 0 Z9 0 U1 8 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2016 VL 15 IS 11 BP 3373 EP 3387 DI 10.1074/mcp.M116.060723 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA EB6OX UT WOS:000387505500004 PM 27624304 ER PT J AU Nagaya, T Nakamura, Y Sato, K Harada, T Choyke, PL Kobayashi, H AF Nagaya, Tadanobu Nakamura, Yuko Sato, Kazuhide Harada, Toshiko Choyke, Peter L. Kobayashi, Hisataka TI Near infrared photoimmunotherapy of B-cell lymphoma SO MOLECULAR ONCOLOGY LA English DT Article DE Near infrared photoimmunotherapy; CD20; B-cell lymphoma; Monoclonal antibodies; Near infrared light; Molecular imaging ID ADULT BURKITT-LYMPHOMA; ENHANCED PERMEABILITY; IN-VIVO; ANTIBODY; RITUXIMAB; IMMUNOTHERAPY; CHEMOTHERAPY; CD20; LYMPHOCYTES; DEPLETION AB Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular target for this disease. Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines (Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated with IRDye700DX, showed specific binding, and cell-specific killing only after exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v. only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups ( p < 0.001 for both tumors), and survival was significantly prolonged in both tumors ( p < 0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More than half of tumors were cured with this single regimen of NIR-PIT. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. C1 [Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; 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, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research [ZIA BC011513] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIA BC011513). NR 26 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD NOV PY 2016 VL 10 IS 9 BP 1404 EP 1414 DI 10.1016/j.molonc.2016.07.010 PG 11 WC Oncology SC Oncology GA EA8BR UT WOS:000386860800003 PM 27511870 ER PT J AU Lucas, CL Chandra, A Nejentsev, S Condliffe, AM Okkenhaug, K AF Lucas, Carrie L. Chandra, Anita Nejentsev, Sergey Condliffe, Alison M. Okkenhaug, Klaus TI PI3K delta and primary immunodeficiencies SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID PHOSPHOINOSITIDE 3-KINASE P110-DELTA; T-CELL DIFFERENTIATION; CLASS-IA PI3K; CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANSCRIPTION FACTOR FOXO1; CLASS-SWITCH RECOMBINATION; GERMINAL CENTER REACTION; HYPER IGM SYNDROME; GAIN-OF-FUNCTION; IMPAIRED B-CELL AB Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110 delta) and PIK3R1 (which encodes p85 alpha) that cause a combined immunodeficiency syndrome, referred to as activated PI3K delta syndrome (APDS; also known as p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3K delta in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3K delta gleaned from these patients, as well as implications of these findings for clinical therapy. C1 [Lucas, Carrie L.] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lucas, Carrie L.] NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lucas, Carrie L.] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06511 USA. [Chandra, Anita; Okkenhaug, Klaus] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England. [Chandra, Anita; Nejentsev, Sergey] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England. [Condliffe, Alison M.] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2RX, S Yorkshire, England. RP Okkenhaug, K (reprint author), Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England. EM klaus.okkenhaug@babraham.ac.uk FU Intramural Research Program of NIAID, NIH; National Heart, Lung and Blood Institute (NHLBI), NIH [K99/R00]; Yale University; Wellcome Trust, UK; UK medical Research Council [MR/M012328/2]; GlaxoSmithKline; EU FP7 collaborative grant [261441]; UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre; British Lung Foundation [RG14-1]; Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/B/000C0407, BBS/E/B/000C0409]; Wellcome Trust [095691/Z/11/Z] FX The authors thank R. Kissinger at Visual Medical Arts, Research and Technologies Branch, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH) for artistic contributions to initial drafts of figures 1-4. C.L.L. was supported by the Intramural Research Program of NIAID, NIH and is now supported by a K99/R00 award from the National Heart, Lung and Blood Institute (NHLBI), NIH and Yale University. A.C. and S.N. are supported by fellowships from the Wellcome Trust, UK. S.N., A.M.C. and K.O. are recipients of a programme grant MR/M012328/2 from the UK medical Research Council and GlaxoSmithKline to investigate APDS. S.N. is also supported by the EU FP7 collaborative grant 261441 and the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. A.M.C. also received funding from the British Lung Foundation (RG14-1). Work in the K.O. laboratory is also supported by grants from the Biotechnology and Biological Sciences Research Council (BBSRC: BBS/E/B/000C0407, BBS/E/B/000C0409) and from the Wellcome Trust (095691/Z/11/Z). We are grateful to the many colleagues who have contributed to our understanding of APDS. The authors apologize to those whose contributions could not be cited owing to space constraints. NR 91 TC 3 Z9 3 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2016 VL 16 IS 11 BP 702 EP 714 DI 10.1038/nri.2016.93 PG 13 WC Immunology SC Immunology GA EB1RF UT WOS:000387131400010 PM 27616589 ER PT J AU Bowen, LN Smith, B Reich, D Quezado, M Nath, A AF Bowen, Lauren N. Smith, Bryan Reich, Daniel Quezado, Martha Nath, Avindra TI HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment SO NATURE REVIEWS NEUROLOGY LA English DT Review ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; TUBERCULOUS MENINGITIS PRESENTATION; IMMUNODEFICIENCY-SYNDROME AIDS; CRYPTOCOCCAL MENINGITIS; CEREBRAL TOXOPLASMOSIS; CYTOMEGALOVIRUS RETINITIS; CEREBROSPINAL-FLUID; IMMUNE RECONSTITUTION; MAINTENANCE THERAPY AB Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis. ART in the setting of these opportunistic infections can lead to a paradoxical worsening caused by an immune reconstitution inflammatory syndrome (IRIS). In this Review, we discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leuko-encephalopathy (PML), tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, we discuss the risk factors, pathophysiology and management of IRIS. We also summarize the challenges that remain in management of CNS opportunistic infections, which includes the lack of phase II and III clinical trials, absence of antimicrobials for infections such as PML, and controversy regarding the use of corticosteroids for treatment of IRIS. C1 [Bowen, Lauren N.; Smith, Bryan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, 10 Ctr Dr,Bldg 10-7C 103, Bethesda, MD 28092 USA. [Reich, Daniel] NINDS, Translat Neuroradiol Unit, NIH, 10 Ctr Dr,Bldg 10-5C 103, Bethesda, MD 28092 USA. [Quezado, Martha] NCI, Dept Pathol, NIH, 10 Ctr Dr,Bldg 10 Magnuson CC 2A10, Bethesda, MD 20892 USA. RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, 10 Ctr Dr,Bldg 10-7C 103, Bethesda, MD 28092 USA. EM natha@ninds.nih.gov NR 114 TC 0 Z9 0 U1 9 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD NOV PY 2016 VL 12 IS 11 BP 662 EP 674 DI 10.1038/nrneurol.2016.149 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA EB2AZ UT WOS:000387160400007 PM 27786246 ER PT J AU Chen, X Oppenheim, JJ AF Chen, Xin Oppenheim, Joost J. TI Paradoxical effects of targeting TNF signalling in the treatment of autoimmunity SO NATURE REVIEWS RHEUMATOLOGY LA English DT Editorial Material ID REGULATORY T-CELLS; EXPANSION AB Adalimumab, an anti-TNF monoclonal antibody used to treat rheumatoid arthritis and other autoimmune disorders, paradoxically enhances the capacity of TNF to expand TNF receptor type II-expressing regulatory T cells. This provocative finding opens a new avenue for exploring the mechanisms that underlie efficacy, non-responsiveness and adverse effects associated with therapeutic targeting of TNF signalling. C1 [Chen, Xin] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China. [Chen, Xin; Oppenheim, Joost J.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Chen, X (reprint author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China.; Chen, X (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM xchen@umac.mo; oppenhej@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 NR 10 TC 1 Z9 1 U1 5 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4790 EI 1759-4804 J9 NAT REV RHEUMATOL JI Nat. Rev. Rheumatol. PD NOV PY 2016 VL 12 IS 11 BP 625 EP 626 DI 10.1038/nrrheum.2016.145 PG 2 WC Rheumatology SC Rheumatology GA EB0SF UT WOS:000387055000001 PM 27586383 ER PT J AU Wendell, CR Zonderman, AB Katzel, LI Rosenberger, WF Plamadeala, VV Hosey, MM Waldstein, SR AF Wendell, Carrington R. Zonderman, Alan B. Katzel, Leslie I. Rosenberger, William F. Plamadeala, Victoria V. Hosey, Megan M. Waldstein, Shari R. TI Nonlinear Associations Between Plasma Cholesterol Levels and Neuropsychological Function SO NEUROPSYCHOLOGY LA English DT Article DE lipids; cognitive function; aging ID BIRACIAL COMMUNITY POPULATION; ALL-CAUSE MORTALITY; BODY-MASS INDEX; COGNITIVE FUNCTION; SERUM-CHOLESTEROL; BLOOD-PRESSURE; WHITEHALL-II; LATE-LIFE; PERFORMANCE; WOMEN AB Objective: Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Method: Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. Results: A significant quadratic effect of Total Cholesterol(2) x Age was identified for Logical Memory II (b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol(2) x Age were identified for Visual Reproduction II (b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Conclusions: Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. C1 [Wendell, Carrington R.; Hosey, Megan M.; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. [Wendell, Carrington R.; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Katzel, Leslie I.] Univ Maryland, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA. [Katzel, Leslie I.; Waldstein, Shari R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Rosenberger, William F.] George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. [Hosey, Megan M.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Sch Med, Baltimore, MD 21218 USA. RP Wendell, CR (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM crwendell@umbc.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health (NIH) [R29 AG15112, 5RO1 AG015112, P30 AG028747, K24 AG00930]; Veterans Affairs Merit Grant; Department of Veterans Affairs Baltimore Geriatric Research Education and Clinical Center; National Institute on Aging Intramural Research Program of the NIH FX This work was supported by National Institutes of Health (NIH) Grants R29 AG15112, 5RO1 AG015112, P30 AG028747, and K24 AG00930; a Veterans Affairs Merit Grant; and the Department of Veterans Affairs Baltimore Geriatric Research Education and Clinical Center. The National Institute on Aging Intramural Research Program of the NIH also supported a portion of this research. NR 51 TC 0 Z9 0 U1 6 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2016 VL 30 IS 8 BP 980 EP 987 DI 10.1037/neu0000298 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA EB3DI UT WOS:000387242200009 PM 27280580 ER PT J AU Chiorini, JA AF Chiorini, John A. TI And one to bind them all SO ORAL DISEASES LA English DT Editorial Material ID ADENOASSOCIATED VIRUS TYPE-2; GROWTH-FACTOR RECEPTOR; HEPARAN-SULFATE PROTEOGLYCAN; SIALIC-ACID BINDING; GENE-TRANSFER; IN-VIVO; TRANSDUCTION; IDENTIFICATION; INFECTION; CORECEPTOR C1 [Chiorini, John A.] Natl Inst Dent & Craniofacial Res, AAV Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, AAV Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD NOV PY 2016 VL 22 IS 8 BP 716 EP 718 DI 10.1111/odi.12495 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DZ8ZU UT WOS:000386163200002 PM 27109444 ER PT J AU El-Toukhy, S Sabado, M Choi, K AF El-Toukhy, Sherine Sabado, Melanie Choi, Kelvin TI Trends in Susceptibility to Smoking by Race and Ethnicity SO PEDIATRICS LA English DT Article ID HIGH-SCHOOL-STUDENTS; CIGARETTE-SMOKING; UNITED-STATES; TOBACCO PRODUCTS; ASIAN-AMERICAN; ADOLESCENTS; INITIATION; RISK; TRAJECTORIES; VALIDATION AB OBJECTIVES: Examine racial/ethnic differences in smoking susceptibility among US youth nonsmokers over time and age. METHODS: We used nationally representative samples of youths who never tried cigarettes (N = 143 917; age, 9-21, mean, 14.01 years) from National Youth Tobacco Survey, 1999 to 2014. We used time-varying effect modeling to examine nonlinear trends in smoking susceptibility adjusted for demographics, living with smokers, and exposure to tobacco advertising. RESULTS: Compared with non-Hispanic whites (NHWs), Hispanics were more susceptible to smoking from 1999 to 2014 (highest adjusted odds ratio [aOR], 1.67 in 2012). Non-Hispanic blacks were less susceptible to smoking than NHWs from 2000 to 2009 (lowest aOR, 0.80 in 2003-2005). Non-Hispanic Asian Americans were less susceptible to smoking from 2000 to 2009 (aOR, 0.83), after which they did not differ from NHWs. Other non-Hispanics were more susceptible to smoking than NHWs from 2012 to 2014 (highest aOR, 1.40 in 2014). Compared with NHWs, non-Hispanic blacks and other non-Hispanics were more susceptible to smoking at ages 11 to 13 (highest aOR, 1.22 at age 11.5) and 12 to 14 (highest aOR, 1.27 at age 12), respectively. Hispanics were more susceptible to smoking throughout adolescence peaking at age 12 (aOR, 1.60) and age 16.5 (aOR, 1.46). Non-Hispanic Asian Americans were less susceptible to smoking at ages 11 to 15 (lowest aOR, 0.76 at ages 11-13). CONCLUSIONS: Racial/ethnic disparities in smoking susceptibility persisted over time among US youth nonsmokers, especially at ages 11 to 13. Interventions to combat smoking susceptibility are needed. C1 [El-Toukhy, Sherine; Sabado, Melanie; Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, NIH, Bethesda, MD USA. RP El-Toukhy, S (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, Bldg 3,Room 5E11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sherine.el-toukhy@nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Minority Health and Health Disparities; National Institutes of Health (NIH) FX The effort of Drs El-Toukhy, Sabado, and Choi was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Minority Health and Health Disparities. Funded by the National Institutes of Health (NIH). NR 34 TC 0 Z9 0 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2016 VL 138 IS 5 AR e20161254 DI 10.1542/peds.2016-1254 PG 10 WC Pediatrics SC Pediatrics GA EB5UV UT WOS:000387447000028 ER PT J AU Gao, Y Meyer, JR Nelson, SW AF Gao, Yang Meyer, Jennifer R. Nelson, Scott W. TI A network of allosterically coupled residues in the bacteriophage T4 Mre11-Rad50 complex SO PROTEIN SCIENCE LA English DT Article DE Rad50; Mre11; MR complex; gp46/47; allostery; bacteriophage; statistical coupling analysis; ATPase; nuclease; double mutant cycle ID MULTIPLE SEQUENCE ALIGNMENT; STRAND-BREAK REPAIR; PROTEIN-STRUCTURE; ATP HYDROLYSIS; MRE11; DOMAIN; 2-AMINOPURINE; ENDONUCLEASE; EXONUCLEASE; INTERFACE AB The Mre11-Rad50 (MR) protein complex, made up of a nuclease and ATPase, respectively, is involved in the processing of double-strand breaks as part of an intricate mechanism for their repair. Although it is clear that the MR complex is subject to allosteric regulation and that there is communication between the nuclease and ATPase active sites, the underlying mechanisms are poorly understood. We performed statistical coupling analysis on Mre11 and Rad50 to predict linked residues based on their evolutionary correlation. This analysis predicted a coevolving sector of six residues that may be allosterically coupled. The prediction was tested using double-mutant cycle analysis of nuclease and ATPase activity. The results indicate that a tyrosine residue located near the active site of Mre11 is allosterically coupled to several Rad50 residues located over 40 angstrom away. This allosteric coupling may be the basis for the reciprocal regulation of the ATPase and nuclease activities of the complex. C1 [Gao, Yang; Meyer, Jennifer R.; Nelson, Scott W.] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA. [Gao, Yang] NIDDK, Mol Biol Lab, NIH, 5 Mem Dr,Room B1-03, Bethesda, MD 20892 USA. RP Nelson, SW (reprint author), Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA. EM swn@iastate.edu FU Carver Trust [10-3603]; National Science Foundation [MCB-1121693] FX Grant sponsor: Carver Trust Young Investigator; Grant number: 10-3603; Grant sponsor: National Science Foundation grant; Grant number: MCB-1121693. NR 42 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2016 VL 25 IS 11 BP 2054 EP 2065 DI 10.1002/pro.3028 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB1YE UT WOS:000387151900014 PM 27571435 ER PT J AU Gonzales, FA Hurtado-de-Mendoza, A Santoyo-Olsson, J Napoles, AM AF Gonzales, Felisa A. Hurtado-de-Mendoza, Alejandra Santoyo-Olsson, Jasmine Napoles, Anna Maria TI Do coping strategies mediate the effects of emotional support on emotional well-being among Spanish-speaking Latina breast cancer survivors? SO PSYCHO-ONCOLOGY LA English DT Article DE breast cancer; oncology; emotional support; emotional well-being; coping; Latino; Hispanic ID QUALITY-OF-LIFE; STRESS-MANAGEMENT INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; SOCIAL SUPPORT; FUNCTIONAL ASSESSMENT; NUEVO-AMANECER; WOMEN; HEALTH; MODELS; BENEFIT AB ObjectiveThis study aimed to assess the relationship between emotional social support and emotional well-being among Latina immigrants with breast cancer and test whether two culturally relevant coping strategies, fatalism and acceptance, mediate this relationship. MethodsOne hundred fifty Spanish-speaking Latinas within 1year of breast cancer diagnosis participating in a randomized trial of a stress management intervention were assessed in person at baseline and via telephone 6months later. Survey measures included baseline emotional support, fatalism, and acceptance and emotional well-being 6months later. Generalized linear models estimated direct effects of emotional support on emotional well-being and indirect effects through fatalism and acceptance. ResultsMean age was 50.1 (SD=10.9) years; most women had low education and acculturation levels. Emotional support was negatively associated with fatalism (r=-0.24, p<0.01) and positively associated with acceptance (r=0.30, p<0.001). Emotional support (r=0.23, p=0.005) and acceptance (r=0.28, p=0.001) were positively associated with emotional well-being, whereas fatalism (r=-0.36, p<0.0001) was negatively associated with emotional well-being. In multivariable models, emotional support was associated with emotional well-being (b=0.88, 95% CI: 0.24, 1.52). This direct effect remained significant when additionally controlling for fatalism (b=0.66, 95% CI: 0.03, 1.30) and acceptance (b=0.73, 95% CI: 0.09, 1.37) in separate models. There was a significant indirect effect of emotional support on emotional well-being through fatalism (b=0.21, 95% CI: 0.04, 0.51) as well as a marginally significant effect through acceptance (b=0.15, 95% CI: 0.001, 0.43). ConclusionsEmotional support may increase well-being among Spanish-speaking Latina cancer survivors by reducing cancer fatalism.Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Gonzales, Felisa A.] NCI, Canc Prevent Fellowship Program, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Hurtado-de-Mendoza, Alejandra] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol,Canc Prevent & Control Program, Washington, DC 20007 USA. [Santoyo-Olsson, Jasmine; Napoles, Anna Maria] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Santoyo-Olsson, Jasmine; Napoles, Anna Maria] Univ Calif San Francisco, Dept Med, Ctr Aging Div Communities, San Francisco, CA USA. RP Gonzales, FA (reprint author), Univ Calif San Francisco, 3333 Calif St,Suite 335, San Francisco, CA 94118 USA. EM anapoles@ucsf.edu FU California Breast Cancer Research Grants Program Office of the University of California [15BB-1300, 15BB-1301]; National Cancer Institute [1U54CA153511]; National Institute on Aging [1 P30 AG15272] FX This research was supported by the California Breast Cancer Research Grants Program Office of the University of California grants number 15BB-1300 and 15BB-1301, grant number 1U54CA153511 from the National Cancer Institute, and grant number 1 P30 AG15272 from the National Institute on Aging. NR 39 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD NOV PY 2016 VL 25 IS 11 BP 1286 EP 1292 DI 10.1002/pon.3953 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA EB4KK UT WOS:000387340300005 PM 26352186 ER PT J AU Wang, LX Graubard, BI Li, Y AF Wang, Lingxiao Graubard, Barry I. Li, Yan TI A composite likelihood approach in testing for Hardy Weinberg Equilibrium using family-based genetic survey data SO STATISTICS IN MEDICINE LA English DT Article DE complex sampling; condensed coefficients of identity; intracluster correlation; national genetic household surveys; Taylor linearization variances ID ASSOCIATION; DISEQUILIBRIUM AB In population-based household surveys, for example, the National Health and Nutrition Examination Survey, households are often sampled by stratified multistage cluster sampling, and multiple individuals related by blood are often sampled within households. Therefore, genetic data collected from these population-based household surveys, called National Genetic Household Surveys, can be correlated because of two levels of correlation. One level of correlation is caused by the multistage geographical cluster sampling and the other is caused by biological inheritance among participants within the same sampled family. In this paper, we develop an efficient Hardy Weinberg Equilibrium (HWE) test utilizing pairwise composite likelihood methods that incorporate the sample weighting effect induced by the differential selection probabilities in complex sample designs, as well as the two-level clustering (correlation) effects described above. Monte Carlo simulation studies show that the proposed HWE test maintains the nominal levels, and is more powerful than existing methods (Li et al. 2011) under various (non) informative sample designs that depend on genotypes (explicitly or implicitly), family relationships or both, especially when within-household sampling depends on the genotypes. The developed tests are further evaluated using simulated genetic data based on the Hispanic Health and Nutrition Survey. Copyright (C) 2016 John Wiley & Sons, Ltd. C1 [Wang, Lingxiao; Li, Yan] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA. [Graubard, Barry I.; Li, Yan] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. RP Li, Y (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. EM yli6@umd.edu FU NCI NIH HHS [R03 CA171064] NR 31 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD NOV PY 2016 VL 35 IS 27 BP 5040 EP 5050 DI 10.1002/sim.7044 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA EB4NA UT WOS:000387347400010 PM 27481259 ER PT J AU Sanossian, N Apibunyopas, KC Liebeskind, DS Starkman, S Burgos, AM Conwit, R Eckstein, M Pratt, F Stratton, S Hamilton, S Saver, JL AF Sanossian, Nerses Apibunyopas, Kathleen C. Liebeskind, David S. Starkman, Sidney Burgos, Adrian M. Conwit, Robin Eckstein, Marc Pratt, Frank Stratton, Sam Hamilton, Scott Saver, Jeffrey L. CA FAST-MAG Field Adm Stroke Ther TI Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study SO STROKE LA English DT Article DE aged; emergency medical services; hemorrhage; quality of life; stroke ID METHODOLOGY; THERAPY AB Background and Purpose-Greater numbers of individuals aged 80 years enjoy a high quality of life, yet historically stroke trials have excluded this population. We aimed to describe a population of very elderly successfully enrolled into an acute stroke trial and compare their characteristics and outcomes with the younger cohort. Methods-We analyzed consecutive patients enrolled <2 hours of symptom onset in a prehospital stroke treatment trial, the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium). We gathered demographic, treatment, and outcome data for nonelderly (<80 years old), very elderly (>= 80 years old), and extreme elderly (>= 90 years old). We describe key differences in the population of elderly and the impact of their inclusion on the clinical trial. Results-Of 1700 participants in FAST-MAG, there were 1210 nonelderly, 490 very elderly, and 60 extreme elderly subjects. Very elderly stroke patients successfully enrolled in a research study were more likely to be women, white, and have an ischemic mechanism rather than an intracerebral hemorrhage. Although the very elderly had generally poorer outcomes, 4 in 10 were functionally independent at 90 days. Conclusions-Inclusion of the very elderly population in acute stroke clinical trials would both significantly increase study participation and generalizability of future acute stroke clinical trials. C1 [Sanossian, Nerses; Apibunyopas, Kathleen C.; Burgos, Adrian M.] Univ Southern Calif, Dept Neurol, Roxanna Todd Hodges Comprehens Stroke Clin, Los Angeles, CA USA. [Eckstein, Marc] Univ Southern Calif, Dept Emergency Med, Los Angeles, CA USA. [Liebeskind, David S.; Starkman, Sidney; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Stroke Ctr, Los Angeles, CA 90024 USA. [Liebeskind, David S.] Univ Calif Los Angeles, Neurovasc Imaging Core Lab, Los Angeles, CA USA. [Stratton, Sam] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Conwit, Robin] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Pratt, Frank] Torrance Mem Med Ctr, Dept Emergency Med, Torrance, CA USA. [Hamilton, Scott] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. RP Sanossian, N (reprint author), Univ Southern Calif, 1540 Alcazar St,Suite 209, Los Angeles, CA 90089 USA. EM sanossia@yahoo.com FU NIH-NINDS [U01 NS 44364] FX This study was supported by NIH-NINDS Award U01 NS 44364. NR 14 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD NOV PY 2016 VL 47 IS 11 BP 2737 EP 2741 DI 10.1161/STROKEAHA.116.013318 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA EA8WH UT WOS:000386920000023 PM 27679533 ER PT J AU Hussain, SK Makgoeng, SB Everly, MJ Goodman, MT Martinez-Maza, O Morton, LM Clarke, CA Lynch, CF Snyder, J Israni, A Kasiske, BL Engels, EA AF Hussain, Shehnaz K. Makgoeng, Solomon B. Everly, Matthew J. Goodman, Marc T. Martinez-Maza, Otoniel Morton, Lindsay M. Clarke, Christina A. Lynch, Charles F. Snyder, Jon Israni, Ajay Kasiske, Bertram L. Engels, Eric A. TI HLA and Risk of Diffuse Large B cell Lymphoma After Solid Organ Transplantation SO TRANSPLANTATION LA English DT Article ID NON-HODGKIN-LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; ANTIGEN CLASS-I; UNITED-STATES; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; KAPOSIS-SARCOMA; CANCER-RISK; RECIPIENTS; ASSOCIATION AB Background. Solid organ transplant recipients have heightened risk for diffuse large B cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established. Methods. We examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number. Results. Compared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [95% CI], 0.61-0.95; one: IRR, 0.83; 95% CI, 0.69-1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all 3 loci (P = 0.0003). Several individual recipient HLA-A, -B, -C, -DR, and -DQ antigens were also associated with DLBCL risk, including DR13 (IRR, 0.74; 95% CI, 0.57-0.93) and B38 (IRR, 1.48; 95% CI, 1.10-1.93), confirming prior findings that these 2 antigens are associated with risk of infection-associated cancers. Conclusions. In conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients or chronic immune stimulation. C1 [Hussain, Shehnaz K.; Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Hussain, Shehnaz K.; Makgoeng, Solomon B.; Martinez-Maza, Otoniel] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Everly, Matthew J.] Terasaki Fdn Lab, Los Angeles, CA USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Morton, Lindsay M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA. [Clarke, Christina A.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy & Med, Stanford, CA 94305 USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Snyder, Jon; Israni, Ajay; Kasiske, Bertram L.] Sci Registry Transplant Recipients, Minneapolis, MN USA. [Snyder, Jon; Israni, Ajay; Kasiske, Bertram L.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. RP Hussain, SK (reprint author), Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control Res, 8700 Beverly Blvd,SCCT 1S31, Los Angeles, CA 90048 USA. EM shehnaz.hussain@cshs.org FU Minneapolis Medical Research Foundation, Minneapolis, MN [HHSH250201000018C]; SEER Program of the National Cancer Institute: California [HHSN261201000036C, HHSN261201000035C, HHSN261201000034C]; SEER Program of the National Cancer Institute, Connecticut [HHSN261201000024C]; SEER Program of the National Cancer Institute, Hawaii [HHSN261201000037C, N01-PC-35137, N01-PC-35139]; SEER Program of the National Cancer Institute, Iowa [HSN261201000032C, N01-PC-35143]; SEER Program of the National Cancer Institute, New Jersey [HHSN261201300021I, N01-PC2013-00021]; SEER Program of the National Cancer Institute, Seattle-Puget Sound [N01-PC-35142]; SEER Program of the National Cancer Institute, Utah [HHSN2612013000171]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: California [1U58 DP000807-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Colorado [U58 DP000848-04]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Georgia [5U58DP003875-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Illinois [5U58DP003883-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Maryland [U58DP12-1205 3919-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Michigan [5U58DP003921-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, NewJersey [5U58/DP003931-02]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, New York [U58DP003879]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, North Carolina [U58DP000832]; National Program of Cancer Registries of the Centers for Disease Control and Prevention, Texas [5U58DP000824-04]; state of California; state of Colorado; state of Connecticut; state of Illinois; state of Iowa; state of Massachusetts (Massachusetts Cancer Prevention and Control) [5458DP003920]; state of New Jersey; state of New York (Cancer Surveillance Initiative); state of Texas; state of Utah; state of Washington; University of Utah; Fred Hutchinson Cancer Research Center in Seattle, WA FX The SRTR is currently operated under contract number HHSH250201000018C (Health Resources and Services Administration) by the Minneapolis Medical Research Foundation, Minneapolis, MN. During the initial period when registry linkages were performed, the SRTR was managed by Arbor Research Collaborative for Health in Ann Arbor, MI (contract HHSH234200537009C). The following cancer registries were supported by the SEER Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C, and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii (HHSN261201000037C, N01-PC-35137, and N01-PC-35139), Iowa (HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201300021I, N01-PC2013-00021), Seattle-Puget Sound (N01-PC-35142), and Utah (HHSN2612013000171). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois (5U58DP003883-03), Maryland (U58DP12-1205 3919-03), Michigan (5U58DP003921-03), NewJersey (5U58/DP003931-02), New York (U58DP003879), North Carolina (U58DP000832) and Texas (5U58DP000824-04). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, Massachusetts (Massachusetts Cancer Prevention and Control Cooperative Agreement 5458DP003920), New Jersey, New York (including the Cancer Surveillance Initiative), Texas, Utah, and Washington, as well as the University of Utah and Fred Hutchinson Cancer Research Center in Seattle, WA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2016 VL 100 IS 11 BP 2453 EP 2460 DI 10.1097/TP.0000000000001025 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA EB4UT UT WOS:000387370000035 PM 26636741 ER PT J AU Rivas, G Minton, AP AF Rivas, German Minton, Allen P. TI Macromolecular Crowding In Vitro, In Vivo, and In Between SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID EXCLUDED-VOLUME INTERACTIONS; PROTEIN SELF-ASSOCIATION; BOVINE SERUM-ALBUMIN; ESCHERICHIA-COLI; PHYSIOLOGICAL CONSEQUENCES; SEDIMENTATION EQUILIBRIUM; CHEMICAL INTERACTIONS; BIOCHEMICAL REACTIONS; POLYETHYLENE-GLYCOLS; LIGHT-SCATTERING AB Biochemical processes take place in heterogeneous and highly volume occupied or crowded environments that can considerably influence the reactivity and distribution of participating macromolecules. We summarize here the thermodynamic consequences of excluded-volume and long-range nonspecific intermolecular interactions for macromolecular reactions in volume-occupied media. In addition, we summarize and compare the information content of studies of crowding in vitro and in vivo. We emphasize the importance of characterizing the behavior not only of labeled tracer macromolecules but also the composition and behavior of unlabeled macromolecules in the immediate vicinity of the tracer. Finally, we propose strategies for extending quantitative analyses of crowding in simple model systems to increasingly complex media up to and including intact cells. C1 [Rivas, German] CSIC, Ctr Invest Biol, Madrid, Spain. [Minton, Allen P.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Rivas, G (reprint author), CSIC, Ctr Invest Biol, Madrid, Spain.; Minton, AP (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM grivas@cib.csic.es; minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 FU Spanish Government [BFU2014-52070-C2-2-P]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Damien Hail (Australian National University) and Martin Gruebele (University of Illinois) for useful discussions, and Dr Gruebele for Figure 3B. Research of G.R. is supported by the Spanish Government through grant BFU2014-52070-C2-2-P, and that of A.P.M. by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 96 TC 3 Z9 3 U1 25 U2 25 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 2016 VL 41 IS 11 BP 970 EP 981 DI 10.1016/j.tibs.2016.08.013 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB2MK UT WOS:000387196300008 PM 27669651 ER PT J AU Malcolm, GL Groen, IIA Baker, CI AF Malcolm, George L. Groen, Iris I. A. Baker, Chris I. TI Making Sense of Real-World Scenes SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID DEEP NEURAL-NETWORKS; INFERIOR TEMPORAL CORTEX; OCCIPITAL PLACE AREA; HUMAN VISUAL-CORTEX; EYE-MOVEMENTS; NATURAL SCENES; HUMAN BRAIN; PARAHIPPOCAMPAL CORTEX; SPATIAL-FREQUENCY; SELECTIVE CORTEX AB To interact with the world, we have to make sense of the continuous sensory input conveying information about our environment. A recent surge of studies has investigated the processes enabling scene understanding, using increasingly complex stimuli and sophisticated analyses to highlight the visual features and brain regions involved. However, there are two major challenges to producing a comprehensive framework for scene understanding. First, scene perception is highly dynamic, subserving multiple behavioral goals. Second, a multitude of different visual properties co-occur across scenes and may be correlated or independent. We synthesize the recent literature and argue that for a complete view of scene understanding, it is necessary to account for both differing observer goals and the contribution of diverse scene properties. C1 [Malcolm, George L.] Univ East Anglia, Sch Psychol, Norwich, Norfolk, England. [Groen, Iris I. A.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Malcolm, GL (reprint author), Univ East Anglia, Sch Psychol, Norwich, Norfolk, England. EM g.malcolm@uea.ac.uk RI Groen, Iris/A-1462-2017 OI Groen, Iris/0000-0002-5536-6128 FU NIMH [ZIAMH002909]; Rubicon Fellowship from The Netherlands Organization of Scientific Research (NWO) FX G.L.M., I.I.A.G., and C.I.B. are supported by the intramural research program of NIMH (ZIAMH002909). I.I.A.G. is supported by a Rubicon Fellowship from The Netherlands Organization of Scientific Research (NWO). We thank Wilma Bainbridge, Michelle Greene, Assaf Harel, Antje Nuthmann, and Edward Silson for commenting on earlier versions of this manuscript. NR 147 TC 3 Z9 3 U1 19 U2 19 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD NOV PY 2016 VL 20 IS 11 BP 843 EP 856 DI 10.1016/j.tics.2016.09.003 PG 14 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA EB2MN UT WOS:000387196600009 PM 27769727 ER PT J AU Lewis, MD Kelly, JM AF Lewis, Michael D. Kelly, John M. TI Putting Infection Dynamics at the Heart of Chagas Disease SO TRENDS IN PARASITOLOGY LA English DT Review ID TRYPANOSOMA-CRUZI INFECTION; REAL-TIME PCR; IN-VIVO; PARASITE PERSISTENCE; NERVOUS-SYSTEM; MOLECULAR-IDENTIFICATION; RANDOMIZED-TRIAL; ADIPOSE-TISSUE; NITRIC-OXIDE; MICE AB In chronic Trypanosoma cruzi infections, parasite burden is controlled by effective, but nonsterilising immune responses. Infected cells are difficult to detect because they are scarce and focally distributed in multiple sites. However, advances in detection technologies have established a link between parasite persistence and the pathogenesis of Chagas heart disease. Long-term persistence likely involves episodic reinvasion as well as continuous infection, to an extent that varies between tissues. The primary reservoir sites in humans are not definitively known, but analysis of murine models has identified the gastrointestinal tract. Here, we highlight that quantitative, spatial, and temporal aspects of T. cruzi infection are central to a fuller understanding of the association between persistence, pathogenesis, and immunity, and for optimising treatment. C1 [Lewis, Michael D.; Kelly, John M.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England. [Lewis, Michael D.] NIAID, Lab Parasit Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Lewis, MD (reprint author), London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England.; Lewis, MD (reprint author), NIAID, Lab Parasit Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM michael.lewis@lshtm.ac.uk FU Wellcome Trust [084175]; British Heart Foundation [PG/13/88/30556]; Drugs for Neglected Diseases Initiative; European Commission Marie Curie Individual Fellowships programme; Division of Intramural Research, NIAID, NIH FX The authors are grateful for support from the Wellcome Trust (Grant 084175), the British Heart Foundation (Grant PG/13/88/30556), the Drugs for Neglected Diseases Initiative and the European Commission Marie Curie Individual Fellowships programme. This work was supported in part by the Division of Intramural Research, NIAID, NIH. We thank Martin Taylor and Amanda Francisco for insightful discussions and comments on the manuscript. NR 111 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 EI 1471-5007 J9 TRENDS PARASITOL JI Trends Parasitol. PD NOV PY 2016 VL 32 IS 11 BP 899 EP 911 DI 10.1016/j.pt.2016.08.009 PG 13 WC Parasitology SC Parasitology GA EB2LZ UT WOS:000387195200010 PM 27612651 ER PT J AU Li, X Zhuang, P Hallett, M Zhang, Y Li, J Li, Y AF Li, X. Zhuang, P. Hallett, M. Zhang, Y. Li, J. Li, Y. TI Subthalamic oscillatory activity in parkinsonian patients with off-period dystonia SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE dyskinesia; microelectrode recording; oscillation; Parkinson's disease; subthalamic nucleus ID LEVODOPA-INDUCED DYSKINESIAS; DEEP BRAIN-STIMULATION; HIGH-FREQUENCY STIMULATION; HUMAN BASAL GANGLIA; NEURONAL-ACTIVITY; GLOBUS-PALLIDUS; DISEASE; NUCLEUS; CORTEX; PATHOPHYSIOLOGY AB Objectives - The study was aimed to explore oscillatory activity in the subthalamic nucleus (STN) in Parkinson's disease (PD) with off-period dystonia, a type of levodopa-induced dyskinesias (LID). Methods - Eighteen patients with PD who underwent STN DBS were studied. Nine patients had dyskinesia defined as the LID group and nine patients who did not present any sign of dyskinesia were defined as the control group. Microelectrode recordings in the STN together with electromyogram (EMG) were recorded. Spectral and coherence analyses were performed to study the neuronal oscillations in relation to limb muscles. Results - Two hundred and fifteen neurons were identified. There were 39 neurons with tremor-frequency band (47 Hz) oscillation, 57 neurons with beta-frequency band (12-30 Hz, beta-FB) oscillation and 100 neurons without oscillation, and 19 neurons with very low-frequency band oscillation at a mean peak power of 1.2 +/- 0.5 Hz (LFB). These LFB oscillatory neurons (n = 15) were frequently significantly coherent with EMG of off-period dystonia. Notably, 89% (n = 17) neurons with LFB oscillation were found in the patients in the off-dystonia group. The age at onset of PD, duration of PD, and levodopa equivalent dose daily consumption were statistically different between two groups (P < 0.05). Conclusions - Subthalamic LFB oscillatory neurons seem to play an important role in the genesis of off-period dystonia in advanced PD. Clinical and demographic analyses confirmed that the earlier age at onset of PD, longer duration of PD, and levodopa exposure are important risk factors in the development of the type of LID. C1 [Li, X.; Zhuang, P.; Zhang, Y.; Li, J.; Li, Y.] Capital Med Univ, Beijing Inst Funct Neurosurg, Xuanwu Hosp, Beijing, Peoples R China. [Hallett, M.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Zhuang, P.] Beijing Inst Brain Disorders, Ctr Parkinsons Dis, Beijing, Peoples R China. [Zhuang, P.] Capital Med Univ, Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China. RP Zhuang, P (reprint author), 45 Changchun St, Beijing 100053, Peoples R China. EM zhuangp@vip.sina.com FU National Scientific Foundation of China [81171061, 81371256, 81361128012]; Ministry of Education of Republic of China [BIBD-PXM2013-014226-07-000084]; International Alliance of Translational Neuroscience [PXM2014-014226-000015]; National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA FX The work was funded by National Scientific Foundation of China (No. 81171061, 81371256, 81361128012), Ministry of Education of Republic of China (BIBD-PXM2013-014226-07-000084), and Seed Grant of International Alliance of Translational Neuroscience (PXM2014-014226-000015). Dr. Hallett is supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA. NR 41 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6314 EI 1600-0404 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD NOV PY 2016 VL 134 IS 5 BP 327 EP 338 DI 10.1111/ane.12547 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA EA6QB UT WOS:000386752700002 PM 27696368 ER PT J AU Pucci, M Di Bonaventura, MVM Giusepponi, ME Romano, A Filaferro, M Maccarrone, M Ciccocioppo, R Cifani, C D'Addario, C AF Pucci, Mariangela Di Bonaventura, Maria Vittoria Micioni Giusepponi, Maria Elena Romano, Adele Filaferro, Monica Maccarrone, Mauro Ciccocioppo, Roberto Cifani, Carlo D'Addario, Claudio TI Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption SO ADDICTION BIOLOGY LA English DT Article DE Binge eating; corticotropin-releasing factor system; food restriction; frustration stress; nociceptin; orphanin FQ system; palatable food ID VENTRAL TEGMENTAL AREA; CRF-INDUCED ANOREXIA; ORPHANIN-FQ; PARAVENTRICULAR NUCLEUS; FUNCTIONAL ANTAGONISM; CALORIC RESTRICTION; DIETARY RESTRAINT; CENTRAL AMYGDALA; COCAINE-SEEKING; BULIMIA-NERVOSA AB Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds. C1 [Pucci, Mariangela; D'Addario, Claudio] Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Teramo, Italy. [Di Bonaventura, Maria Vittoria Micioni; Giusepponi, Maria Elena; Ciccocioppo, Roberto; Cifani, Carlo] Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna Carceri 9, I-62032 Camerino, MC, Italy. [Romano, Adele] Sapienza Univ Rome, Dept Physiol & Pharmacol, Rome, Italy. [Filaferro, Monica] Univ Modena & Reggio Emilia, Dept Biomed Metab Sci & Neurosci, Reggio Emilia, Italy. [Maccarrone, Mauro] Campus Biomed Univ Rome, Rome, Italy. [Maccarrone, Mauro] Santa Lucia Fdn, European Ctr Brain Res CERC, Rome, Italy. [Cifani, Carlo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [D'Addario, Claudio] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Stockholm, Sweden. RP D'Addario, C (reprint author), Univ Teramo, Fac Biosci & Technol Food Agr & Environm, Teramo, Italy.; Cifani, C (reprint author), Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna Carceri 9, I-62032 Camerino, MC, Italy. EM carlo.cifani@unicam.it; cdaddario@unite.it RI Pucci, Mariangela/K-6379-2016; OI Pucci, Mariangela/0000-0003-4657-6075; GIUSEPPONI, MARIA ELENA/0000-0002-1388-3186 FU Italian Ministry of University and Research [FIRB-RBFR12DELS, PRIN-2012JTX3KL] FX This work was supported by the Italian Ministry of University and Research under grants FIRB-RBFR12DELS to C.C. and C.D. and PRIN-2012JTX3KL to C.C. NR 93 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD NOV PY 2016 VL 21 IS 6 BP 1168 EP 1185 DI 10.1111/adb.12303 PG 18 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA EA9NX UT WOS:000386972100009 PM 26387568 ER PT J AU van der Straten, A Panther, L Laborde, N Hoesley, CJ Cheng, H Husnik, MJ Horn, S Nel, A Soto-Torres, L Chen, BA AF van der Straten, Ariane Panther, Lori Laborde, Nicole Hoesley, Craig J. Cheng, Helen Husnik, Marla J. Horn, Stephanie Nel, Annalene Soto-Torres, Lydia Chen, Beatrice A. TI Adherence and Acceptability of a Multidrug Vaginal Ring for HIV Prevention in a Phase I Study in the United States SO AIDS AND BEHAVIOR LA English DT Article DE HIV prevention; Pre-exposure prophylaxis; Microbicides; Adherence; Acceptability; Vaginal ring ID PREEXPOSURE PROPHYLAXIS; TRIAL; ADOLESCENT; AFRICA; WOMEN AB We evaluated the adherence and acceptability of a vaginal ring containing dapivirine, maraviroc, or both drugs for 28 days during a Phase I placebo-controlled trial in 48 HIV-negative sexually abstinent U.S. women aged 18-40. Adherence was assessed weekly by clinical interview and computer-assisted self-interviewing; acceptability assessment occurred at the last product-use visit. Study retention was 98 % (47/48); 94 % (45/48) reported being fully adherent with ring use during the 28-day period. Two participants experienced the ring partially coming out. Analysis was blinded and behavioral data were combined across study groups. Most women reported being very comfortable having the ring in their vagina; 44 % preferred continuous use, whereas 51 % had no preference compared to episodic use. Although a range of minor ring concerns were expressed, few were actually experienced. High adherence to and acceptability of this vaginal ring in this Phase I trial contributes to its promise as a sustained mechanism for multidrug vaginal microbicide delivery. C1 [van der Straten, Ariane; Laborde, Nicole; Cheng, Helen] RTI Int, WGHI, 351 Calif St,Suite 500, San Francisco, CA 94104 USA. [van der Straten, Ariane] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. [Panther, Lori] Fenway Inst, Boston, MA USA. [Hoesley, Craig J.] Univ Alabama Birmingham, Birmingham, AL USA. [Husnik, Marla J.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, 1124 Columbia St, Seattle, WA 98104 USA. [Horn, Stephanie] FHI 360, Durham, NC USA. [Nel, Annalene] Int Partnership Microbicides, Silver Spring, MD USA. [Soto-Torres, Lydia] NIAID, DAIDS, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Chen, Beatrice A.] Magee Womens Res Inst, Pittsburgh, PA USA. [Chen, Beatrice A.] Univ Pittsburgh, Pittsburgh, PA USA. RP van der Straten, A (reprint author), RTI Int, WGHI, 351 Calif St,Suite 500, San Francisco, CA 94104 USA.; van der Straten, A (reprint author), Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. EM ariane@rti.org FU National Institute of Allergy and Infectious Diseases component of the U.S. National Institutes of Health [UM1AI068633, UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of Child Health and Human Development component of the U.S. National Institutes of Health; National Institute of Mental Health component of the U.S. National Institutes of Health FX We would like to acknowledge the women who participated in this study and to extend special thanks to the clinical research sites' teams in Pittsburgh, PA, Birmingham, AL, and Boston, MA. The full MTN-013/IPM 026 study team can be viewed at http://www.mtnstopshiv.org/studies/2241. The study was designed and implemented by the Microbicide Trials Network (MTN). The MTN is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The International Partnership for Microbicides (IPM), IND sponsor, supplied the products used in this study [Dapivirine vaginal ring (VR), maraviroc VR, maraviroc/dapivirine VR, placebo VR]. NR 26 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2016 VL 20 IS 11 BP 2644 EP 2653 DI 10.1007/s10461-016-1299-8 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA EA3KA UT WOS:000386499800017 PM 26837628 ER PT J AU Mensch, BS Brown, ER Liu, K Marrazzo, J Chirenje, ZM Gomez, K Piper, J Patterson, K van der Straten, A AF Mensch, Barbara S. Brown, Elizabeth R. Liu, Karen Marrazzo, Jeanne Chirenje, Zvavahera Mike Gomez, Kailazarid Piper, Jeanna Patterson, Karen van der Straten, Ariane TI Reporting of Adherence in the VOICE Trial: Did Disclosure of Product Nonuse Increase at the Termination Visit? SO AIDS AND BEHAVIOR LA English DT Article DE Microbicide trials; Self-reports of adherence; sub-Saharan Africa ID HIV-INFECTION; PREEXPOSURE PROPHYLAXIS; AFRICAN WOMEN; SOUTH-AFRICA; PLACEBO GEL; MICROBICIDE; ACCEPTABILITY; NONADHERENCE; EFFICACY AB VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, aeyen90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report. C1 [Mensch, Barbara S.] Populat Council, One Dag Hammarskjold Plaza, New York, NY 10017 USA. [Brown, Elizabeth R.; Marrazzo, Jeanne] Univ Washington, Seattle, WA 98195 USA. [Brown, Elizabeth R.; Liu, Karen; Patterson, Karen] SCHARP FHCRC, Seattle, WA USA. [Chirenje, Zvavahera Mike] UZ UCSF Collaborat Res Programme, Harare, Zimbabwe. [Gomez, Kailazarid] FHI360, Durham, NC USA. [Piper, Jeanna] NIAID, DAIDS, Rockville, MD USA. [van der Straten, Ariane] RTI Int, Womens Global Hlth Imperat, San Francisco, CA USA. RP Mensch, BS (reprint author), Populat Council, One Dag Hammarskjold Plaza, New York, NY 10017 USA. EM bmensch@popcouncil.org OI Marrazzo, Jeanne/0000-0002-9277-7364 FU National Institute of Allergy and Infectious Diseases component of the U.S. National Institutes of Health [UM1AI068633, UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of Child Health and Human Development component of the U.S. National Institutes of Health; National Institute of Mental Health component of the U.S. National Institutes of Health FX The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 22 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2016 VL 20 IS 11 BP 2654 EP 2661 DI 10.1007/s10461-016-1312-2 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA EA3KA UT WOS:000386499800018 PM 26906023 ER PT J AU Mukamal, KJ Clowry, CM Murray, MM Hendriks, HFJ Rimm, EB Sink, KM Adebamowo, CA Dragsted, LO Lapinski, PS Lazo, M Krystal, JH AF Mukamal, Kenneth J. Clowry, Catherine M. Murray, Margaret M. Hendriks, Henk F. J. Rimm, Eric B. Sink, Kaycee M. Adebamowo, Clement A. Dragsted, Lars O. Lapinski, P. Scott Lazo, Mariana Krystal, John H. TI Moderate Alcohol Consumption and Chronic Disease: The Case for a Long-Term Trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Randomized Controlled Trial; Feeding Studies ID CORONARY-HEART-DISEASE; DIETARY MODIFICATION TRIAL; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; CONTROLLED INTERVENTION; MYOCARDIAL-INFARCTION; ATRIAL-FIBRILLATION; DIABETES-MELLITUS AB Drinking within recommended limits is highly prevalent in much of the world, and strong epidemiological associations exist between moderate alcohol consumption and risk of several major chronic diseases, including coronary heart disease, diabetes, and breast cancer. In many cases, plausible biological mediators for these associations have been identified in randomized trials, but gold standard evidence that moderate drinking causes or prevents any chronic disease remains elusive and important concerns about available evidence have been raised. Although long-term randomized trials to test the observed associations have been termed impossible, clinical investigators have now successfully completed randomized trials of complex nutritional interventions in a variety of settings, along with trials of alcohol consumption itself of up to 2years duration. The successful completion of these trials suggests that objections to the execution of a full-scale, long-term clinical trial of moderate drinking on chronic disease are increasingly untenable. We present potential lessons learned for such a trial and discuss key features to maximize its feasibility and value. C1 [Mukamal, Kenneth J.; Clowry, Catherine M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Murray, Margaret M.] NIAAA, Rockville, MD 20852 USA. [Hendriks, Henk F. J.] Hendriks Nutr Support Business, Zeist, Netherlands. [Rimm, Eric B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Rimm, Eric B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Sink, Kaycee M.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Dragsted, Lars O.] Univ Copenhagen, Dept Nutr Exercise & Sports, Copenhagen, Denmark. [Lapinski, P. Scott] Harvard Univ, Countway Lib Med, Boston, MA 02115 USA. [Lazo, Mariana] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA.; Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Primary Care Res Program, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu FU NIAAA NIH HHS [U10 AA025286, U13 AA023452, U34 AA023258] NR 63 TC 0 Z9 0 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2016 VL 40 IS 11 BP 2283 EP 2291 DI 10.1111/acer.13231 PG 9 WC Substance Abuse SC Substance Abuse GA EA8VT UT WOS:000386918400003 PM 27688006 ER PT J AU Litten, RZ AF Litten, Raye Z. TI Nociceptin Receptor as a Target to Treat Alcohol Use Disorder: Challenges in Advancing Medications Development SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID DEPENDENT INDIVIDUALS; ADDICTION MEDICINE; SEEKING BEHAVIOR; ANIMAL-MODELS; HEALTH-CARE; ACAMPROSATE; NALTREXONE; ADOPTION; ANTAGONIST; ETHANOL C1 [Litten, Raye Z.] NIAAA, Div Medicat Dev, 5635 Fishers Lane, Bethesda, MD 20892 USA. RP Litten, RZ (reprint author), NIAAA, Div Medicat Dev, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM rlitten@mail.nih.gov NR 55 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2016 VL 40 IS 11 BP 2299 EP 2304 DI 10.1111/acer.13222 PG 6 WC Substance Abuse SC Substance Abuse GA EA8VT UT WOS:000386918400006 PM 27696442 ER PT J AU Akinfiresoye, LR Miranda, C Lovinger, DM N'Gouemo, P AF Akinfiresoye, Luli R. Miranda, Clive Lovinger, David M. N'Gouemo, Prosper TI Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior Colliculus SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Intoxication; Audiogenic Seizures; Phosphorylation; Protein Kinase A ID AUDIOGENIC-SEIZURE SUSCEPTIBILITY; GENE-TRANSCRIPTION FACTOR; ELEMENT-BINDING PROTEIN; EPILEPSY-PRONE RATS; ETHANOL WITHDRAWAL; CYCLIC-NUCLEOTIDE; ADENYLYL-CYCLASE; IN-VITRO; CAMP; PHOSPHORYLATION AB BackgroundCyclic AMP-dependent protein kinase A (PKA) signaling is a key target for the action of alcohol and may therefore play a role in the pathophysiology of alcohol withdrawal seizures (AWSs). Here, we investigated the role of PKA activity with respect to increased seizure susceptibility in rats that were subjected to alcohol withdrawal. MethodsAdult male Sprague Dawley rats received 3 daily doses of ethanol (EtOH) (or vehicle) for 4 consecutive days. Rats were then tested for susceptibility to acoustically evoked AWSs 3, 24, and 48hours after the last alcohol dose. In separate experiments, the inferior colliculus (IC) was collected at these same time points from rats subjected to alcohol withdrawal and control rats following alcohol withdrawal. PKA activity, catalytic C (PKA(C)) protein, regulatory RII (PKA(RII)) protein, and RII (PKA(RII)) protein were measured in the IC. Lastly, insitu pharmacological studies were performed to evaluate whether inhibiting PKA activity in the IC suppressed AWSs. ResultsIn the EtOH-treated group, AWSs were observed at the 24-hour time point, but not at the 3-hour or 48-hour time points. In the IC, PKA activity was significantly higher both 3hours (i.e., before AWS susceptibility) and 24hours after the last alcohol dose (when AWS susceptibility peaked) than in control rats. Consistent with these findings, protein levels of the PKA(C) subunit were significantly increased in the IC both 3 and 24hours after the last alcohol dose. Lastly, insitu inhibition of PKA activity within the IC suppressed AWSs. ConclusionsThe increase in PKA activity and PKA(C) protein expression in the IC preceded the occurrence of AWSs, and inhibiting PKA activity within the IC suppressed acoustically evoked AWSs. Together, these findings suggest that altered PKA activity plays a key role in the pathogenesis of AWSs. C1 [Akinfiresoye, Luli R.; Miranda, Clive; N'Gouemo, Prosper] Georgetown Univ, Dept Pediat, Med Ctr, Bldg D,Room 285,4000 Reservoir Rd NW, Washington, DC 20057 USA. [Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA. [Akinfiresoye, Luli R.] Howard Univ, Coll Med, Dept Pharmacol, 520 W St NW, Washington, DC 20059 USA. RP N'Gouemo, P (reprint author), Georgetown Univ, Dept Pediat, Med Ctr, Bldg D,Room 285,4000 Reservoir Rd NW, Washington, DC 20057 USA. EM pn@georgetown.edu FU NIAAA NIH HHS [R01 AA020073] NR 41 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2016 VL 40 IS 11 BP 2359 EP 2367 DI 10.1111/acer.13223 PG 9 WC Substance Abuse SC Substance Abuse GA EA8VT UT WOS:000386918400014 PM 27716957 ER PT J AU Spagnolo, PA Ramchandani, VA Schwandt, ML Kwako, LE George, DT Mayo, LM Hillard, CJ Heilig, M AF Spagnolo, Primavera A. Ramchandani, Vijay A. Schwandt, Melanie L. Kwako, Laura E. George, David T. Mayo, Leah M. Hillard, Cecilia J. Heilig, Markus TI FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Stress; Fatty Acid Amide Hydrolase; Endocannabinoids; Alcohol Use Disorders; Post-traumatic Stress Disorder ID ACID AMIDE HYDROLASE; POSITRON-EMISSION-TOMOGRAPHY; MEDIATED FEAR EXTINCTION; PITUITARY-ADRENAL AXIS; ENDOCANNABINOID SYSTEM; ANANDAMIDE HYDROLYSIS; AMYGDALA; ANXIETY; ACTIVATION; INHIBITION AB BackgroundA common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. MethodsForty-nine patients with PTSD and AD were admitted for 4weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. ResultsFAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. ConclusionsThis is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics. C1 [Spagnolo, Primavera A.; Schwandt, Melanie L.; Kwako, Laura E.; George, David T.] NIAAA, Off Clin Director, NIH, Bethesda, MD USA. [Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Div Intramural Clin & Biomed Res, NIH, Bethesda, MD USA. [Mayo, Leah M.; Heilig, Markus] Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. [Hillard, Cecilia J.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. [Hillard, Cecilia J.] Med Coll Wisconsin, Neurosci Res Ctr, Milwaukee, WI 53226 USA. RP Heilig, M (reprint author), Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. EM markus.heilig@liu.se OI Mayo, Leah/0000-0002-0645-4869 NR 49 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2016 VL 40 IS 11 BP 2426 EP 2434 DI 10.1111/acer.13210 PG 9 WC Substance Abuse SC Substance Abuse GA EA8VT UT WOS:000386918400022 PM 27716956 ER PT J AU Freed, MC AF Freed, Michael C. TI Nudge This: It is a Rational Fact That Donors Can Save the 22 People Who Die Daily Awaiting Organ Transplantation SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID HEALTH C1 [Freed, Michael C.] NIMH, Bethesda, MD 20892 USA. [Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Freed, MC (reprint author), NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. EM mfreed@cbhw.org NR 11 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD NOV PY 2016 VL 16 IS 11 BP 22 EP 25 DI 10.1080/15265161.2016.1222010 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA EA5GZ UT WOS:000386648700009 PM 27749179 ER PT J AU Matthews, CE Keadle, SK Troiano, RP Kahle, L Koster, A Brychta, R Van Domelen, D Caserotti, P Chen, KY Harris, TB Berrigan, D AF Matthews, Charles E. Keadle, Sarah Kozey Troiano, Richard P. Kahle, Lisa Koster, Annemarie Brychta, Robert Van Domelen, Dane Caserotti, Paolo Chen, Kong Y. Harris, Tamara B. Berrigan, David TI Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE sedentary behavior; physical activity; mortality; accelerometer; light-intensity activity; moderate-to-vigorous intensity activity ID ALL-CAUSE MORTALITY; REGRESSION-MODELS; UNITED-STATES; CARDIOVASCULAR-DISEASE; 2-REGRESSION MODEL; LIFE EXPECTANCY; BEHAVIOR; ACTIGRAPH; NHANES; RISK AB Background: Moderate-to-vigorous intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose-response for sedentary time and light- and moderate-to-vigorous intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. Design: US adults (n = 4840) from NHANES (2003-2006) wore an accelerometer for <= 7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light- and moderate-to-vigorous intensity physical activity. Splines were used to graphically present behavior-mortality relation. Isotemporal models estimated replacement associations for sedentary time, and separate models were fit for low- (<5.8 h total activity/d) and high-active participants to account for nonlinear associations. Results: Over a mean of 6.6 y, 700 deaths occurred. Compared with less-sedentary adults (6 sedentary h/d), those who spent 10 sedentary h/d had 29% greater risk (HR: 1.29; 95% CI: 1.1, 1.5). Compared with those who did less light activity (3 h/d), those who did 5 h of light activity/d had 23% lower risk (HR: 0.77; 95% CI: 0.6, 1.0). There was no association with mortality for sedentary time or light or moderate-to-vigorous activity in highly active adults. In less-active adults, replacing 1 h of sedentary time with either light or moderate-to-vigorous intensity activity was associated with 18% and 42% lower mortality, respectively. Conclusions: Health promotion efforts for physical activity have mostly focused on moderate-to-vigorous activity. However, our findings derived from accelerometer-based measurements suggest that increasing light-intensity activity and reducing sedentary time are also important, particularly for inactive adults. C1 [Matthews, Charles E.; Keadle, Sarah Kozey] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Troiano, Richard P.] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. [Berrigan, David] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kahle, Lisa] Informat Management Serv Inc, Silver Spring, MD USA. [Brychta, Robert; Chen, Kong Y.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, Bethesda, MD USA. [Koster, Annemarie] Maastricht Univ, Care & Publ Hlth Res Inst, Sch Publ Hlth & Primary Care, Dept Social Med, Maastricht, Netherlands. [Van Domelen, Dane; Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Matthews, CE (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. EM charles.matthews2@nih.gov RI Koster, Annemarie/E-7438-2010; OI Chen, Kong/0000-0002-0306-1904 NR 49 TC 0 Z9 0 U1 11 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2016 VL 104 IS 5 BP 1424 EP 1432 DI 10.3945/ajcn.116.135129 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EA9WD UT WOS:000386994500029 PM 27707702 ER PT J AU Hall, KD Chen, KY Guo, J Leibel, RL Mayer, LES Reitman, ML Rosenbaum, M Smith, SR Walsh, BT Ravussin, E AF Hall, Kevin D. Chen, Kong Y. Guo, Juen Leibel, Rudolph L. Mayer, Laurel E. S. Reitman, Marc L. Rosenbaum, Michael Smith, Steven R. Walsh, B. Timothy Ravussin, Eric TI Raising the bar on the low-carbohydrate diet Reply SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID ENERGY-EXPENDITURE; BODY-COMPOSITION; WEIGHT-LOSS C1 [Hall, Kevin D.; Chen, Kong Y.; Guo, Juen; Reitman, Marc L.] NIDDK, Bethesda, MD 20892 USA. [Leibel, Rudolph L.; Mayer, Laurel E. S.; Rosenbaum, Michael; Walsh, B. Timothy] Columbia Univ, New York, NY USA. [Ravussin, Eric] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. [Smith, Steven R.] Translat Res Inst Metab & Diabet, Orlando, FL USA. RP Hall, KD (reprint author), NIDDK, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov NR 10 TC 0 Z9 0 U1 8 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2016 VL 104 IS 5 BP 1488 EP 1490 DI 10.3945/ajcn.116.143628 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EA9WD UT WOS:000386994500039 PM 27802997 ER PT J AU Moss, JL Reiter, PL Brewer, NT AF Moss, Jennifer L. Reiter, Paul L. Brewer, Noel T. TI Concomitant Adolescent Vaccination in the US, 2007-2012 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HUMAN-PAPILLOMAVIRUS VACCINE; IMMUNIZATION SURVEY-TEEN; UNITED-STATES; SERIES INITIATION; NATIONAL-SURVEY; NORTH-CAROLINA; SAFETY; COVERAGE; PARENTS; HEALTH AB Introduction: Concomitant (same-day) delivery of two or more vaccines to adolescents is effective, safe, and efficient. Increasing concomitant vaccination could improve coverage for recommended adolescent vaccines, but little is known about who receives vaccines concomitantly. Methods: Data came from healthcare provider-verified records on 70,144 adolescents (aged 13-17 years) in the 2008-2012 versions of the National Immunization Survey-Teen who had received at least one dose of tetanus, diphtheria, and acellular pertussis (Tdap) booster; meningococcal conjugate vaccine (MenACWY); or human papillomavirus (HPV) vaccine. Separately for each vaccine, multivariable logistic regression identified adolescent and household correlates of concomitant versus single vaccination, stratified by adolescent sex. Vaccination took place in 2007-2012, data collection in 2008-2012, and data analysis in 2015. Results: Among vaccinated adolescents, 51%-65% of girls and 25%-53% of boys received two vaccines concomitantly. Concomitant uptake of each vaccine increased over survey years (e.g., 2012 vs 2008: girls' Tdap booster, OR=1.88, 95% CI=1.56, 2.26; boys' Tdap booster, OR=2.62, 95% CI=2.16, 3.16), with the exception of HPV vaccination among boys. Additionally, concomitant vaccination was less common as adolescents got older and in the Northeast (all p < 0.05). For MenACWY and HPV vaccine, concomitant uptake was less common for girls whose mothers had higher versus lower education and for boys who lived in metropolitan versus non-metropolitan areas (all p < 0.05). Conclusions: Missed opportunities for concomitant adolescent vaccination persist, particularly for HPV vaccine. Future interventions targeting groups with low rates of concomitant vaccination could improve population-level coverage with recommended vaccines. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Moss, Jennifer L.; Brewer, Noel T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Moss, Jennifer L.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Reiter, Paul L.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Brewer, Noel T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. RP Moss, JL (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E514,MSC 9765, Bethesda, MD 20892 USA. EM jennifer.moss@nih.gov OI Moss, Jennifer/0000-0002-3794-1344 FU NIH grant [F31 CA189411]; Merck; Cervical Cancer-Free America; GlaxoSmithKline FX This study was supported by an NIH grant (F31 CA189411; Principal Investigator: Moss). The research in this article was conducted while JLM was a Special Sworn Status researcher of the U.S. Census Bureau at the Center for Economic Studies. All results have been reviewed by the National Center for Health Statistics to ensure that no confidential information is disclosed. Research results and conclusions expressed herein are those of the authors and do not necessarily reflect the views of the National Cancer Institute or the National Center for Health Statistics.; PLR has received research grants from Merck and from Cervical Cancer-Free America, via an unrestricted educational grant from GlaxoSmithKline. NTB has served on paid advisory boards or received research grants from Merck and GlaxoSmithKline. These entities had no role in the study design, data analysis, or reporting of the results. No other financial disclosures were reported by the authors of this paper. NR 46 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2016 VL 51 IS 5 BP 693 EP 705 DI 10.1016/j.amepre.2016.05.013 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7CG UT WOS:000386785100012 PM 27374208 ER PT J AU James, P Jankowska, M Marx, C Hart, JE Berrigan, D Kerr, J Hurvitz, PM Hipp, JA Laden, F AF James, Peter Jankowska, Marta Marx, Christine Hart, Jaime E. Berrigan, David Kerr, Jacqueline Hurvitz, Philip M. Hipp, J. Aaron Laden, Francine TI "Spatial Energetics" Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY LEVELS; BUILT ENVIRONMENT; ACTIVITY MONITORS; TRAVEL BEHAVIOR; HEALTH RESEARCH; NEIGHBORHOOD; EXPOSURE; VALIDATION; CHILDREN; DESIGN AB To address the current obesity and inactivity epidemics, public health researchers have attempted to identify spatial factors that influence physical inactivity and obesity. Technologic and methodologic developments have led to a revolutionary ability to examine dynamic, high-resolution measures of temporally matched location and behavior data through GPS, accelerometry, and GIS. These advances allow the investigation of spatial energetics, high-spatiotemporal resolution data on location and time-matched energetics, to examine how environmental characteristics, space, and time are linked to activity-related health behaviors with far more robust and detailed data than in previous work. Although the transdisciplinary field of spatial energetics demonstrates promise to provide novel insights on how individuals and populations interact with their environment, there remain significant conceptual, technical, analytical, and ethical challenges stemming from the complex data streams that spatial energetics research generates. First, it is essential to better understand what spatial energetics data represent, the relevant spatial context of analysis for these data, and if spatial energetics can establish causality for development of spatially relevant interventions. Second, there are significant technical problems for analysis of voluminous and complex data that may require development of spatially aware scalable computational infrastructures. Third, the field must come to agreement on appropriate statistical methodologies to account for multiple observations per person. Finally, these challenges must be considered within the context of maintaining participant privacy and security. This article describes gaps in current practice and understanding and suggests solutions to move this promising area of research forward. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [James, Peter; Laden, Francine] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 401 Pk Dr,3rd Floor West, Boston, MA 02215 USA. [Jankowska, Marta] Calit2, La Jolla, CA USA. [Marx, Christine] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Hart, Jaime E.; Laden, Francine] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Hart, Jaime E.; Laden, Francine] Harvard Med Sch, Boston, MA USA. [Hart, Jaime E.; Laden, Francine] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Berrigan, David] NCI, Hlth Behav Res Branch, Behav Res Program, Bethesda, MD 20892 USA. [Kerr, Jacqueline] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. [Kerr, Jacqueline] San Diego State Univ, Grad Sch Publ Hlth, Dept Psychol, San Diego, CA 92182 USA. [Hurvitz, Philip M.] Univ Washington, Urban Form Lab, Seattle, WA 98195 USA. [Hipp, J. Aaron] North Carolina State Univ, Dept Pk Recreat & Tourism Management, Raleigh, NC USA. RP James, P (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 401 Pk Dr,3rd Floor West, Boston, MA 02215 USA. EM pjames@hsph.harvard.edu FU National Cancer Institute (NCI) Centers for Transdisciplinary Research on Energetics and Cancer (TREC) [U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155796, U01 CA116850]; NCI as part of the TREC initiative; Harvard National Heart, Lung, and Blood Institute Cardiovascular Epidemiology Training Grant [T32 HL 098048]; NIH [UM1 CA176726, R01 ES017017] FX This work was supported by the National Cancer Institute (NCI) Centers for Transdisciplinary Research on Energetics and Cancer (TREC) (U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155796, U01 CA116850). All authors were funded by NCI as part of the TREC initiative (except Berrigan and Hurvitz). The opinions or assertions contained herein are the private ones of the authors and are not considered as official or reflecting the views of NIH. Work was also supported by the Harvard National Heart, Lung, and Blood Institute Cardiovascular Epidemiology Training Grant T32 HL 098048 and NIH Grants UM1 CA176726 and R01 ES017017. We thank the TREC Spatial and Contextual Measures and Modeling Working Group, who contributed greatly to this analysis. NR 74 TC 0 Z9 0 U1 13 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2016 VL 51 IS 5 BP 792 EP 800 DI 10.1016/j.amepre.2016.06.006 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7CG UT WOS:000386785100022 PM 27528538 ER PT J AU Tansil, KA Esser, MB Sandhu, P Reynolds, JA Elder, RW Williamson, RS Chattopadhyay, SK Bohm, MK Brewer, RD McKnight-Eily, LR Hungerford, DW Toomey, TL Hingson, RW Fielding, JE AF Tansil, Kristin A. Esser, Marissa B. Sandhu, Paramjit Reynolds, Jeffrey A. Elder, Randy W. Williamson, Rebecca S. Chattopadhyay, Sajal K. Bohm, Michele K. Brewer, Robert D. McKnight-Eily, Lela R. Hungerford, Daniel W. Toomey, Traci L. Hingson, Ralph W. Fielding, Jonathan E. CA Community Preventive Serv Task For TI Alcohol Electronic Screening and Brief Intervention A Community Guide Systematic Review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; INTERACTIVE VOICE RESPONSE; TELEPHONE BRIEF INTERVENTION; CONTROLLED CLINICAL-TRIAL; IDENTIFICATION TEST AUDIT; REDUCING HEAVY DRINKING; WEB-BASED FEEDBACK; UNIVERSITY-STUDENTS; PRIMARY-CARE; PROBLEM DRINKERS AB Context: Excessive drinking is responsible for one in ten deaths among working-age adults in the U.S. annually. Alcohol screening and brief intervention is an effective but underutilized intervention for reducing excessive drinking among adults. Electronic screening and brief intervention (e-SBI) uses electronic devices to deliver key elements of alcohol screening and brief intervention, with the potential to expand population reach. Evidence acquisition: Using Community Guide methods, a systematic review of the scientific literature on the effectiveness of e-SBI for reducing excessive alcohol consumption and related harms was conducted. The search covered studies published from 1967 to October 2011. A total of 31 studies with 36 study arms met quality criteria and were included in the review. Analyses were conducted in 2012. Evidence synthesis: Twenty-four studies (28 study arms) provided results for excessive drinkers only and seven studies (eight study arms) reported results for all drinkers. Nearly all studies found that e-SBI reduced excessive alcohol consumption and related harms: nine study arms reported a median 23.9% reduction in binge-drinking intensity (maximum drinks/binge episode) and nine study arms reported a median 16.5% reduction in binge-drinking frequency. Reductions in drinking measures were sustained for up to 12 months. Conclusions: According to Community Guide rules of evidence, e-SBI is an effective method for reducing excessive alcohol consumption and related harms among intervention participants. Implementation of e-SBI could complement population-level strategies previously recommended by the Community Preventive Services Task Force for reducing excessive drinking (e.g., increasing alcohol taxes and regulating alcohol outlet density). Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Tansil, Kristin A.; Esser, Marissa B.; Sandhu, Paramjit; Reynolds, Jeffrey A.; Elder, Randy W.; Williamson, Rebecca S.; Chattopadhyay, Sajal K.; Bohm, Michele K.] Ctr Dis Control & Prevent CDC, Community Guide Branch, Div Publ Hlth Informat Disseminat, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA USA. [Brewer, Robert D.] CDC, Div Populat Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [McKnight-Eily, Lela R.; Hungerford, Daniel W.] CDC, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Toomey, Traci L.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Hingson, Ralph W.] NIAAA, Bethesda, MD USA. [Fielding, Jonathan E.] Los Angeles Cty Dept Publ Hlth, Los Angeles, CA USA. RP Elder, RW (reprint author), Ctr Dis Control & Prevent, Community Guide Branch, Div Publ Hlth Informat Disseminat, Ctr Surveillance Epidemiol & Lab Serv, 1600 Clifton Rd,MS E-69, Atlanta, GA 30329 USA. EM rfe3@cdc.gov FU Intramural CDC HHS [CC999999] NR 77 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2016 VL 51 IS 5 BP 801 EP 811 DI 10.1016/j.amepre.2016.04.013 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7CG UT WOS:000386785100023 PM 27745678 ER PT J AU Patrick, K Hekler, EB Estrin, D Mohr, DC Riper, H Crane, D Godino, J Riley, WT AF Patrick, Kevin Hekler, Eric B. Estrin, Deborah Mohr, David C. Riper, Heleen Crane, David Godino, Job Riley, William T. TI The Pace of Technologic Change Implications for Digital Health Behavior Intervention Research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID TIME ADAPTIVE INTERVENTIONS; RANDOMIZED CONTROLLED-TRIAL; SYSTEMATIC ANALYSIS; CHRONIC DISEASE; GLOBAL BURDEN; OLDER-ADULTS; GUT MICROBES; RISK-FACTORS; 21 REGIONS; MOBILE AB This paper addresses the rapid pace of change in the technologies that support digital interventions; the complexity of the health problems they aim to address; and the adaptation of scientific methods to accommodate the volume, velocity, and variety of data and interventions possible from these technologies. Information, communication, and computing technologies are now part of every societal domain and support essentially every facet of human activity. Ubiquitous computing, a vision articulated fewer than 30 years ago, has now arrived. Simultaneously, there is a global crisis in health through the combination of lifestyle and age-related chronic disease and multiple comorbidities. Computationally intensive health behavior interventions may be one of the most powerful methods to reduce the consequences of this crisis, but new methods are needed for health research and practice, and evidence is needed to support their widespread use. The challenges are many, including a reluctance to abandon timeworn theories and models of health behavior-and health interventions more broadly-that emerged in an era of self-reported data; medical models of prevention, diagnosis, and treatment; and scientific methods grounded in sparse and expensive data. There are also many challenges inherent in demonstrating that newer approaches are, indeed, effective. Potential solutions may be found in leveraging methods of research that have been shown to be successful in other domains, particularly engineering. A more "agile science" may be needed that streamlines the methods through which elements of health interventions are shown to work or not, and to more rapidly deploy and iteratively improve those that do. There is much to do to advance the issues discussed in this paper, and the papers in this theme issue. It remains an open question whether interventions based in these new models and methods are, in fact, equally if not more efficacious as what is available currently. Economic analyses of these new approaches are needed because assumptions of net worth compared to other approaches are just that, assumptions. Human-centered design research is needed to ensure that users ultimately benefit. Finally, a translational research agenda will be needed, as the status quo will likely be resistant to change. (C) 2016 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Patrick, Kevin; Godino, Job] Univ Calif San Diego, Ctr Wireless & Populat Hlth Syst, 9500 Gilman Dr,Dept 0811, La Jolla, CA 92093 USA. [Hekler, Eric B.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA. [Estrin, Deborah] Cornell Univ, Dept Comp Sci, Cornell NYC Tech, New York, NY 10021 USA. [Mohr, David C.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Riper, Heleen] Vrije Univ Amsterdam, Fac Behav & Movement Sci, Sect Clin Psychol, Amsterdam, Netherlands. [Crane, David] UCL, Ctr Behav Change, London, England. [Riley, William T.] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Patrick, K (reprint author), Univ Calif San Diego, Ctr Wireless & Populat Hlth Syst, 9500 Gilman Dr,Dept 0811, La Jolla, CA 92093 USA. EM kpatrick@ucsd.edu FU NIH Office of Behavioral and Social Sciences Research (OBSSR); Medical Research Council (MRC)/National Institute for Health Research (NIHR) Methodology Research Program; OBSSR; Robert Wood Johnson Foundation; National Science Foundation [1539846] FX This 2016 theme section of the American Journal of Preventive Medicine is supported by funding from the NIH Office of Behavioral and Social Sciences Research (OBSSR) to support the dissemination of research on digital health interventions, methods, and implications for preventive medicine.; This paper is one of the outputs of two workshops, one supported by the Medical Research Council (MRC)/National Institute for Health Research (NIHR) Methodology Research Program (PI Susan Michie), the OBSSR (William Riley, Director) and the Robert Wood Johnson Foundation (PI Kevin Patrick); and the other by the National Science Foundation (PI Donna Spruitj-Metz, proposal # 1539846). NR 77 TC 1 Z9 1 U1 12 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2016 VL 51 IS 5 BP 816 EP 824 DI 10.1016/j.amepre.2016.05.001 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7CG UT WOS:000386785100026 PM 27745681 ER PT J AU Carr, NJ Cecil, TD Gonzalez-Moreno, S Mohamed, F Moran, BJ Sobin, LH Sugarbaker, PH AF Carr, Norman J. Cecil, Thomas D. Gonzalez-Moreno, Santiago Mohamed, Faheez Moran, Brendan J. Sobin, Leslie H. Sugarbaker, Paul H. TI Letter to the Editor With Regard to the Article Entitled: "A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritoneii and Associated Appendiceal Neoplasia" Reply SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID MUCINOUS NEOPLASMS; CLINICOPATHOLOGICAL ANALYSIS C1 [Carr, Norman J.; Cecil, Thomas D.; Mohamed, Faheez; Moran, Brendan J.] Basingstoke & North Hampshire Hosp, Peritoneal Malignancy Inst, Basingstoke, Hants, England. [Gonzalez-Moreno, Santiago] MD Anderson Canc Ctr, Surg Oncol, Madrid, Spain. [Sobin, Leslie H.] NCI, Frederick Natl Lab Canc Res, Rockville, MD USA. [Sugarbaker, Paul H.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. RP Carr, NJ (reprint author), Basingstoke & North Hampshire Hosp, Peritoneal Malignancy Inst, Basingstoke, Hants, England. NR 5 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2016 VL 40 IS 11 BP 1578 EP 1578 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA EA8WQ UT WOS:000386921000015 PM 27755021 ER PT J AU Wise, SA AF Wise, Stephen A. TI In honor of Professor Kiyokatsu Jinno SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Editorial Material C1 [Wise, Stephen A.] NIH, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA. RP Wise, SA (reprint author), NIH, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA. EM stephen.wise@nih.gov NR 6 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 EI 1618-2650 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD NOV PY 2016 VL 408 IS 28 BP 7889 EP 7891 DI 10.1007/s00216-016-9962-5 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA EA5VS UT WOS:000386693000003 PM 27743020 ER PT J AU McGowan, EC Matsui, EC Peng, R Salo, PM Zeldin, DC Keet, CA AF McGowan, Emily C. Matsui, Elizabeth C. Peng, Roger Salo, Paivi M. Zeldin, Darryl C. Keet, Corinne A. TI Racial/ethnic and socioeconomic differences in self-reported food allergy among food-sensitized children in National Health and Nutrition Examination Survey III SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID UNITED-STATES; IGE; POPULATION; PREVALENCE; RISK C1 [McGowan, Emily C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD USA. [Matsui, Elizabeth C.; Keet, Corinne A.] Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD USA. [Peng, Roger] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Salo, Paivi M.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Keet, CA (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD USA. EM ckeet1@jhmi.edu FU NIAID NIH HHS [K23 AI103187] NR 11 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 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2016 VL 117 IS 5 BP 570 EP + DI 10.1016/j.anai.2016.08.034 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA EA3JI UT WOS:000386497900035 PM 27788892 ER PT J AU Tan, S Dasgupta, A Yao, JH Flynn, JA Yao, L Ward, MM AF Tan, Sovira Dasgupta, Abhijit Yao, Jianhua Flynn, John A. Yao, Lawrence Ward, Michael M. TI Spatial distribution of syndesmophytes along the vertebral rim in ankylosing spondylitis: preferential involvement of the posterolateral rim SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID INFLAMMATION; FEATURES; STRAIN; SPINE; CT AB Objective Syndesmophytes in ankylosing spondylitis (AS) can occur anywhere along the vertebral rim, but little is known about how and where they develop, and particularly if they first form in certain locations along the rim. This information might provide clues to their aetiology. We examined the spatial distribution of syndesmophytes in the thoracolumbar spine in patients with AS using CT. Methods We performed lumbar spine CT scans in 50 patients and used a validated computer algorithm to measure syndesmophyte heights in six intervertebral disc spaces. We measured heights every five radial degrees around the rim of each superior and inferior vertebral endplate. Results Syndesmophytes were observed in 208 of 296 intervertebral disc spaces. Both ascending and descending syndesmophytes were non-randomly distributed along the vertebral rim (p<0.0001 for deviation from uniform distribution). Syndesmophytes occurred most often at the posterolateral vertebral rim, and least commonly at the posterior rim and anterior rim. In disc spaces with only small isolated syndesmophytes, these were also most likely to occur at the posterolateral rim. Syndesmophyte distribution varied with the vertebral level. Localisation at the posterolateral rim was most pronounced at T10-T11, T12-T12 and T12-L1, while L2-L3 and L3-L4 exhibited little localisation. Conclusions Syndesmophytes are not randomly distributed around the vertebral rim, as might be expected if they develop solely in response to inflammation. Rather, they preferentially occur, and likely develop first, at the posterolateral rim. Studying factors that can lead to this pattern may help elucidate how syndesmophytes develop. C1 [Tan, Sovira; Dasgupta, Abhijit; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Yao, Jianhua; Yao, Lawrence] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Flynn, John A.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. RP Ward, MM (reprint author), NIAMSD, Bldg 10 CRC,Room 4-1339, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health; Clinical Center, National Institutes of Health; Johns Hopkins University School of Medicine General Clinical Research Center from the National Center for Research Resources/NIH [M01-RR00052] FX This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and by the Clinical Center, National Institutes of Health, and the Johns Hopkins University School of Medicine General Clinical Research Center (grant number M01-RR00052 from the National Center for Research Resources/NIH). NR 21 TC 0 Z9 0 U1 7 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2016 VL 75 IS 11 BP 1951 EP 1957 DI 10.1136/annrheumdis-2015-208802 PG 7 WC Rheumatology SC Rheumatology GA EA3AH UT WOS:000386469300012 PM 26797721 ER PT J AU Lin, NY Distler, A Beyer, C Philipi-Schobinger, A Breda, S Dees, C Stock, M Tomcik, M Niemeier, A Dell'Accio, F Gelse, K Mattson, MP Schett, G Distler, JHW AF Lin, Neng-Yu Distler, Alfiya Beyer, Christian Philipi-Schoebinger, Ariella Breda, Silvia Dees, Clara Stock, Michael Tomcik, Michal Niemeier, Andreas Dell'Accio, Francesco Gelse, Kolja Mattson, Mark P. Schett, Georg Distler, Joerg H. W. TI Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ARTICULAR-CARTILAGE; INDIAN HEDGEHOG; ENDOCHONDRAL OSSIFICATION; OSTEOCLAST PRECURSORS; CELLS; EXPRESSION; PATHWAY; MOUSE; TUMORIGENESIS; DEGENERATION AB Objectives Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Methods Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and mu CT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Results Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Conclusions Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. C1 [Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schoebinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Schett, Georg; Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schoebinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Schett, Georg; Distler, Joerg H. W.] Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany. [Breda, Silvia] Univ Pavia, IRCCS Policlin San Matteo Fdn, Div Rheumatol, Pavia, Italy. [Tomcik, Michal] Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic. [Tomcik, Michal] Charles Univ Prague, Fac Med 1, Dept Rheumatol, Prague, Czech Republic. [Niemeier, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Orthoped, Hamburg, Germany. [Dell'Accio, Francesco] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Gelse, Kolja] Univ Erlangen Nurnberg, Dept Surg, Div Trauma Surg & Orthoped Surg, Erlangen, Germany. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Distler, JHW (reprint author), Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany.; Distler, JHW (reprint author), Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany. EM joerg.distler@uk-erlangen.de OI LIN, NENG-YU/0000-0003-0746-0483 FU Interdisciplinary Center of Clinical Research (IZKF) in Erlangen [A57, J29, J39]; German Research Foundation of the Deutsche Forschungsgemeinschaft [DI 1537/5-1, DI 1537/7-1, DI 1537/8-1, DI 1537/9-1, DE 2414/2-1]; ELAN-Foundation Erlangen; Ministry of Health of the Czech Republic [00023728]; IMI; Ernst-Jung Foundation; BMBF; National Institute on Aging; Bavarian Research Foundation; [SVV262512] FX This study was supported by grants A57, J29 and J39 of the Interdisciplinary Center of Clinical Research (IZKF) in Erlangen, grants from the German Research Foundation (DI 1537/5-1, DI 1537/7-1, DI 1537/8-1, DI 1537/9-1, DE 2414/2-1 of the Deutsche Forschungsgemeinschaft), a grant of the ELAN-Foundation Erlangen to NYL and project grants 00023728 from the Ministry of Health of the Czech Republic and SVV262512. The study was also supported by the IMI-funded project BTCure, the carrier support award of the Ernst-Jung Foundation, the BMBF project ANCYLOSS and the Intramural Research Program of the National Institute on Aging. Neng-Yu Lin had a doctoral scholarship by Bavarian Research Foundation. NR 50 TC 1 Z9 1 U1 7 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2016 VL 75 IS 11 BP 2037 EP 2044 DI 10.1136/annrheumdis-2015-208420 PG 8 WC Rheumatology SC Rheumatology GA EA3AH UT WOS:000386469300024 PM 26851274 ER PT J AU Tektonidou, MG Wang, Z Ward, MM AF Tektonidou, Maria G. Wang, Zhong Ward, Michael M. TI Brief Report: Trends in Hospitalizations Due to Acute Coronary Syndromes and Stroke in Patients With Systemic Lupus Erythematosus, 1996 to 2012 SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; RISK-FACTORS; POPULATION; MORTALITY; OUTCOMES; BURDEN AB ObjectiveCardiovascular disease (CVD) has been recognized as a major cause of morbidity in patients with systemic lupus erythematosus (SLE), but it is not clear whether increased awareness of these risks has translated into improvements in CVD morbidity at the population level. The aim of this study was to examine trends in hospitalization rates for CVD events in a representative sample of adult patients with SLE in the US from 1996 to 2012. MethodsWe used the Nationwide Inpatient Sample to estimate the rates of hospitalization for acute myocardial infarction (MI), unstable angina, and ischemic stroke from 1996 to 2012 in patients with SLE. We compared these trends with those in the general population. ResultsDuring the study years, there were an estimated 31,012 hospitalizations for acute MI, 4,160 hospitalizations for unstable angina, and 26,144 hospitalizations for ischemic stroke among patients with SLE. The rates of hospitalization for acute MI and ischemic stroke increased over time in patients with SLE, while the rates for unstable angina decreased. The rates for all 3 conditions decreased in the general population over these years, with hospitalization rates for unstable angina decreasing faster in the general population than in patients with SLE. ConclusionIncreased awareness of the burden of CVD in patients with SLE has not yet translated into decreased rates of hospitalization for acute MI or stroke. This may be due to barriers in implementation of CVD risk factor modification or to SLE-specific risks that have not yet been identified or effectively targeted. C1 [Tektonidou, Maria G.] Univ Athens, Joint Acad Rheumatol Programme, Sch Med, Dept Internal Med 1, Athens, Greece. [Wang, Zhong; Ward, Michael M.] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU NIH Intramural Research Program from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIA-AR-041153] FX Supported by the NIH Intramural Research Program (grant ZIA-AR-041153 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases). NR 16 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD NOV PY 2016 VL 68 IS 11 BP 2680 EP 2685 DI 10.1002/art.39758 PG 6 WC Rheumatology SC Rheumatology GA EA9CT UT WOS:000386939500015 PM 27273732 ER PT J AU Swinstead, EE Paakinaho, V Presman, DM Hager, GL AF Swinstead, Erin E. Paakinaho, Ville Presman, Diego M. Hager, Gordon L. TI Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: A new perspective: Multiple transcription factors can effect chromatin pioneer functions through dynamic interactions with ATP-dependent chromatin remodeling factors SO BIOESSAYS LA English DT Article DE chromatin binding; dynamic assisted loading; estrogen receptor; FoxA1; glucocorticoid receptor; pioneer factors; residence time ID ESTROGEN-RECEPTOR-ALPHA; EMBRYONIC STEM-CELLS; GLUCOCORTICOID-RECEPTOR; IN-VIVO; COMPACTED CHROMATIN; NUCLEOSOME-BINDING; CRYSTAL-STRUCTURE; MMTV PROMOTER; SELF-RENEWAL; DNA-BINDING AB Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co-activators, co-repressors, multiple TFs, histone-modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP-Seq, digital genomic footprinting, DHS-Seq, live cell protein dynamics, and biochemical studies of ATP-dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy-dependent, non-equilibrium steady states. C1 [Swinstead, Erin E.; Paakinaho, Ville; Presman, Diego M.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov OI Presman, Diego/0000-0003-4515-8058 FU Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute (NCI); Center for Cancer Research (CCR); Sigrid Juselius Foundation FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), the National Cancer Institute (NCI) and the Center for Cancer Research (CCR). V.P. was supported, in part, by the Sigrid Juselius Foundation. NR 89 TC 3 Z9 3 U1 10 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD NOV PY 2016 VL 38 IS 11 BP 1150 EP 1157 DI 10.1002/bies.201600137 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA EB0SC UT WOS:000387054600015 PM 27633730 ER PT J AU Mule, MP Mannis, GN Wood, BL Radich, JR Hwang, J Ramos, NR Andreadis, C Damon, L Logan, AC Martin, TG Hourigan, CS AF Mule, Matthew P. Mannis, Gabriel N. Wood, Brent L. Radich, Jerald R. Hwang, Jimmy Ramos, Nestor R. Andreadis, Charalambos Damon, Lloyd Logan, Aaron C. Martin, Thomas G. Hourigan, Christopher S. TI Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Acute myeloid leukemia; Autologous hematopoietic cell transplantation; Measurable residual disease ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; 1ST COMPLETE REMISSION; AML PATIENTS; INTENSIVE CHEMOTHERAPY; POSTREMISSION THERAPY; INTRAVENOUS BUSULFAN; MULTICENTER TRIAL; ADULT PATIENTS; WORKING PARTY AB We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts"). Autograft MRD was assessed by molecular methods (real-time quantitative PCR [RQ-PCR] for Wilms tumor 1 (WT1) alone or a multigene panel) and by multiparameter flow cytometry (MPFC). WT1 RQ-PCR testing of the autograft had low sensitivity for relapse prediction (14%) and a negative predictive value of 51%. MPFC failed to identify MRD in any of 34 autografts tested. Combinations of molecular MRD assays, however, improved prediction of post-auto-HCT relapse. In multivariate analysis of clinical variables, including age, gender, race, cytogenetic risk category, and CD34(+) cell dose, only autograft multigene MRD as assessed by RQ-PCR was statistically significantly associated with relapse. One year after transplantation, only 28% patients with detectable autograft MRD were relapse free, compared with 67% in the MRD-negative cohort. Multigene MRD, while an improvement on other methods tested, was however suboptimal for relapse prediction in unselected patients, with specificity of 83% and sensitivity of 46%. In patients with known chromosomal abnormalities or mutations, however, better predictive value was observed with no relapses observed in MRD-negative patients in the first year after auto-HCT compared with 83% incidence of relapse in the MRD-positive patients (hazard ratio, 12.45; P=.0016). In summary, increased personalization of MRD monitoring by use of a multigene panel improved the ability to risk stratify patients for post-auto-HCT relapse. WT1 RQ-PCR and flow cytometric assessment for AML MRD in autograft samples had limited value for predicting relapse after auto-HCT. We demonstrate that cryopreserved autograft material presents unique challenges for AML MRD testing because of the masking effects of previous GCSF exposure on gene expression and flow cytometry signatures. In the absence of information regarding diagnostic characteristics, sources other than GCSF-stimulated PBSC leukapheresis specimens should be considered as alternatives for MRD testing in AML patients undergoing auto-HCT. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation. C1 [Mule, Matthew P.; Ramos, Nestor R.; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mannis, Gabriel N.; Hwang, Jimmy; Andreadis, Charalambos; Damon, Lloyd; Logan, Aaron C.; Martin, Thomas G.] Univ Calif San Francisco, Dept Med, Div Hematol & Blood & Marrow Transplantat, San Francisco, CA USA. [Wood, Brent L.; Radich, Jerald R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Room 6C 103C,10 Ctr Dr, Bethesda, MD 20892 USA. EM hourigan@nih.gov RI Hourigan, Christopher/S-2476-2016 OI Hourigan, Christopher/0000-0002-6189-8067 FU Intramural Research Program of the NIH, National Heart Lung and Blood Institute; NIH [R01 CA 175008-01A1] FX This research was supported in part by the Intramural Research Program of the NIH, National Heart Lung and Blood Institute and by NIH grant R01 CA 175008-01A1. NR 60 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2016 VL 22 IS 11 BP 1974 EP 1982 DI 10.1016/j.bbmt.2016.08.014 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA EA3YC UT WOS:000386544200010 PM 27544285 ER PT J AU Xiao, S Chen, YC Buehler, E Mandal, S Mandal, A Betenbaugh, M Park, MH Martin, S Shiloach, J AF Xiao, Su Chen, Yu Chi Buehler, Eugen Mandal, Swati Mandal, Ajeet Betenbaugh, Michael Park, Myung Hee Martin, Scott Shiloach, Joseph TI Genome-Scale RNA Interference Screen Identifies Antizyme 1 (OAZ1) as a Target for Improvement of Recombinant Protein Production in Mammalian Cells SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE siRNA; HEK 293; OAZ1; luciferase; protein production ID ORNITHINE-DECARBOXYLASE; CELLULAR POLYAMINES; GENE; EXPRESSION; CONFORMATION; SUPPRESSION; PETUNIA AB For the purpose of improving recombinant protein production from mammalian cells, an unbiased, high-throughput whole-genome RNA interference screen was conducted using human embryonic kidney 293 (HEK 293) cells expressing firefly luciferase. A 21,585 human genes were individually silenced with three different siRNAs for each gene. The screen identified 56 genes that led to the greatest improvement in luciferase expression. These genes were found to be included in several pathways involved in spliceosome formation and mRNA processing, transcription, metabolic processes, transport, and protein folding. The 10 genes that most enhanced protein expression when downregulated, were further confirmed by measuring the effect of their silencing on the expression of three additional recombinant proteins. Among the confirmed genes, OAZ1-the gene encoding the ornithine decarboxylase antizyme1-was selected for detailed investigation, since its silencing improved the reporter protein production without affecting cell viability. Silencing OAZ1 caused an increase of the ornithine decarboxylase enzyme and the cellular levels of putrescine and spermidine; an indication that increased cellular polyamines enhances luciferase expression without affecting its transcription. The study shows that OAZ1 is a novel target for improving expression of recombinant proteins. The genome-scale screening performed in this work can establish the foundation for targeted design of an efficient mammalian cell platform for various biotechnological applications. (C) 2016 Wiley Periodicals, Inc. C1 [Xiao, Su; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Xiao, Su; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA. [Chen, Yu Chi; Buehler, Eugen; Martin, Scott] Natl Ctr Adv Translat Sci, Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Mandal, Swati; Mandal, Ajeet; Park, Myung Hee] NIDCR, Mol & Cellular Biochem Sect, NIH, Bethesda, MD USA. [Martin, Scott] Genentech Inc, Funct Genom, San Francisco, CA 94080 USA. [Chen, Yu Chi] Novartis, Ctr Proteome Chem, Basel, Switzerland. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.; Martin, S (reprint author), Natl Ctr Adv Translat Sci, Chem Genom Ctr, NIH, Rockville, MD 20850 USA.; Martin, S (reprint author), Genentech Inc, Funct Genom, San Francisco, CA 94080 USA. EM martin.scott.everett@gmail.com; josephs@niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH); National Center for Advancing Translational Sciences (NCATS/NIH) FX Contract grant sponsor: Intramural Research Program of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH); Contract grant sponsor: National Center for Advancing Translational Sciences (NCATS/NIH) NR 33 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 EI 1097-0290 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD NOV PY 2016 VL 113 IS 11 BP 2403 EP 2415 DI 10.1002/bit.26017 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EA6QX UT WOS:000386755000011 PM 27215166 ER PT J AU Zhao, X Tian, X Kajigaya, S Cantilena, CR Strickland, S Savani, BN Mohan, S Feng, XM Keyvanfar, K Dunavin, N Townsley, DM Dumitriu, B Battiwalla, M Rezvani, K Young, NS Barrett, AJ Ito, S AF Zhao, Xin Tian, Xin Kajigaya, Sachiko Cantilena, Caroline R. Strickland, Stephen Savani, Bipin N. Mohan, Sanjay Feng, Xingmin Keyvanfar, Keyvan Dunavin, Neil Townsley, Danielle M. Dumitriu, Bogdan Battiwalla, Minoo Rezvani, Katayoun Young, Neal S. Barrett, A. John Ito, Sawa TI Epigenetic landscape of the TERT promoter: a potential biomarker for high risk AML/MDS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE telomerase reverse transcriptase promoter; methylation profile; mutation analysis; acute myeloid leukaemia; survival curve ID TELOMERASE-REVERSE-TRANSCRIPTASE; CANCER-CELL-LINES; ACUTE MYELOID-LEUKEMIA; DNA METHYLATION; HTERT GENE; APLASTIC-ANEMIA; HUMAN GENOME; CPG ISLAND; EXPRESSION; MUTATIONS AB Although recent observations implicate the importance of telomerase activity in acute myeloid leukaemia (AML), the roles of epigenetic regulations of the TERT gene in leukaemogenesis, drug resistance and clinical prognosis in AML are not fully understood. We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n=43). Prognostic impact of methylation status of the upstream TERT promoter region was assessed by the Kaplan-Meier method. The activity of the telomerase inhibitor, imetelstat, was measured using leukaemia cell lines. The TERTpro/Ex1 region was highly methylated in all cell lines and primary leukaemia cells showed diverse methylation profiles. Most cases showed hypermethylated regions at the upstream TERTpro/Ex1 region, which were associated with inferior patient survival. TERTpro/Ex1 methylation status was correlated with the cytotoxicity to imetelstat and its combination with hypomethylating agent enhanced the cytotoxicity of imetelstat. AML cell lines and primary blasts harbour distinct TERTpro/Ex1 methylation profiles that could serve as a prognostic biomarker of AML. However, validation in a large cohort of patients is necessary to confirm our findings. C1 [Zhao, Xin; Kajigaya, Sachiko; Cantilena, Caroline R.; Feng, Xingmin; Keyvanfar, Keyvan; Dunavin, Neil; Townsley, Danielle M.; Dumitriu, Bogdan; Battiwalla, Minoo; Young, Neal S.; Barrett, A. John; Ito, Sawa] NHLBI, Hematol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Strickland, Stephen; Savani, Bipin N.; Mohan, Sanjay] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Ito, S (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM itos2@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health; Vanderbilt-Ingram Cancer Center; MD Anderson Cancer Center FX We thank Samantha Miner, Fariba Chinian, and Yasutaka Ueda (Hematology Branch, NHLBI, NIH, USA) for their technical support. We also thank all patients who donated the samples to this study. This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health, Vanderbilt-Ingram Cancer Center, and MD Anderson Cancer Center. Imetelstat was obtained through Material Cooperative Research and Development Agreement (MCRADA) between Geron Corporation and National, Heart, Lung, and Blood Institute, National Institutes of Health. NR 46 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2016 VL 175 IS 3 BP 427 EP 439 DI 10.1111/bjh.14244 PG 13 WC Hematology SC Hematology GA EA8SG UT WOS:000386908300010 PM 27433923 ER PT J AU Breton, A Theodorou, A Aktuna, S Sonzogni, L Darling, D Chan, L Menzel, S van der Spek, PJ Swagemakers, SMA Grosveld, F Philipsen, S Thein, SL AF Breton, Amandine Theodorou, Andria Aktuna, Suleyman Sonzogni, Laura Darling, David Chan, Lucas Menzel, Stephan van der Spek, Peter J. Swagemakers, Sigrid M. A. Grosveld, Frank Philipsen, Sjaak Thein, Swee Lay TI ASH1L (a histone methyltransferase protein) is a novel candidate globin gene regulator revealed by genetic study of an English family with beta-thalassaemia unlinked to the beta-globin locus SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE ASH1L; Trithorax protein; beta-thalassaemia ID LINKAGE ANALYSIS AB In 1993, we described an English family with beta-thalassaemia that was not linked to the beta-globin locus. Whole genome sequence analyses revealed potential causative mutations in 15 different genes, of which 4 were consistently and uniquely associated with the phenotype in all 7 affected family members, also confirmed by genetic linkage analysis. Of the 4 genes, which are present in a centromeric region of chromosome 1, ASH1L was proposed as causative through functional mRNA knock-down and chromatin-immunoprecipitation studies in human erythroid progenitor cells. Our data suggest a putative role for ASH1L (Trithorax protein) in the regulation of globin genes. C1 [Breton, Amandine; Theodorou, Andria; Aktuna, Suleyman; Sonzogni, Laura; Menzel, Stephan; Thein, Swee Lay] Kings Coll London, Fac Life Sci & Med, Div Canc Studies, Mol Haematol, London SE5 9NU, England. [Darling, David; Chan, Lucas; Thein, Swee Lay] Kings Coll Hosp NHS Fdn Trust, Dept Haematol Med, London SE5 9RS, England. [van der Spek, Peter J.; Swagemakers, Sigrid M. A.] Erasmus MC, Dept Bioinformat, Rotterdam, Netherlands. [Grosveld, Frank; Philipsen, Sjaak] Erasmus MC, Dept Cell Biol, Rotterdam, Netherlands. [Grosveld, Frank; Philipsen, Sjaak] Erasmus MC, Netherlands Consortium Syst Biol, Rotterdam, Netherlands. [Grosveld, Frank] Erasmus MC, Ctr Biomed Genet, Rotterdam, Netherlands. [Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bldg 10 CRC,Room 5E-5142,10 Ctr Dr, Bethesda, MD 20892 USA. RP Thein, SL (reprint author), NHLBI, Sickle Cell Branch, NIH, Bldg 10 CRC,Room 5E-5142,10 Ctr Dr, Bethesda, MD 20892 USA. EM sl.thein@nih.gov FU EU-FP7 THALAMOSS consortium; EMBO travel fellowship; Landsteiner Foundation for Blood Transfusion Research [LSBR 1040]; Netherlands Organization for Health Research and Development [NWO/ZonMw TOP 40-00812-98-12128]; Medical Research Council, UK (MRC) [G0000111, ID51640]; Dutch CTMM Biochip grant FX We thank members of the Grosveld laboratory for training and advice on the ChIP-qPCR procedure and members of the Farzaneh laboratory for technical support in lentiviral production for RNA interference experiments. This work was supported by the EU-FP7 THALAMOSS consortium (SP and SLT) and an EMBO travel fellowship to visit the Grosveld laboratory (AB). FG and SP were supported by the Landsteiner Foundation for Blood Transfusion Research (LSBR 1040); SP by the Netherlands Organization for Health Research and Development (NWO/ZonMw TOP 40-00812-98-12128); SLT, by the Medical Research Council, UK (MRC Grant No. G0000111, ID51640). Bioinformatics activities were supported from the Dutch CTMM Biochip grant. NR 15 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2016 VL 175 IS 3 BP 525 EP 530 DI 10.1111/bjh.14256 PG 6 WC Hematology SC Hematology GA EA8SG UT WOS:000386908300021 PM 27434206 ER PT J AU Duggan, MC Jochems, C Donahue, RN Richards, J Karpa, V Foust, E Paul, B Brooks, T Tridandapani, S Olencki, T Pan, XL Lesinski, GB Schlom, J Carson, WE AF Duggan, Megan C. Jochems, Caroline Donahue, Renee N. Richards, Jacob Karpa, Volodymyr Foust, Elizabeth Paul, Bonnie Brooks, Taylor Tridandapani, Susheela Olencki, Thomas Pan, Xueliang Lesinski, Gregory B. Schlom, Jeffrey Carson, William E., III TI A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-alpha-2b in patients with CEA-expressing carcinomas SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Vaccines; Carcinoembryonic antigen (CEA); Colorectal cancer; Immunotherapy; Interferon alpha-2b ID HUMAN CARCINOEMBRYONIC ANTIGEN; METASTATIC COLORECTAL-CANCER; TUMOR-ASSOCIATED ANTIGENS; MHC CLASS-I; ALPHA-INTERFERON TREATMENT; T-CELL-ACTIVATION; MONOCLONAL-ANTIBODY; SUPPRESSOR-CELLS; MELANOMA PATIENTS; HUMAN-BREAST AB Prime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) and rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells and direct expression of co-stimulatory molecules. We hypothesized that co-administration of vaccine with GM-CSF and interferon alpha (IFN-alpha) would have efficacy in CEA-expressing cancers. Patients with CEA-expressing cancers received the rV-CEA(6D)-TRICOM vaccine subcutaneously (s.c.) on day 1 followed by GM-CSF s.c. to the injection site on days 1-4. In Cycle 1, patients received thrice weekly s.c. injections of IFN-alpha-2b the week after rV-CEA(6D)-TRICOM. In Cycles 2-4, patients received thrice weekly s.c. injections of IFN-alpha-2b the same week that rF-CEA(6D)-TRICOM was given. The first cohort received no IFN followed by dose escalation of IFN-alpha in subsequent cohorts. Thirty-three patients were accrued (mean 59.8 years). Grade 3 toxicities included fatigue and hyperglycemia. Grade 4-5 adverse events (unrelated to treatment) were confusion (1), elevated aspartate transaminase (AST)/alanine transaminase (ALT) (1), and sudden death (1). No patients had a partial response, and eight patients exhibited stable disease of aeyen3 months. Median progression-free survival and overall survival (OS) were 1.8 and 6.3 months, respectively. Significantly higher serum CD27 levels were observed after vaccine therapy (p = 0.006 post 1-2 cycles, p = 0.003 post 3 cycles, p = 0.03 post 4-7 cycles) and 42 % of patients assayed developed CEA-specific T cell responses. Pre-treatment levels of myeloid-derived suppressor cells correlated with overall survival (p = 0.04). Administration of IFN-alpha led to significantly increased OS (p = 0.02) compared to vaccine alone. While the vaccine regimen produced no clinical responses, IFN-alpha administration was associated with improved survival. C1 [Duggan, Megan C.; Karpa, Volodymyr; Foust, Elizabeth; Paul, Bonnie; Brooks, Taylor; Tridandapani, Susheela; Lesinski, Gregory B.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Jochems, Caroline; Donahue, Renee N.; Richards, Jacob; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. [Olencki, Thomas] Ohio State Univ, Div Med Oncol, Columbus, OH 43210 USA. [Pan, Xueliang] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Carson, William E., III] Ohio State Univ, Div Surg Oncol, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. [Richards, Jacob] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Carson, WE (reprint author), Ohio State Univ, Div Surg Oncol, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM william.carson@osumc.edu FU NIH [P01 CA095426, P30 CA016058, T32 GM068412] FX This work was supported by NIH Grants: P01 CA095426 (W. Carson), P30 CA016058 (W. Carson), and T32 GM068412 (M. Duggan). NR 47 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2016 VL 65 IS 11 BP 1353 EP 1364 DI 10.1007/s00262-016-1893-7 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA EA4UN UT WOS:000386610800007 PM 27581603 ER PT J AU Eke, I Makinde, AY Aryankalayil, MJ Ahmed, MM Coleman, CN AF Eke, Iris Makinde, Adeola Y. Aryankalayil, Molykutty J. Ahmed, Mansoor M. Coleman, C. Norman TI Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine SO CANCER LETTERS LA English DT Review DE Molecular profiling; Precision medicine; Radiation oncology; Targeted therapy ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; ISOCITRATE DEHYDROGENASE MUTATIONS; RESISTANT PROSTATE-CANCER; ACUTE MYELOID-LEUKEMIA; ADVANCED RECTAL-CANCER; PHASE-III; PHOSPHOPROTEOMIC ANALYSIS; GLIOBLASTOMA-MULTIFORME; PROMOTER METHYLATION AB New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd. C1 [Eke, Iris; Makinde, Adeola Y.; Aryankalayil, Molykutty J.; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ahmed, Mansoor M.; Coleman, C. Norman] NCI, Radiat Res Program, NIH, Rockville, MD 20892 USA. RP Eke, I (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM iris.eke@nih.gov RI Eke, Iris/B-9251-2016 OI Eke, Iris/0000-0002-3591-019X FU NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research FX This study was supported by the NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research. The authors thank the NIH Fellows Editorial Board for editorial assistance and Katherine Wilsdon (NCI, NIH) for critical reading and discussion of the manuscript. NR 127 TC 1 Z9 1 U1 6 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD NOV 1 PY 2016 VL 382 IS 1 BP 118 EP 126 DI 10.1016/j.canlet.2016.01.041 PG 9 WC Oncology SC Oncology GA EA9SU UT WOS:000386985800013 PM 26828133 ER PT J AU Yacoob, C Pancera, M Vigdorovich, V Oliver, BG Glenn, JA Feng, J Sather, DN McGuire, AT Stamatatos, L AF Yacoob, Christina Pancera, Marie Vigdorovich, Vladimir Oliver, Brian G. Glenn, Jolene A. Feng, Junli Sather, D. Noah McGuire, Andrew T. Stamatatos, Leonidas TI Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors SO CELL REPORTS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL PRECURSORS; STRUCTURAL BASIS; HIV-1-NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; DISEASE PROGRESSION; MATURATION PATHWAY; CD4-BINDING SITE; RATIONAL DESIGN; CD4 BINDING AB Elicitation of broadly neutralizing antibodies remains a long-standing goal of HIV vaccine research. Although such antibodies can arise during HIV-1 infection, gaps in our knowledge of their germline, pre-immune precursor forms, as well as on their interaction with viral Env, limit our ability to elicit them through vaccination. Studies of broadly neutralizing antibodies from the VRC01-class provide insight into progenitor B cell receptors (BCRs) that could develop into this class of antibodies. Here, we employed high-throughput heavy chain variable region (VH)/light chain variable region (VL) deep sequencing, combined with biophysical, structural, and modeling antibody analyses, to interrogate circulating potential VRC01-progenitor BCRs in healthy individuals. Our study reveals that not all humans are equally predisposed to generate VRC01-class antibodies, not all predicted progenitor VRC01-expressing B cells can bind to Env, and the CDRH3 region of germline VRC01 antibodies influence their ability to recognize HIV-1. These findings will be critical to the design of optimized immunogens that should consider CDRH3 interactions. C1 [Yacoob, Christina; Pancera, Marie; Glenn, Jolene A.; Feng, Junli; McGuire, Andrew T.; Stamatatos, Leonidas] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave North, Seattle, WA 98109 USA. [Pancera, Marie] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Vigdorovich, Vladimir; Oliver, Brian G.; Sather, D. Noah] Ctr Infect Dis Res, 307 Westlake Ave North 500, Seattle, WA 98109 USA. [Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, 1410 Northeast Campus Pkwy, Seattle, WA 98195 USA. RP Pancera, M; Stamatatos, L (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave North, Seattle, WA 98109 USA.; Pancera, M (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.; Stamatatos, L (reprint author), Univ Washington, Dept Global Hlth, 1410 Northeast Campus Pkwy, Seattle, WA 98195 USA. EM mpancera@fredhutch.org; lstamata@fredhutch.org FU NIH [R01 AI104384, R01 AI081625]; J.B. Pendleton Charitable Trust FX This study was supported by NIH grants R01 AI104384 and R01 AI081625 (L.S.). We acknowledge many helpful discussions with Pamela Bjorkman and Anthony West on the topics discussed here. We also acknowledge the support by the J.B. Pendleton Charitable Trust. NR 48 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 1 PY 2016 VL 17 IS 6 BP 1560 EP 1570 DI 10.1016/j.celrep.2016.10.017 PG 11 WC Cell Biology SC Cell Biology GA EA9BS UT WOS:000386936200009 PM 27806295 ER PT J AU Grainger, S Richter, J Palazon, RE Pouget, C Lonquich, B Wirth, S Grassme, KS Herzog, W Swift, MR Weinstein, BM Traver, D Willert, K AF Grainger, Stephanie Richter, Jenna Palazon, Raquel Espin Pouget, Claire Lonquich, Brianna Wirth, Sara Grassme, Kathrin Sabine Herzog, Wiebke Swift, Matthew R. Weinstein, Brant M. Traver, David Willert, Karl TI Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells SO CELL REPORTS LA English DT Article ID C-MYC EXPRESSION; IN-VIVO; CYCLE PROGRESSION; ZEBRAFISH EMBRYO; SELF-RENEWAL; HEMOGENIC ENDOTHELIUM; ACTS UPSTREAM; SPECIFICATION; NOTCH; PATHWAY AB All mature blood cell types in the adult animal arise from hematopoietic stem and progenitor cells ( HSPCs). However, the developmental cues regulating HSPC ontogeny are incompletely understood. In particular, the details surrounding a requirement for Wnt/beta-catenin signaling in the development of mature HSPCs are controversial and difficult to consolidate. Using zebrafish, we demonstrate that Wnt signaling is required to direct an amplification of HSPCs in the aorta. Wnt9a is specifically required for this process and cannot be replaced by Wnt9b or Wnt3a. This proliferative event occurs independently of initial HSPC fate specification, and the Wnt9a input is required prior to aorta formation. HSPC arterial amplification occurs prior to seeding of secondary hematopoietic tissues and proceeds, in part, through the cell cycle regulator myca (c-myc). Our results support a general paradigm, in which early signaling events, including Wnt, direct later HSPC developmental processes. C1 [Grainger, Stephanie; Richter, Jenna; Palazon, Raquel Espin; Pouget, Claire; Lonquich, Brianna; Wirth, Sara; Traver, David; Willert, Karl] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA. [Richter, Jenna] Univ Calif San Diego, Biomed Sci Grad Studies, La Jolla, CA 92037 USA. [Grassme, Kathrin Sabine; Herzog, Wiebke] Univ Munster, D-48149 Munster, Germany. [Herzog, Wiebke] Max Planck Inst Mol Biomed, Munster, Germany. [Herzog, Wiebke] Univ Munster, Cells In Mot Cluster Excellence EXC CiM 1003, D-48149 Munster, Germany. [Swift, Matthew R.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. [Weinstein, Brant M.] NICHD, Sect Vertebrate Organogenesis, Div Dev Biol, NIH, Bethesda, MD 20892 USA. RP Traver, D; Willert, K (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA. EM dtraver@ucsd.edu; kwillert@ucsd.edu FU American Heart Association [14POST18340021]; Leukemia and Lymphoma Society [5431-15, 1657-13]; muCSD Interdisciplinary Stem Cell Training Program (CIRM) [TG2-01154]; UCSD Stem Cell Program; CIRM Major Facilities grant [FA1-00607]; CIRM [RB4-06158] FX IWP-L6 was a gift from L. Lum. We thank R. Rainville and K. Ong for fish husbandry; E. D. O'Connor, C. Fine, and K. E. Marquez for FACS assistance; and C. Bickers, E. Butko, B. Weijts, and N. Del Cid for technical assistance and reading of the manuscript. S.G. was supported by awards from the American Heart Association (14POST18340021) and the Leukemia and Lymphoma Society (5431-15). J.R. was supported in part by the mu CSD Interdisciplinary Stem Cell Training Program (CIRM TG2-01154). This work was supported in part by funding to K.W. from the UCSD Stem Cell Program and was made possible in part by the CIRM Major Facilities grant (FA1-00607) to the Sanford Consortium for Regenerative Medicine. D.T. was supported by Scholar Award 1657-13 from The Leukemia and Lymphoma Society and CIRM (RB4-06158). NR 84 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 1 PY 2016 VL 17 IS 6 BP 1595 EP 1606 DI 10.1016/j.celrep.2016.10.027 PG 12 WC Cell Biology SC Cell Biology GA EA9BS UT WOS:000386936200012 PM 27806298 ER PT J AU Sumner, AE Duong, MT Bingham, BA Aldana, PC Ricks, M Mabundo, LS Tulloch-Reid, MK Chung, ST Sacks, DB AF Sumner, Anne E. Duong, Michelle T. Bingham, Brianna A. Aldana, Paola C. Ricks, Madia Mabundo, Lilian S. Tulloch-Reid, Marshall K. Chung, Stephanie T. Sacks, David B. TI Glycated Albumin Identifies Prediabetes Not Detected by Hemoglobin A(1c): The Africans in America Study SO CLINICAL CHEMISTRY LA English DT Article ID LIFE-STYLE INTERVENTION; GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; DIABETES PREVENTION; FOLLOW-UP; A1C; PREVALENCE; RISK; POPULATION; REDUCTION AB BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A(1c) (Hb A(1c)) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m(2)) and obese (BMI >= 30 kg/m(2)) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m(2)]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A(1c), and glycated albumin was determined by thresholds at the upper quartile for each [Hb A(1c) >= 5.7% (39 mmol/mol), glycated albumin >= 13.77%]. RESULTS: Based on glucose criteria for the OGTT, pre-diabetes was detected in 36% (85/236). BMI and Hb A(1c) were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A(1c) alone(72% vs 37%, P < 0.01). In the obese, Hb A(1c) was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A(1c) in nonobese African immigrants. (C) 2016 American Association for Clinical Chemistry C1 [Sumner, Anne E.; Duong, Michelle T.; Bingham, Brianna A.; Aldana, Paola C.; Ricks, Madia; Mabundo, Lilian S.; Chung, Stephanie T.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Tulloch-Reid, Marshall K.] Univ West Indies, Res Inst Trop Med, Kingston, Jamaica. [Sacks, David B.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIH, Bldg 10 CRC,Rm 6-5940,MSC 1612, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU NIH intramural programs of NIDDK; NIH intramural programs of NIMHD; NIH intramural programs of Clinical Center; PUNGH; NIH; NIDDK; NIMHD; NIH Clinical Center FX NIH intramural programs of NIDDK, the NIMHD and the Clinical Center. Asahi Kasei Pharma provided reagents for the Lucica GA-L assay. PUNGH funding and NIH; A.E. Sumner, intramural program of NIDDK and intramural program of NIMHD; M.T. Duong, intramural program of NIDDK; B.A. Bingham, intramural program of NIDDK; P.C. Aldana, intramural program of NIDDK; M. Ricks, intramural program of NIDDK; L.S. Mabundo, intramural program of NIDDK; S.T. Chung, intramural program of NIDDK; D.B. Sacks, Intramural Research Program of the NIH Clinical Center. NR 40 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2016 VL 62 IS 11 BP 1524 EP 1532 DI 10.1373/clinchem.2016.261255 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA EA3XD UT WOS:000386541700015 PM 27624138 ER PT J AU Srbely, J Vadasz, B Shah, J Gerber, NL Sikdar, S Kumbhare, D AF Srbely, John Vadasz, Brian Shah, Jay Gerber, Naomi Lynn Sikdar, Siddhartha Kumbhare, Dinesh TI Central Sensitization: A Clinical Conundrum SO CLINICAL JOURNAL OF PAIN LA English DT Letter ID CHRONIC PELVIC PAIN; NEUROTROPHIC FACTOR; OSTEOARTHRITIS; ENDOMETRIOSIS; STIMULATION; DEPRESSION; MEDIATORS; OUTCOMES; DISEASE; MARKERS C1 [Srbely, John] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON, Canada. [Vadasz, Brian] Univ Toronto, Toronto, ON, Canada. [Kumbhare, Dinesh] Univ Toronto, Dept Med, Div Phys Med & Rehabil, Toronto, ON, Canada. [Shah, Jay] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Gerber, Naomi Lynn] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA. [Sikdar, Siddhartha] George Mason Univ, Bioengn Elect & Comp Engn, Fairfax, VA 22030 USA. RP Srbely, J (reprint author), Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON, Canada. NR 25 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD NOV PY 2016 VL 32 IS 11 BP 1011 EP 1013 DI 10.1097/AJP.0000000000000374 PG 3 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA EA3DH UT WOS:000386479000011 PM 27760054 ER PT J AU Papadakis, GZ Millo, C Bagci, U Blau, J Collins, MT AF Papadakis, Georgios Z. Millo, Corina Bagci, Ulas Blau, Jenny Collins, Michael T. TI F-18-NaF and F-18-FDG PET/CT in Gorham-Stout Disease SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE Gorham-Stout disease; vanishing hone disease; F-18-NaF PET/CT; F-18-FDG PET/CT ID DISAPPEARING BONE AB Gorham-Stout disease (GSD) is an extremely- rare skeletal disorder of unknown etiology characterized by benign proliferation of vascular or lymphatic channels, leading to progressive bone resorption. We report on a patient diagnosed with GSD affecting the right scapula and the right ribs, who underwent PET/CT scans using F-18-FDG and F-18-NaF. The remnant upper portion of the affected scapula did not Show F-18-FDG uptake but demonstrated markedly increased demon F-18-NaF activity Furthermore, intense F-18-NaF activity was seen on the right posterior ribs, which were actively being re sorbed, suggesting the potential application of F-18-NaF-PET/CT imaging in GSD diagnosis and follow-up. C1 [Papadakis, Georgios Z.] NIH, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. [Millo, Corina] NIH, Div Nucl Med, RAD&IS, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Bagci, Ulas] Univ Cent Florida, Ctr Comp Vis Res, Dept Elect & Comp Sci, Orlando, FL 32816 USA. [Blau, Jenny] NICHHD, NIH, Bethesda, MD 20892 USA. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, NIH, Bldg 30,Room 228 MSC 4320, Bethesda, MD 20892 USA. EM mcollins@dir.nidcr.nih.gov FU Intramural NIH HHS [Z01 DE000649-14] NR 10 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD NOV PY 2016 VL 41 IS 11 BP 884 EP 885 DI 10.1097/RLU.0000000000001369 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EA4GU UT WOS:000386569900020 PM 27648707 ER PT J AU Ricordi, C Goldstein, JS Balamurugan, AN Szot, GL Kin, T Liu, CY Czarniecki, CW Barbaro, B Bridges, ND Cano, J Clarke, WR Eggerman, TL Hunsicker, LG Kaufman, DB Khan, A Lafontant, DE Linetsky, E Luo, XR Markmann, JF Naji, A Korsgren, O Oberholzer, J Turgeon, NA Brandhorst, D Friberg, AS Lei, J Wang, LJ Wilhelm, JJ Willits, J Zhang, XM Hering, BJ Posselt, AM Stock, PG Shapiro, AMJ AF Ricordi, Camillo Goldstein, Julia S. Balamurugan, A. N. Szot, Gregory L. Kin, Tatsuya Liu, Chengyang Czarniecki, Christine W. Barbaro, Barbara Bridges, Nancy D. Cano, Jose Clarke, William R. Eggerman, Thomas L. Hunsicker, Lawrence G. Kaufman, Dixon B. Khan, Aisha Lafontant, David-Erick Linetsky, Elina Luo, Xunrong Markmann, James F. Naji, Ali Korsgren, One Oberholzer, Jose Turgeon, Nicole A. Brandhorst, Daniel Friberg, Andrew S. Lei, Ji Wang, Ling-jia Wilhelm, Joshua J. Willits, Jamie Zhang, Xiaomin Hering, Bernhard J. Posselt, Andrew M. Stock, Peter G. Shapiro, A. M. James TI National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities SO DIABETES LA English DT Article ID SINGLE-DONOR; EDMONTON PROTOCOL; CULTURED ISLETS; PANCREAS; PRESERVATION; LANGERHANS; PERFUSION; OUTCOMES; YIELD AB Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed. C1 [Ricordi, Camillo; Khan, Aisha; Linetsky, Elina] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. [Goldstein, Julia S.; Czarniecki, Christine W.; Bridges, Nancy D.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Balamurugan, A. N.; Wilhelm, Joshua J.; Hering, Bernhard J.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA. [Balamurugan, A. N.; Wilhelm, Joshua J.; Hering, Bernhard J.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. [Szot, Gregory L.; Posselt, Andrew M.; Stock, Peter G.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Kin, Tatsuya; Shapiro, A. M. James] Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada. [Kin, Tatsuya; Shapiro, A. M. James] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Liu, Chengyang; Naji, Ali] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Liu, Chengyang; Naji, Ali] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Liu, Chengyang; Naji, Ali] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barbaro, Barbara; Oberholzer, Jose] Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA. [Cano, Jose; Turgeon, Nicole A.] Emory Univ, Dept Surg, Emory Transplant Ctr, Div Transplantat, Atlanta, GA 30322 USA. [Clarke, William R.; Hunsicker, Lawrence G.; Lafontant, David-Erick; Willits, Jamie] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA. [Eggerman, Thomas L.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kaufman, Dixon B.; Luo, Xunrong; Wang, Ling-jia; Zhang, Xiaomin] Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA. [Markmann, James F.; Lei, Ji] Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA. [Korsgren, One; Friberg, Andrew S.] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Brandhorst, Daniel] Uppsala Univ, Dept Clin Immunol, Rudbeck Lab, Uppsala, Sweden. [Balamurugan, A. N.] Univ Louisville, Dept Surg, Islet Cell Lab, Cardiovasc Innovat Inst, Louisville, KY 40292 USA. [Kaufman, Dixon B.] Univ Wisconsin, Madison, WI USA. RP Ricordi, C (reprint author), Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA.; Goldstein, JS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ricordi@miami.edu; goldsteinj@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institute for Diabetes and Digestive and Kidney Diseases [U01-AI-089317]; Northwestern University (Evanston, IL) [U01-AI-089316]; University of Alberta (Edmonton, Alberta, Canada) [U01-AI-065191]; University of California, San Francisco (San Francisco, CA) [U01-DK-085531]; University of Illinois at Chicago (Chicago, IL) [5U01-DK-070431-10]; University of Iowa (Iowa City, IA) [U01-DK-070431]; University of Miami (Miami, FL) [U01-DK-070460]; University of Minnesota (Minneapolis, MN) [U01-AI-065193]; University of Pennsylvania (Philadelphia, PA) [U01-DK-070430]; Uppsala University (Uppsala, Sweden) [U01-AI-065192]; General Clinical Research Center Awards and Clinical and Translational Science Awards: Emory University [UL1-TR-000454]; Northwestern University [5UL1-RR-025741, 8UL1-TR-000150]; University of California, San Francisco [UL1-TR-000004]; University of Illinois at Chicago [UL1-TR-000050]; University of Miami [1UL1-TR-000460]; University of Minnesota [5M01-RR-000400, UL1-TR-000114]; University of Pennsylvania [M01-RR-00040, UL1-TR-000003] FX This research was supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute for Diabetes and Digestive and Kidney Diseases to the following institutions: Emory University (Atlanta, GA), U01-AI-089317; Northwestern University (Evanston, IL), U01-AI-089316; University of Alberta (Edmonton, Alberta, Canada), U01-AI-065191; University of California, San Francisco (San Francisco, CA), U01-DK-085531; University of Illinois at Chicago (Chicago, IL), 5U01-DK-070431-10; University of Iowa (Iowa City, IA), U01-DK-070431; University of Miami (Miami, FL), U01-DK-070460; University of Minnesota (Minneapolis, MN), U01-AI-065193; University of Pennsylvania (Philadelphia, PA), U01-DK-070430; and Uppsala University (Uppsala, Sweden), U01-AI-065192. In addition, the study was supported by the following General Clinical Research Center Awards and Clinical and Translational Science Awards: Emory University, UL1-TR-000454; Northwestern University, 5UL1-RR-025741 and 8UL1-TR-000150; University of California, San Francisco, UL1-TR-000004; University of Illinois at Chicago, UL1-TR-000050; University of Miami, 1UL1-TR-000460; University of Minnesota, 5M01-RR-000400 and UL1-TR-000114; and University of Pennsylvania, M01-RR-00040 and UL1-TR-000003. NR 53 TC 3 Z9 3 U1 3 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2016 VL 65 IS 11 BP 3418 EP 3428 DI 10.2337/db16-0234 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA3VX UT WOS:000386538500020 PM 27465220 ER PT J AU Zhu, YY Mendola, P Albert, PS Bao, W Hinkle, SN Tsai, MY Zhang, CL AF Zhu, Yeyi Mendola, Pauline Albert, Paul S. Bao, Wei Hinkle, Stefanie N. Tsai, Michael Y. Zhang, Cuilin TI Insulin-Like Growth Factor Axis and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort SO DIABETES LA English DT Article ID BINDING-PROTEINS; FACTOR-I; PREGNANCY; SERUM; RISK; GLUCOSE; PLASMA; WOMEN; HOMEOSTASIS; RESISTANCE AB The insulin-like growth factor (IGF) axis may be implicated in glucose homeostasis, but its longitudinal profile across gestation in relation to the development of gestational diabetes mellitus (GDM) is largely unknown. We prospectively investigated IGF axis biomarkers in early-to-midpregnancy in relation to subsequent GDM risk in a case-control study of 107 case subjects with GDM and 214 control subjects without GDM, with blood sample collection at gestational weeks 10-14, 15-26, 23-31, and 33-39. Conditional logistic regression was used, adjusting for major risk factors including prepregnancy BMI. Plasma IGF-I and IGF binding protein 3 (IGFBP-3) concentrations and molar ratio of IGF-1 to IGFBP-3 increased, whereas IGFBP-2 decreased throughout pregnancy. At gestational weeks 10-14, both IGF-I and IGF-I/IGFBP-3 were positively associated with GDM risk; adjusted odds ratio (OR) comparing the highest versus lowest quartile (ORQ4-Q1) was 2.93 (95% CI 1.18, 7.30) for IGF-1 and 3.31 (1.10, 9.98) for IGF-I/IGFBP-3. In contrast, higher IGFBP-2 levels were related to a substantially lower risk of GDM (ORQ4-Q1 0.04 [0.01, 0.06]). Similar results were observed at gestational weeks 15-26. In sum, the IGF axis, IGFBP-2 in particular, may be implicated in the pathogenesis of GDM, with significant associations and incremental predictive value detected as early as gestational weeks 10-14, similar to 10-18 weeks earlier before GDM is typically screened for. C1 [Zhu, Yeyi; Mendola, Pauline; Hinkle, Stefanie N.; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20847 USA. [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Rockville, MD USA. [Bao, Wei] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20847 USA. EM zhangcu@mail.nih.gov OI Mendola, Pauline/0000-0001-5330-2844 FU NICHD [HHSN275200800013C, HHSN2752008000021, HHSN27500006, HHSN2752008000031C, HHSN275200800014C, HHSN275200800012C, HH5N275200800028C, HHSN275201000009C, HHSN275201000001Z] FX This research was supported by the NICHD intramural funding and included American Recovery and Reinvestment Act funding via contract numbers HHSN275200800013C, HHSN2752008000021, HHSN27500006, HHSN2752008000031C, HHSN275200800014C, HHSN275200800012C, HH5N275200800028C, HHSN275201000009C, and HHSN275201000001Z. NR 36 TC 3 Z9 3 U1 2 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2016 VL 65 IS 11 BP 3495 EP 3504 DI 10.2337/db16-0514 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA3VX UT WOS:000386538500027 PM 27468747 ER PT J AU Li, M Wang, YN Zhu, YJ Dai, YX Hong, XF Liu, Q Li, TM Qin, JX Ma, XW Lu, HY Xu, J Otto, M AF Li, Min Wang, Yanan Zhu, Yuanjun Dai, Yingxin Hong, Xufen Liu, Qian Li, Tianming Qin, Juanxiu Ma, Xiaowei Lu, Huiying Xu, Jie Otto, Michael TI Increased Community-Associated Infections Caused by Panton-Valentine Leukocidin-Negative MRSA, Shanghai, 2005-2014 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; EPIDEMIOLOGY; VIRULENCE AB During 2005-2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community associated methicillin-resistant S. aureus. C1 [Li, Min] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai, Peoples R China. [Wang, Yanan; Zhu, Yuanjun; Dai, Yingxin; Hong, Xufen; Liu, Qian; Li, Tianming; Qin, Juanxiu; Ma, Xiaowei; Lu, Huiying; Xu, Jie] Shanghai Jiao Tong Univ, Shanghai, Peoples R China. [Otto, Michael] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, NIH, Bacteriol Lab, Bldg 50,Rm 6154,50 South Dr, Bethesda, MD 20814 USA. EM motto@niaid.nih.gov FU National Institutes of Health National Institute of Allergy and Infectious Diseases Intramural Research Program [ZIA AI000904]; National Natural Science Foundation of China [81322025, 81371875]; Shanghai Shuguang Talent Project [12SG03]; Shanghai Committee of Science and Technology, China [14140901000, 15411960500]; Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81421001] FX This work was supported by the National Institutes of Health National Institute of Allergy and Infectious Diseases Intramural Research Program (grant ZIA AI000904 to M.O.), the National Natural Science Foundation of China (grants 81322025 and 81371875 to M. L.), the Shanghai Shuguang Talent Project (grant 12SG03 to M. L.), the Shanghai Committee of Science and Technology, China (grants 14140901000 and 15411960500 to M. L.), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (grant 81421001 to M. L.). NR 14 TC 0 Z9 0 U1 2 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2016 VL 22 IS 11 BP 1988 EP 1991 DI 10.3201/eid2211.160587 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA EA3XS UT WOS:000386543200024 PM 27767912 ER PT J AU James-Todd, TM Meeker, JD Huang, TY Hauser, R Ferguson, KK Rich-Edwards, JW McElrath, TF Seely, EW AF James-Todd, Tamarra M. Meeker, John D. Huang, Tianyi Hauser, Russ Ferguson, Kelly K. Rich-Edwards, Janet W. McElrath, Thomas F. Seely, Ellen W. TI Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Phthalates; Gestational diabetes; Body mass index; Gestational weight gain; Impaired glucose tolerance; Pregnancy ID BODY-MASS INDEX; ENDOCRINE DISRUPTORS; WAIST CIRCUMFERENCE; NATIONAL-HEALTH; BISPHENOL-A; INSULIN-RESISTANCE; DIETHYL PHTHALATE; CIGARETTE-SMOKING; MATERNAL OBESITY; PRETERM BIRTH AB Background: Epidemiologic studies suggest phthalate metabolite concentrations are associated with type 2 diabetes. GDMis a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors (i.e. 1st trimester body mass index (BMI), gestational weight gain (GWG), and 2nd trimester glucose levels). Methods: A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concentrations. Nine specific gravity-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess associations between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concentrations and categorized GWG and impaired glucose tolerance defined as glucose >= 140 mg/dL based on a 50-gram glucose load test. Models were adjusted for potential confounders. Results: There were no associations between 1st trimester urinary phthalate metabolite concentrations and 1st trimester BMI. Mono-ethyl phthalate concentrations averaged across pregnancy were associated with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester mono-ethyl phthalate was associated with increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). A summary measure of di-2-ethylhexyl phthalate metabolite concentrations were inversely associated with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). Conclusions: Higher exposure to mono-ethyl phthalate, a metabolite of the parent compound of di-ethyl phthalate, may be associated with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was associated with reduced odds of impaired glucose tolerance. (C) 2016 Elsevier Ltd. All rights reserved. C1 [James-Todd, Tamarra M.; Hauser, Russ] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [James-Todd, Tamarra M.; Hauser, Russ] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [James-Todd, Tamarra M.; Huang, Tianyi; Rich-Edwards, Janet W.] Harvard Med Sch, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth,Dept Med, Boston, MA 02120 USA. [Meeker, John D.; Ferguson, Kelly K.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Huang, Tianyi] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ferguson, Kelly K.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [McElrath, Thomas F.] Harvard Med Sch, Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. [Seely, Ellen W.] Harvard Med Sch, Brigham & Womens Hosp, Div Endocrine Diabet & Hypertens, Boston, MA 02115 USA. RP James-Todd, TM (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02120 USA. EM tjtodd@hsph.harvard.edu OI Huang, Tianyi/0000-0001-8420-9167; Ferguson, Kelly/0000-0001-8467-3250 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD051959]; National Institute of Environmental Health Sciences [R01ES018872, P30ES017885]; National Heart Lung and Blood Institute [K24RR018613]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [R01ES026166] FX This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051959), the National Institute of Environmental Health Sciences (R01ES018872, P30ES017885), and the National Heart Lung and Blood Institute (K24RR018613). Funding support for KKF was provided by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (R01ES026166). The authors have no competing financial interests. NR 54 TC 0 Z9 0 U1 15 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD NOV PY 2016 VL 96 BP 118 EP 126 DI 10.1016/j.envint.2016.09.009 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA EA9AU UT WOS:000386933300014 PM 27649471 ER PT J AU Cote, I Andersen, ME Ankley, GT Barone, S Birnbaum, LS Boekelheide, K Bois, F Burgoon, LD Chiu, WA Crawford-Brown, D Crofton, KM DeVito, M Devlin, RB Edwards, SW Guyton, KZ Hattis, D Judson, RS Knight, D Krewski, D Lambert, J Maull, EA Mendrick, D Paoli, GM Patel, CJ Perkins, EJ Poje, G Portier, CJ Rusyn, I Schulte, PA Simeonov, A Smith, MT Thayer, KA Thomas, RS Thomas, R Tice, RR Vandenberg, JJ Villeneuve, DL Wesselkamper, S Whelan, M Whittaker, C White, R Xia, M Yauk, C Zeise, L Zhao, J DeWoskin, RS AF Cote, Ila Andersen, Melvin E. Ankley, Gerald T. Barone, Stanley Birnbaum, Linda S. Boekelheide, Kim Bois, FredericY. Burgoon, Lyle D. Chiu, Weihsueh A. Crawford-Brown, Douglas Crofton, Kevin M. DeVito, Michael Devlin, Robert B. Edwards, Stephen W. Guyton, Kathryn Z. Hattis, Dale Judson, Richard S. Knight, Derek Krewski, Daniel Lambert, Jason Maull, Elizabeth Anne Mendrick, Donna Paoli, Gregory M. Patel, Chirag Jagdish Perkins, Edward J. Poje, Gerald Portier, Christopher J. Rusyn, Ivan Schulte, Paul A. Simeonov, Anton Smith, Martyn T. Thayer, Kristina A. Thomas, Russell S. Thomas, Reuben Tice, Raymond R. Vandenberg, John J. Villeneuve, Daniel L. Wesselkamper, Scott Whelan, Maurice Whittaker, Christine White, Ronald Xia, Menghang Yauk, Carole Zeise, Lauren Zhao, Jay DeWoskin, Robert S. TI The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID ADVERSE OUTCOME PATHWAYS; BRONCHIAL EPITHELIAL-CELLS; THROUGHPUT SCREENING DATA; IN-VIVO HAZARD; ENVIRONMENTAL CHEMICALS; HUMAN HEALTH; GENE-EXPRESSION; POPULATION VARIABILITY; PREDICTIVE TOXICOLOGY; ESTROGEN-RECEPTOR AB BACKGROUND: The Next Generation (NexGen) of Risk Assessment effort is a multi-year collaboration among several organizations evaluating new, potentially more efficient molecular, computational, and systems biology approaches to risk assessment. This article summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions. OBJECTIVE: Our specific objectives were to test whether advanced biological data and methods could better inform our understanding of public health risks posed by environmental exposures. METHODS: New data and methods were applied and evaluated for use in hazard identification and dose-response assessment. Biomarkers of exposure and effect, and risk characterization were also examined. Consideration was given to various decision contexts with increasing regulatory and public health impacts. Data types included transcriptomics, genomics, and proteomics. Methods included molecular epidemiology and clinical studies, bioinformatic knowledge mining, pathway and network analyses, short-duration in vivo and in vitro bioassays, and quantitative structure activity relationship modeling. DISCUSSION: NexGen has advanced our ability to apply new science by more rapidly identifying chemicals and exposures of potential concern, helping characterize mechanisms of action that influence conclusions about causality, exposure-response relationships, susceptibility and cumulative risk, and by elucidating new biomarkers of exposure and effects. Additionally, NexGen has fostered extensive discussion among risk scientists and managers and improved confidence in interpreting and applying new data streams. CONCLUSIONS: While considerable uncertainties remain, thoughtful application of new knowledge to risk assessment appears reasonable for augmenting major scope assessments, forming the basis for or augmenting limited scope assessments, and for prioritization and screening of very data limited chemicals. C1 [Cote, Ila; Vandenberg, John J.; DeWoskin, Robert S.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Andersen, Melvin E.] ScitoVation, Res Triangle Pk, NC USA. [Ankley, Gerald T.; Villeneuve, Daniel L.] US EPA, Natl Hlth & Environm Effects Res Lab, Duluth, MN USA. [Barone, Stanley] US EPA, Off Chem Safety & Pollut Prevent, Washington, DC 20460 USA. [Birnbaum, Linda S.; DeVito, Michael; Maull, Elizabeth Anne; Thayer, Kristina A.; Tice, Raymond R.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.; DeVito, Michael; Maull, Elizabeth Anne; Thayer, Kristina A.; Tice, Raymond R.] NIH, Natl Toxicol Program, DHHS, Res Triangle Pk, NC USA. [Boekelheide, Kim] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Bois, FredericY.] Inst Natl Environm Ind & Risques, Unite Modeles Icotoxicol & Toxicol, Verneuil En Halatte, France. [Burgoon, Lyle D.] US Army, Engineer Res & Dev Ctr, Res Triangle Pk, NC USA. [Chiu, Weihsueh A.; Rusyn, Ivan] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX USA. [Crawford-Brown, Douglas] Univ Cambridge, Dept Land Econ, Cambridge, England. [Crofton, Kevin M.; Judson, Richard S.; Thomas, Russell S.] Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA. [Devlin, Robert B.; Edwards, Stephen W.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Guyton, Kathryn Z.] Int Agcy Res Canc, Lyon, France. [Hattis, Dale] Clark Univ, George Perkins Marsh Inst, Worcester, MA 01610 USA. [Knight, Derek] European Chem Agcy, Helsinki, Finland. [Krewski, Daniel] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada. [Lambert, Jason; Wesselkamper, Scott; Zhao, Jay] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. [Mendrick, Donna] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Paoli, Gregory M.] Risk Sci Int, Ottawa, ON, Canada. [Patel, Chirag Jagdish] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA. [Perkins, Edward J.] US Army, Engineer Res & Dev Ctr, Vicksburg, MS USA. [Poje, Gerald] Grant Consulting Grp, Washington, DC USA. [Portier, Christopher J.] Environm Def Fund, Washington, DE USA. [Schulte, Paul A.; Whittaker, Christine] Ctr Dis Control & Prevent, Natl Inst Occupat Safety & Hlth, Educ & Informat Div, Cincinnati, OH USA. [Simeonov, Anton; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, DHHS, Bethesda, MD USA. [Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Thomas, Reuben] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. [Whelan, Maurice] European Commiss Joint Res Ctr, Syst Toxicol Unit, Ispra, Italy. [White, Ronald] Ctr Effect Govt, Washington, DE USA. [Yauk, Carole] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON, Canada. [Zeise, Lauren] Calif EPA, Off Environm Hlth Hazard Assessment, Oakland, CA USA. RP Cote, I (reprint author), US EPA, Reg 8,Room 8152,1595 Wynkoop St, Denver, CO 80202 USA. EM cote.ila@epa.gov RI Bois, Frederic/E-9241-2012; Rusyn, Ivan/S-2426-2016; OI Bois, Frederic/0000-0002-4154-0391; Vandenberg, John/0000-0003-2619-9460; Burgoon, Lyle/0000-0003-4977-5352 FU NIEHS NIH HHS [R21 ES025052, K99 ES023504, P42 ES005948, R00 ES023504] NR 152 TC 0 Z9 0 U1 32 U2 32 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP 1671 EP 1682 DI 10.1289/EHP233 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800010 PM 27091369 ER PT J AU Parks, CG Hoppin, JA De Roos, AJ Costenbader, KH Alavanja, MC Sandler, DP AF Parks, Christine G. Hoppin, Jane A. De Roos, Anneclaire J. Costenbader, Karen H. Alavanja, Michael C. Sandler, Dale P. TI Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EXPERT PANEL WORKSHOP; AUTOIMMUNE-DISEASES; IN-VITRO; ENVIRONMENTAL EXPOSURES; OCCUPATIONAL EXPOSURES; UNITED-STATES; NURSES HEALTH; WOMEN; RISK AB BACKGROUND: Farming has been associated with rheumatoid arthritis (RA), but the role of pesticides is not known. OBJECTIVES: We examined associations between RA and pesticides or other agricultural exposures among female spouses of licensed pesticide applicators in the Agricultural Health Study. METHODS: Women were enrolled between 1993 and 1997 and followed through 2010. Cases (n=275 total, 132 incident), confirmed by a physician or by self-reported use of disease modifying antirheumatic drugs, were compared with noncases (n=24,018). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusted for age, state, and smoking pack-years. RESULTS: Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides (OR=1.4; 95% CI: 1.0, 1.6). Of the 15 pesticides examined, maneb/mancozeb (OR=3.3; 95% CI: 1.5, 7.1) and glyphosate (OR=1.4; 95% CI: 1.0, 2.1) were associated with incident RA compared with no pesticide use. An elevated, but non-statistically significant association with incident RA was seen for DDT (OR=1.9; 95% CI: 0.97, 3.6). Incident RA was also associated with the application of chemical fertilizers (OR=1.7; 95% CI: 1.1, 2.7) and cleaning with solvents (OR=1.6; 95% CI: 1.1, 2.4), but inversely associated with lifetime livestock exposure as a child and adult (OR=0.48; 95% CI: 0.24, 0.97) compared with no livestock exposure. CONCLUSIONS: Our results suggest that specific agricultural pesticides, solvents, and chemical fertilizers may increase the risk of RA in women, while exposures involving animal contact may be protective. C1 [Parks, Christine G.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA. [Hoppin, Jane A.] North Carolina State Univ, Dept Biol Sci, Ctr Human Hlth & Environm, Raleigh, NC 27695 USA. [De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [Costenbader, Karen H.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Alavanja, Michael C.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA. EM Parks1@mail.nih.gov OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute/NIH [Z01-CP010119] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (Z01-ES049030) and National Cancer Institute/NIH (Z01-CP010119). NR 53 TC 0 Z9 0 U1 5 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP 1728 EP 1734 DI 10.1289/EHP129 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800017 PM 27285288 ER PT J AU Jones, RR Weyer, PJ DellaValle, CT Inoue-Choi, M Anderson, KE Cantor, KP Krasner, S Robien, K Freeman, LEB Silverman, DT Ward, MH AF Jones, Rena R. Weyer, Peter J. DellaValle, Curt T. Inoue-Choi, Maki Anderson, Kristin E. Cantor, Kenneth P. Krasner, Stuart Robien, Kim Freeman, Laura E. Beane Silverman, Debra T. Ward, Mary H. TI Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID N-NITROSO COMPOUNDS; DISINFECTION BY-PRODUCTS; UNITED-STATES; OLDER WOMEN; RISK; HEALTH; NITRITE; MEAT; NITROSODIMETHYLAMINE; QUESTIONNAIRE AB BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. OBJECTIVES: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 mu g/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). RESULTS: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; p(trend) = 0.11), and we found significant associations among those exposed >= 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; p(trend) = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and >= 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. C1 [Jones, Rena R.; DellaValle, Curt T.; Inoue-Choi, Maki; Cantor, Kenneth P.; Freeman, Laura E. Beane; Silverman, Debra T.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. [Weyer, Peter J.] Univ Iowa, Ctr Hlth Effects Environm Contaminat, Iowa City, IA USA. [Inoue-Choi, Maki] Natl Inst Minor Hlth & Hlth Dispar, NIH, DHHS, Bethesda, MD USA. [Anderson, Kristin E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.] Univ Minnesota, Prevent & Etiol Res Program, Mason Canc Ctr, Minneapolis, MN USA. [Krasner, Stuart] Metropolitan Water Dist So Calif, La Verne, CA USA. [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. RP Jones, RR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E124, Rockville, MD 20850 USA. EM rena.jones@nih.gov OI Robien, Kim/0000-0002-2120-2280 FU Intramural Research Program of the National Cancer Institute (NCI) of the National Institutes of Health; NCI [R01-CA39742] FX This work was supported in part by the Intramural Research Program of the National Cancer Institute (NCI) of the National Institutes of Health and by NCI extramural grant R01-CA39742. NR 51 TC 0 Z9 0 U1 11 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP 1751 EP 1758 DI 10.1289/EHP191 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800020 PM 27258851 ER PT J AU Liu, R Young, MT Chen, JC Kaufman, JD Chen, HL AF Liu, Rui Young, Michael T. Chen, Jiu-Chiuan Kaufman, Joel D. Chen, Honglei TI Ambient Air Pollution Exposures and Risk of Parkinson Disease SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PARTICULATE MATTER; PM2.5 CONCENTRATIONS; PLASMA URATE; YOUNG-ADULTS; HEALTH; DEPOSITION; PARTICLES; CHILDREN; BARRIER; WOMEN AB BACKGROUND: Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD). OBJECTIVE: We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 mu m in diameter (PM10) and < 2.5 mu m in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk. METHODS: Our nested case-control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders. RESULTS: We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 (vs. Q1) = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 (vs. Q1) = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 (vs. Q1) = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 (vs. Q1) = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations. CONCLUSIONS: Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. C1 [Liu, Rui; Chen, Honglei] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Young, Michael T.; Kaufman, Joel D.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Chen, Jiu-Chiuan] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA USA. [Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU NIH; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Institute of Neurological Disorders and Stroke [R01-NS060722, U01-NS082151]; National Cancer Institute [Z01 CP010196-02]; U.S. Environmental Protection Agency (EPA) FX This study was supported by the intramural and extramural research programs of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), the National Institute of Neurological Disorders and Stroke (R01-NS060722 and U01-NS082151), and the National Cancer Institute (Z01 CP010196-02). This publication was developed in part through a STAR research assistance agreement, No. RD831697 Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), awarded by the U.S. Environmental Protection Agency (EPA). NR 39 TC 2 Z9 2 U1 18 U2 18 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP 1759 EP 1765 DI 10.1289/EHP135 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800021 PM 27285422 ER PT J AU Wang, Y Adgent, M Su, PH Chen, HY Chen, PC Hsiung, CA Wang, SL AF Wang, Yan Adgent, Margaret Su, Pen-Hua Chen, Hsiao-Yen Chen, Pau-Chung Hsiung, Chao A. Wang, Shu-Li TI Prenatal Exposure to Perfluorocarboxylic Acids (PFCAs) and Fetal and Postnatal Growth in the Taiwan Maternal and Infant Cohort Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PERFLUORINATED FATTY-ACIDS; CARBON-CHAIN LENGTH; PERFLUOROOCTANOIC ACID; PERFLUOROALKYL ACIDS; BIRTH-WEIGHT; REPRODUCTIVE/DEVELOPMENTAL TOXICITY; PREGNANT-WOMEN; SERUM SAMPLES; TIME TRENDS; HALF-LIFE AB BACKGROUND: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C-8) and long-chain PFCAs (C-9-C-20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. OBJECTIVES: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. METHODS: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between in-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. RESULTS: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., beta(birth weight) (kg) = -0.06, 95% CI: -0.11,-0.01 per 1 In-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. CONCLUSIONS: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. C1 [Wang, Yan] Natl Fdn Ctr Dis Control & Prevent, Atlanta, GA USA. [Wang, Yan; Adgent, Margaret] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Su, Pen-Hua] Chung Shan Med Univ, Dept Pediat, Taichung, Taiwan. [Chen, Hsiao-Yen; Wang, Shu-Li] Natl Inst Environm Hlth Sci, Natl Hlth Res Inst, 35 Keyan Rd, Zhunan 350, Miaoli County, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei, Taiwan. [Hsiung, Chao A.] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Miaoli County, Taiwan. [Wang, Shu-Li] Natl Def Med Ctr, Dept Publ Hlth, Taipei, Taiwan. [Wang, Shu-Li] China Med Univ, Dept Publ Hlth, Coll Publ Hlth, Taichung, Taiwan. RP Wang, SL (reprint author), Natl Inst Environm Hlth Sci, Natl Hlth Res Inst, 35 Keyan Rd, Zhunan 350, Miaoli County, Taiwan. EM slwang@nhri.org.tw OI Chen, Pau-Chung/0000-0002-6242-5974 FU National Health Research Institutes, Taiwan [EO-104-PP-05, EM-105-PP-05]; Ministry of Science and Technology, Taiwan [MOST 103-2314-B-400-006, MOST 104-2314-B-400-001]; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX The study was funded by the National Health Research Institutes, Taiwan (EO-104-PP-05, EM-105-PP-05), and the Ministry of Science and Technology, Taiwan (MOST 103-2314-B-400-006, MOST 104-2314-B-400-001). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 43 TC 0 Z9 0 U1 7 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP 1794 EP 1800 DI 10.1289/ehp.1509998 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800025 PM 26895313 ER PT J AU Bucher, JR Birnbaum, LS AF Bucher, John R. Birnbaum, Linda S. TI Commemorating Toxicology at the National Institute of Environmental Health Sciences on the Occasion of Its 50th Anniversary SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PERINATAL EXPOSURE; COMPARATIVE CARCINOGENICITY; DEVELOPMENTAL TOXICITY; B6C3F1 MICE; PROGRAM; RATS; CHEMICALS; RESOURCE; UPDATE AB In 1978, the National Toxicology Program (NTP) was established and headquartered at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. On the occasion of the 50th Anniversary of the NIEHS, this article documents some of the historical and current NTP programs and scientific advances that have been made possible through this long-standing relationship. C1 [Bucher, John R.] NIH, Div Natl Toxicol Program NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Bucher, John R.; Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NTP, POB 12233,Mail Drop K2-02, Res Triangle Pk, NC 27709 USA.; Bucher, JR (reprint author), NIEHS, POB 12233,Mail Drop K2-02, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov NR 28 TC 0 Z9 0 U1 4 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP A192 EP A195 DI 10.1289/EHP463 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800001 PM 27801649 ER PT J AU Parks, CG Hoppin, JA De Roos, AJ Costenbader, KH Sandler, DP AF Parks, Christine G. Hoppin, Jane A. De Roos, Anneclaire J. Costenbader, Karen H. Sandler, Dale P. TI Response to "Comment on 'Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures'" SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID CRYSTALLINE SILICA; HEAVY-METALS; POPULATION; SOILS C1 [Parks, Christine G.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Hoppin, Jane A.] North Carolina State Univ, Dept Biol Sci, Ctr Human Hlth & Environm, Raleigh, NC USA. [De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [Costenbader, Karen H.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA. EM parks1@mail.nih.gov OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018 NR 10 TC 0 Z9 0 U1 2 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2016 VL 124 IS 11 BP A197 EP A197 DI 10.1289/EHP944 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EA8UF UT WOS:000386913800003 PM 27801650 ER PT J AU Estrada, A Boyce, AM Brillante, BA Guthrie, LC Gafni, RI Collins, MT AF Estrada, Andrea Boyce, Alison M. Brillante, Beth A. Guthrie, Lori C. Gafni, Rachel I. Collins, Michael T. TI Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CHILDREN; TESTOLACTONE; HEIGHT; AGE AB Objective: McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Design: Retrospective cohort analysis. Methods: Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. Results: Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 +/- 2.6 years (mean +/- 1 s.d.) (range: 0.5-10.9) and mean follow-up was 6.0 +/- 3.3 years (range: 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (Delta BA/Delta CA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 +/- 2.3 to -0.6 +/- 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from -2.9 +/- 3.2 to -0.8 +/- 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from -1.5 to 1.7 (median: -0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. Conclusions: In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. C1 [Estrada, Andrea; Boyce, Alison M.; Brillante, Beth A.; Guthrie, Lori C.; Gafni, Rachel I.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders & Mineral Homestasis, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Estrada, Andrea; Boyce, Alison M.] Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC 20010 USA. [Estrada, Andrea; Boyce, Alison M.] Childrens Natl Hlth Syst, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. RP Boyce, AM (reprint author), Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders & Mineral Homestasis, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.; Boyce, AM (reprint author), Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC 20010 USA.; Boyce, AM (reprint author), Childrens Natl Hlth Syst, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. EM boyceam@mail.nih.gov FU Division of Intramural Research of the NIDCR, NICHD; Division of Intramural Research Program of the NIH, DHHS; Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Health System FX This research was supported in part by the Division of Intramural Research of the NIDCR, NICHD, of the Intramural Research Program of the NIH, DHHS, and the Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Health System. NR 24 TC 0 Z9 0 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 2016 VL 175 IS 5 BP 477 EP 483 DI 10.1530/EJE-16-0526 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA8UD UT WOS:000386913600018 PM 27562402 ER PT J AU Hansson, MG Lochmuller, H Riess, O Schaefer, F Orth, M Rubinstein, Y Molster, C Dawkins, H Taruscio, D Posada, M Woods, S AF Hansson, Mats G. Lochmuller, Hanns Riess, Olaf Schaefer, Franz Orth, Michael Rubinstein, Yaffa Molster, Caron Dawkins, Hugh Taruscio, Domenica Posada, Manuel Woods, Simon TI The risk of re-identification versus the need to identify individuals in rare disease research SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENERAL-PRACTICE; EPIDEMIOLOGIC RESEARCH; PERSONAL INFORMATION; HEALTH INFORMATION; PRIVACY; RECORDS; VIEWS; CONFIDENTIALITY; CONSENT; PROTECTION AB There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders. In this article, we identify the needs and arguments related to de-identification and re-identification of patients and research subjects and suggest how the different needs may be balanced within a framework of using unique encrypted identifiers. C1 [Hansson, Mats G.] Uppsala Univ, Dept Publ Hlth & Caring Sci, Ctr Res Eth & Bioeth, Uppsala, Sweden. [Lochmuller, Hanns] Newcastle Univ, Inst Med Genet, John Walton Muscular Dystrophy Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England. [Riess, Olaf] Univ Tubingen, Rare Dis Ctr, Inst Med Genet & Appl Genom, Tubingen, Germany. [Schaefer, Franz] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. [Orth, Michael] Ulm Univ Hosp, Dept Neurol, Ulm, Germany. [Rubinstein, Yaffa] NIH, ORDR, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Molster, Caron; Dawkins, Hugh] Dept Hlth Govt Western Australia, Off Populat Hlth Genom, Publ Hlth & Clin Serv Div, Perth, WA, Australia. [Dawkins, Hugh] Murdoch Univ, Ctr Comparat Genom, Murdoch, WA, Australia. [Dawkins, Hugh] Curtin Univ Technol, Ctr Populat Hlth Res, Bentley, WA, Australia. [Dawkins, Hugh] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA, Australia. [Taruscio, Domenica] Ist Super Sanita, Natl Ctr Rare Dis, Rome, Italy. [Posada, Manuel] SpainRDR, ISCIII, Inst rare Dis Res, Madrid, Spain. [Posada, Manuel] CIBERER, Madrid, Spain. [Woods, Simon] Newcastle Univ, Policy Eth & Life Sci Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England. RP Hansson, MG (reprint author), Ctr Res Eth & Bioeth, Dept Publ Hlth & Caring Sci, POB 564, S-75122 Uppsala, Sweden. EM mats.hansson@crb.uu.se FU European Union Seventh Framework Programme [305444, 305121]; Innovative Medicines Initiative project BT-Cure [115142-1]; BioBanking and Molecular Resource Infrastructure of Sweden project - Swedish Research Council; European Union Seventh Framework Programme Euro-TEAM; European Union Seventh Framework Programme BiobankCloud; European Union Seventh Framework Programme BBMRI-LPC; Australian National Health and Medical Research Council RD-Connect project under NHMRC-European Union Collaborative Research Grants scheme [APP1055319] FX We acknowledge their involvement in the International Rare Disease Research Consortium (IRDiRC). Funding for this research was received by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 305444 (RD-Connect) and 305121 (Neuromics). Hansson also received funding by the Innovative Medicines Initiative project BT-Cure (grant agreement number 115142-1), the BioBanking and Molecular Resource Infrastructure of Sweden project (financed by the Swedish Research Council), and the European Union Seventh Framework Programmes Euro-TEAM, BiobankCloud and BBMRI-LPC. Dawkins acknowledges support-in-part from the Australian National Health and Medical Research Council RD-Connect project APP1055319 under the NHMRC-European Union Collaborative Research Grants scheme. NR 44 TC 1 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2016 VL 24 IS 11 BP 1553 EP 1558 DI 10.1038/ejhg.2016.52 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EA5UX UT WOS:000386690500010 PM 27222291 ER PT J AU Ito, T Lee, L Jensen, RT AF Ito, Tetsuhide Lee, Lingaku Jensen, Robert T. TI Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE Acid hypersecretion; carcinoid syndrome; chemoembolization; chemotherapy; cytoreductive surgery; embolization; gastrinoma; insulinoma; Lanreotide; multiple endocrine Neoplasia type 1; neuroendocrine tumor; pancreatic endocrine tumor; peptide radio-receptor therapy; octreotide; radioembolization; radio-frequency ablation; SIRT; somatostatin analogues; telotristat; Zollinger-Ellison syndrome ID ZOLLINGER-ELLISON-SYNDROME; RECEPTOR RADIONUCLIDE THERAPY; ENETS CONSENSUS GUIDELINES; ENDOCRINE NEOPLASIA TYPE-1; GUIDED ETHANOL ABLATION; LAPAROSCOPIC RADIOFREQUENCY ABLATION; HEPATIC-ARTERY CHEMOEMBOLIZATION; METASTATIC CARCINOID-TUMORS; LU-177 DOTATATE INDUCTION; LONG-ACTING OCTREOTIDE AB Introduction: Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is aggressive and a proportion has a functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there have been many advances, well-covered in reviews/consensus papers on imaging-NETs; new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed.Areas covered: Advances in the last 5-years are concentrated on, but a review of literature from the last 10-years was performed. PubMed and other databases (Cochrane, etc.) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies [serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies (octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib),cytoreductive surgery, liver-directed therapies (embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and I-131-MIBG, ablation of primary F-NETs.Expert opinion: Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas,such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large,controlled studies. C1 [Ito, Tetsuhide; Lee, Lingaku] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka, Japan. [Jensen, Robert T.] NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIH, Digest Dis Branch, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU Intramural Digestive Diseases Branch, NIDDK, NIH [Z-021] FX Partial funding for this study was provided by Intramural Digestive Diseases Branch, NIDDK, NIH (Z-021). NR 193 TC 1 Z9 1 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD NOV PY 2016 VL 17 IS 16 BP 2191 EP 2205 DI 10.1080/14656566.2016.1236916 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EA6ZQ UT WOS:000386778200008 PM 27635672 ER PT J AU Mire, CE Geisbert, TW Feldmann, H Marzi, A AF Mire, Chad E. Geisbert, Thomas W. Feldmann, Heinz Marzi, Andrea TI Ebola virus vaccines - reality or fiction? SO EXPERT REVIEW OF VACCINES LA English DT Review DE Ebolavirus; filovirus; prophylaxis; vaccine; animal model ID PROTECTS NONHUMAN-PRIMATES; EQUINE ENCEPHALITIS-VIRUS; I CLINICAL-TRIAL; HEMORRHAGIC-FEVER; MARBURG VIRUS; LETHAL EBOLA; DNA VACCINES; GUINEA-PIGS; MOUSE MODEL; NEUTRALIZING ANTIBODIES AB For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although patient zero has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the gold-standard nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic. C1 [Mire, Chad E.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Mire, Chad E.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Feldmann, Heinz; Marzi, Andrea] NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT 59840 USA. RP Marzi, A (reprint author), NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT 59840 USA. EM marzia@niaid.nih.gov FU Division of Intramural Research, NIAID, NIH; Galveston National Laboratory [UC7AI094660] FX Filovirus research is supported in part by the Division of Intramural Research, NIAID, NIH and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory. H Feldmann and TW Geisbert claim intellectual property regarding the vesicular stomatitis virus-based filo-virus vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 89 TC 2 Z9 2 U1 13 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD NOV PY 2016 VL 15 IS 11 BP 1421 EP 1430 DI 10.1080/14760584.2016.1178068 PG 10 WC Immunology SC Immunology GA EA4OC UT WOS:000386591200007 PM 27078187 ER PT J AU Blithe, DL AF Blithe, Diana L. TI Pipeline for contraceptive development SO FERTILITY AND STERILITY LA English DT Article DE Contraception; female contraception; male contraception; nonhormonal contraceptive development; green contraception ID MULTIPURPOSE PREVENTION TECHNOLOGIES; MALE HORMONAL CONTRACEPTION; VAGINAL RING; DIMETHANDROLONE UNDECANOATE; ULIPRISTAL ACETATE; ETHINYL ESTRADIOL; ALPHA-4 ISOFORM; MALE-FERTILITY; ESTROGEN-FREE; NORMAL WOMEN AB The high rates of unplanned pregnancy reflect an unmet need for effective contraceptive methods for women, especially for individuals with health risks such as obesity, diabetes, hypertension, and other conditions that may contraindicate use of an estrogen-containing product. Improvements in safety, user convenience, acceptability, and availability of products remain important goals of the contraceptive development program. Another important goal is to minimize the impact of the products on the environment. Development of new methods for male contraception has the potential to address many of these issues of safety for women who have contraindications to effective contraceptive methods but want to protect against pregnancy. It would also address a huge unmet need for men who want to control their fertility. Products under development for men would not introduce ecotoxic hormones into the water system. (C) 2016 by American Society for Reproductive Medicine. C1 [Blithe, Diana L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept Res Branch, NIH, Bethesda, MD USA. RP Blithe, DL (reprint author), 6710A Rockledge Dr,Room 2337, Bethesda, MD 20892 USA. EM blithed@nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 83 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2016 VL 106 IS 6 BP 1295 EP 1302 DI 10.1016/j.fertnstert.2016.07.1115 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA7RP UT WOS:000386829800007 PM 27523300 ER PT J AU Mumford, SL Sapra, KJ King, RB Louis, JF Louis, GMB AF Mumford, Sunni L. Sapra, Katherine J. King, Rosalind B. Louis, Jean Fredo Louis, Germaine M. Buck TI Pregnancy intentions-a complex construct and call for new measures SO FERTILITY AND STERILITY LA English DT Article DE Pregnancy intentions; unintended; unplanned pregnancy ID MEASURING UNINTENDED PREGNANCY; AFRICAN-AMERICAN WOMEN; UNITED-STATES; UNPLANNED PREGNANCY; UNDERSTANDING PREGNANCY; FERTILITY INTENTIONS; READINESS MEASURES; IDENTIFYING WOMEN; CONTRACEPTIVE USE; NATIONAL-SURVEY AB Objective: To estimate the prevalence of unintended pregnancies under relaxed assumptions regarding birth control use compared with a traditional constructed measure. Design: Cross-sectional survey. Setting: Not applicable. Patient(s): Nationally representative sample of U.S. women aged 15-44 years. Intervention(s): None. Main Outcome Measure(s): Prevalence of intended and unintended pregnancies as estimated by [1] a traditional constructed measure from the National Survey of Family Growth (NSFG), and [2] a constructed measure relaxing assumptions regarding birth control use, reasons for nonuse, and pregnancy timing. Result(s): The prevalence of unintended pregnancies was 6% higher using the traditional constructed measure as compared with the approach with relaxed assumptions (NSFG: 44%, 95% confidence interval [CI] 41, 46; new construct 38%, 95% CI, 36, 41). Using the NSFG approach, only 92% of women who stopped birth control to become pregnant and 0 women who were not using contraceptives at the time of the pregnancy and reported that they did not mind getting pregnant were classified as having intended pregnancies, compared with 100% using the new construct. Conclusion(s): Current measures of pregnancy intention may overestimate rates of unintended pregnancy, with over 340,000 pregnancies in the United States misclassified as unintended using the current approach, corresponding to an estimated savings of $678 million in public health-care expenditures. Current constructs make assumptions that may not reflect contemporary reproductive practices, so improved measures are needed. (C) 2016 by American Society for Reproductive Medicine.) C1 [Mumford, Sunni L.; Sapra, Katherine J.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [King, Rosalind B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Populat Dynam Branch, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Louis, Jean Fredo] Glotech Inc, Rockville, MD USA. RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6710B Rockledge Dr MSC 7004, Bethesda, MD 20892 USA. EM mumfords@mail.nih.gov OI Louis, Jean F/0000-0003-0339-647X; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 73 TC 1 Z9 1 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2016 VL 106 IS 6 BP 1453 EP 1462 DI 10.1016/j.fertnstert.2016.07.1067 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA7RP UT WOS:000386829800033 PM 27490044 ER PT J AU Killian, JK Dorssers, LCJ Trabert, B Gillis, AJM Cook, MB Wang, YH Waterfall, JJ Stevenson, H Smith, WI Noyes, N Retnakumar, P Stoop, JH Oosterhuis, JW Meltzer, PS McGlynn, KA Looijenga, LHJ AF Killian, J. Keith Dorssers, Lambert C. J. Trabert, Britton Gillis, Ad J. M. Cook, Michael B. Wang, Yonghong Waterfall, Joshua J. Stevenson, Holly Smith, William I., Jr. Noyes, Natalia Retnakumar, Parvathy Stoop, J. Hans Oosterhuis, J. Wolter Meltzer, Paul S. McGlynn, Katherine A. Looijenga, Leendert H. J. TI Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors SO GENOME RESEARCH LA English DT Article ID CARCINOMA-IN-SITU; EMBRYONIC STEM-CELLS; DNA METHYLATION; EXPRESSION PATTERNS; COPY NUMBER; CYTOGENETIC ANALYSIS; OVARIAN TERATOMAS; HYDATIDIFORM MOLE; ANALYSIS REVEALS; HUMAN GENOME AB Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and differentiated somatic references. Most generally, TGCTs conserve PGC-lineage erasure of maternal and paternal genomic imprints and DPPA3 (also known as STELLA); however, like ESCs, TGCTs show focal recurrent imprinted domain hypermethylation. In this setting of shared physiologic erasure, NSEs harbor a malignancy-associated hypermethylation core, akin to that of a diverse cancer compendium. Beyond these concordances, we found subtype epigenetic homology with pluripotent versus differentiated states. ECs demonstrate a striking convergence of both CpG and CpH (non-CpG) methylation with pluripotent states; the pluripotential methyl-CpH signature crosses species boundaries and is distinct from neuronal methyl-CpH. EC differentiation to TE and YST entails reprogramming toward the somatic state, with loss of methyl-CpH but de novo methylation of pluripotency loci such as NANOG. Extreme methyl-depletion among SE reflects the PGC methylation nadir. Adjacent to TGCTs, benign testis methylation profiles are determined by spermatogenetic proficiency measured by Johnsen score. In sum, TGCTs share collective entrapment in a PGC-like state of genomic-imprint and DPPA3 erasure, recurrent hypermethylation of cancer-associated targets, and subtype-dependent pluripotent, germline, or somatic methylation. C1 [Killian, J. Keith; Wang, Yonghong; Waterfall, Joshua J.; Stevenson, Holly; Noyes, Natalia; Retnakumar, Parvathy; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dorssers, Lambert C. J.; Gillis, Ad J. M.; Stoop, J. Hans; Oosterhuis, J. Wolter; Looijenga, Leendert H. J.] Univ Med Ctr, Erasmus MC, Dept Pathol, NL-3015 Rotterdam, Netherlands. [Trabert, Britton; Cook, Michael B.; McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD 20814 USA. RP Meltzer, PS (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Looijenga, LHJ (reprint author), Univ Med Ctr, Erasmus MC, Dept Pathol, NL-3015 Rotterdam, Netherlands.; McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov; mcglynnk@mail.nih.gov; l.looijenga@erasmusmc.nl RI Trabert, Britton/F-8051-2015 FU Intramural Research Program of the National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute. We thank all contributors of high-quality data to public databases. NR 86 TC 0 Z9 0 U1 4 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2016 VL 26 IS 11 BP 1490 EP 1504 DI 10.1101/gr.201293.115 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA EA4UB UT WOS:000386609300004 PM 27803193 ER PT J AU Wang, IX Grunseich, C Chung, YG Kwak, H Ramrattan, G Zhu, ZW Cheung, VG AF Wang, Isabel X. Grunseich, Christopher Chung, Youree G. Kwak, Hojoong Ramrattan, Girish Zhu, Zhengwei Cheung, Vivian G. TI RNA-DNA sequence differences in Saccharomyces cerevisiae SO GENOME RESEARCH LA English DT Article ID R-LOOP FORMATION; HUMAN TRANSCRIPTOME; WIDESPREAD RNA; PROTEIN STABILITY; TOPOISOMERASE-I; RIBONUCLEASE-H; COLORECTAL-CANCER; GENE-EXPRESSION; MESSENGER-RNA; RIBOSOMAL-RNA AB Alterations of RNA sequences and structures, such as those from editing and alternative splicing, result in two or more RNA transcripts from a DNA template. It was thought that in yeast, RNA editing only occurs in tRNAs. Here, we found that Saccharomyces cerevisiae have all 12 types of RNA-DNA sequence differences (RDDs) in the mRNA. We showed these sequence differences are propagated to proteins, as we identified peptides encoded by the RNA sequences in addition to those by the DNA sequences at RDD sites. RDDs are significantly enriched at regions with R-loops. A screen of yeast mutants showed that RDD formation is affected by mutations in genes regulating R-loops. Loss-of-function mutations in ribonuclease H, senataxin, and topoisomerase I that resolve RNA-DNA hybrids lead to increases in RDD frequency. Our results demonstrate that RDD is a conserved process that diversifies transcriptomes and proteomes and provide a mechanistic link between R-loops and RDDs. C1 [Wang, Isabel X.; Kwak, Hojoong; Ramrattan, Girish; Zhu, Zhengwei; Cheung, Vivian G.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Grunseich, Christopher] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Chung, Youree G.] Univ Michigan, Coll Engn, Ann Arbor, MI 48109 USA. [Kwak, Hojoong; Ramrattan, Girish; Cheung, Vivian G.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Cheung, Vivian G.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Cheung, Vivian G.] Univ Michigan, Dept Genet, Ann Arbor, MI 48109 USA. RP Wang, IX; Cheung, VG (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.; Cheung, VG (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.; Cheung, VG (reprint author), Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.; Cheung, VG (reprint author), Univ Michigan, Dept Genet, Ann Arbor, MI 48109 USA. EM ixwang@umich.edu; vgcheung@umich.edu FU National Institutes of Health; Howard Hughes Medical Institute FX We thank Drs. Susana Cerritelli, Robert Crouch, Daniel Klionsky, Thomas Kunkel, and Rolf Sternglanz for providing yeast strains, insightful suggestions, and discussions; Drs. Nicholas Proudfoot, Konstantina Skourti-Stathaki, and Stephen Leppla for providing S9.6 antibody and discussions; Dr. John Lis for the many discussions and encouragements; Dr. Hsin-Yao Tang at Wistar Proteomic Center for technical support and discussion on proteomic analysis; Mr. Hongjiu Zhang in Dr. Yang Zhang's laboratory for help and suggestions on protein structure prediction; and Ms. Jennifer Fox and Ms. Yaojuan Liu for technical support. This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute. NR 74 TC 0 Z9 0 U1 4 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2016 VL 26 IS 11 BP 1544 EP 1554 DI 10.1101/gr.207878.116 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA EA4UB UT WOS:000386609300008 PM 27638543 ER PT J AU Sheeran, P Maki, A Montanaro, E Avishai-Yitshak, A Bryan, A Klein, WMP Miles, E Rothman, AJ AF Sheeran, Paschal Maki, Alexander Montanaro, Erika Avishai-Yitshak, Aya Bryan, Angela Klein, William M. P. Miles, Eleanor Rothman, Alexander J. TI The Impact of Changing Attitudes, Norms, and Self-Efficacy on Health-Related Intentions and Behavior: A Meta-Analysis SO HEALTH PSYCHOLOGY LA English DT Article DE health behavior; interventions; attitude; norm; self-efficacy ID PLANNED BEHAVIOR; IMPLEMENTATION INTENTIONS; REASONED ACTION; CHANGE INTERVENTIONS; PHYSICAL-ACTIVITY; BELIEF MODEL; PREDICTING BEHAVIOR; CONDOM USE; HABITS; EXERCISE AB Objective: Several health behavior theories converge on the hypothesis that attitudes, norms, and self-efficacy are important determinants of intentions and behavior. However, inferences regarding the relation between these cognitions and intention or behavior rest largely on correlational data that preclude causal inferences. To determine whether changing attitudes, norms, or self-efficacy leads to changes in intentions and behavior, investigators need to randomly assign participants to a treatment that significantly increases the respective cognition relative to a control condition, and test for differences in subsequent intentions or behavior. The present review analyzed findings from 204 experimental tests that met these criteria. Method: Studies were located using computerized searches and informal sources and meta-analyzed using STATA Version 11. Results: Experimentally induced changes in attitudes, norms, and self-efficacy all led to medium-sized changes in intention (d(+) = .48, .49, and .51, respectively), and engendered small to medium-sized changes in behavior (attitudes-d(+) = .38, norms-d(+) = .36, self-efficacy-d(+) = .47). These effect sizes generally were not qualified by the moderator variables examined (e.g., study quality, theoretical basis of the intervention, methodological characteristics, and features of the targeted behavior), although effects were larger for interventions designed to increase (vs. decrease) behavioral performance. Conclusion: The present review lends novel, experimental support for key predictions from health behavior theories, and demonstrates that interventions that modify attitudes, norms, and self-efficacy are effective in promoting health behavior change. C1 [Sheeran, Paschal; Avishai-Yitshak, Aya] Univ N Carolina, Dept Psychol & Neurosci, Davie Hall, Chapel Hill, NC 27599 USA. [Maki, Alexander; Rothman, Alexander J.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Montanaro, Erika] Univ Colorado Boulder, Dept Psychol, Boulder, CO USA. [Bryan, Angela] Univ Colorado Boulder, Dept Psychol & Neurosci, Boulder, CO USA. [Klein, William M. P.] NCI, Behav Res Branch, Bethesda, MD 20892 USA. [Miles, Eleanor] Univ Sussex, Dept Psychol, Brighton BN1 9RH, E Sussex, England. RP Sheeran, P (reprint author), Univ N Carolina, Dept Psychol & Neurosci, Davie Hall, Chapel Hill, NC 27599 USA. EM psheeran@unc.edu NR 76 TC 1 Z9 1 U1 22 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2016 VL 35 IS 11 BP 1178 EP 1188 DI 10.1037/hea0000387 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA EA2TV UT WOS:000386448700002 PM 27280365 ER PT J AU Edison, N Belhanes-Peled, H Eitan, Y Guthmann, Y Yeremenko, Y Raffeld, M Elmalah, I Trougouboff, P AF Edison, Natalia Belhanes-Peled, Hila Eitan, Yuval Guthmann, Yifat Yeremenko, Yelena Raffeld, Mark Elmalah, Irit Trougouboff, Philippe TI Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis SO HUMAN PATHOLOGY LA English DT Article DE Indolent T-cell lymphoproliferative disease; Immunosuppression; Inflammatory bowel disease; Tumor necrosis factor-alpha inhibitor ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR AB We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-alpha (TNF-alpha) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-beta F1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-alpha inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-alpha inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma. (C) 2016 Elsevier Inc. All rights reserved. C1 [Edison, Natalia; Trougouboff, Philippe] Emek Med Ctr, Hematopathol Unit, Inst Tissue Diagnost & Canc Res, IL-1834111 Afula, Israel. [Edison, Natalia; Belhanes-Peled, Hila; Eitan, Yuval; Guthmann, Yifat; Elmalah, Irit; Trougouboff, Philippe] Emek Med Ctr, Inst Tissue Diagnost & Canc Res, IL-1834111 Afula, Israel. [Eitan, Yuval; Guthmann, Yifat] Emek Med Ctr, Inst Tissue Diagnost & Canc Res, Mol Pathol Unit, IL-1834111 Afula, Israel. [Yeremenko, Yelena] Emek Med Ctr, Gastroenterol Inst, IL-1834111 Afula, Israel. [Raffeld, Mark] NCI, Mol Diagnost Sect, NIH, Bethesda, MD 20892 USA. RP Trougouboff, P (reprint author), Emek Med Ctr, Inst Tissue Diagnost & Canc Res, Yitzhak Rabin Blvd 12, IL-1834107 Afula, Israel. EM phil.t@clalit.org.il NR 21 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2016 VL 57 BP 45 EP 50 DI 10.1016/j.humpath.2016.06.021 PG 6 WC Pathology SC Pathology GA EA5FK UT WOS:000386644600008 PM 27402301 ER PT J AU Freeley, S Kemper, C Le Friec, G AF Freeley, Simon Kemper, Claudia Le Friec, Gaelle TI The "ins and outs" of complement-driven immune responses SO IMMUNOLOGICAL REVIEWS LA English DT Review DE adaptive immunity; cell metabolism; complement; complosome; inflammasomes; T cells ID DECAY-ACCELERATING FACTOR; REGULATORY T-CELLS; NLRP3 INFLAMMASOME ACTIVATION; VEIN ENDOTHELIAL-CELLS; COFACTOR PROTEIN MCP; DENDRITIC CELLS; INNATE IMMUNITY; POLYMORPHONUCLEAR LEUKOCYTES; C3 DEFICIENCY; COMPONENT C3 AB The complement system represents an evolutionary old and critical component of innate immunity where it forms the first line of defense against invading pathogens. Originally described as a heat-labile fraction of the serum responsible for the opsonization and subsequent lytic killing of bacteria, work over the last century firmly established complement as a key mediator of the general inflammatory response but also as an acknowledged vital bridge between innate and adaptive immunity. However, recent studies particularly spanning the last decade have provided new insights into the novel modes and locations of complement activation and highlighted unexpected additional biological functions for this ancient system, for example, in regulating basic processes of the cell. In this review, we will cover the current knowledge about complement's established and novel roles in innate and adaptive immunity with a focus on the functional differences between serum circulating and intracellularly active complement and will describe and discuss the newly discovered cross-talks of complement with other cell effector systems particularly during T-cell induction and contraction. C1 [Freeley, Simon; Kemper, Claudia; Le Friec, Gaelle] Kings Coll London, Guys Hosp, Div Transplant Immunol & Mucosal Biol, MRC Ctr Transplantat, London, England. [Kemper, Claudia] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Kemper, Claudia] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Kemper, C (reprint author), Kings Coll London, Guys Hosp, Div Transplant Immunol & Mucosal Biol, MRC Ctr Transplantat, London, England. EM claudia.kemper@kcl.ac.uk FU MRC Centre [MR/J006742/1]; EU-funded Innovative Medicines Initiative BTCURE; Wellcome Trust [102932/Z/13/Z]; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH; intramural research program of NIAID, NIH FX Work in the Kemper Laboratory is supported by the MRC Centre grant MR/J006742/1, an EU-funded Innovative Medicines Initiative BTCURE (C. K.), a Wellcome Trust Investigator Award grant 102932/Z/13/Z (C. K.), the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH and the intramural research program of NIAID, NIH. NR 170 TC 2 Z9 2 U1 18 U2 18 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 NOV PY 2016 VL 274 IS 1 BP 16 EP 32 DI 10.1111/imr.12472 PG 17 WC Immunology SC Immunology GA EB0TU UT WOS:000387059600003 PM 27782335 ER PT J AU Campbell, DW Campbell, JC Yarandi, HN O'Connor, AL Dollar, E Killion, C Sloand, E Callwood, GB Cesar, NM Hassan, M Gary, F AF Campbell, Doris W. Campbell, Jacquelyn C. Yarandi, Hossein N. O'Connor, Annie Lewis Dollar, Emily Killion, Cheryl Sloand, Elizabeth Callwood, Gloria B. Cesar, Nicole M. Hassan, Mona Gary, Faye TI Violence and abuse of internally displaced women survivors of the 2010 Haiti earthquake SO INTERNATIONAL JOURNAL OF PUBLIC HEALTH LA English DT Article DE Gender-based violence; Intimate partner violence and abuse; Women's health; Natural disasters and violence; Internally displaced disaster survivors; Culturally sensitive research ID INTIMATE PARTNER VIOLENCE; POSTTRAUMATIC-STRESS-DISORDER; AFRICAN CARIBBEAN WOMEN; GENDER-BASED VIOLENCE; NATURAL DISASTERS; HURRICANE KATRINA; RISK-ASSESSMENT; AMERICAN; HEALTH; CARE AB Limited research following disasters suggests that internally displaced women are disproportionately vulnerable to violence and abuse. An interdisciplinary collaborative of researchers and practitioners in Haiti, the US Virgin Islands, and the US Mainland investigated gender-based violence (GBV) pre- and post-earthquake and health outcomes among Haitian women living in tent cities/camps following the 2010 earthquake. A comparative descriptive correlational design using culturally sensitive and language appropriate computer-assisted interviews of 208 internally displaced women 2011-2013. Found high rates of violence and abuse both before (71.2 %) and after (75 %) p = 0.266, the earthquake primarily perpetrated by boy friends or husbands. Significantly more mental and physical health problems were reported by abused than non-abused women. The majority (60-78 %) of abused women did not report personal or community tolerance for violence and abuse, but acknowledged a community context of limited involvement. Coordinated planning and implementation of needed interventions are essential to provide a balanced approach to the care of displaced women after natural disasters with sensitivity to the abusive experiences of many women both before and after the disasters. C1 [Campbell, Doris W.; Callwood, Gloria B.] Univ Virgin Isl, Caribbean Exploratory NIMHD Res Ctr, St Thomas, VI USA. [Campbell, Jacquelyn C.; Sloand, Elizabeth] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Yarandi, Hossein N.] Wayne State Univ, Coll Nursing, Off Hlth Res, Detroit, MI 48202 USA. [O'Connor, Annie Lewis; Dollar, Emily] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, 75 Francis St, Boston, MA 02115 USA. [Killion, Cheryl; Hassan, Mona; Gary, Faye] Case Western Reserve Univ, Sch Nursing, Frances Payne Bolton, Cleveland, OH 44106 USA. [Cesar, Nicole M.] Haiti Womens Project, Port Au Prince, Haiti. RP Campbell, DW (reprint author), Univ Virgin Isl, Caribbean Exploratory NIMHD Res Ctr, St Thomas, VI USA. EM dcampbe@uvi.edu FU National Institute on Minority Health Disparities (NIMHD/ NIH, USA) [P20MD002286] FX National Institute on Minority Health Disparities (NIMHD/ NIH Grant # P20MD002286, USA.) NR 38 TC 0 Z9 0 U1 6 U2 6 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1661-8556 EI 1661-8564 J9 INT J PUBLIC HEALTH JI Int. J. Public Health PD NOV PY 2016 VL 61 IS 8 BP 981 EP 992 DI 10.1007/s00038-016-0895-8 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA6VD UT WOS:000386766200015 PM 27624625 ER PT J AU Kim, SM Roy, SG Chen, B Nguyen, TM McMonigle, RJ McCracken, AN Zhang, YL Kofuji, S Hou, J Selwan, E Finicle, BT Nguyen, TT Ravi, A Ramirez, MU Wiher, T Guenther, GG Kano, M Sasaki, AT Weisman, LS Potma, EO Tromberg, BJ Edwards, RA Hanessian, S Edinger, AL AF Kim, Seong M. Roy, Saurabh G. Chen, Bin Nguyen, Tiffany M. McMonigle, Ryan J. McCracken, Alison N. Zhang, Yanling Kofuji, Satoshi Hou, Jue Selwan, Elizabeth Finicle, Brendan T. Nguyen, Tricia T. Ravi, Archna Ramirez, Manuel U. Wiher, Tim Guenther, Garret G. Kano, Mari Sasaki, Atsuo T. Weisman, Lois S. Potma, Eric O. Tromberg, Bruce J. Edwards, Robert A. Hanessian, Stephen Edinger, Aimee L. TI Targeting cancer metabolism by simultaneously disrupting parallel nutrient access pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FLUORESCENCE LIFETIME MICROSCOPY; IN-VIVO; TRANSPORTER EXPRESSION; PROSTATE-CANCER; PHASOR APPROACH; CELLS; PIKFYVE; ACTIVATION; FTY720; PROTEIN AB Oncogenic mutations drive anabolic metabolism, creating a dependency on nutrient influx through transporters, receptors, and macropinocytosis. While sphingolipids suppress tumor growth by downregulating nutrient transporters, macropinocytosis and autophagy still provide cancer cells with fuel. Therapeutics that simultaneously disrupt these parallel nutrient access pathways have potential as powerful starvation agents. Here, we describe a water-soluble, orally bioavailable synthetic sphingolipid, SH-BC-893, that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways. SH-BC-893 activated protein phosphatase 2A (PP2A), leading to mislocalization of the lipid kinase PIKfyve. The concomitant mislocalization of the PlKfyve product PI(3,5)P2 triggered cytosolic vacuolation and blocked lysosomal fusion reactions essential for LDL, autophagosome, and macropinosome degradation. By simultaneously limiting access to both extracellular and intracellular nutrients, SH-BC-893 selectively killed cells expressing an activated form of the anabolic oncogene Ras in vitro and in vivo. However, slower-growing, autochthonous PTEN-deficient prostate tumors that did not exhibit a classic Warburg phenotype were equally sensitive. Remarkably, normal proliferative tissues were unaffected by doses of SH-BC-893 that profoundly inhibited tumor growth. These studies demonstrate that simultaneously blocking parallel nutrient access pathways with sphingolipid-based drugs is broadly effective and cancer selective, suggesting a potential strategy for overcoming the resistance conferred by tumor heterogeneity. C1 [Kim, Seong M.; Roy, Saurabh G.; Nguyen, Tiffany M.; McMonigle, Ryan J.; McCracken, Alison N.; Selwan, Elizabeth; Finicle, Brendan T.; Nguyen, Tricia T.; Ravi, Archna; Ramirez, Manuel U.; Wiher, Tim; Guenther, Garret G.; Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Chen, Bin; Hanessian, Stephen] Univ Montreal, Dept Chem, Montreal, PQ, Canada. [Zhang, Yanling; Weisman, Lois S.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Kofuji, Satoshi; Sasaki, Atsuo T.] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH USA. [Kofuji, Satoshi; Sasaki, Atsuo T.] Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA. [Kofuji, Satoshi; Sasaki, Atsuo T.] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH USA. [Hou, Jue; Potma, Eric O.; Tromberg, Bruce J.] UCI, Dept Biomed Engn, Irvine, CA USA. [Kano, Mari] NIDDK, Bethesda, MD 20892 USA. [Edwards, Robert A.] Univ Calif Irvine, Sch Med, Dept Pathol, Irvine, CA 92717 USA. [Hanessian, Stephen] UCI, Dept Pharmaceut Sci, Irvine, CA USA. RP Edinger, AL (reprint author), Univ Calif Irvine, 2128 Nat Sci 1, Irvine, CA 92697 USA. EM aedinger@uci.edu FU NIH [R01 GM089919, R21 CA178230, R01 NS064015, R01 GM050403, R01 NS089815, T32 CA009054]; Congressionally Directed Medical Research Programs (CDMRP) [W81XWH-11-1-0535, W81XWH-15-1-0010]; American Cancer Society [RSG-11-111-01-CDD]; William Lawrence and Blanche Hughes Foundation; UCI Council on Research Computing and Libraries (CORCL); Laser Microbeam and Medical Program (LAMMP) from the NIH, National Institute of Biomedical Imaging and Bioengineering (NIBIB) [P41EB015890]; Graduate Assistance in Areas of National Need (GAANN) [P200A120207]; Cancer Center Support grant [P30 CA62203]; National Center for Advancing Translational Sciences (NCATS) [UL1 TR000153] FX The authors thank Jennifer Prescher, Susanne Rafelski, Michelle Digman, Adeela Syed, Kris Kenney, Richard Van Etten, Jon Neumann, Farah Aktar (UC Irvine, Irvine, California, USA) and Richard Proia (NIH, Bethesda, Maryland, USA) for advice, reagents, and/or access to equipment; Seth Field, Thomas Weide, Ana Maria Cuervo (Albert Einstein College of Medicine, Bronx, New York, USA), Haoxing Xu, and Anand Ganesan for plasmids; and Marian Waterman and David Fruman (UC Irvine, Irvine, California, USA) for comments on the manuscript. This work was supported by grants to ALE from the NIH (R01 GM089919, R21 CA178230); the Congressionally Directed Medical Research Programs (CDMRP) (W81XWH-11-1-0535 and W81XWH-15-1-0010); the American Cancer Society (RSG-11-111-01-CDD); the William Lawrence and Blanche Hughes Foundation; and the UCI Council on Research Computing and Libraries (CORCL). Support was also provided by NIH grants to LSW (R01 NS064015 and R01 GM050403) and ATS (R01 NS089815). BJT, EOP, and JH were supported by Laser Microbeam and Medical Program (LAMMP) grant P41EB015890 from the NIH, National Institute of Biomedical Imaging and Bioengineering (NIBIB). SMK was supported by Graduate Assistance in Areas of National Need (GAANN) grant P200A120207 and ES by NIH grant T32 CA009054. The core facilities at UCI were supported by Cancer Center Support grant P30 CA62203 and the normal blood donor program by National Center for Advancing Translational Sciences (NCATS) grant UL1 TR000153. NR 61 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2016 VL 126 IS 11 BP 4088 EP 4102 DI 10.1172/JCI87148 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EA9VN UT WOS:000386992900006 PM 27669461 ER PT J AU Dawson, AL Tinker, SC Jamieson, DJ Hobbs, CA Berry, RJ Rasmussen, SA Anderka, M Keppler-Noreuil, KM Lin, AE Reefhuis, J AF Dawson, April L. Tinker, Sarah C. Jamieson, Denise J. Hobbs, Charlotte A. Berry, R. J. Rasmussen, Sonja A. Anderka, Marlene Keppler-Noreuil, Kim M. Lin, Angela E. Reefhuis, Jennita CA Natl Birth Defects Prevention TI Twinning and major birth defects, National Birth Defects Prevention Study, 1997-2007 SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID ASSISTED REPRODUCTIVE TECHNOLOGY; MULTIPLE BIRTHS; INCREASED RISK; UNITED-STATES; MATERNAL AGE; YOUNG TWINS; QUESTIONNAIRE; EPIDEMIOLOGY; ASSOCIATION; ANOMALIES AB Background Twinning has been associated with many types of birth defects, although previous studies have had inconsistent findings. Many studies lack information about potential confounders, particularly use of fertility treatment. Our objective was to assess the association between twinning and birth defects in the National Birth Defects Prevention Study (NBDPS). Methods We used data from the NBDPS, a population-based, case-control study of major birth defects in the USA, to evaluate associations between twinning and birth defects. The study population included mothers of twin and singleton controls (live-born infants without major birth defects), and cases (fetuses or infants with a major birth defect) born October 1997-December 2007. Adjusted ORs and 95% CIs were estimated using multivariable logistic regression stratified by use of fertility treatment. Twin sex-pairing data and a simulation approach were used to estimate the zygosity of twins. Results In the unassisted conception stratum, we observed significant positive associations between twinning and 29 of 45 defect groups. The largest effect estimates were observed for multiple ventricular septal defects and cloacal exstrophy. Among mothers reporting any use of fertility treatments, we observed a significant association with twinning for 5 of 25 defect groups, with the largest effect estimates for hypoplastic left heart syndrome and omphalocele. OR estimates in the estimated monozygotic stratum were generally further from the null than in the dizygotic stratum. Conclusions Compared with singletons, a wide range of birth defects are significantly more common among twins. Birth defect risk in twins may be differential by use of fertility treatment. C1 [Dawson, April L.; Tinker, Sarah C.; Berry, R. J.; Reefhuis, Jennita] CDC, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,MS-E86, Atlanta, GA 30333 USA. [Jamieson, Denise J.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Hobbs, Charlotte A.] Univ Arkansas Med Sci, Coll Med, Fayetteville, AR USA. [Rasmussen, Sonja A.] CDC, Off Infect Dis, Atlanta, GA 30333 USA. [Anderka, Marlene; Lin, Angela E.] Massachusetts Ctr Birth Defects Res & Prevent, Boston, MA USA. [Keppler-Noreuil, Kim M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Dawson, AL (reprint author), CDC, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,MS-E86, Atlanta, GA 30333 USA. EM isp3@cdc.gov FU Intramural CDC HHS [CC999999] NR 27 TC 0 Z9 0 U1 5 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD NOV PY 2016 VL 70 IS 11 BP 1114 EP 1121 DI 10.1136/jech-2015-206302 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA3PP UT WOS:000386516300009 PM 27325867 ER PT J AU Thet, MM Pholphirul, P AF Thet, Mya Mya Pholphirul, Piriya TI The Perception of Myanmar Development on its Return Migrants: Implications for Burmese Migrants in Thailand SO JOURNAL OF INTERNATIONAL MIGRATION AND INTEGRATION LA English DT Article DE Development of Myanmar; Burmese migration in Thailand; Return migration ID MIGRATION AB Recent development in Myanmar has created stronger pull factors on emigrant Burmese workers to return to their motherland. Using a survey of 433 Burmese migrants in Thailand as a case study, this paper examines the impact of Myanmar's development on the probability of the return of Burmese migrants to Myanmar from Thailand. Development factors such as more foreign direct investment, deregulation, and improvement of public services will encourage Burmese migrant workers to return home. Additionally, in terms of economic development, better job opportunities and political stability are also major pull factors for return migration. The main policy implication of these findings is that the chances that Burmese migrant workers will return home are high if investment opportunities followed by job availability and adequate wages can be found in Myanmar. Myanmar and Thailand should implement education programs set up by the Thai government and facilitate Burmese migrants' children's access to these programs as well as protecting migrants' rights during the period of structural adjustment in Thailand. C1 [Thet, Mya Mya] Minist Labour Employment & Social Secur, Dept Labour, Nay Pyi Taw, Myanmar. [Pholphirul, Piriya] NIDA, Grad Sch Dev Econ, Serithai Rd, Bangkok 20140, Thailand. [Thet, Mya Mya; Pholphirul, Piriya] ICONIDA, Serithai Rd, Bangkok 20140, Thailand. RP Pholphirul, P (reprint author), NIDA, Grad Sch Dev Econ, Serithai Rd, Bangkok 20140, Thailand.; Pholphirul, P (reprint author), ICONIDA, Serithai Rd, Bangkok 20140, Thailand. EM mya2thet1981@gmail.com; pholphir@hotmail.com NR 33 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1488-3473 EI 1874-6365 J9 J INT MIGR INTEGR JI J. Int. Migr. Integr. PD NOV PY 2016 VL 17 IS 4 BP 995 EP 1014 DI 10.1007/s12134-015-0446-9 PG 20 WC Demography SC Demography GA EA5KO UT WOS:000386659400002 ER PT J AU Gimotty, PA Shore, R Lozon, NL Whitlock, J He, SD Vigneau, FD Dickie, L Elder, DE Xu, XW Schwartz, AG Guerry, D AF Gimotty, Phyllis A. Shore, Ronald Lozon, Nancy L. Whitlock, Jeanne He, Sidan Vigneau, Fawn D. Dickie, Lois Elder, David E. Xu, Xiaowei Schwartz, Ann G. Guerry, DuPont TI Miscoding of Melanoma Thickness in SEER: Research and Clinical Implications SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MULTIVARIABLE PREDICTION MODEL; THIN CUTANEOUS MELANOMA; INDIVIDUAL PROGNOSIS; SURVIVAL; QUEENSLAND; AUSTRALIA; REGISTRY AB Melanoma-related deaths and metastases among patients with thin (<= 1 mm) and ultrathin (<= 0.25 mm) melanomas have been reported. These observations might reflect adverse biology and/or errors in administrative data. Cumulative melanoma-related death rates for thickness groups of patients with thin melanomas were compared among five cohorts including the Surveillance, Epidemiology, and End Results (SEER) registry. Thickness in one SEER region was reexamined in pathology reports. The 5-year cumulative melanoma-related death rate of patients with ultrathin melanomas was higher in SEER (2.8%) compared with other registries (0.6-0.9%). The rates across the 16 SEER regions were 0.25% to 8.4%. In SEER, 21% of thin melanomas were ultrathin; in other registries, they comprised 5.8-15%. A reexamination of thickness in one SEER site revealed that 114 of 447 ultrathin melanomas had errors; after correction, only 17 of the 114 remained ultrathin. The majority of errors were related to decimal point placement. The 86 thin melanomas reclassified to >1.00 mm included 96% of the original ultrathin-associated deaths and 100% of the original positive lymph nodes. Significant miscoding of thickness that is concentrated in ultrathin lesions is present in SEER and results in mischaracterization of patient outcomes. When using administrative data, validation of results can identify critical data issues. C1 [Gimotty, Phyllis A.; He, Sidan] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, 631 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Shore, Ronald; Lozon, Nancy L.; Whitlock, Jeanne; Vigneau, Fawn D.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Dickie, Lois] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Elder, David E.; Xu, Xiaowei] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Guerry, DuPont] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Gimotty, PA (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, 631 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM pgimotty@mail.med.upenn.edu FU CCR NIH HHS [HHSN261201300011C]; NCI NIH HHS [P50 CA174523, HHSN261201000028C, P30 CA022453, P30 CA016520, HHSN261201300011I] NR 17 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2016 VL 136 IS 11 BP 2168 EP 2172 DI 10.1016/j.jid.2016.05.121 PG 5 WC Dermatology SC Dermatology GA EB0CS UT WOS:000387011600015 PM 27354265 ER PT J AU Brahler, S Yu, HY Suleiman, H Krishnan, GM Saunders, BT Kopp, JB Miner, JH Zinselmeyer, BH Shaw, AS AF Brahler, Sebastian Yu, Haiyang Suleiman, Hani Krishnan, Gokul M. Saunders, Brian T. Kopp, Jeffrey B. Miner, Jeffrey H. Zinselmeyer, Bernd H. Shaw, Andrey S. TI Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; 2-PHOTON MICROSCOPY; DISEASE; ACTIVATION; EXPRESSION; INJURY; CELLS; RAC1 AB In glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro. However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two-photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1, however, podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Constitutive activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we detected detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. Podocyte membrane activity also increased in the inflammatory environment of immune complex-mediated GN. Our results provide evidence that podocytes transition from a static to a dynamic state in vivo, shedding new light on mechanisms in foot process effacement. C1 [Brahler, Sebastian; Yu, Haiyang; Suleiman, Hani; Krishnan, Gokul M.; Saunders, Brian T.; Zinselmeyer, Bernd H.; Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. [Miner, Jeffrey H.] Washington Univ, Sch Med, Div Nephrol, St Louis, MO USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. RP Zinselmeyer, BH (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA.; Shaw, AS (reprint author), Genentech Inc, One DNA Way,Mail Stop 93b, San Francisco, CA 94080 USA. EM bzinselmeyer@path.wustl.edu; shaw.andrey@gene.com FU Deutsche Forschungsgemeinschaft [BR4917/1-1]; National Institutes of Health [R01DK078314, R01DK058366]; Howard Hughes Medical Institute FX This work was supported by the Deutsche Forschungsgemeinschaft scholarship BR4917/1-1 (to S.B.), the National Institutes of Health grants R01DK078314 (to J.H.M.) and R01DK058366 (to A.S.S.), and the Howard Hughes Medical Institute (A.S.S.). NR 18 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2016 VL 27 IS 11 BP 3285 EP 3290 DI 10.1681/ASN.2015121303 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA EA3VV UT WOS:000386538300010 PM 27036737 ER PT J AU Oosthuyzen, W Scullion, KM Ivy, JR Morrison, EE Hunter, RW Lewis, PJS O'Duibhir, E Street, JM Caporali, A Gregory, CD Forbes, SJ Webb, DJ Bailey, MA Dear, JW AF Oosthuyzen, Wilna Scullion, Kathleen M. Ivy, Jessica R. Morrison, Emma E. Hunter, Robert W. Lewis, Philip J. Starkey O'Duibhir, Eoghan Street, Jonathan M. Caporali, Andrea Gregory, Christopher D. Forbes, Stuart J. Webb, David J. Bailey, Matthew A. Dear, James W. TI Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HUMAN URINARY EXOSOMES; PROTEIN-KINASE-A; ENDOCYTOSIS; INHIBITOR; MICRORNAS; DYNASORE; DYNAMIN; SODIUM; PLASMA; LINE AB Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCD(C11)) and into primary cells. Exposure of mCCD(C11) cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCD(C11) cells required CAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo. We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease. C1 [Oosthuyzen, Wilna; Scullion, Kathleen M.; Ivy, Jessica R.; Morrison, Emma E.; Hunter, Robert W.; Caporali, Andrea; Webb, David J.; Bailey, Matthew A.; Dear, James W.] Univ Edinburgh, British Heart Fdn Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [Gregory, Christopher D.] Univ Edinburgh, Queens Med Res Inst, Med Res Council Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. [Lewis, Philip J. Starkey; O'Duibhir, Eoghan; Forbes, Stuart J.] Scottish Ctr Regenerat Med, Med Res Council Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Street, Jonathan M.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Dear, JW (reprint author), Univ Edinburgh, Queens Med Res Inst, Univ BHF Ctr Cardiovasc Sci, 47 Little France Crescent, Edinburgh EH16 4JT, Midlothian, Scotland. EM james.dear@ed.ac.uk OI Gregory, Chris/0000-0002-7553-0132 FU Diabetes Research & Wellness Foundation; British Heart Foundation [FS/15/63/32033, FS/11/78/29328]; National Health Service Research Scotland through National Health Service Lothian; British Heart Foundation Centre of Research Excellence Award [RE/08/001]; United Kingdom Regenerative Medicine Platform Niche Hub FX W.O. was funded by a grant from the Diabetes Research & Wellness Foundation, and K.M.S. and J.R.I. were funded by British Heart Foundation studentships (FS/15/63/32033 and FS/11/78/29328, respectively). J.W.D. acknowledges the support of the National Health Service Research Scotland through National Health Service Lothian. All the authors acknowledge the contribution of the British Heart Foundation Centre of Research Excellence Award (RE/08/001) and the United Kingdom Regenerative Medicine Platform Niche Hub. NR 29 TC 2 Z9 2 U1 5 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2016 VL 27 IS 11 BP 3345 EP 3355 DI 10.1681/ASN.2015050568 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA EA3VV UT WOS:000386538300016 PM 27020854 ER PT J AU Fischer, MJ Hsu, JY Lora, CM Ricardo, AC Anderson, AH Bazzano, L Cuevas, MM Hsu, CY Kusek, JW Renteria, A Ojo, AO Raj, DS Rosas, SE Pan, Q Yaffe, K Go, AS Lash, JP AF Fischer, Michael J. Hsu, Jesse Y. Lora, Claudia M. Ricardo, Ana C. Anderson, Amanda H. Bazzano, Lydia Cuevas, Magdalena M. Hsu, Chi-yuan Kusek, John W. Renteria, Amada Ojo, Akinlolu O. Raj, Dominic S. Rosas, Sylvia E. Pan, Qiang Yaffe, Kristine Go, Alan S. Lash, James P. CA Chronic Renal Insufficiency Cohort TI CKD Progression and Mortality among Hispanics and Non-Hispanics SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RENAL-INSUFFICIENCY COHORT; NUTRITION EXAMINATION SURVEY; BASE-LINE CHARACTERISTICS; EVALUATION PROGRAM KEEP; 3RD NATIONAL-HEALTH; ETHNIC-DIFFERENCES; RACIAL-DIFFERENCES; CARDIOVASCULAR-DISEASE; DIABETIC-NEPHROPATHY AB Although recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes. C1 [Fischer, Michael J.; Lora, Claudia M.; Ricardo, Ana C.; Renteria, Amada; Lash, James P.] Univ Illinois, Dept Med, Chicago, IL USA. [Fischer, Michael J.] Jesse Brown VA Med Ctr, Med Serv, Chicago, IL USA. [Fischer, Michael J.] Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Res Serv, Hines, IL USA. [Hsu, Jesse Y.; Anderson, Amanda H.; Cuevas, Magdalena M.; Pan, Qiang] Univ Penn, Dept Epidemiol & Biostat, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bazzano, Lydia] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hsu, Chi-yuan; Go, Alan S.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Ojo, Akinlolu O.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Raj, Dominic S.] George Washington Univ, Dept Med, Washington, DC USA. [Rosas, Sylvia E.] Harvard Med Sch, Joslin Diabet Ctr, Kidney & Hypertens Unit, Boston, MA USA. [Rosas, Sylvia E.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Nephrol Sect, Boston, MA 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. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Fischer, MJ (reprint author), Hines VA Hosp, Ctr Innovat Complex Chron Healthcare, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM fischerm@uic.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U0IDK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) [UL1 TR-000003]; Johns Hopkins University [UL1 TR-000424]; University of Maryland General Clinical Research Center [M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland; NCATS component of the NIH [UL1 TR-000439]; NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research [UL1 TR-000433]; University of Illinois at Chicago Clinical and Translational Science Award [UL1 RR-029879]; Tulane University Translational Research in Hypertension and Renal Biology [P30GMI03337]; Kaiser Permanente NIH/National Center for Research Resources, University of California-San Francisco Clinical & Translational Science Institute [UL1 RR-024131]; National Center for Minority Health and Health Disparities; NIH; Department of Veterans Affairs Health Services Research and Development Service; NIH/NIDDK [K24-DK092290, K23 DK091313, K23 DK094829] FX Funding for the Chronic Renal Insufficiency Cohort Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U0IDK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award and the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) (UL1 TR-000003), Johns Hopkins University (UL1 TR-000424), University of Maryland General Clinical Research Center (M01 RR-16500), Clinical and Translational Science Collaborative of Cleveland, UL1 TR-000439 from the NCATS component of the NIH and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (UL1 TR-000433), University of Illinois at Chicago Clinical and Translational Science Award (UL1 RR-029879), Tulane University Translational Research in Hypertension and Renal Biology (P30GMI03337), and Kaiser Permanente NIH/National Center for Research Resources, University of California-San Francisco Clinical & Translational Science Institute (UL1 RR-024131). Additional support was provided by the National Center for Minority Health and Health Disparities, the NIH, and Department of Veterans Affairs Health Services Research and Development Service (to M.J.F.). Support was provided from NIH/NIDDK K24-DK092290 (to J.P.L.), K23 DK091313 (to C.M.L.), K23 DK094829 (to A.C.R.). NR 43 TC 0 Z9 0 U1 6 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2016 VL 27 IS 11 BP 3488 EP 3497 DI 10.1681/ASN.2015050570 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA EA3VV UT WOS:000386538300030 PM 27151925 ER PT J AU Muller, L Jackson, SN Woods, AS AF Muller, Ludovic Jackson, Shelley N. Woods, Amina S. TI Rat kidney lipid composition addressed by mass spectrometry imaging Reply SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Muller, Ludovic; Jackson, Shelley N.; Woods, Amina S.] NIDA, Struct Biol Unit, IRP, NIH, 333 Cassell Dr,Room 1120, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, Struct Biol Unit, IRP, NIH, 333 Cassell Dr,Room 1120, Baltimore, MD 21224 USA. EM awoods@mail.nih.gov NR 3 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2016 VL 90 IS 5 BP 1130 EP 1131 DI 10.1016/j.kint.2016.08.002 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA EA3ZF UT WOS:000386547100029 PM 27742184 ER PT J AU Brown, P AF Brown, Patricia TI A Word from OLAW SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bldg 10, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 EI 1548-4475 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2016 VL 45 IS 11 BP 424 EP 424 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA EA3ZI UT WOS:000386547400016 PM 27763615 ER PT J AU Babaei, Z Malihi, N Zia-Ali, N Sharifi, I Mohammadi, MA Kagnoff, MF Eckmann, L Singer, SM Solaymani-Mohammadi, S AF Babaei, Zahra Malihi, Najmeh Zia-Ali, Naser Sharifi, Iraj Mohammadi, Mohammad A. Kagnoff, Martin F. Eckmann, Lars Singer, Steven M. Solaymani-Mohammadi, Shahram TI Adaptive immune response in symptomatic and asymptomatic enteric protozoal infection: evidence for a determining role of parasite genetic heterogeneity in host immunity to human giardiasis SO MICROBES AND INFECTION LA English DT Article DE Human; Protozoa; Giardia duodenalis; Cytokines ID REAL-TIME PCR; IFN-GAMMA; PROTECTIVE IMMUNITY; LAMBLIA INFECTIONS; TOXOPLASMA-GONDII; GUT INFECTION; MICE; DUODENALIS; INTESTINALIS; CHILDREN AB The genetic basis of the ultimate clinical outcomes of human giardiasis has been the subject of numerous investigations. We previously demonstrated roles for both host and parasite factors in determining the outcome of enteric infection in a murine model of Giardia duodenalis infection. In the current study, fecal and serum specimens from healthy controls and human subjects infected with the intestinal parasite G. duodenalis were assessed. Using a semi-nested PCR method, clinical isolates were genetically characterized based on the gdh and tpi loci, and the phylogenetic trees were constructed. Using a sandwich ELISA method, the serum levels of representative T-H1 and T-H2 cytokines were measured in infected human subjects and healthy controls. Here we showed that symptomatic human giardiasis was characterized by significantly elevated serum levels of the T-H1 cytokine IFN-gamma compared to healthy controls, whereas asymptomatic human subjects and healthy controls had comparable levels of serum IFN-gamma. Further analyses showed that human subjects infected with G. duodenalis genotype AI had significantly elevated levels of serum IFN-gamma and IL-10, but not IL-5, whereas human subjects infected with AII had similar levels of those cytokines compared to healthy controls. These data demonstrate roles for both host and parasite factors in the determination of the outcome of enteric infections and may further broaden our understanding of host-parasite interaction during enteric protozoal infections. (C) 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Babaei, Zahra; Malihi, Najmeh; Zia-Ali, Naser; Sharifi, Iraj; Mohammadi, Mohammad A.] Kerman Univ Med Sci, Dept Med Parasitol & Mycol, Kerman, Iran. [Babaei, Zahra; Sharifi, Iraj] Kerman Univ Med Sci, Leishmaniasis Res Ctr, Kerman, Iran. [Kagnoff, Martin F.; Eckmann, Lars; Solaymani-Mohammadi, Shahram] Univ Calif La Jolla, Lab Mucosal Immunol, Sch Med, La Jolla, CA USA. [Singer, Steven M.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA. [Singer, Steven M.] Georgetown Univ, Ctr Infect Dis, Washington, DC USA. [Solaymani-Mohammadi, Shahram] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41-Rm D702,41 Medlars Dr, Bethesda, MD 20892 USA. RP Solaymani-Mohammadi, S (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41-Rm D702,41 Medlars Dr, Bethesda, MD 20892 USA. EM shahram.sm@nih.gov FU Kerman University of Medical Sciences Vice Chancellor for Research [93/60]; NIH/NIAID [AI109591, AI112594] FX This work was supported by a grant from the Kerman University of Medical Sciences Vice Chancellor for Research (to ZB, SSM), under contract 93/60 and by NIH/NIAID grants AI109591 (to SMS) and AI112594 (to LE). We thank patients and healthy volunteers who participated in this study. We are grateful to Saied Suleimany and Najmeh Zandi for technical assistance, and Thorsten Demberg and Anja Bloom for advice. NR 49 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD NOV PY 2016 VL 18 IS 11 BP 687 EP 695 DI 10.1016/j.micinf.2016.06.009 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EA7BA UT WOS:000386781900004 PM 27401766 ER PT J AU Camp, KM Krotoski, D Parisi, MA Gwinn, KA Cohen, BH Cox, CS Enns, GM Falk, MJ Goldstein, AC Gopal-Srivastava, R Gorman, GS Hersh, SP Hirano, M Hoffman, FA Karaa, A MacLeod, EL McFarland, R Mohan, C Mulberg, AE Odenkirchen, JC Parikh, S Rutherford, PJ Suggs-Anderson, SK Tang, WHW Vockley, J Wolfe, LA Yannicelli, S Yeske, PE Coates, PM AF Camp, Kathryn M. Krotoski, Danuta Parisi, Melissa A. Gwinn, Katrina A. Cohen, Bruce H. Cox, Christine S. Enns, Gregory M. Falk, Marni J. Goldstein, Amy C. Gopal-Srivastava, Rashmi Gorman, Grainne S. Hersh, Stephen P. Hirano, Michio Hoffman, Freddie Ann Karaa, Amel MacLeod, Erin L. McFarland, Robert Mohan, Charles Mulberg, Andrew E. Odenkirchen, Joanne C. Parikh, Sumit Rutherford, Patricia J. Suggs-Anderson, Shawne K. Tang, W. H. Wilson Vockley, Jerry Wolfe, Lynne A. Yannicelli, Steven Yeske, Philip E. Coates, Paul M. TI Nutritional interventions in primary mitochondrial disorders: Developing an evidence base SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Primary mitochondrial disorders; Mitochondrial disease; Nutritional interventions; Dietary supplements; Medical foods; OXPHOS ID RESPIRATORY-CHAIN DEFECTS; COMPLEX-I-DEFICIENCY; KETOGENIC DIET; METHYLMALONIC ACIDEMIA; CARDIOVASCULAR-DISEASE; PRACTICE PATTERNS; INBORN-ERRORS; C. ELEGANS; CHILDREN; EPILEPSY AB In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD. (C) 2016 Elsevier Inc. All rights reserved. C1 [Camp, Kathryn M.; Coates, Paul M.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. [Krotoski, Danuta; Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Gwinn, Katrina A.; Odenkirchen, Joanne C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Cohen, Bruce H.] Akron Childrens Hosp, Dept Pediat, Akron, OH 44308 USA. [Cox, Christine S.] MitoAction, Boston, MA 02205 USA. [Enns, Gregory M.] Stanford Univ, Div Med Genet, Stanford, CA 94305 USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Goldstein, Amy C.] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA 15224 USA. [Gopal-Srivastava, Rashmi] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Gorman, Grainne S.; McFarland, Robert] Newcastle Univ, Wellcome Trust Ctr Mitochondrial Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Hersh, Stephen P.] J Willard & Alice S Marriott Fdn, Bethesda, MD 20817 USA. [Hirano, Michio] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Hoffman, Freddie Ann] HeteroGeneity LLC, Washington, DC 20011 USA. [Karaa, Amel] Massachusetts Gen Hosp, Genet Unit, Boston, MA 02114 USA. [MacLeod, Erin L.] Childrens Natl Hlth Syst, Div Genet & Metab, Washington, DC 20010 USA. [Mohan, Charles; Yeske, Philip E.] United Mitochondrial Dis Fdn, Pittsburgh, PA 15239 USA. [Mulberg, Andrew E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Parikh, Sumit] Cleveland Clin, Neurosci, Cleveland, OH 44195 USA. [Rutherford, Patricia J.] Vitaflo Int Ltd, Liverpool L3 4BQ, Merseyside, England. [Suggs-Anderson, Shawne K.] US FDA, Off Nutr & Food Labeling, College Pk, MD 20740 USA. [Tang, W. H. Wilson] Cleveland Clin, Ctr Clin Genom, Cleveland, OH 44195 USA. [Vockley, Jerry] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15224 USA. [Wolfe, Lynne A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Yannicelli, Steven] Nutricia North Amer, Med & Sci Affairs, Rockville, MD 20850 USA. [Mulberg, Andrew E.] US FDA, Rockville, MD 20857 USA. RP Camp, KM (reprint author), 6100 Execut Blvd, Rockville, MD 20892 USA. EM campkm@od.nih.gov; krotoskd@mail.nih.gov; parisima@mail.nih.gov; gwinnk@ninds.nih.gov; bcohen@chmca.org; outreach@mitoaction.org; genns@stanford.edu; falkm@email.chop.edu; amy.goldstein@chp.edu; rashmi.gopal-srivastava@nih.gov; grainne.gorman@newcastle.ac.uk; hershs@starpower.net; mh29@cumc.columbia.edu; fhoffman@heterogeneity-LLC.com; akaraa@mgh.harvard.edu; emacleod@childrensnational.org; robert.mcfarland@newcastle.ac.uk; chuckm@umdf.org; amulberg@amicusrx.com; jo21x@nih.gov; parikhs@ccf.org; triciarutherford@vitaflo.co.uk; shawne.suggs-anderson@fda.hhs.gov; tangw@ccf.org; gerard.vockley@chp.edu; lynne.wolfe@nih.gov; steven.yannicelli@nutricia.com; philip.yeske@umdf.org; coatesp@od.nih.gov OI Gwinn, Katrina/0000-0002-8277-651X FU Edison; Raptor; Reata Pharmaceutical companies; Stealth Peptides; Raptor Pharmaceuticals; Vitaflo; NIH; Neurovive; Stealth Biopeptides; Muscular Dystrophy Association; Santhera Pharmaceuticals; Edison Pharmaceuticals; BioMarin; Medical Research Council; Wellcome Trust; Ryan Stanford Appeal; Lily Foundation; International Foundation for CDKL5 Research (IFCR); Edison Pharmaceutical company; Reata Pharmaceutical company FX The following authors declared financial relationships: B.H. Cohen receives research funding from Edison, Raptor, and Reata Pharmaceutical companies, research funding from and consults to Stealth Peptides, was a consultant to Transgenomic labs and on the speakers board for Courtagen labs; G.M. Enns was a consultant to Mitobridge and runs clinical trials for Edison and Raptor Pharmaceutical companies; M.J. Falk consults to MitoBridge and the KC Group, receives or received research funding from Raptor Pharmaceuticals, Vitaflo, NIH, Neurovive, and Stealth Biopeptides, and has stock options from Perlstein Labs, Inc., LLC; A.C. Goldstein was a consultant to Stealth Biotherapeutics; M. Hirano has been a consultant to MitoBridge, Raptor, Stealth Biopeptides Pharmaceuticals and has received research funding from NIH, Muscular Dystrophy Association, Santhera Pharmaceuticals and Edison Pharmaceuticals; A. Karaa is on the advisory board of Stealth Biotherapeutics and consults to and is on the advisory board of Genzyme; E.L. MacLeod is on the advisory board for Nutricia North America, receives honoraria from Nutricia North America and Cambrooke Therapeutics, and research funding from BioMarin; R. McFarland receives research funding from the Medical Research Council, the Wellcome Trust, the Ryan Stanford Appeal, and the Lily Foundation; S. Parikh receives research funding from NIH, Edison Pharmaceuticals, and International Foundation for CDKL5 Research (IFCR); P.J. Rutherford is employed by VitaFlo Intl, LTD.; W.H. Wilson Tang receives research funding from NIH; J. Vockley participates in clinical trials sponsored by Edison and Reata Pharmaceutical companies, and Stealth Peptides; S. Yannicelli is employed by and owns stock in Nutricia North America. NR 108 TC 1 Z9 1 U1 6 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2016 VL 119 IS 3 BP 187 EP 206 DI 10.1016/j.ymgme.2016.09.002 PG 20 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EA9TH UT WOS:000386987100001 PM 27665271 ER PT J AU O'Brien, KJ Lozier, J Cullinane, AR Osorio, B Nghiem, K Speransky, V Zein, WM Mullikin, JC Neff, AT Simon, KL Malicdan, MCV Gahl, WA Young, LR Gochuico, BR AF O'Brien, Kevin J. Lozier, Jay Cullinane, Andrew R. Osorio, Brigitte Nghiem, Khanh Speransky, Vladislav Zein, Wadih M. Mullikin, James C. Neff, Anne T. Simon, Karen L. Malicdan, May Christine V. Gahl, William A. Young, Lisa R. Gochuico, Bernadette R. TI Identification of a novel mutation in HPS6 in a patient with hemophilia B and oculocutaneous albinism SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Hermansky-Pudlak syndrome; Platelet storage pool disorder; Oculocutaneous albinism; Christmas disease; Hemophilia B; Factor IX deficiency ID HERMANSKY-PUDLAK-SYNDROME; PULMONARY-FIBROSIS; FORM AB Purpose: Hemophilia B, an X-linked disease, manifests with recurrent soft tissue bleeding episodes. Hermansky-Pudlak syndrome, a rare autosomal recessive disorder, is characterized by oculocutaneous albinism and an increased tendency to bleed due to a platelet storage pool defect. We report a novel mutation in HPS6 in a Caucasian man with hemophilia B and oculocutaneous albinism. Results: The patient was diagnosed with hemophilia B at age 4 months due to recurrent soft tissue bleeding episodes, and he was also diagnosed with Hermansky-Pudlak syndrome at 32 years of age due to unexplained oculocutaneous albinism. His factor IX level was markedly reduced at 13%; whole exome and Sanger sequencing showed the Durham mutation in F9 (NM_000133.3). The diagnosis of Hermansky-Pudlak syndrome subtype 6 was established by demonstrating absence of platelet delta granules on whole mount electron microscopy, an abnormal secondary wave in platelet aggregation studies, and a novel homozygous c.1114 C>T (p.Arg372*) mutation in HPS6 (NM_024747.5) on exome analysis and Sanger sequencing. Clinical phenotyping revealed no evidence of recurrent or unusual infections, interstitial lung disease or pulmonary fibrosis, or neurological disorders. The patient was treated with fresh frozen plasma, recombinant factor IX, and aminocaproic acid. Treatment with desmopressin was added to his regimen after he was diagnosed with Hermansky-Pudlak syndrome. Treatment of bleeding episodes results in effective hemostasis, and the patient has not required platelet or blood product transfusions. Conclusions: This report highlights the need to consider Hermansky-Pudlak syndrome as an etiology of oculocutaneous albinism even in patients with known hematologic disorders associated with bleeding. Identification of a novel mutation in HPS6 in an individual with hemophilia B shows that, although quite rare, patients may be diagnosed with two independent inherited bleeding disorders. No evidence of lung disease was found in this adult patient with Hermansky-Pudlak syndrome subtype 6. Published by Elsevier Inc. C1 [O'Brien, Kevin J.; Osorio, Brigitte; Gahl, William A.] NHGRI, Off Clin Director, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. [Lozier, Jay; Nghiem, Khanh] NIH, Dept Lab Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. [Cullinane, Andrew R.; Simon, Karen L.; Malicdan, May Christine V.; Gahl, William A.; Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. [Cullinane, Andrew R.] Howard Univ, Dept Anat, Coll Med, 520 W St NW, Washington, DC 20059 USA. [Speransky, Vladislav] Natl Inst Biomed Imaging & Bioengn, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. [Mullikin, James C.] NIH, Intramural Sequencing Ctr, 5625 Fishers Lane, Rockville, MD 20852 USA. [Neff, Anne T.] Cleveland Clin, Dept Hematol Med Oncol, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Malicdan, May Christine V.; Gahl, William A.] NIH, Undiagnosed Dis Program, Common Fund, Off Director, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Young, Lisa R.] Vanderbilt Univ, Sch Med, Div Pediat Allergy Immunol & Pulm Med, 2200 Childrens Way,11215 Doctors Off Tower, Nashville, TN 37232 USA. [Young, Lisa R.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, 1161 21st Ave South,T-1217 Med Ctr North, Nashville, TN 37232 USA. RP Gochuico, BR (reprint author), 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM gochuicb@mail.nih.gov FU Intramural Research Programs of the National Human Genome Research Institute, the Clinical Center; National Institute of Biomedical Imaging and Bioengineering; National Eye Institute; Office of the Director, National Institutes of Health; NCATS; National Heart, Lung, and Blood Institute; [HL119503]; [HL127672] FX We thank our patients who participate in our research program. This study was supported in part by the Intramural Research Programs of the National Human Genome Research Institute, the Clinical Center, the National Institute of Biomedical Imaging and Bioengineering, the National Eye Institute, and the Office of the Director, National Institutes of Health; HL119503 (LRY); and HL127672 (LRY). The Rare Lung Diseases Consortium (U54 HL127672) is part of Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences. This consortium is funded through collaboration between NCATS and the National Heart, Lung, and Blood Institute. NR 15 TC 0 Z9 0 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2016 VL 119 IS 3 BP 284 EP 287 DI 10.1016/j.ymgme.2016.08.009 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EA9TH UT WOS:000386987100011 PM 27641950 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI PROTEIN DYNAMICS Conformational footprints SO NATURE CHEMICAL BIOLOGY LA English DT News Item ID FREE-ENERGY LANDSCAPE; ACTIVATION AB The mechanisms by which proteins evolve new functions can be slow and mysterious. Comprehensive structural analysis of enzyme variants reveal how gradual enrichments of pre-existing populations with the right productive dynamics for new functions can accomplish this aim. C1 [Ma, Buyong; Nussinov, Ruth] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21701 USA. [Ma, Buyong; Nussinov, Ruth] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. RP Nussinov, R (reprint author), Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21701 USA.; Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. EM Ruth.Nussinov@nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X NR 10 TC 0 Z9 0 U1 13 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD NOV PY 2016 VL 12 IS 11 BP 890 EP 891 DI 10.1038/nchembio.2212 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA7GP UT WOS:000386798800002 PM 27755531 ER PT J AU Middlebrooks, CD Banday, AR Matsuda, K Udquim, KI Onabajo, OO Paquin, A Figueroa, JD Zhu, B Koutros, S Kubo, M Shuin, T Freedman, ND Kogevinas, M Malats, N Chanock, SJ Garcia-Closas, M Silverman, DT Rothman, N Prokunina-Olsson, L AF Middlebrooks, Candace D. Banday, A. Rouf Matsuda, Konichi Udquim, Krizia-Ivana Onabajo, Olusegun O. Paquin, Ashley Figueroa, Jonine D. Zhu, Bin Koutros, Stella Kubo, Michiaki Shuin, Taro Freedman, Neal D. Kogevinas, Manolis Malats, Nuria Chanock, Stephen J. Garcia-Closas, Montserrat Silverman, Debra T. Rothman, Nathaniel Prokunina-Olsson, Ludmila TI Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BREAST-CANCER; BLADDER-CANCER; DELETION POLYMORPHISM; DNA-DAMAGE; CYTIDINE DEAMINASES; IN-VITRO; MUTAGENESIS; INTERFERON; HYPERMUTATION AB High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here we explored the contribution of two common germline variants in the APOBEC3 region. SNP rs1014971 was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30-kb deletion that eliminates APOBEC3B and creates an APOBEC3A-APOBEC3B chimera was not important in bladder cancer, whereas it was associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors. In vitro, APOBEC3B expression was predominantly induced by treatment with a DNA-damaging drug in bladder cancer cell lines, and APOBEC3A expression was induced as part of the antiviral interferon-stimulated response in breast cancer cell lines. These findings suggest a tissue-specific role of environmental oncogenic triggers, particularly in individuals with germline APOBEC3 risk variants. C1 [Middlebrooks, Candace D.; Banday, A. Rouf; Udquim, Krizia-Ivana; Onabajo, Olusegun O.; Paquin, Ashley; Prokunina-Olsson, Ludmila] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Matsuda, Konichi] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci, Tokyo, Japan. [Figueroa, Jonine D.] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. [Zhu, Bin; Koutros, Stella; Freedman, Neal D.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Silverman, Debra T.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Kubo, Michiaki] RIKEN, Inst Phys & Chem Res, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. [Shuin, Taro] Kochi Univ, Sch Med, Dept Urol, Kochi, Japan. [Kogevinas, Manolis] Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain. [Kogevinas, Manolis] Hosp del Mar, Res Inst IMIM, Barcelona, Spain. [Kogevinas, Manolis] Ctr Invest Biomed Red CIBER, Epidemiol & Salud Publ CIBERESP, Madrid, Spain. [Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov RI Kogevinas, Manolis/C-3918-2017; OI Malats, Nuria/0000-0003-2538-3784 FU federal funds from the Intramural Research Program (IRP), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health Genes, Environment, and Health Initiative (GEI) [HG-06-033-NCI-01, RO1HL091172-01]; NIH [HHSN268200782096C]; NCI [N02-CP-11015]; Ministry of Education, Culture, Sports, Science and Technology of the Japanese government; [U01HG004438] FX We thank the Breast Cancer Association Consortium (BCAC) for access to summary results for the association between rs1014971 and breast cancer risk. The results presented here are in part based upon data generated by the TCGA Research Network. The study was supported by federal funds from the Intramural Research Program (IRP), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (contract HHSN261200800001E). The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was funded with National Institutes of Health Genes, Environment, and Health Initiative (GEI) grants HG-06-033-NCI-01 and RO1HL091172-01, U01HG004438, and NIH HHSN268200782096C. The Spanish Bladder Cancer Study (SBCS) was funded with intramural contract NCI N02-CP-11015. FIS/Spain 98/1274, FIS/Spain 00/0745, PI061614, and G03/174, Fundacio Marato TV3, Red Tematica Investigation Cooperativa en Cancer (RTICC), Consolider ONCOBIO, EU-FP7-201663; and RO1-CA089715 and CA34627. The Biobank Japan Project was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government. The funders did not have a role in study design, data collection and analysis, writing, or submission of the manuscript. NR 48 TC 3 Z9 3 U1 8 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2016 VL 48 IS 11 BP 1330 EP 1338 DI 10.1038/ng.3670 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA EA3XU UT WOS:000386543400009 PM 27643540 ER PT J AU Gordon, JA AF Gordon, Joshua A. TI On being a circuit psychiatrist SO NATURE NEUROSCIENCE LA English DT Article ID NEURAL CIRCUITS; AMYGDALA; DISORDERS; MEMORY; STIMULATION; ATTENTION; DELIVERY; THERAPY AB At this unique and exciting time for psychiatry, novel therapies for individuals with mental illnesses seem just around the corner. In particular, recent technological advancements in the study of neural circuits provide reasons to be optimistic that the field is headed in the right direction. Nonetheless, maximizing the chances of translating these advancements into real improvements in patient care requires a carefully considered road map. C1 [Gordon, Joshua A.] NIMH, Bethesda, MD 20892 USA. RP Gordon, JA (reprint author), NIMH, Bethesda, MD 20892 USA. EM joshua.gordon@nih.gov NR 24 TC 2 Z9 2 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2016 VL 19 IS 11 BP 1385 EP 1386 PG 2 WC Neurosciences SC Neurosciences & Neurology GA EA3WL UT WOS:000386539900003 PM 27786177 ER PT J AU Breen, G Li, QQ Roth, BL O'Donnell, P Didriksen, M Dolmetsch, R O'Reilly, PF Gaspar, HA Manji, H Huebel, C Kelsoe, JR Malhotra, D Bertolino, A Posthuma, D Sklar, P Kapur, S Sullivan, PF Collier, DA Edenberg, HJ AF Breen, Gerome Li, Qingqin Roth, Bryan L. O'Donnell, Patricio Didriksen, Michael Dolmetsch, Ricardo O'Reilly, Paul F. Gaspar, Helena A. Manji, Husseini Huebel, Christopher Kelsoe, John R. Malhotra, Dheeraj Bertolino, Alessandro Posthuma, Danielle Sklar, Pamela Kapur, Shitij Sullivan, Patrick F. Collier, David A. Edenberg, Howard J. TI Translating genome-wide association findings into new therapeutics for psychiatry SO NATURE NEUROSCIENCE LA English DT Article ID DRUG DISCOVERY; DIABETES RISK; GENETIC RISK; SCHIZOPHRENIA; POPULATION; DISEASE; OPPORTUNITIES; CHOLESTEROL; PREVENTION; PREDICTION AB Genome-wide association studies (GWAS) in psychiatry, once they reach sufficient sample size and power, have been enormously successful. The Psychiatric Genomics Consortium (PGC) aims for mega-analyses with sample sizes that will grow to >1 million individuals in the next 5 years. This should lead to hundreds of new findings for common genetic variants across nine psychiatric disorders studied by the PGC. The new targets discovered by GWAS have the potential to restart largely stalled psychiatric drug development pipelines, and the translation of GWAS findings into the clinic is a key aim of the recently funded phase 3 of the PGC. This is not without considerable technical challenges. These approaches complement the other main aim of GWAS studies, risk prediction approaches for improving detection, differential diagnosis, and clinical trial design. This paper outlines the motivations, technical and analytical issues, and the plans for translating PGC phase 3 findings into new therapeutics. C1 [Breen, Gerome; O'Reilly, Paul F.; Gaspar, Helena A.; Huebel, Christopher; Collier, David A.] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London, England. [Breen, Gerome; Gaspar, Helena A.; Huebel, Christopher; Collier, David A.] South London & Maudsley Hosp, Biomed Res Ctr Mental Hlth, UK Natl Inst Hlth Res NIHR, London, England. [Li, Qingqin; Manji, Husseini] Janssen Res & Dev LLC, Neurosci Therapeut Area, Titusville, NJ USA. [Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA. [Roth, Bryan L.] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC USA. [O'Donnell, Patricio] Pfizer Inc, Neurosci Res Unit, Cambridge, MA USA. [Didriksen, Michael] H Lundbeck NS, Synapt Transmiss, Neurosci Res DK, Valby, Denmark. [Dolmetsch, Ricardo] Novartis Inst BioMed Res, Dept Neurosci, Cambridge, MA USA. [Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Malhotra, Dheeraj] F Hoffmann La Roche, Pharma Res & Early Dev, Neurosci Discovery & Translat Area, Basel, Switzerland. [Bertolino, Alessandro] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Inst Psychiat, Bari, Italy. [Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Clin Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Fnedman Brain Inst, New York, NY 10029 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Kapur, Shitij] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, London, England. [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sullivan, Patrick F.] Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA. [Collier, David A.] Eli Lilly & Co Ltd, Discovery Neurosci Res, Windlesham, Surrey, England. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. RP Breen, G (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London, England.; Breen, G (reprint author), South London & Maudsley Hosp, Biomed Res Ctr Mental Hlth, UK Natl Inst Hlth Res NIHR, London, England. EM gerome.breen@kcl.ac.uk OI Gaspar, Helena/0000-0002-5540-2707 FU Medical Research Council [G0701748]; NIMH NIH HHS [U01 MH109536] NR 45 TC 1 Z9 1 U1 6 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2016 VL 19 IS 11 BP 1392 EP 1396 PG 5 WC Neurosciences SC Neurosciences & Neurology GA EA3WL UT WOS:000386539900006 PM 27786187 ER PT J AU Averbeck, BB Chafee, MV AF Averbeck, Bruno B. Chafee, Matthew V. TI Using model systems to understand errant plasticity mechanisms in psychiatric disorders SO NATURE NEUROSCIENCE LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; CONTEXT-PROCESSING DEFICITS; POST-RETRIEVAL EXTINCTION; FEAR-POTENTIATED STARTLE; BASAL GANGLIA ORIGIN; METHYL-D-ASPARTATE; WORKING-MEMORY; ANIMAL-MODELS; NUCLEUS-ACCUMBENS; ANXIETY DISORDERS AB In vivo model systems are a critical tool for gaining insight into the pathology underlying psychiatric disorders. Although modern functional imaging tools allow study of brain correlates of behavior in clinical groups and genome-wide association studies are beginning to uncover the complex genetic architecture of psychiatric disorders, there is less understanding of pathology at intervening levels of organization. Several psychiatric disorders derive from pathological neural plasticity, and studying the mechanisms that underlie these processes, including reinforcement learning and spike-timing-dependent plasticity, requires the use of animals. It will be particularly important to understand how individual differences in plasticity mechanisms at a cellular level confer resilience on some but lead to disease in others. C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. [Chafee, Matthew V.] Univ Minnesota, Dept Neurosci, Minneapolis, MN USA. [Chafee, Matthew V.] Virginia Med Ctr, Brain Sci Ctr, Minneapolis, MN USA. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov FU intramural research program of the National Institute of Mental Health; NIH [ZIA MH002928-01, 1R01MH107491] FX This work was funded in part by the intramural research program of the National Institute of Mental Health and NIH grants ZIA MH002928-01 (B.B.A.) and 1R01MH107491 (M.V.C.). NR 146 TC 1 Z9 1 U1 13 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2016 VL 19 IS 11 BP 1418 EP 1425 DI 10.1038/nn.4413 PG 8 WC Neurosciences SC Neurosciences & Neurology GA EA3WL UT WOS:000386539900009 PM 27786180 ER PT J AU Fromer, M Roussos, P Sieberts, SK Johnson, JS Kavanagh, DH Perumal, TM Ruderfer, DM Oh, EC Topol, A Shah, HR Klei, LL Kramer, R Pinto, D Gumus, ZH Cicek, AE Dang, KK Browne, A Lu, C Xie, L Readhead, B Stahl, EA Xiao, JQ Parvizi, M Hamamsy, T Fullard, JF Wang, YC Mahajan, MC Derry, JMJ Dudley, JT Hemby, SE Logsdon, BA Talbot, K Raj, T Bennett, DA De Jager, PL Zhu, J Zhang, B Sullivan, PF Chess, A Purcell, SM Shinobu, LA Mangravite, LM Toyoshiba, H Gur, RE Hahn, CG Lewis, DA Haroutunian, V Peters, MA Lipska, BK Buxbaum, JD Schadt, EE Hirai, K Roeder, K Brennand, KJ Katsanis, N Domenici, E Devlin, B Sklar, P AF Fromer, Menachem Roussos, Panos Sieberts, Solveig K. Johnson, Jessica S. Kavanagh, David H. Perumal, Thanneer M. Ruderfer, Douglas M. Oh, Edwin C. Topol, Aaron Shah, Hardik R. Klei, Lambertus L. Kramer, Robin Pinto, Dalila Gumus, Zeynep H. Cicek, A. Ercument Dang, Kristen K. Browne, Andrew Lu, Cong Xie, Lu Readhead, Ben Stahl, Eli A. Xiao, Jianqiu Parvizi, Mahsa Hamamsy, Tymor Fullard, John F. Wang, Ying-Chih Mahajan, Milind C. Derry, Jonathan M. J. Dudley, Joel T. Hemby, Scott E. Logsdon, Benjamin A. Talbot, Konrad Raj, Towfique Bennett, David A. De Jager, Philip L. Zhu, Jun Zhang, Bin Sullivan, Patrick F. Chess, Andrew Purcell, Shaun M. Shinobu, Leslie A. Mangravite, Lara M. Toyoshiba, Hiroyoshi Gur, Raquel E. Hahn, Chang-Gyu Lewis, David A. Haroutunian, Vahram Peters, Mette A. Lipska, Barbara K. Buxbaum, Joseph D. Schadt, Eric E. Hirai, Keisuke Roeder, Kathryn Brennand, Kristen J. Katsanis, Nicholas Domenici, Enrico Devlin, Bernie Sklar, Pamela TI Gene expression elucidates functional impact of polygenic risk for schizophrenia SO NATURE NEUROSCIENCE LA English DT Article ID NEURAL PROGENITOR CELLS; PREFRONTAL CORTEX; TRANSCRIPTOMIC ANALYSIS; ALZHEIMERS-DISEASE; MULTIPLE GENES; HUMAN BRAIN; MUTATIONS; VARIANTS; NETWORKS; METAANALYSIS AB Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource,similar to 20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were <= 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases. C1 [Fromer, Menachem; Roussos, Panos; Johnson, Jessica S.; Kavanagh, David H.; Ruderfer, Douglas M.; Topol, Aaron; Pinto, Dalila; Browne, Andrew; Stahl, Eli A.; Hamamsy, Tymor; Fullard, John F.; Purcell, Shaun M.; Haroutunian, Vahram; Buxbaum, Joseph D.; Brennand, Kristen J.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Fromer, Menachem; Roussos, Panos; Kavanagh, David H.; Ruderfer, Douglas M.; Shah, Hardik R.; Pinto, Dalila; Gumus, Zeynep H.; Browne, Andrew; Readhead, Ben; Stahl, Eli A.; Hamamsy, Tymor; Wang, Ying-Chih; Mahajan, Milind C.; Dudley, Joel T.; Raj, Towfique; Zhu, Jun; Zhang, Bin; Chess, Andrew; Purcell, Shaun M.; Schadt, Eric E.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos; Chess, Andrew; Buxbaum, Joseph D.; Brennand, Kristen J.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] JJ Peters Virginia Med Ctr, Psychiat, Bronx, NY USA. [Sieberts, Solveig K.; Perumal, Thanneer M.; Dang, Kristen K.; Derry, Jonathan M. J.; Logsdon, Benjamin A.; Mangravite, Lara M.; Peters, Mette A.] Sage Bionetworks, Syst Biol, Seattle, WA USA. [Oh, Edwin C.; Parvizi, Mahsa; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC USA. [Oh, Edwin C.] Duke Univ, Dept Neurol, Durham, NC USA. [Klei, Lambertus L.; Xie, Lu; Lewis, David A.; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Kramer, Robin; Lipska, Barbara K.] NIMH, Human Brain Collect Core, NIH, Bethesda, MD 20892 USA. [Pinto, Dalila; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Cicek, A. Ercument] Carnegie Mellon Univ, Sch Comp Sci, Dept Computat Biol, Pittsburgh, PA 15213 USA. [Lu, Cong] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Hemby, Scott E.] High Point Univ, Fred Wilson Sch Pharm, Dept Basic Pharmaceut Sci, High Point, NC USA. [Talbot, Konrad] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Raj, Towfique; Haroutunian, Vahram; Brennand, Kristen J.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Raj, Towfique; De Jager, Philip L.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Chess, Andrew] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Shinobu, Leslie A.; Hirai, Keisuke] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, CNS Drug Discovery Unit, Fujisawa, Kanagawa, Japan. [Toyoshiba, Hiroyoshi] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Integrated Technol Res Labs, Fujisawa, Kanagawa, Japan. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Hahn, Chang-Gyu] Univ Penn, Dept Psychiat, Perelman Sch Med, Neuropsychiat Signaling Program, Philadelphia, PA 19104 USA. [Katsanis, Nicholas] Duke Univ, Dept Cell Biol & Pediat, Durham, NC USA. [Domenici, Enrico] Univ Trento, Ctr Integrat Biol CIBIO, Lab Neurogen Biomarkers, Trento, Italy. [Roeder, Kathryn; Devlin, Bernie] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. RP Sklar, P (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA.; Sklar, P (reprint author), Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.; Sklar, P (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. EM pamela.sklar@mssm.edu RI Brennand, Kristen/J-8704-2012; Lipska, Barbara/E-4569-2017; Fromer, Menachem/G-2116-2012; OI Brennand, Kristen/0000-0003-0993-5956; Fromer, Menachem/0000-0003-3749-4342; Domenici, Enrico/0000-0001-7436-6919 FU Takeda Pharmaceuticals Company Limited; F. Hoffman-La Roche Ltd; VA VISN3 MIRECC; NIMH Intramural program; New York Stem Cell Foundation; Silvio O Conte Center grant [P50MH094268]; NARSAD; Stanley Medical Research Institute; NIMH [R01MH074313, R01AG036836, U01AG046152, R01AG017917, R01AG046170, R01MH109706]; [R01MH093725-02S1]; [P50MH066392]; [R01MH097276]; [R01MH075916]; [P50MH096891]; [P50MH084053-S1]; [R37MH057881]; [R37MH057881S1]; [R01MH085542-S1]; [U01MH096296-S2]; [HHSN271201300031C]; [R01MH101454]; [R01MH109677]; [R01AG050986]; [VA Merit BX002395]; [R01 AG036836] FX We thank the patients and families who donated material for these studies. We thank T. Lehner for his early and inspirational ideas about this project, as well as organizational and intellectual support. We thank X. He for discussions regarding Sherlock, J. Scarpa for help running and interpreting WGCNA, L. Essioux for support in establishing and managing interactions with the Consortium, and A. Bertolino and A. Ghosh for continuous encouragement. Data and results were generated as part of the CommonMind Consortium supported by funding from Takeda Pharmaceuticals Company Limited, F. Hoffman-La Roche Ltd; grants R01MH093725-02S1 (J.D.B.), P50MH066392 (J.D.B.), R01MH097276 (P.S., E.E.S.), R01MH075916 (C.-G.H.), P50MH096891 C.-G.H., REG, P50MH084053-S1 (D.A.L.), R37MH057881 (B.D.), R37MH057881S1 (B.D.), R01MH085542-S1 (P.S.), U01MH096296-S2 (P.S.), HHSN271201300031C (V.H.), VA VISN3 MIRECC (V.H.), P50MH066392 (J.D.B.), NIMH Intramural program (B.K.L.), R01MH101454 (K.J.B.), R01MH109677 (P.R.), R01AG050986 (P.R.), VA Merit BX002395 (P.R.) and R01 AG036836 (P.D.H.); New York Stem Cell Foundation (K.J.B.); the Silvio O Conte Center grant P50MH094268 (N.K.); NARSAD (E.C.O.) and NARSAD Young Investigator (D.M.R., P.R., E.A.S.); the Stanley Medical Research Institute for Funding for Non-Human Primate Research; and NIMH grants R01MH074313 (S.E.H.); R01AG036836, U01AG046152 and R01AG017917 (D.A.B. and P.I.D.J.); R01AG046170 (E.S.S., B.Z., J.Z., and P.R.); and R01MH109706 (E.C.O.). Brain tissues for the study were obtained from the following brain bank collections: the Mount Sinai NIH Brain and Tissue Repository, the University of Pennsylvania Alzheimer's Disease Core Center, the University of Pittsburgh Brain Tissue Donation Program, the NIMH Human Brain Collection Core and Wake Forest University. CMC Leadership: P. Sklar and J.D. Buxbaum (Icahn School of Medicine at Mount Sinai), B. Devlin and D.A. Lewis (University of Pittsburgh), R.E. Gur and C.-G. Hahn (University of Pennsylvania), K. Hirai and H. Toyoshiba (Takeda Pharmaceuticals Company Limited), E. Domenici and L. Essioux (F. Hoffman-La Roche Ltd), L.M. Mangravite and M.A. Peters (Sage Bionetworks), and T. Lehner and B.K. Lipska (NIMH). NR 51 TC 5 Z9 5 U1 10 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2016 VL 19 IS 11 BP 1442 EP 1453 DI 10.1038/nn.4399 PG 12 WC Neurosciences SC Neurosciences & Neurology GA EA3WL UT WOS:000386539900014 PM 27668389 ER PT J AU Pommier, Y Sung, YL Huang, SYN Nitiss, JL AF Pommier, Yves Sung, Yilun Huang, Shar-yin N. Nitiss, John L. TI Roles of eukaryotic topoisomerases in transcription, replication and genomic stability SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID TYROSYL-DNA-PHOSPHODIESTERASE; DOUBLE-STRAND BREAKS; RNA-POLYMERASE-II; FAITHFUL CHROMOSOME SEGREGATION; DIOL EPOXIDE ADDUCTS; R-LOOP FORMATION; INTERTWINED CATENATED DIMERS; THERAPY-RELATED LEUKEMIA; CELL-CYCLE PROGRESSION; FINE ANAPHASE BRIDGES AB Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2 alpha, TOP2 beta,TOP3 alpha and TOP3 beta), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF-ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer. C1 [Pommier, Yves; Huang, Shar-yin N.] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Pommier, Yves; Huang, Shar-yin N.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sung, Yilun; Nitiss, John L.] Univ Illinois, Coll Pharm, Rockford, IL 61107 USA. RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.; Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Nitiss, JL (reprint author), Univ Illinois, Coll Pharm, Rockford, IL 61107 USA. EM pommier@nih.gov; jlnitiss@uic.edu FU Center for Cancer Research; NCI Intramural Program [Z01 BC006161]; NCI [CA52814, CA187651] FX The authors are grateful to numerous colleagues who provided helpful discussion on the diverse topics of this Review, especially D. Levens (US National Cancer Institute (NCI)), J. Berger (Johns Hopkins University, USA), N. Osheroff (Vanderbilt University, USA), P. McKinnon (St. Jude Children's Research Hospital, USA) and other members of the Pommier and Nitiss laboratories. The authors apologize to colleagues whose work could not be cited owing to space limitations. The authors' studies are supported by the Center for Cancer Research, the NCI Intramural Program (Z01 BC006161) and NCI grants CA52814 and CA187651 (to J.L.N.). NR 242 TC 6 Z9 6 U1 19 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2016 VL 17 IS 11 BP 703 EP 721 DI 10.1038/nrm.2016.111 PG 19 WC Cell Biology SC Cell Biology GA EA9TE UT WOS:000386986800009 PM 27649880 ER PT J AU Branzoli, F Ercan, E Valabregue, R Wood, ET Buijs, M Webb, A Ronen, I AF Branzoli, Francesca Ercan, Ece Valabregue, Romain Wood, Emily T. Buijs, Mathijs Webb, Andrew Ronen, Itamar TI Differentiating between axonal damage and demyelination in healthy aging by combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the human corpus callosum at 7 T SO NEUROBIOLOGY OF AGING LA English DT Article DE Diffusion-weighted MRS; Intracellular metabolites; DTI; Healthy aging; White matter ID MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; WHITE-MATTER; HUMAN BRAIN; WATER DIFFUSION; SPINAL-CORD; MULTIPLE-SCLEROSIS; CEREBRAL-ISCHEMIA; NMR-SPECTROSCOPY; NERVOUS-SYSTEM AB Diffusion-tensor imaging and single voxel diffusion-weighted magnetic resonance spectroscopy were used at 7T to explore in vivo age-related microstructural changes in the corpus callosum. Sixteen healthy elderly (age range 60-71 years) and 13 healthy younger controls (age range 23-32 years) were included in the study. In healthy elderly, we found lower water fractional anisotropy and higher water mean diffusivity and radial diffusivity in the corpus callosum, indicating the onset of demyelination processes with healthy aging. These changes were not associated with a concomitant significant difference in the cytosolic diffusivity of the intra-axonal metabolite N-acetylaspartate (p = 0.12), the latter representing a pure measure of intra-axonal integrity. It was concluded that the possible intra-axonal changes associated with normal aging processes are below the detection level of diffusion-weighted magnetic resonance spectroscopy in our experiment (e.g., smaller than 10%) in the age range investigated. Lower axial diffusivity of total creatine was observed in the elderly group (p = 0.058), possibly linked to a dysfunction in the energy metabolism associated with a deficit in myelin synthesis. (C) 2016 Elsevier Inc. All rights reserved. C1 [Branzoli, Francesca; Valabregue, Romain] Inst Cerveau & Moelle Epiniere ICM, Ctr NeuroImagerie Rech CENIR, Paris, France. [Branzoli, Francesca; Valabregue, Romain] UPMC Paris 06, Sorbonne Univ, CNRS UMR 7225, Inserm UMR S 1127, Paris, France. [Ercan, Ece; Buijs, Mathijs; Webb, Andrew; Ronen, Itamar] Leiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, Leiden, Netherlands. [Wood, Emily T.] NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Branzoli, F (reprint author), CENIR Ctr Neuroimagerie Rech, Batiment ICM,47 Blvd Hop, F-75013 Paris, France. EM f.branzoli-ihu@icm-institute.org OI Ercan, Ece/0000-0002-8187-2075 FU IHU; Institut des neurosciences translationnelle [ANR-10-IAIHU-06]; Infrastructure d'avenir en Biologie Sante [ANR-11-INBS-0006] FX The authors thank the support of the IHU and the following grants: Institut des neurosciences translationnelle - ANR-10-IAIHU-06, and Infrastructure d'avenir en Biologie Sante - ANR-11-INBS-0006. NR 56 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2016 VL 47 BP 210 EP 217 DI 10.1016/j.neurobiolaging.2016.07.022 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA EA9PO UT WOS:000386976500022 PM 27616673 ER PT J AU Gang, Q Bettencourt, C Machado, PM Brady, S Holton, JL Pittman, AM Hughes, D Healy, E Parton, M Hilton-Jones, D Shieh, PB Needham, M Liang, C Zanoteli, E de Camargo, LV De Paepe, B De Bleecker, J Shaibani, A Ripolone, M Violano, R Moggio, M Barohn, RJ Dimachkie, MM Mora, M Mantegazza, R Zanotti, S Singleton, AB Hanna, MG Houlden, H AF Gang, Qiang Bettencourt, Conceicao Machado, Pedro M. Brady, Stefen Holton, Janice L. Pittman, Alan M. Hughes, Deborah Healy, Estelle Parton, Matthew Hilton-Jones, David Shieh, Perry B. Needham, Merrilee Liang, Christina Zanoteli, Edmar de Camargo, Leonardo Valente De Paepe, Boel De Bleecker, Jan Shaibani, Aziz Ripolone, Michela Violano, Raffaella Moggio, Maurizio Barohn, Richard J. Dimachkie, Mazen M. Mora, Marina Mantegazza, Renato Zanotti, Simona Singleton, Andrew B. Hanna, Michael G. Houlden, Henry CA Muscle Study Group Int IBM Genetics Consortium TI Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis SO NEUROBIOLOGY OF AGING LA English DT Article DE Sporadic inclusion body myositis; sIBM; SQSTM1; VCP; Genetic risk factor ID AMYOTROPHIC-LATERAL-SCLEROSIS; VALOSIN-CONTAINING PROTEIN; FRONTOTEMPORAL DEMENTIA; PAGET-DISEASE; MUTATION; MYOPATHY; PATHOGENESIS; BONE; EXPRESSION; ALS AB Genetic factors have been suggested to be involved in the pathogenesis of sporadic inclusion body myositis (sIBM). Sequestosome 1 (SQSTM1) and valosin-containing protein (VCP) are 2 key genes associated with several neurodegenerative disorders but have yet to be thoroughly investigated in sIBM. A candidate gene analysis was conducted using whole-exome sequencing data from 181 sIBM patients, and whole-transcriptome expression analysis was performed in patients with genetic variants of interest. We identified 6 rare missense variants in the SQSTM1 and VCP in 7 sIBM patients (4.0%). Two variants, the SQSTM1 p.G194R and the VCP p.R159C, were significantly overrepresented in this sIBM cohort compared with controls. Five of these variants had been previously reported in patients with degenerative diseases. The messenger RNA levels of major histocompatibility complex genes were upregulated, this elevation being more pronounced in SQSTM1 patient group. We report for the first time potentially pathogenic SQSTM1 variants and expand the spectrum of VCP variants in sIBM. These data suggest that defects in neurodegenerative pathways may confer genetic susceptibility to sIBM and reinforce the mechanistic overlap in these neurodegenerative disorders. (C) 2016 The Author(s). Published by Elsevier Inc. C1 [Gang, Qiang; Bettencourt, Conceicao; Machado, Pedro M.; Pittman, Alan M.; Hughes, Deborah; Hanna, Michael G.; Houlden, Henry] UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England. [Gang, Qiang; Machado, Pedro M.; Brady, Stefen; Holton, Janice L.; Healy, Estelle; Parton, Matthew; Hanna, Michael G.; Houlden, Henry] UCL, Inst Neurol, MRC Ctr Neuromuscular Dis, Queen Sq, London, England. [Bettencourt, Conceicao] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, Queen Sq, London, England. [Machado, Pedro M.] UCL, Div Med, Ctr Rheumatol, London, England. [Brady, Stefen; Hilton-Jones, David] John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford, England. [Pittman, Alan M.] UCL Inst Neurol, Reta Lila Weston Labs, London, England. [Shieh, Perry B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Needham, Merrilee] Univ Western Australia, WANRI, Perth, WA, Australia. [Needham, Merrilee] Murdoch Univ, Fiona Stanley Hosp, Perth, WA, Australia. [Liang, Christina] Royal North Shore Hosp, Dept Neurol, St Leonards, NSW, Australia. [Zanoteli, Edmar; de Camargo, Leonardo Valente] Univ Sao Paulo FMUSP, Sch Med, Dept Neurol, Sao Paulo, Brazil. [De Paepe, Boel; De Bleecker, Jan] Ghent Univ Hosp, Dept Neurol, Ghent, Belgium. [De Paepe, Boel; De Bleecker, Jan] Ghent Univ Hosp, Neuromuscular Reference Ctr, Ghent, Belgium. [Shaibani, Aziz] Nerve & Muscle Ctr Texas, Houston, TX USA. [Ripolone, Michela; Violano, Raffaella; Moggio, Maurizio] Univ Milan, Dino Ferrari Ctr, IRCCS Fdn Ca Granda Osped Maggiore Policlin, Neuromuscular Unit, Milan, Italy. [Barohn, Richard J.; Dimachkie, Mazen M.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Mora, Marina; Mantegazza, Renato; Zanotti, Simona] Fdn IRCCS Ist Neurol C Besta, Neuromuscular Dis & Neuroimmunol Unit, Milan, Italy. [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Houlden, Henry] UCL, Inst Neurol, Neurogenet Lab, Queen Sq, London, England. RP Hanna, MG; Houlden, H (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, MRC Ctr Neuromuscular Dis, Queen Sq, London WC1N 3BG, England. EM m.hanna@ucl.ac.uk; h.houlden@ucl.ac.uk RI Houlden, Henry/C-1532-2008; De Paepe, Boel/B-7548-2013; OI Houlden, Henry/0000-0002-2866-7777; De Paepe, Boel/0000-0001-9403-4401; Lilleker, James/0000-0002-9230-4137; Chinoy, Hector/0000-0001-6492-1288; Mora, Marina/0000-0002-5765-2320 FU University College London (UCL); Chinese Scholarship Council; Wellcome Trust; National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration; NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC); MRC Centre [MR/K000608/01]; MRC grant [MR/J004758/1]; Telethon Italy [GTB12001]; EuroBioBank network [GTB12001] FX Qiang Gang is supported by a University College London (UCL) Impact Studentship and a scholarship from the Chinese Scholarship Council. Conceicao Bettencourt is supported by the Wellcome Trust. Pedro M. Machado is supported by the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration and by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC). Michael G. Hanna is supported by an MRC Centre grant 2013-2018 (MR/K000608/01). The International IBM Consortium Genetic Study is also supported by an MRC grant (MR/J004758/1). We thank all the study collaborators from UK, USA, Australia, Europe, and Brazil and especially thank all the patients and their families for participating in our study. This publication was supported by researchers at the UCL/UCLH NIHR BRC. We wish to acknowledge the National Institute of Health, USA, for providing the neuropathologically healthy control exomes. We also wish to acknowledge the Queen Square Brain Bank in London and the MRC Sudden Death Brain and Tissue Bank in Edinburgh, UK, which provided us the control tissues. We also wish to acknowledge colleagues from the UCL Department of Pathology and Boel De Paepe for providing the muscle biopsy slides. We also wish to acknowledge "The BioBank of Skeletal Muscle, Nerve Tissue, DNA and Cell Lines" and "The Biobank Cells, Tissue and DNA from Patients with Neuromuscular Diseases" that provided us with case specimens. Both are members of the Telethon Network of Genetic Biobanks (grant number GTB12001), funded by Telethon Italy and the EuroBioBank network. We also acknowledge all the participants of the International IBM Genetics Consortium and the Muscle Study Group, who have endorsed this project-Michael G. Hanna, Henry Houlden, Pedro M. Machado, Qiang Gang, Conceicao Bettencourt, Estelle Healy, Matthew Parton, and Janice L. Holton: Department of Molecular Neuroscience and MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, Queen Square, London, UK; Stefen Brady and David Hilton-Jones: Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Perry B. Shieh: Neuromuscular Division, Department of Neurology, UCLA Medical Centre, USA; Edmar Zanoteli and Leonardo Valente de Camargo: Department of Neurology, Medical School of the University of Sao Paulo (FMUSP), Sao Paulo, Brazil; Boel De Paepe and Jan De Bleecker: Ghent University Hospital, Department of Neurology and Neuromuscular Reference Centre, Ghent, Belgium; Aziz Shaibani: Nerve and Muscle Centre of Texas, Houston, TX, USA; Michela Ripolone, Raffaella Violano, and Maurizio Moggio: Neuromuscular Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, University of Milan, Milan, Italy; Richard J. Barohn, Mazen M. Dimachkie, April L. McVey, Mamatha Pasnoor, Melanie Glenn, Omar Jawdat, Jeffrey Statland, and Gabrielle Rico: The University of Kansas Medical Centre, Kansas City, USA; Marina Mora, Renato Mantegazza, and Simona Zanotti: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Isitituto Neurologico C. Besta, Milano, Italy; Merrilee Needham and Frank Mastaglia: Western Australian Neurosciences Research Institute, University of Western Australia and Murdoch University, Fiona Stanley Hospital, Perth, Australia; Christina Liang: Royal North Shore Hospital, New South Wales, Australia; Marinos C.; Dalakas and Angie Biba: Neuroimmunology Unit, Department of Pathophysiology, National University of Athens Medical School, Athens, Greece; Hector Chinoy and James B. Lilleker: Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; Janine Lamb and Hazel Platt: Centre for Integrated Genomic Medical Research, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; Robert G. Cooper: MRC/ARUK Institute for Ageing and Chronic Disease, University of Liverpool, Liverpool, UK; James A. L. Miller: Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, UK; Mark Roberts: Salford Royal NHS Foundation Trust, UK; Elizabeth Househam, David Hilton, and Aditya Shivane: Derriford Hospital, Plymouth, UK; Amy Bartlett and John T. Kissel: The Ohio State University Wexner Medical Center, USA; Heidi Runk and Matthew Wicklund: Penn State Milton S. Hershey Medical Center, USA; and David S. Saperstein and Lynette R. McKinney: Phoenix Neurological Associates, USA. NR 45 TC 2 Z9 2 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2016 VL 47 AR 218.e1 DI 10.1016/j.neurobiolaging.2016.07.024 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA EA9PO UT WOS:000386976500023 PM 27594680 ER PT J AU Shih, RY Smirniotopoulos, JG AF Shih, Robert Y. Smirniotopoulos, James G. TI Posterior Foss Tumors on Adult Patients SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Adult posterior fossa tumors; Cerebellum; Brainstem; Fourth ventricle ID LHERMITTE-DUCLOS-DISEASE; BRAIN-STEM GLIOMAS; RADIOLOGIC-PATHOLOGICAL CORRELATION; CENTRAL-NERVOUS-SYSTEM; HIPPEL-LINDAU-DISEASE; OF-THE-LITERATURE; JUVENILE PILOCYTIC ASTROCYTOMAS; FORMING GLIONEURONAL TUMORS; CHOROID-PLEXUS PAPILLOMA; CEREBELLAR LIPONEUROCYTOMA AB In adults, the most common expansile "mass" lesion in the posterior fossa is a subacute stroke, whereas the most common neoplastic lesion in the posterior fossa is cerebellar metastasis (intra-axial) or vestibular schwannoma (extra-axial). Those diseases fall outside the scope of this article, which focuses on primary intra-axial tumors of the posterior fossa in adults. This category of tumors is uncommon and more frequently encountered in children. This article reviews tumors of the cerebellum, brainstem, and fourth ventricle that are seen in adult patients, following categories from the 2007 World Health Organization classification of central nervous system tumors. C1 [Shih, Robert Y.] Amer Inst Radiol Pathol, 1100 Wayne Ave,Suite 1020, Silver Spring, MD 20910 USA. [Smirniotopoulos, James G.] Natl Lib Med, MedPix, 8600 Rockville Pike, Bethesda, MD 20894 USA. [Smirniotopoulos, James G.] George Washington Univ, Dept Radiol, 2121 Eye St Northwest, Washington, DC 20052 USA. RP Shih, RY (reprint author), Amer Inst Radiol Pathol, 1100 Wayne Ave,Suite 1020, Silver Spring, MD 20910 USA. EM ryshih@gmail.com NR 83 TC 0 Z9 0 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2016 VL 26 IS 4 BP 493 EP + DI 10.1016/j.nic.2016.06.003 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EA3ZB UT WOS:000386546700003 PM 27712791 ER PT J AU Drake-Perez, M Smirniotopoulos, JG AF Drake-Perez, Marta Smirniotopoulos, James G. TI Extraparenchymal Lesions in Adults SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Extra-axial; Tumors; Neoplasm; Cyst; Imaging; Meningioma; Hemangiopericytoma; Pituitary ID RADIOLOGIC-PATHOLOGICAL CORRELATION; OF-THE-LITERATURE; GERM-CELL TUMORS; MENINGIOMA; PITUITARY; SARCOIDOSIS; CYSTS; CRANIOPHARYNGIOMA; MANIFESTATIONS; SPECTROSCOPY AB This article reviews the most frequent extra-axial tumors of the central nervous system, from the most common meningioma to some uncommon conditions, like Rosai-Dorfman disease, focusing on imaging techniques, pearls, and pitfalls as well as a more practical approach. C1 [Drake-Perez, Marta] Marques de Valdecilla Univ Hosp DIVAL, Dept Radiol, Avda Valdecilla 25, Santander 39008, Cantabria, Spain. [Smirniotopoulos, James G.] Natl Lib Med, MedPix, 8600 Rockville Pike, Bethesda, MD 20894 USA. [Smirniotopoulos, James G.] George Washington Univ, Dept Radiol, 2121 Eye St Northwest, Washington, DC 20052 USA. RP Drake-Perez, M (reprint author), Marques de Valdecilla Univ Hosp DIVAL, Dept Radiol, Avda Valdecilla 25, Santander 39008, Cantabria, Spain. EM drake.marta@gmail.com NR 39 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2016 VL 26 IS 4 BP 621 EP + DI 10.1016/j.nic.2016.06.009 PG 27 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EA3ZB UT WOS:000386546700009 PM 27712797 ER PT J AU Guyer, AE Silk, JS Nelson, EE AF Guyer, Amanda E. Silk, Jennifer S. Nelson, Eric E. TI The neurobiology of the emotional adolescent: From the inside out SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article DE Affect; Brain; fMRI; Puberty; Physiology; Individual differences; Social context ID ANTICIPATED PEER EVALUATION; PREFRONTAL CORTEX; RISK-TAKING; NEURAL RESPONSES; DECISION-MAKING; PUBERTAL DEVELOPMENT; BRAIN-DEVELOPMENT; SOCIAL ANXIETY; UNDERSTANDING ADOLESCENCE; NEUROSCIENCE PERSPECTIVE AB Adolescents are commonly portrayed as highly emotional, with their behaviors often hijacked by their emotions. Research on the neural substrates of adolescent affective behavior is beginning to paint a more nuanced picture of how neurodevelopmental changes in brain function influence affective behavior, and how these influences are modulated by external factors in the environment. Recent neurodevelopmental models suggest that the brain is designed to promote emotion regulation, learning, and affiliation across development, and that affective behavior reciprocally interacts with age-specific social demands and different social contexts. In this review, we discuss current findings on neurobiological mechanisms of adolescents' affective behavior and highlight individual differences in and social-contextual influences on adolescents' emotionality. Neurobiological mechanisms of affective processes related to anxiety and depression are also discussed as examples. As the field progresses, it will be critical to test new hypotheses generated from the foundational empirical and conceptual work and to focus on identifying more precisely how and when neural networks change in ways that promote or thwart adaptive affective behavior during adolescence. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Guyer, Amanda E.] Univ Calif Davis, Dept Human Ecol, Davis, CA 95618 USA. [Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95618 USA. [Silk, Jennifer S.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Nelson, Eric E.] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA. RP Guyer, AE (reprint author), Univ Calif Davis, Ctr Mind & Brain, Dept Human Ecol, 267 Cousteau Pl, Davis, CA 95618 USA. EM aeguyer@ucdavis.edu FU National Institutes of Health [R01MH098370, R01MH093605, R01MH103241, R01MH091327]; National Institute of Mental Health, Intramural Research Program FX Financial support for the writing of the article was provided by the National Institutes of Health awards R01MH098370 (A. E. G.), R01MH093605 (A. E. G.), R01MH103241 (J. S.), R01MH091327 (J. S.), and the National Institute of Mental Health, Intramural Research Program (E. E. N.). These sponsors played no role in the preparation or publication of this report. NR 156 TC 1 Z9 1 U1 26 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD NOV PY 2016 VL 70 SI SI BP 74 EP 85 DI 10.1016/j.neubiorev.2016.07.037 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA EA9RH UT WOS:000386981900007 PM 27506384 ER PT J AU Ernst, M AF Ernst, Monique TI Commentary on the special issue on the adolescent brain A tribute to the adolescent brain SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Editorial Material DE Intrinsic functional connectivity; Resting state networks; Social processes; Plasticity; Organizational and sensitive window; Puberty; Neural systems model; Dual attention system; Learning ID FUNCTIONAL CONNECTIVITY; ATTENTION C1 [Ernst, Monique] NIMH, NIH, DHHS, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Neurodev Reward Syst, SNFA, NIH,DHHS, 15 K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov NR 17 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD NOV PY 2016 VL 70 SI SI BP 334 EP 338 DI 10.1016/j.neubiorev.2016.06.017 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA EA9RH UT WOS:000386981900029 PM 27328225 ER PT J AU Lan, Q Vermeulen, R Dai, Y Ren, D Hu, W Duan, H Niu, Y Xu, J Fu, W Meliefste, K Zhou, B Yang, J Ye, M Jia, X Meng, T Bin, P Kim, C Bassig, BA Hosgood, HD Silverman, D Zheng, Y Rothman, N AF Lan, Q. Vermeulen, R. Dai, Y. Ren, D. Hu, W. Duan, H. Niu, Y. Xu, J. Fu, W. Meliefste, K. Zhou, B. Yang, J. Ye, M. Jia, X. Meng, T. Bin, P. Kim, C. Bassig, B. A. Hosgood, H. D., III Silverman, D. Zheng, Y. Rothman, N. TI Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets (vol 72, pg 354, 2015) SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Correction C1 [Lan, Q.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E138, Rockville, MD 20850 USA. [Zheng, Y.] China CDC, Natl Inst Occupat Hlth & Poison Control, 29 Nanwei Rd, Beijing 100050, Peoples R China. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E138, Rockville, MD 20850 USA.; Zheng, Y (reprint author), China CDC, Natl Inst Occupat Hlth & Poison Control, 29 Nanwei Rd, Beijing 100050, Peoples R China. EM qingl@mail.nih.gov; zhengyx@chinacdc.cn RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 1 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 2016 VL 73 IS 11 BP 804 EP 804 DI 10.1136/oemed-2014-102556corr1 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA2ZA UT WOS:000386465000016 ER PT J AU Uc, A Andersen, DK Bellin, MD Bruce, JI Drewes, AM Engelhardt, JF Forsmark, CE Lerch, MM Lowe, ME Neuschwander-Tetri, BA O'Keefe, SJ Palermo, TM Pasricha, P Saluja, AK Singh, VK Szigethy, EM Whitcomb, DC Yadav, D Conwell, DL AF Uc, Aliye Andersen, Dana K. Bellin, Melena D. Bruce, Jason I. Drewes, Asbjorn M. Engelhardt, John F. Forsmark, Christopher E. Lerch, Markus M. Lowe, Mark E. Neuschwander-Tetri, Brent A. O'Keefe, Stephen J. Palermo, Tonya M. Pasricha, Pankaj Saluja, Ashok K. Singh, Vikesh K. Szigethy, Eva M. Whitcomb, David C. Yadav, Dhiraj Conwell, Darwin L. TI Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop SO PANCREAS LA English DT Article ID ENZYME REPLACEMENT THERAPY; CATIONIC TRYPSINOGEN GENE; BETA-CELL DYSFUNCTION; HEREDITARY PANCREATITIS; CYSTIC-FIBROSIS; CHRONIC PAIN; EXOCRINE INSUFFICIENCY; TOTAL PANCREATECTOMY; MELLITUS SECONDARY; HIGH PREVALENCE AB A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology, (2) exocrine complications, (3) endocrine complications, and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to design better tools to diagnose CP and its sequelae early and reliably, identify predisposing risk factors for disease progression, develop standardized protocols to distinguish type 3c diabetes mellitus from other types of diabetes, and design effective therapeutic strategies through novel cell culture technologies, animal models mimicking human disease, and pain management tools. Gene therapy and cystic fibrosis conductance regulator potentiators as possible treatments of CP were discussed. Importantly, the need for CP end points and intermediate targets for future drug trials was emphasized. C1 [Uc, Aliye] Univ Iowa, Stead Family Dept Pediat, Div Gastroenterol, Hepatol,Nutr, Iowa City, IA USA. [Andersen, Dana K.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Bellin, Melena D.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Bellin, Melena D.] Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN 55455 USA. [Bruce, Jason I.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Drewes, Asbjorn M.] Aalborg Univ Hosp, Dept Gastroenterol & Hepatol, Aalborg, Denmark. [Engelhardt, John F.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA USA. [Forsmark, Christopher E.] Univ Florida, Dept Med, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA. [Lerch, Markus M.] Univ Med Greifswald, Dept Med, Greifswald, Germany. [Lowe, Mark E.] Childrens Hosp Pittsburgh, Dept Pediat, Div Gastroenterol, Hepatol,Nutr, Pittsburgh, PA 15213 USA. [Neuschwander-Tetri, Brent A.] St Louis Univ, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. [O'Keefe, Stephen J.; Szigethy, Eva M.; Whitcomb, David C.; Yadav, Dhiraj] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Palermo, Tonya M.] Univ Washington, Ctr Child Hlth Behav & Dev, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Pasricha, Pankaj; Singh, Vikesh K.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21205 USA. [Saluja, Ashok K.] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA. [Conwell, Darwin L.] Ohio State Univ, Wexner Med Ctr, Div Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA. RP Conwell, DL (reprint author), Ohio State Univ, Wexner Med Ctr, Div Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA.; Uc, A (reprint author), Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, BT1120-C,200 Hawkins Dr, Iowa City, IA 52242 USA. EM aliye-uc@uiowa.edu; darwin.conwell@osumc.edu FU National Institutes of Health [DK108334, DK097820, DK096327, DK096518]; Dompe Pharmaceuticals; Leverhulme Trust; Wellcome Trust Institutional Strategic Support Fund; Pancreatic Cancer Research Fund; Medical Research Council; Hyperion Inc; Minneamrita Therapeutics; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research; European Union FX A.U. (DK108334, DK097820, DK096327, and DK096518), D.K.A., J.F.E., C.E.F., M.E.L., T.M.P., M.D.B., P.P., A.K.S., D.Y., D.L.C., and V.K.S. reported research funding from the National Institutes of Health; received research support from Dompe Pharmaceuticals (M.D.B.), Leverhulme Trust (J.I.B.), Wellcome Trust Institutional Strategic Support Fund (J.I.B.), Pancreatic Cancer Research Fund (J.I.B.), Medical Research Council (J.I.B.), Hyperion Inc (M.E.L.), Minneamrita Therapeutics (A.K.S.), Deutsche Forschungsgemeinschaft (M. M. L.), German Federal Ministry of Education and Research (M. M. L.), European Union (M. M. L.). Consultant for Abbvie Inc (M.D.B., D.C.W., E.M.S., M.E.L., V.K.S., and M.M.L.), Ariel Precision Medicine (M.D.B. and D.C.W.), National Pancreas Foundation (M.E.L.), Regeneron (D.C.W.), Novo Nordisk (V.K.S.), Calcimedica (V.K.S.), Nordmark, Mylan, Abvie, Astra-Zeneca, and Ionis (M.M.L.); received Royalties from EMD Millipore (M.E.L.), Up-to-Date Inc (M.E.L. and D.Y.); and holds equity in Ariel Precision Medicine (D.C.W.), Minneamrita Therapeutics (A.K.S.), and Matanomics Healths (M.M.L.). NR 108 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2016 VL 45 IS 10 BP 1365 EP 1375 DI 10.1097/MPA.0000000000000713 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA9QG UT WOS:000386978400003 PM 27748719 ER PT J AU Lujan-Barroso, L Zhang, W Olson, SH Gao, YT Yu, H Baghurst, PA Bracci, PM Bueno-de-Mesquita, HB Foretova, L Gallinger, S Holcatova, I Janout, V Ji, BT Kurtz, RC La Vecchia, C Lagiou, P Li, DH Miller, AB Serraino, D Zatonski, W Risch, HA Duell, EJ AF Lujan-Barroso, Leila Zhang, Wei Olson, Sara H. Gao, Yu-Tang Yu, Herbert Baghurst, Peter A. Bracci, Paige M. Bas Bueno-de-Mesquita, H. Foretova, Lenka Gallinger, Steven Holcatova, Ivana Janout, Vladimir Ji, Bu-Tian Kurtz, Robert C. La Vecchia, Carlo Lagiou, Pagona Li, Donghui Miller, Anthony B. Serraino, Diego Zatonski, Witold Risch, Harvey A. Duell, Eric J. TI Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4) SO PANCREAS LA English DT Article DE pancreatic cancer; menstrual and reproductive factors; exogenous hormones; hysterectomy; consortium ID RANDOMIZED CONTROLLED-TRIAL; FRANCISCO-BAY AREA; POSTMENOPAUSAL WOMEN; LIFE-STYLE; CARCINOMA; HEALTH; HYSTERECTOMY; METAANALYSIS; ESTROGEN; COHORT AB Objectives We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). Methods Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. Results An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). Conclusions Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary. C1 [Lujan-Barroso, Leila; Duell, Eric J.] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona, Spain. [Zhang, Wei; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Zhang, Wei; Gao, Yu-Tang] Jiao Tong Univ, Shanghai, Peoples R China. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Yu, Herbert] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Baghurst, Peter A.] Womens & Childrens Hosp, Publ Hlth, Adelaide, SA, Australia. [Bracci, Paige M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bas Bueno-de-Mesquita, H.] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bas Bueno-de-Mesquita, H.] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Bas Bueno-de-Mesquita, H.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Bas Bueno-de-Mesquita, H.] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. [Foretova, Lenka] Inst & MF MU, Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Gallinger, Steven] Univ Toronto, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Janout, Vladimir] Palacky Univ, Dept Prevent Med, Fac Med, Olomouc, Czech Republic. [Ji, Bu-Tian] NCI, Bethesda, MD 20892 USA. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Lagiou, Pagona] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece. [Lagiou, Pagona] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Li, Donghui] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Serraino, Diego] IRCCS, Natl Canc Inst, CRO Aviano, Unit Epidemiol & Biostat, Aviano, Italy. [Zatonski, Witold] Ctr Canc, Warsaw, Poland. [Zatonski, Witold] Inst Oncol, Warsaw, Poland. [Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. RP Duell, EJ (reprint author), Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Unit Nutr & Canc, Avda Gran Via 199-203, Barcelona 08908, Spain. EM eduell@iconcologia.net RI Gallinger, Steven/E-4575-2013 FU Red Tematica de Investigacion Cooperativa en Cancer (RTICC) [Rd06/0020/0091, Rd12/0036/0018]; Generalitat de Catalunya; Grant Agency of Ministry of Health of the Czech Republic [IGA MZ CR 8090-3, 9422-3]; MH CZ - DRO (MMCI) [00209805]; RECAMO [CZ. 1.05/2.1.00/03.0101]; Italian Association for Cancer Research (AIRC) [10068]; Italian Foundation for Cancer Research (FIRC); NIH [R01 CA098380]; Prevention, Control, and Population Research Goldstein Award; Society of MSKCC; Geoffrey Beene Cancer Research Fund; National Cancer Institute [CA059706, CA108370, CA109767, CA089726, CA098889]; Rombauer Pancreatic Cancer Research Fund; California Department of Public Health, the National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136]; Cancer Research Society; U.S. National Institute of Health [5R01 CA114421]; Science and Technology Commission of Shanghai Municipality; Shanghai Cancer Institute [SB10-06] FX This work was supported by the Red Tematica de Investigacion Cooperativa en Cancer (RTICC) [Rd06/0020/0091 and Rd12/0036/0018] and by the Generalitat de Catalunya. The Central Europe study was supported by the Grant Agency of Ministry of Health of the Czech Republic (IGA MZ CR 8090-3 and 9422-3). The center of Brno, Czech Republic-within the Central Europe study-was supported by MH CZ - DRO (MMCI, 00209805) and RECAMO CZ. 1.05/2.1.00/03.0101. The Italy and Milan studies were supported by the Italian Association for Cancer Research (AIRC grant 10068), and the Italian Foundation for Cancer Research (FIRC). The MD Anderson Cancer Center study was supported by the NIH Research Project Grant Program (R01 CA098380). The Pancreatic Cancer Family Registry at the Memorial Sloan Kettering Cancer Center (MSKCC) was supported by the Prevention, Control, and Population Research Goldstein Award; the Society of MSKCC; and the Geoffrey Beene Cancer Research Fund. The University of California, San Francisco (UCSF) study work was supported in part by National Cancer Institute grants CA059706, CA108370, CA109767, CA089726, CA098889, and by the Rombauer Pancreatic Cancer Research Fund. Cancer incidence data collection in the UCSF study was supported by the California Department of Public Health, the National Cancer Institute's Surveillance, Epidemiology and End Results Program contract N01-PC-35136 awarded to the Northern California Cancer Center. The Montreal investigation in the Surveillance of Environmental Aspects Related to Cancer in Humans study was supported by the Cancer Research Society, the Toronto contribution was supported by the National Cancer Institute of Canada, and the Netherlands contribution was supported by the Dutch Ministry of Public Health, Welfare and Sports (formerly Welfare, Health and Culture). The Shanghai Pancreas Cancer Study (study II) was supported by U.S. National Institute of Health grant 5R01 CA114421, by grants from the Science and Technology Commission of Shanghai Municipality, and from the Shanghai Cancer Institute (SB10-06). In all of the study support, the sponsors had no roles in the collection, analysis, or interpretation of study data. NR 49 TC 1 Z9 1 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2016 VL 45 IS 10 BP 1401 EP 1410 DI 10.1097/MPA.0000000000000635 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA9QG UT WOS:000386978400007 PM 27088489 ER PT J AU Makarova-Rusher, OV Ulahannan, S Greten, TF Duffy, A AF Makarova-Rusher, Oxana V. Ulahannan, Susanna Greten, Tim F. Duffy, Austin TI Pancreatic Squamous Cell Carcinoma: A Population-Based Study of Epidemiology, Clinicopathologic Characteristics and Outcomes SO PANCREAS LA English DT Article DE pancreatic cancer; pancreatic squamous cell carcinoma; pancreas; carcinoma; squamous cancer; squamous metaplasia ID OF-THE-LITERATURE; CANCER RATES; SURVIVAL; RISK; DIFFERENTIATION; ADENOCARCINOMA; DIAGNOSIS; DYSPLASIA; PROGNOSIS; TUMOR AB Objectives Squamous metaplasia is commonly detected in pancreatic parenchyma; however, primary pancreatic squamous cell carcinoma (SCC) is a rare malignancy with unknown incidence and unclear prognosis. Methods Surveillance, Epidemiology, and End Results (SEER) registries were examined identifying pancreatic SCC and adenocarcinoma cases from 2000 to 2012. Age-adjusted incidence rates were calculated. Patients with SCC versus adenocarcinoma were compared by clinical features and relative survival outcomes. Results We identified 214 patients with SCC and 72,860 with adenocarcinoma. For SCC, incidence rates tripled between 2000 and 2012. Significantly higher SCC incidence rates were observed in older age groups, blacks, and males. Greater proportion of patients with SCC than those with adenocarcinoma had poorly differentiated histology (73.0% vs 43.7%, P < 0.001). In both subtypes, majority of patients had stage IV disease, 59.0% for adenocarcinoma versus 62.6% for SCC. The 1- and 2-year relative survival rate was significantly lower in patients with SCC versus adenocarcinoma. The 1-year relative survival was 14.0% (95% confidence interval, 9.5%-19.4%) for SCC, compared with 24.5% (95% confidence interval, 24.2%-24.8%) for adenocarcinoma. Conclusions Although primary pancreatic SCC is a rare neoplasm, incidence rates for this subtype are increasing. Relative to adenocarcinoma, pancreatic SCC is characterized by poorly differentiated histology and worse survival. C1 [Makarova-Rusher, Oxana V.; Ulahannan, Susanna; Greten, Tim F.; Duffy, Austin] NCI, Gastrointestinal Malignancy Sect, Thorac & GI Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Duffy, A (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA. EM duffya@mail.nih.gov FU Intramural Research Program of the NIH, NCI FX This research was supported by the Intramural Research Program of the NIH, NCI. NR 39 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2016 VL 45 IS 10 BP 1432 EP 1437 DI 10.1097/MPA.0000000000000658 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA9QG UT WOS:000386978400011 PM 27214394 ER PT J AU Mankongpaisarnrung, C Burks, J Nadella, S Wang, J Hahm, JI Tucker, R Mahmaud, A Stern, S Smith, J AF Mankongpaisarnrung, C. Burks, J. Nadella, S. Wang, J. Hahm, J. -I. Tucker, R. Mahmaud, A. Stern, S. Smith, J. TI Targeted Polyplex Nanoparticle to Gastrin Inhibits Growth and Decreases Metastases of Pancreatic Cancer SO PANCREAS LA English DT Meeting Abstract C1 [Mankongpaisarnrung, C.; Nadella, S.; Wang, J.; Smith, J.] Georgetown Univ, Dept Med, Gastroenterol, Washington, DC USA. [Burks, J.] Georgetown Univ, Div Oncol, Dept Med, Washington, DC USA. [Hahm, J. -I.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA. [Tucker, R.] Georgetown Univ, Dept Comparat Med, Washington, DC USA. [Mahmaud, A.; Stern, S.] NIH, Nanotechnol Characterizat Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2016 VL 45 IS 10 BP 1522 EP 1523 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA9QG UT WOS:000386978400139 ER PT J AU Tarca, AL Hernandez-Andrade, E Ahn, H Garcia, M Xu, Z Korzeniewski, SJ Saker, H Chaiworapongsa, T Hassan, SS Yeo, L Romero, R AF Tarca, Adi L. Hernandez-Andrade, Edgar Ahn, Hyunyoung Garcia, Maynor Xu, Zhonghui Korzeniewski, Steven J. Saker, Homam Chaiworapongsa, Tinnakorn Hassan, Sonia S. Yeo, Lami Romero, Roberto TI Single and Serial Fetal Biometry to Detect Preterm and Term Small- and Large-for-Gestational-Age Neonates: A Longitudinal Cohort Study SO PLOS ONE LA English DT Article ID GROWTH RESTRICTION; 3RD TRIMESTER; INTERGROWTH-21ST PROJECT; INTERNATIONAL STANDARDS; ABDOMINAL CIRCUMFERENCE; ULTRASOUND MEASUREMENTS; WEIGHT; FETUSES; IDENTIFICATION; PREGNANCIES AB Objectives To assess the value of single and serial fetal biometry for the prediction of small- (SGA) and large-for-gestational-age (LGA) neonates delivered preterm or at term. Methods A cohort study of 3,971 women with singleton pregnancies was conducted from the first trimester until delivery with 3,440 pregnancies (17,334 scans) meeting the following inclusion criteria: 1) delivery of a live neonate after 33 gestational weeks and 2) two or more ultrasound examinations with fetal biometry parameters obtained at <= 36 weeks. Primary outcomes were SGA (<5th centile) and LGA (>95th centile) at birth based on INTERGROWTH-21st gender-specific standards. Fetus-specific estimated fetal weight (EFW) trajectories were calculated by linear mixed-effects models using data up to a fixed gestational age (GA) cutoff (28, 32, or 36 weeks) for fetuses having two or more measurements before the GA cutoff and not already delivered. A screen test positive for single biometry was based on Z-scores of EFW at the last scan before each GA cut-off so that the false positive rate (FPR) was 10%. Similarly, a screen test positive for the longitudinal analysis was based on the projected (extrapolated) EFW at 40 weeks from all available measurements before each cutoff for each fetus. Results Fetal abdominal and head circumference measurements, as well as birth weights in the Detroit population, matched well to the INTERGROWTH-21st standards, yet this was not the case for biparietal diameter (BPD) and femur length (FL) (up to 9% and 10% discrepancy for mean and confidence intervals, respectively), mainly due to differences in the measurement technique. Single biometry based on EFW at the last scan at <= 32 weeks (GA IQR: 27.4-30.9 weeks) had a sensitivity of 50% and 53% (FPR = 10%) to detect preterm and term SGA and LGA neonates, respectively (AUC of 82% both). For the detection of LGA using data up to 32- and 36-week cutoffs, single biometry analysis had higher sensitivity than longitudinal analysis (52% vs 46% and 62% vs 52%, respectively; both p<0.05). Restricting the analysis to subjects with the last observation taken within two weeks from the cutoff, the sensitivity for detection of LGA, but not SGA, increased to 65% and 72% for single biometry at the 32- and 36-week cutoffs, respectively. SGA screening performance was higher for preterm (<37 weeks) than for term cases (73% vs 46% sensitivity; p<0.05) for single biometry at <= 32 weeks. Conclusions When growth abnormalities are defined based on birth weight, growth velocity (captured in the longitudinal analysis) does not provide additional information when compared to the last measurement for predicting SGA and LGA neonates, with both approaches detecting one-half of the neonates (FPR = 10%) from data collected at <= 32 weeks. Unlike for SGA, LGA detection can be improved if ultrasound scans are scheduled as close as possible to the gestational-age cutoff when a decision regarding the clinical management of the patient needs to be made. Screening performance for SGA is higher for neonates that will be delivered preterm. C1 [Tarca, Adi L.; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Garcia, Maynor; Xu, Zhonghui; Korzeniewski, Steven J.; Saker, Homam; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Tarca, Adi L.; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Garcia, Maynor; Xu, Zhonghui; Korzeniewski, Steven J.; Saker, Homam; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Tarca, Adi L.; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Garcia, Maynor; Korzeniewski, Steven J.; Saker, Homam; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. [Tarca, Adi L.] Wayne State Univ, Coll Engn, Dept Comp Sci, Detroit, MI USA. [Korzeniewski, Steven J.; Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Tarca, AL; Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.; Tarca, AL; Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.; Tarca, AL (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA.; Tarca, AL (reprint author), Wayne State Univ, Coll Engn, Dept Comp Sci, Detroit, MI USA.; Romero, R (reprint author), Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.; Romero, R (reprint author), Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.; Romero, R (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. EM atarca@med.wayne.edu; 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/DHHS); NICHD/NIH/DHHS [HHSN275201300006C]; Perinatal Initiative of the Wayne State University School of Medicine (WSUSOM); Department of Obstetrics and Gynecology of the WSUSOM 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/DHHS), and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C. ALT and SJK were supported by the Perinatal Initiative of the Wayne State University School of Medicine (WSUSOM), and the Department of Obstetrics and Gynecology of the WSUSOM. NR 45 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 1 PY 2016 VL 11 IS 11 AR e0164161 DI 10.1371/journal.pone.0164161 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA6CX UT WOS:000386714200005 PM 27802270 ER PT J AU Xu, L Wang, W Gotte, D Yang, F Hare, AA Welch, TR Li, BC Shin, JH Chong, J Strathern, JN Dervan, PB Wang, D AF Xu, Liang Wang, Wei Gotte, Deanna Yang, Fei Hare, Alissa A. Welch, Timothy R. Li, Benjamin C. Shin, Ji Hyun Chong, Jenny Strathern, Jeffrey N. Dervan, Peter B. Wang, Dong TI RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Py-Im polyamide; transcription inhibition; minor groove; DNA ID MEDIATED GENE-EXPRESSION; STRUCTURAL BASIS; TRANSCRIPTIONAL FIDELITY; SUBSTRATE-SPECIFICITY; ANGSTROM RESOLUTION; ELONGATION COMPLEX; BINDING POLYAMIDE; SMALL MOLECULES; BASE-PAIRS; RECOGNITION AB RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a "minor groove sensor." Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy. C1 [Xu, Liang; Wang, Wei; Shin, Ji Hyun; Chong, Jenny; Wang, Dong] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Gotte, Deanna; Strathern, Jeffrey N.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Yang, Fei; Hare, Alissa A.; Welch, Timothy R.; Li, Benjamin C.; Dervan, Peter B.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. RP Wang, D (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.; Strathern, JN (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Dervan, PB (reprint author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. EM strathej@mail.nih.gov; dervan@caltech.edu; dongwang@ucsd.edu FU NIH [GM102362, GM27681, F32CA173977]; Intramural Research Program of the NIH, National Cancer Institute, and the Center for Cancer Research FX This work was supported in part by NIH Grants GM102362 (to D.W.) and GM27681 (to P.B.D.); D.G. and J.N.S. were supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and the Center for Cancer Research; and A.A.H. was supported in part by a postdoctoral Fellowship F32CA173977 from the NIH. NR 62 TC 0 Z9 0 U1 9 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP 12426 EP 12431 DI 10.1073/pnas.1612745113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200044 PM 27791148 ER PT J AU Deshmukh, L Louis, JM Ghirlando, R Clore, GM AF Deshmukh, Lalit Louis, John M. Ghirlando, Rodolfo Clore, G. Marius TI Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1 Gag; HIV-1 protease; drug resistance mutations; invisible states; paramagnetic relaxation enhancement ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESIDUAL DIPOLAR COUPLINGS; CLEAVAGE SITES; CRYSTAL-STRUCTURES; RELAXATION ENHANCEMENT; SEDIMENTATION-VELOCITY; HIGH-RESOLUTION; SUBSTRATE; DYNAMICS; SPECTROSCOPY AB Cleavage of the group-specific antigen (Gag) polyprotein by HIV-1 protease represents the critical first step in the conversion of immature noninfectious viral particles to mature infectious virions. Selective pressure exerted by HIV-1 protease inhibitors, a mainstay of current anti-HIV-1 therapies, results in the accumulation of drug resistance mutations in both protease and Gag. Surprisingly, a large number of these mutations (known as secondary or compensatory mutations) occur outside the active site of protease or the cleavage sites of Gag (located within intrinsically disordered linkers connecting the globular domains of Gag to one another), suggesting that transient encounter complexes involving the globular domains of Gag may play a role in guiding and facilitating access of the protease to the Gag cleavage sites. Here, using large fragments of Gag, as well as catalytically inactive and active variants of protease, we probe the nature of such rare encounter complexes using intermolecular paramagnetic relaxation enhancement, a highly sensitive technique for detecting sparsely populated states. We show that Gag-protease encounter complexes are primarily mediated by interactions between protease and the globular domains of Gag and that the sites of transient interactions are correlated with surface exposed regions that exhibit a high propensity to mutate in the presence of HIV-1 protease inhibitors. C1 [Deshmukh, Lalit; Louis, John M.; Clore, G. Marius] NIDDK, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. EM mariusc@mail.nih.gov FU Intramural Program of NIDDK/NIH; AIDS Targeted Antiviral Program of the Office of the NIH FX We thank M. Bayro, J. Werner-Allen, C.D. Schwieters, D. Appella, and V. Tugarinov for useful discussions; Y. Shen for help with CS-ROSETTA calculations; Y. Kim for help with DOTA-Gd3+ purification; A. Aniana for technical assistance; and J. Lloyd [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Advanced Mass Spectrometry Core] for technical support. This work was supported by the Intramural Program of NIDDK/NIH and the AIDS Targeted Antiviral Program of the Office of the NIH Director (to G.M.C.). NR 50 TC 0 Z9 0 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP 12456 EP 12461 DI 10.1073/pnas.1615342113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200049 PM 27791180 ER PT J AU Scheibye-Knudsen, M Tseng, A Jensen, MB Scheibye-Alsing, K Fang, EF Iyama, T Bharti, SK Marosi, K Froetscher, L Kassahun, H Eckley, DM Maul, RW Bastian, P De, S Ghosh, S Nilsen, H Goldberg, IG Mattson, MP Wilson, DM Brosh, RM Gorospe, M Bohr, VA AF Scheibye-Knudsen, Morten Tseng, Anne Jensen, Martin Borch Scheibye-Alsing, Karsten Fang, Evandro Fei Iyama, Teruaki Bharti, Sanjay Kumar Marosi, Krisztina Froetscher, Lynn Kassahun, Henok Eckley, David Mark Maul, Robert W. Bastian, Paul De, Supriyo Ghosh, Soumita Nilsen, Hilde Goldberg, Ilya G. Mattson, Mark P. Wilson, David M., III Brosh, Robert M., Jr. Gorospe, Myriam Bohr, Vilhelm A. TI Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cockayne syndrome; aging; polymerase; transcription; nucleolus; CSA; CSB ID G-QUADRUPLEX STRUCTURES; TATA-BINDING PROTEIN; NUCLEAR-DNA; POLY(ADP-RIBOSE) POLYMERASE-1; CAENORHABDITIS-ELEGANS; DAMAGE; BIOGENESIS; ACTIVATION; DISEASE; REPAIR AB Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition of ribosomal DNA transcription leads to mitochondrial dysfunction in a number of cell lines. Furthermore, machine-learning algorithms predict that diseases with defects in ribosomal DNA (rDNA) transcription have mitochondrial dysfunction, and, accordingly, this is found when factors involved in rDNA transcription are knocked down. Mechanistically, loss of CSA or CSB leads to polymerase stalling at non-B DNA in a neuroblastoma cell line, in particular at G-quadruplex structures, and recombinant CSB can melt G-quadruplex structures. Indeed, stabilization of G-quadruplex structures activates PARP1 and leads to accelerated aging in Caenorhabditis elegans. In conclusion, this work supports a role for impaired ribosomal DNA transcription in Cockayne syndrome and suggests that transcription-coupled resolution of secondary structures may be a mechanism to repress spurious activation of a DNA damage response. C1 [Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, DK-2300 Copenhagen, Denmark. [Scheibye-Knudsen, Morten; Tseng, Anne; Fang, Evandro Fei; Iyama, Teruaki; Bharti, Sanjay Kumar; Froetscher, Lynn; Wilson, David M., III; Brosh, Robert M., Jr.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Jensen, Martin Borch] Buck Inst Res Aging, Novato, CA 94945 USA. [Marosi, Krisztina; Mattson, Mark P.] NIA, Lab Neurosci, NIH, Baltimore, MD 21224 USA. [Kassahun, Henok; Nilsen, Hilde] Inst Clin Med, N-0167 Lorenskog, Norway. [Nilsen, Hilde] Univ Oslo, N-0167 Lorenskog, Norway. [Nilsen, Hilde] Akershus Univ Hosp, N-0167 Lorenskog, Norway. [Eckley, David Mark; Bastian, Paul; De, Supriyo; Goldberg, Ilya G.; Gorospe, Myriam] NIA, Lab Genet & Genom, NIH, Baltimore, MD 21224 USA. [Maul, Robert W.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Ghosh, Soumita] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. RP Scheibye-Knudsen, M (reprint author), Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, DK-2300 Copenhagen, Denmark.; Scheibye-Knudsen, M; Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM mscheibye@sund.ku.dk; vbohr@nih.gov OI Scheibye-Knudsen, Morten/0000-0002-6637-1280; De, Supriyo/0000-0002-2075-7655; Eckley, D. Mark/0000-0003-2296-5164 FU South East Regional Health Authority; Intramural Research Program of the NIH, National Institute on Aging FX We thank Jennifer L. Martindale and Dr. Ruin Moaddel for technical assistance and Elayne Fivenson and Mustafa Okur for feedback on the manuscript. H.N. is supported by funding from the South East Regional Health Authority. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 50 TC 0 Z9 0 U1 13 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP 12502 EP 12507 DI 10.1073/pnas.1610198113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200057 PM 27791127 ER PT J AU Dharmaiah, S Bindu, L Tran, TH Gillette, WK Frank, PH Ghirlando, R Nissley, DV Esposito, D McCormick, F Stephen, AG Simanshu, DK AF Dharmaiah, Srisathiyanarayanan Bindu, Lakshman Tran, Timothy H. Gillette, William K. Frank, Peter H. Ghirlando, Rodolfo Nissley, Dwight V. Esposito, Dominic McCormick, Frank Stephen, Andrew G. Simanshu, Dhirendra K. TI Structural basis of recognition of farnesylated and methylated KRAS4b by PDE delta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prenylation; protein-protein interaction; KRAS4b; KRAS-PDE delta complex; phosphodiesterase-delta ID K-RAS; PLASMA-MEMBRANE; ANALYTICAL ULTRACENTRIFUGATION; SEDIMENTATION-VELOCITY; CATALYTIC SUBUNITS; SPLICE VARIANT; CANCER-THERAPY; N-RAS; PROTEIN; TRANSPORT AB Farnesylation and carboxymethylation of KRAS4b (Kirsten rat sarcoma isoform 4b) are essential for its interaction with the plasma membrane where KRAS-mediated signaling events occur. Phosphodiesterase-delta (PDE delta) binds to KRAS4b and plays an important role in targeting it to cellular membranes. We solved structures of human farnesylated-methylated KRAS4b in complex with PDE delta in two different crystal forms. In these structures, the interaction is driven by the C-terminal amino acids together with the farnesylated and methylated C185 of KRAS4b that binds tightly in the central hydrophobic pocket present in PDEd. In crystal form II, we see the full-length structure of farnesylated-methylated KRAS4b, including the hypervariable region. Crystal form I reveals structural details of farnesylated-methylated KRAS4b binding to PDE delta, and crystal form II suggests the potential binding mode of geranylgeranylated-methylated KRAS4b to PDE delta. We identified a 5-aa-long sequence motif (Lys-Ser-Lys-Thr-Lys) in KRAS4b that may enable PDE delta to bind both forms of prenylated KRAS4b. Structure and sequence analysis of various prenylated proteins that have been previously tested for binding to PDE delta provides a rationale for why some prenylated proteins, such as KRAS4a, RalA, RalB, and Rac1, do not bind to PDE delta. Comparison of all four available structures of PDE delta complexed with various prenylated proteins/peptides shows the presence of additional interactions due to a larger protein-protein interaction interface in KRAS4b-PDE delta complex. This interface might be exploited for designing an inhibitor with minimal off-target effects. C1 [Dharmaiah, Srisathiyanarayanan; Bindu, Lakshman; Tran, Timothy H.; Gillette, William K.; Frank, Peter H.; Nissley, Dwight V.; Esposito, Dominic; McCormick, Frank; Stephen, Andrew G.; Simanshu, Dhirendra K.] Leidos Biomed Res Inc, NCI RAS Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Ghirlando, Rodolfo] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [McCormick, Frank] Univ Calif San Francisco, Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. RP McCormick, F; Simanshu, DK (reprint author), Leidos Biomed Res Inc, NCI RAS Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.; McCormick, F (reprint author), Univ Calif San Francisco, Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. EM frank.mccormick@ucsf.edu; dhirendra.simanshu@fnlcr.nih.gov FU federal funds from National Cancer Institute, NIH [HHSN261200800001E]; Intramural Research Program of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences from National Institutes of Health [P41 GM103403]; NIH-Office of Research Infrastructure Programs High-End Instrumentation [S10 RR029205]; DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357] FX We thank members of the Protein Expression Laboratory (Frederick National Laboratory for Cancer Research) for their help in cloning, protein expression, and purification. We also thank the staff of ID-24-C/E beamline at the Advanced Photon Source, Argonne National Laboratory, for their help with data collection. We thank Drs. Monika Mehta, Jim Hartley, and David Heimbrook for critical reading of this manuscript. This project was funded in whole or in part with federal funds from National Cancer Institute, NIH Contract HHSN261200800001E. This work was funded in part by the Intramural Research Program of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases. Part of this work is based on research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from National Institutes of Health Grant P41 GM103403. The Pilatus 6M detector on 24-ID-C beamline is funded by NIH-Office of Research Infrastructure Programs High-End Instrumentation Grant S10 RR029205. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract DE-AC02-06CH11357. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. NR 61 TC 0 Z9 0 U1 5 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP E6766 EP E6775 DI 10.1073/pnas.1615316113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200009 PM 27791178 ER PT J AU Pageon, SV Tabarin, T Yamamoto, Y Ma, YQ Nicovich, PR Bridgeman, JS Cohnen, A Benzing, C Gao, YJ Crowther, MD Tungatt, K Dolton, G Sewell, AK Price, DA Acuto, O Parton, RG Gooding, JJ Rossy, J Rossjohn, J Gaus, K AF Pageon, Sophie V. Tabarin, Thibault Yamamoto, Yui Ma, Yuanqing Nicovich, Philip R. Bridgeman, John S. Cohnen, Andre Benzing, Carola Gao, Yijun Crowther, Michael D. Tungatt, Katie Dolton, Garry Sewell, Andrew K. Price, David A. Acuto, Oreste Parton, Robert G. Gooding, J. Justin Rossy, Jeremie Rossjohn, Jamie Gaus, Katharina TI Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination (vol 113, pg E5454, 2016) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Correction C1 [Pageon, Sophie V.; Tabarin, Thibault; Yamamoto, Yui; Ma, Yuanqing; Nicovich, Philip R.; Benzing, Carola; Gao, Yijun; Rossy, Jeremie; Gaus, Katharina] Univ New South Wales, Sch Med Sci, European Mol Biol Lab EMBL Australia Node Single, Sydney, NSW 2052, Australia. [Pageon, Sophie V.; Tabarin, Thibault; Yamamoto, Yui; Ma, Yuanqing; Nicovich, Philip R.; Benzing, Carola; Gao, Yijun; Rossy, Jeremie; Gaus, Katharina] Univ New South Wales, Ctr Excellence Adv Mol Imaging, Australian Res Council, Sydney, NSW 2052, Australia. [Bridgeman, John S.; Crowther, Michael D.; Tungatt, Katie; Dolton, Garry; Sewell, Andrew K.; Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Bridgeman, John S.] Cellular Therapeut Ltd, Manchester M13 9XX, Lancs, England. [Cohnen, Andre; Acuto, Oreste] Univ Oxford, Sir William Dunn Sch Pathol, T Cell Signalling Lab, Oxford OX1 3RE, England. [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Parton, Robert G.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia. [Parton, Robert G.] Univ Queensland, Australia Ctr Microscopy & Microanal, St Lucia, Qld 4072, Australia. [Parton, Robert G.; Gooding, J. Justin] Univ Queensland, Ctr Excellence Convergent Bionano Sci & Technol, Australian Res Council, St Lucia, Qld 4072, Australia. [Gooding, J. Justin] Univ New South Wales, Sch Chem, Sydney, NSW 2052, Australia. [Gooding, J. Justin] Univ New South Wales, Australian Ctr NanoMed, Sydney, NSW 2052, Australia. [Rossjohn, Jamie] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Infect & Immun Program, Clayton, Vic 3800, Australia. [Rossjohn, Jamie] Monash Univ, Ctr Excellence Adv Mol Imaging, Australian Res Council, Clayton, Vic 3800, Australia. RP Pageon, SV (reprint author), Univ New South Wales, Sch Med Sci, European Mol Biol Lab EMBL Australia Node Single, Sydney, NSW 2052, Australia.; Pageon, SV (reprint author), Univ New South Wales, Ctr Excellence Adv Mol Imaging, Australian Res Council, Sydney, NSW 2052, Australia. RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Pageon, Sophie/0000-0003-1701-5551 NR 1 TC 0 Z9 0 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP E6905 EP E6905 DI 10.1073/pnas.1615763113 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200026 ER PT J AU Yu, A Alberstein, R Thomas, A Zimmet, A Grey, R Mayer, ML Lau, AY AF Yu, Alvin Alberstein, Robert Thomas, Alecia Zimmet, Austin Grey, Richard Mayer, Mark L. Lau, Albert Y. TI Molecular lock regulates binding of glycine to a primitive NMDA receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glutamate receptors; X-ray crystallography; electrophysiology; molecular dynamics simulations; free energy calculations ID HISTOGRAM ANALYSIS METHOD; FREE-ENERGY CALCULATIONS; D-ASPARTATE RECEPTOR; LIGAND-BINDING; GLUTAMATE-RECEPTOR; CRYSTAL-STRUCTURES; ION-CHANNEL; INTERDOMAIN INTERACTIONS; SUBUNIT ARRANGEMENT; PROTEIN STRUCTURES AB The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi. The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants. C1 [Yu, Alvin; Alberstein, Robert; Lau, Albert Y.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. [Alberstein, Robert; Thomas, Alecia; Zimmet, Austin; Grey, Richard; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. [Alberstein, Robert] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Thomas, Alecia] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Zimmet, Austin] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grey, Richard] NHGRI, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. RP Lau, AY (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.; Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. EM mark.mayer@nih.gov; alau@jhmi.edu FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; intramural research program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Department of Health and Human Services; NIH [R01GM094495] FX We thank Carla Glasser for technical assistance and Drs. Joy Zhao and Peter Schuck for help with analysis of ITC experiments. Data were collected at SER-CAT 22-ID beamline at the APS, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH and resources provided by the Maryland Advanced Research Computing Center at Johns Hopkins University. This work was supported by the intramural research program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Department of Health and Human Services (M.L.M.) and NIH Grant R01GM094495 (to A.Y.L.). NR 47 TC 0 Z9 0 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2016 VL 113 IS 44 BP E6786 EP E6795 DI 10.1073/pnas.1607010113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA4TR UT WOS:000386608200011 PM 27791085 ER PT J AU Balderston, NL Quispe-Escudero, D Hale, E Davis, A O'Connell, K Ernst, M Grillon, C AF Balderston, Nicholas L. Quispe-Escudero, David Hale, Elizabeth Davis, Andrew O'Connell, Katherine Ernst, Monique Grillon, Christian TI Working memory maintenance is sufficient to reduce state anxiety SO PSYCHOPHYSIOLOGY LA English DT Article DE Startle blink; Working memory; Anxiety ID PREFRONTAL CORTEX; TRAIT ANXIETY; COGNITIVE CONTROL; FRONTAL LOBES; ATTENTION; STARTLE; PERFORMANCE; DISTRACTION; MODULATION; MECHANISMS AB According to the attentional control theory (ACT) proposed by Eysenck and colleagues, anxiety interferes with cognitive processing by prioritizing bottom-up attentional processes over top-down attentional processes, leading to competition for access to limited resources in working memory, particularly the central executive (Eysenck, Derakshan, Santos, & Calvo, ). However, previous research using the n-back working memory task suggests that working memory load also reduces state anxiety. Assuming that similar mechanisms underlie the effect of anxiety on cognition, and the effect of cognition on anxiety, one possible implication of the ACT would suggest that the reduction of state anxiety with increasing working memory load is driven by activation of central executive attentional control processes. We tested this hypothesis using the Sternberg working memory paradigm, where maintenance processes can be isolated from central executive processes (Altamura et al., ; Sternberg, ). Consistent with the n-back results, subjects showed decreased state anxiety during the maintenance period of high-load trials relative to low-load trials, suggesting that maintenance processes alone are sufficient to achieve this state anxiety reduction. Given that the Sternberg task does not require central executive engagement, these results are not consistent with an implication of the ACT where the cognition/anxiety relationship and anxiety/cognition relationship are mediated by similar central executive mechanisms. Instead, we propose an extension of the ACT such that engaging working memory maintenance suppresses state anxiety in a load-dependent manner. Furthermore, we hypothesize that the efficacy of this effect may moderate the effect of trait anxiety on cognition. C1 [Balderston, Nicholas L.; Quispe-Escudero, David; Hale, Elizabeth; Davis, Andrew; O'Connell, Katherine; Ernst, Monique; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA. RP Balderston, NL (reprint author), NIMH, 15k North Dr, Bethesda, MD 20892 USA. EM nicholas.balderston@nih.gov OI Balderston, Nicholas/0000-0002-8565-1544 FU National Institute of Mental Health [ZIAMH002798] FX Financial support of this study was provided by the Intramural Research Program of the National Institute of Mental Health, ZIAMH002798 (ClinicalTrial.gov Identifier: NCT00026559: Protocol ID 01-M-0185). NR 57 TC 0 Z9 0 U1 10 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2016 VL 53 IS 11 BP 1660 EP 1668 DI 10.1111/psyp.12726 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA DZ3JX UT WOS:000385744000005 PM 27434207 ER PT J AU Troeschel, A Smith, T Castro, K Treiman, K Lipscomb, J McCabe, RM Clauser, S Friedman, EL Hegedus, PD Portier, K AF Troeschel, Alyssa Smith, Tenbroeck Castro, Kathleen Treiman, Katherine Lipscomb, Joseph McCabe, Ryan M. Clauser, Steven Friedman, Eliot L. Hegedus, Patricia D. Portier, Kenneth TI The development and acceptability of symptom management quality improvement reports based on patient-reported data: an overview of methods used in PROSSES SO QUALITY OF LIFE RESEARCH LA English DT Article DE Cancer; Patient-reported outcomes; Quality improvement reports; Case-mix adjustment; Symptom management ID PROPENSITY SCORE METHODS; CASE-MIX ADJUSTMENT; CANCER-PATIENTS; PERFORMANCE; EXPERIENCE; THERAPY; CARE AB Patient experiences with symptom care need to be assessed and documented to ensure successful management of cancer-related symptoms. This paper details one method for creating symptom management quality improvement (SMQI) reports, including case-mix adjustment of patient-reported measures. Qualitative data regarding the acceptability of these reports at participating cancer centers (CCs) are also provided. Data were collected from 2226 patients treated at 16 CCs via mailed/Web questionnaires. Twelve items assessing patient perceptions of symptom management-pain, fatigue, emotional distress-served as key quality indicators. Medico-demographic variables suitable for case-mix adjustment were selected using an index score combining predictive power and heterogeneity across CCs. SMQI reports were designed with staff feedback and produced for each CC, providing crude and adjusted CC-specific rates, along with study-wide rates for comparison purposes. Cancer type and participant educational level were selected for case-mix adjustment based upon high index scores. The Kendall rank correlation coefficient showed that case-mix adjustments changed the ranking of CCs on the key quality indicators (% Delta rank range: 5-22 %). The key quality indicators varied across CCs (all p < 0.02). SMQI reports were well received by CC staff, who described plans to share them with key personnel (e.g., cancer committee, navigator). This paper provides one method for creating hospital-level SMQI reports, including case-mix adjustment. Variation between CCs on key quality indicators, even after adjustment, suggested room for improvement. SMQI reports based on patient-reported data can inform and motivate efforts to improve care through professional/patient education and applying standards of care. C1 [Troeschel, Alyssa; Smith, Tenbroeck; Portier, Kenneth] Amer Canc Soc, Intramural Res Dept, 250 Williams St, Atlanta, GA 30301 USA. [Castro, Kathleen] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Treiman, Katherine] Res Triangle Inst, Durham, NC USA. [Lipscomb, Joseph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Lipscomb, Joseph] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [McCabe, Ryan M.] Amer Coll Surg, Chicago, IL USA. [Clauser, Steven] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Friedman, Eliot L.] Lehigh Valley Hlth Network, Allentown, PA USA. [Hegedus, Patricia D.] Gibbs Canc Ctr & Res Inst, Spartanburg, SC USA. RP Smith, T (reprint author), Amer Canc Soc, Intramural Res Dept, 250 Williams St, Atlanta, GA 30301 USA. EM Tenbroeck.Smith@cancer.org FU American Cancer Society Intramural Research Department; Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded by the American Cancer Society Intramural Research Department and with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views of 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 37 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD NOV PY 2016 VL 25 IS 11 BP 2833 EP 2843 DI 10.1007/s11136-016-1305-7 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EA1NO UT WOS:000386359200013 PM 27338811 ER PT J AU Pocnet, C Antonietti, JP Strippoli, MPF Glaus, J Preisig, M Rossier, J AF Pocnet, Cornelia Antonietti, Jean-Philippe Strippoli, Marie-Pierre F. Glaus, Jennifer Preisig, Martin Rossier, Jerome TI Individuals' quality of life linked to major life events, perceived social support, and personality traits SO QUALITY OF LIFE RESEARCH LA English DT Article DE Life events; Personality; Perceived social support; Subjective quality of life ID SET-POINT MODEL; MULTIDIMENSIONAL SCALE; ADAPTATION; ADJUSTMENT; HAPPINESS; STRESS; DETERMINANTS; EXTROVERSION; RESOURCES; STABILITY AB The aim of this study was to investigate the relationship between major recent life events that occurred during the last 5 years, social and personal resources, and subjective quality of life (QoL). A total of 1801 participants from the general population (CoLaus/PsyCoLaus study) completed the Life Events Questionnaire, the Social Support Questionnaire, the NEO Five-Factor Inventory Revised, and the Manchester Short Assessment of Quality of Life. Major life events were modestly associated with the QoL (about 5 % of the explained variance). However, QoL was significantly related to perceived social support and personality traits (about 37 % of the explained variance). Particularly, perceived social support, extraversion and conscientiousness personality dimensions were positively linked to life satisfaction, whereas a high level of neuroticism was negatively associated with QoL. This study highlights the negative but temporary association between critical events and QoL. However, a combination of high conscientiousness and extraversion, and positive social support may explain better variances for a high-perceived QoL. C1 [Pocnet, Cornelia; Antonietti, Jean-Philippe; Rossier, Jerome] Univ Lausanne, Inst Psychol, Geopolis, CH-1015 Lausanne, Switzerland. [Strippoli, Marie-Pierre F.; Preisig, Martin] Univ Lausanne Hosp, Dept Psychiat, Psychiat Epidemiol & Psychopathol Res Ctr, Lausanne, Switzerland. [Glaus, Jennifer] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Pocnet, C (reprint author), Univ Lausanne, Inst Psychol, Geopolis, CH-1015 Lausanne, Switzerland. EM Cornelia.Pocnet@unil.ch RI Strippoli, Marie-Pierre/K-8164-2013; Colaus, PsyColaus/K-6607-2013; Glaus, Jennifer/C-7887-2017 OI Strippoli, Marie-Pierre/0000-0003-3053-484X; Glaus, Jennifer/0000-0001-8883-9473 FU GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne; Swiss National Science Foundation [3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30-148401] FX The PsyCoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (Grants 3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, and 33CS30-148401). NR 51 TC 1 Z9 1 U1 11 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD NOV PY 2016 VL 25 IS 11 BP 2897 EP 2908 DI 10.1007/s11136-016-1296-4 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EA1NO UT WOS:000386359200019 PM 27098234 ER PT J AU Knickelbein, JE Hasan, J Nussenblatt, RB Sen, HN AF Knickelbein, Jared E. Hasan, Jesia Nussenblatt, Robert B. Sen, H. Nida TI DELINEATION OF CHOROIDAL AND RETINAL LESIONS IN POSTERIOR UVEITIS BY MULTISPECTRAL WIDE-FIELD SCANNING LASER OPHTHALMOSCOPY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE birdshot chorioretinopathy; primary vitreoretinal lymphoma; multispectral wide-field scanning laser ophthalmoscopy; multimodal imaging ID NEOPLASTIC MASQUERADE SYNDROMES; BIRDSHOT RETINOCHOROIDOPATHY; INTRAOCULAR LYMPHOMA AB Purpose: To investigate whether wide-field multispectral scanning laser ophthalmoscopy could assist in determining depth of chorioretinal pathology in posterior uveitis. Methods: Cross-sectional retrospective review of patients with birdshot chorioretinopathy (BCR; 42 eyes of 21 patients) or active primary vitreoretinal lymphoma (PVRL; 18 eyes of 10 patients) who had multispectral wide-field scanning laser ophthalmoscopy (Optos) images. Images acquired with 532 nm and 635 nm lasers were analyzed separately using Optos V-2 Vantage Pro Review software. Results: All 42 eyes with birdshot chorioretinopathy and 8/18 eyes with active primary vitreoretinal lymphoma had lesions on 635 nm imaging, while 26/42 of the birdshot chorioretinopathy eyes and 18/18 eyes with active primary vitreoretinal lymphoma had lesions on 532 nm imaging. The difference between the 2 groups on both 635 nm and 532 nm was statistically significant (P < 0.05). Conclusion: Retinal and choroidal lesions in patients with posterior uveitis can be differentially visualized with Optos 532 nm and 635 nm lasers, respectively, allowing determination of depth of pathology. C1 [Knickelbein, Jared E.; Hasan, Jesia; Nussenblatt, Robert B.; Sen, H. Nida] NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU NEI Intramural Research Program FX This research was supported by the NEI Intramural Research Program. NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD NOV PY 2016 VL 36 IS 11 BP 2213 EP 2219 PG 7 WC Ophthalmology SC Ophthalmology GA EB1AY UT WOS:000387079800030 PM 27152831 ER PT J AU Kang, HS Chen, LY Lichti-Kaiser, K Liao, G Gerrish, K Bortner, CD Yao, HHC Eddy, EM Jetten, AM AF Kang, Hong Soon Chen, Liang-Yu Lichti-Kaiser, Kristin Liao, Grace Gerrish, Kevin Bortner, Carl D. Yao, Humphrey H. -C. Eddy, Edward M. Jetten, Anton M. TI Transcription Factor GLIS3: A New and Critical Regulator of Postnatal Stages of Mouse Spermatogenesis SO STEM CELLS LA English DT Article DE GLIS3; Spermatogonial stem cell; Spermatogenesis; Gene expression ID SPERMATOGONIAL STEM-CELLS; NEONATAL DIABETES-MELLITUS; ZINC-FINGER PROTEINS; UNDIFFERENTIATED SPERMATOGONIA; PHYSIOLOGICAL FUNCTIONS; PROFILING REVEALS; GENE-EXPRESSION; SELF-RENEWAL; GERM-CELLS; ROR-ALPHA AB In this study, we identify a novel and essential role for the Kruppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in the regulation of postnatal spermatogenesis. We show that GLIS3 is expressed in gonocytes, spermatogonial stem cells (SSCs) and spermatogonial progenitors (SPCs), but not in differentiated spermatogonia and later stages of spermatogenesis or in somatic cells. Spermatogenesis is greatly impaired in GLIS3 knockout mice. Loss of GLIS3 function causes a moderate reduction in the number of gonocytes, but greatly affects the generation of SSCs/SPCs, and as a consequence the development of spermatocytes. Gene expression profiling demonstrated that the expression of genes associated with undifferentiated spermatogonia was dramatically decreased in GLIS3-deficient mice and that the cytoplasmic-to-nuclear translocation of FOXO1, which marks the gonocyte-to-SSC transition and is necessary for SSC self-renewal, is inhibited. These observations suggest that GLIS3 promotes the gonocyte-to-SSC transition and is a critical regulator of the dynamics of early postnatal spermatogenesis. C1 [Kang, Hong Soon; Lichti-Kaiser, Kristin; Liao, Grace; Jetten, Anton M.] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Chen, Liang-Yu; Yao, Humphrey H. -C.; Eddy, Edward M.] NIEHS, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Gerrish, Kevin] NIEHS, Mol Genom Core, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Bortner, Carl D.] NIEHS, Div Intramural Res, Flow Cytometry Ctr, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIH, Immun Inflammat & Dis Lab, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES-100485] FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, the National Institutes of Health [Z01-ES-100485]. The authors thank Laura Miller DeGraff for her excellent assistance with managing the mouse colonies. NR 50 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD NOV PY 2016 VL 34 IS 11 BP 2772 EP 2783 DI 10.1002/stem.2449 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA EB0KZ UT WOS:000387034000014 ER PT J AU Miyagishima, KJ Wan, Q Corneo, B Sharma, R Lotfi, MR Boles, NC Hua, F Maminishkis, A Zhang, CX Blenkinsop, T Khristov, V Jha, BS Memon, OS D'Souza, S Temple, S Miller, SS Bharti, K AF Miyagishima, Kiyoharu J. Wan, Qin Corneo, Barbara Sharma, Ruchi Lotfi, Mostafa R. Boles, Nathan C. Hua, Fang Maminishkis, Arvydas Zhang, Congxiao Blenkinsop, Timothy Khristov, Vladimir Jha, Balendu S. Memon, Omar S. D'Souza, Sunita Temple, Sally Miller, Sheldon S. Bharti, Kapil TI In Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Induced pluripotent stem cell (iPSC); Retinal pigment epithelium; Cell authentication; Cellular therapy; Genetic differences ID MACULAR DEGENERATION; ION-TRANSPORT; SUBRETINAL SPACE; FLUID TRANSPORT; MOLECULAR SIGNATURE; NATIVE TISSUE; RPE CELLS; DIFFERENTIATION; BOVINE; DISEASE AB Induced pluripotent stem cells (iPSCs) can be efficiently differentiated into retinal pigment epithelium (RPE), offering the possibility of autologous cell replacement therapy for retinal degeneration stemming from RPE loss. The generation and maintenance of epithelial apical-basolateral polarity is fundamental for iPSC-derived RPE (iPSC-RPE) to recapitulate native RPE structure and function. Presently, no criteria have been established to determine clonal or donor based heterogeneity in the polarization and maturation state of iPSC-RPE. We provide an unbiased structural, molecular, and physiological evaluation of 15 iPSC-RPE that have been derived from distinct tissues from several different donors. We assessed the intact RPE monolayer in terms of an ATP-dependent signaling pathway that drives critical aspects of RPE function, including calcium and electrophysiological responses, as well as steady-state fluid transport. These responses have key in vivo counterparts that together help determine the homeostasis of the distal retina. We characterized the donor and clonal variation and found that iPSC-RPE function was more significantly affected by the genetic differences between different donors than the epigenetic differences associated with different starting tissues. This study provides a reference dataset to authenticate genetically diverse iPSC-RPE derived for clinical applications. C1 [Miyagishima, Kiyoharu J.; Wan, Qin; Lotfi, Mostafa R.; Hua, Fang; Maminishkis, Arvydas; Zhang, Congxiao; Khristov, Vladimir; Memon, Omar S.; Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA. [Sharma, Ruchi; Jha, Balendu S.; Bharti, Kapil] NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA. [Corneo, Barbara] Columbia Univ, Med Ctr, Columbia Stem Cell Core Facil, New York, NY USA. [Boles, Nathan C.; Temple, Sally] Neural Stem Cell Inst, Rensselaer, NY USA. [Blenkinsop, Timothy] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [D'Souza, Sunita] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Bharti, K (reprint author), NEI, NIH, 10 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM kapilbharti@nei.nih.gov FU National Eye Institute Intramural Funds; NIH Center for Regenerative Medicine; NIH; National Institute of Aging [1RF1AG042932-01] FX This study was supported by National Eye Institute Intramural Funds, NIH Center for Regenerative Medicine, and NIH Common Fund Grants to K.B. and S.M. Production and characterization of iPSCs was supported by National Institute of Aging Grant 1RF1AG042932-01 to S.T. and B.C. We thank Gretchen Kusek, Rachel Wurster, Natalia Lowry, and Carol Charniga (Sally Temple lab) for technical assistance and Dr. Peter Munson for statistical consultation. NR 67 TC 0 Z9 0 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD NOV PY 2016 VL 5 IS 11 BP 1562 EP 1574 DI 10.5966/sctm.2016-0037 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA EA2HQ UT WOS:000386413800017 PM 27400791 ER PT J AU Batra, VK Beard, WA Pedersen, LC Wilson, SH AF Batra, Vinod K. Beard, William A. Pedersen, Lars C. Wilson, Samuel H. TI Structures of DNA Polymerase Mispaired DNA Termini Transitioning to Pre-catalytic Complexes Support an Induced-Fit Fidelity Mechanism SO STRUCTURE LA English DT Article ID ACTIVE-SITE; BASE-PAIR; MISMATCH; BETA; EXTENSION; GEOMETRY; SYSTEM; ERRORS; ACID AB High-fidelity DNA synthesis requires that polymerases display a strong preference for right nucleotide insertion. When the wrong nucleotide is inserted, the polymerase deters extension from the mismatched DNA terminus. Twenty-three crystallographic structures of DNA polymerase beta with terminal template-primer mismatches were determined as binary DNA and ternary pre-catalytic substrate complexes. These structures indicate that the mismatched termini adopt various distorted conformations that attempt to satisfy stacking and hydrogen-bonding interactions. The binary complex structures indicate an induced strain in the mismatched template nucleotide. Addition of a non-hydrolyzable incoming nucleotide stabilizes the templating nucleotide with concomitant strain in the primer terminus. Several dead-end ternary complex structures suggest that DNA synthesis might occur as the enzyme transitions from an open to a closed complex. The structures are consistent with an induced-fit mechanism where a mismatched terminus is misaligned relative to the correct incoming nucleotide to deter or delay further DNA synthesis. C1 [Batra, Vinod K.; Beard, William A.; Pedersen, Lars C.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [1ZIAES050158, 1ZIAES050161, 1ZIAES102645]; NIH [1U19CA105010, P41 GM-103311] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (project numbers: 1ZIAES050158 and 1ZIAES050161, S.H.W; 1ZIAES102645, L.C.P.) and in association with NIH grant 1U19CA105010. Molecular graphics images were produced using the Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 GM-103311). NR 23 TC 2 Z9 2 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD NOV 1 PY 2016 VL 24 IS 11 BP 1863 EP 1875 DI 10.1016/j.str.2016.08.006 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA EA6UO UT WOS:000386764700004 PM 27642161 ER PT J AU Findley, K Williams, DR Grice, EA Bonham, VL AF Findley, Keisha Williams, David R. Grice, Elizabeth A. Bonham, Vence L. TI Health Disparities and the Microbiome SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID VAGINAL MICROBIOME; ENVIRONMENT; CHILDREN; WOMEN; DIET; RACE AB An individual's microbiome is likely to be an important contributor to certain health disparity diseases and conditions. We present a framework to study the role of the microbiome and the multiple factors that are likely to influence differences in disease predisposition, onset, and progression at the individual and population level. C1 [Findley, Keisha; Bonham, Vence L.] NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr Room B1B37-G, Bethesda, MD 20892 USA. [Williams, David R.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg Room 615, Boston, MA 02115 USA. [Grice, Elizabeth A.] Univ Penn, Perelman Sch Med, Dept Dermatol, 421 Curie Blvd,1007 BRB 2-3, Philadelphia, PA 19104 USA. [Grice, Elizabeth A.] Univ Penn, Perelman Sch Med, Dept Microbiol, 421 Curie Blvd,1007 BRB 2-3, Philadelphia, PA 19104 USA. RP Bonham, VL (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr Room B1B37-G, Bethesda, MD 20892 USA. EM bonhamv@mail.nih.gov NR 15 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD NOV PY 2016 VL 24 IS 11 BP 847 EP 850 DI 10.1016/j.tim.2016.08.001 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA EA5FM UT WOS:000386644800001 PM 27712950 ER PT J AU Sankineni, S Smedley, J Bernardo, M Brown, AM Johnson, L Muller, B Griffiths, GL Kobayashi, H Rais-Bahrami, S Pinto, PA Wood, BJ Keele, B Choyke, PL Turkbey, B AF Sankineni, Sandeep Smedley, Jeremy Bernardo, Marcelino Brown, Anna M. Johnson, Linda Muller, Berrend Griffiths, Gary L. Kobayashi, Hisataka Rais-Bahrami, Soroush Pinto, Peter A. Wood, Bradford J. Keele, Brandon Choyke, Peter L. Turkbey, Baris TI Ferumoxytol as an intraprostatic MR contrast agent for lymph node mapping of the prostate: a feasibility study in non-human primates SO ACTA RADIOLOGICA LA English DT Article DE Ferumoxytol; lymph node; prostate cancer; iron oxide nanoparticles; magnetic resonance imaging (MRI) ID SUPERPARAMAGNETIC IRON-OXIDE; INITIAL CLINICAL-EXPERIENCE; RADICAL PROSTATECTOMY; MAGNETOMETER AB Background A variety of magnetic resonance (MR) lymphographic agents have been proposed for mapping the lymph nodes draining the prostate. Purpose To investigate the feasibility of using ferumoxytol (an FDA-approved iron oxide agent) for lymph node mapping of the prostate on imaging (MRI) in a non-human primate (NHP) Macaque model. Material and Methods Four NHPs weighing 5-13kg underwent injection of ferumoxytol after a needle was introduced transrectally under MRI guidance into the prostate using a commercially available intrarectal MRI biopsy guide. Ferumoxytol was administered at dosage in the range of 0.15-0.75mg Fe/kg in a fixed injection volume of 0.2mL. T1-weighted MRI was performed at 3T starting immediately and extending at least 45min post-injection. Two readers evaluated the images in consensus. The NHPs tolerated the ferumoxytol injections at all doses with no evident side effects. Results It was determined that the lowest dose of 0.15mg Fe/kg produced the best outcome in terms of lymph node visualization and draining nodes were reliably visualized at this dose and volume. Conclusion Thus, MRI with intraprostatic injection of ferumoxytol may be considered an effective T1 contrast agent for prospective mapping of lymph nodes draining the prostate and, thus, for attempted sentinel lymph node identification in prostate cancer. Large clinical trials to determine safety and efficacy are needed. C1 [Sankineni, Sandeep; Bernardo, Marcelino; Brown, Anna M.; Johnson, Linda; Muller, Berrend; Kobayashi, Hisataka; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Smedley, Jeremy] UW, Washington Natl Primate Res Ctr, Seattle, WA USA. [Muller, Berrend] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands. [Muller, Berrend; Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Griffiths, Gary L.] Leidos Biomed Res Inc, Clin Res Directorate, CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Dept Urol, Birmingham, AL USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Pinto, Peter A.; Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.; Wood, Bradford J.] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Keele, Brandon] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. 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 9 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0284-1851 EI 1600-0455 J9 ACTA RADIOL JI Acta Radiol. PD NOV PY 2016 VL 57 IS 11 BP 1396 EP 1401 DI 10.1177/0284185115586023 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DZ6YL UT WOS:000386008800018 PM 26013022 ER PT J AU Rosen, JA Langer, O Reece, EA Miodovnik, M AF Rosen, Julie A. Langer, Oded Reece, E. Albert Miodovnik, Menachem TI The History and Contributions of the Diabetes in Pregnancy Study Group of North America (1997-2015) SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE diabetes; pregnancy; obesity; diabesity; gestational diabetes mellitus AB The Diabetes in Pregnancy Study Group of North America (DPSG-NA) was founded in 1997 in San Antonio, Texas, out of the recognition that the field of maternal-fetal medicine should support and conduct research to address the specialized needs of pregnant women with type 1, type 2, or gestational diabetes mellitus. Since its inception, the DPSG-NA meetings have become a vehicle for the dissemination of data, gathered through collaboration among basic, translational, and clinical researchers and care centers, both in the United States and abroad. Although the meetings cover a range of topics related to diabetes in pregnancy, they have often highlighted a major, timely issue. Utilizing presentations, roundtable discussions, and debates, members of the DPSG-NA discussed the latest research, treatments, and approaches to significantly improve the health and wellbeing of pregnant women with diabetes and their offspring. The following commentary highlights the major contributions of each meeting. C1 [Rosen, Julie A.] Univ Maryland, Sch Med, College Pk, MD 20742 USA. [Reece, E. Albert] Univ Maryland, Dept Obstet Gynecol & Reprod Sci, Sch Med, College Pk, MD 20742 USA. [Reece, E. Albert] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, College Pk, MD 20742 USA. [Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Pregnancy & Perinatol, NIH, Bethesda, MD USA. RP Rosen, JA (reprint author), Univ Maryland, Sch Med, 655 W Baltimore St,Room 14-029, Baltimore, MD 21201 USA. EM jwu@som.umaryland.edu NR 13 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1223 EP 1226 DI 10.1055/s-0036-1585082 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900001 PM 27398700 ER PT J AU Goldenberg, RL McClure, EM Harrison, MS Miodovnik, M AF Goldenberg, Robert L. McClure, Elizabeth M. Harrison, Margo S. Miodovnik, Menachem TI Diabetes during Pregnancy in Low- and Middle-Income Countries SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE diabetes; pregnancy; gestational diabetes; obesity; glucose testing ID RISK-FACTORS; SCREENING-PROGRAM; GLOBAL PREVALENCE; ADVERSE OUTCOMES; MELLITUS; OBESITY; HEALTH; WOMEN; IMPLEMENTATION; HYPERGLYCEMIA AB Objective Our objective was to review the literature in relationship to diabetes in pregnancy in low and middle income countries. Study Design We reviewed the English language literature related to diabetes and obesity during pregnancy in low and middle income countries published over the last 20 years. Results The global prevalence of diabetes mellitus is an estimated 8% with approximately 380 million adults with this condition worldwide. Ninety percent of diabetes in adults occurs in low- and middle-income countries (LMIC). However, diabetes is highly correlated with obesity and the highest diabetes rates occur in countries with the highest obesity rates. Hyperglycemia complicates 17% of pregnancies, including women with diagnosed and undiagnosed types 1 and 2 diabetes, and gestational diabetes mellitus (GDM). In many LMIC, as pregnancy becomes more common in wealthier, older, and more obese women, pregnancies complicated by pregestational diabetes and GDM will increase. Approximately half of women with hyperglycemia in pregnancy are undiagnosed. Even with diagnosis, because of the numerous tests and criteria for abnormal glucose levels used worldwide, the prevalence of hyperglycemia in pregnancy can only be approximated. Moving forward, a single set of tests and diagnostic criteria is recommended. Although the risk factors and pregnancy outcomes for pregestational diabetes and GDM are similar in LMIC to wealthier countries, they appear to occur more commonly, and with worse outcomes because of poor access to care. In the poorest areas, inadequate antenatal and general medical care increase the difficulty in managing diabetes and its complications for women and newborns. Conclusion As obesity among women increases, diabetes in pregnancy is becoming increasingly common in LMIC. Because of lack of resources and trained personnel, and other priorities related to reducing maternal, fetal, and neonatal mortality, diagnosing and providing care to women with diabetes in pregnancy is not high on the priority lists in many LMIC. C1 [Goldenberg, Robert L.; Harrison, Margo S.] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, 622 West 168th St, New York, NY 10032 USA. [McClure, Elizabeth M.] Res Triangle Inst, Social Stat & Environm Hlth Sci, Durham, NC USA. [Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol & Pregnancy Branch, Bethesda, MD USA. RP Goldenberg, RL (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, 622 West 168th St, New York, NY 10032 USA. EM rlg88@columbia.edu NR 37 TC 1 Z9 1 U1 5 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1227 EP 1235 DI 10.1055/s-0036-1584152 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900002 PM 27182990 ER PT J AU Mehta, S Khoury, J Miodovnik, M Kawakita, T Ehrlich, S Bowers, K AF Mehta, Supal Khoury, Jane Miodovnik, Menachem Kawakita, Tetsuya Ehrlich, Shelley Bowers, Katherine TI Placental Weight in Pregnant Women with Type 1 Diabetes Mellitus: The Association with Fetal Growth SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE placental weight; type 1 diabetes mellitus; large for gestational age; glycemic control ID BIRTH-WEIGHT; GLYCEMIC CONTROL; HYPERGLYCEMIA AB Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A(1)(HbA(1))>= 8.5% (>= 2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA(1) < 8.5% vs. HbA(1) >= 8.5%) assessed the role of glycemic control on association between PW and LGA. Results PW in 302 pregnancies was positively associated with LGA (first vs. fourth quartile of PW; odds ratio [OR] = 9.56; 95% confidence interval [CI]: 4.14-22.08). Association varied significantly by glycemic control in the first trimester, but not in the second and third trimesters. For women with first trimester HbA(1) concentration < 8.5%, there was no statistically significant association; however, with HbA(1) >= 8.5%, there was a strong association (OR = 13.40, 95% CI: 3.31, 54.27). Conclusion There was a significant positive association between PW and LGA in infants of women with T1DM, particularly evident in pregnancies with poor glycemic control during the first trimester, highlighting the importance of achieving good glycemic control early in gestation. C1 [Mehta, Supal] Loyola Univ, Dept Biol Sci, Chicago, IL 60611 USA. [Mehta, Supal; Khoury, Jane; Ehrlich, Shelley; Bowers, Katherine] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. [Khoury, Jane] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. [Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Kawakita, Tetsuya] MedStar Washington Hosp Ctr, Washington, DC USA. RP Bowers, K (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Katherine.bowers@cchmc.org FU Diabetes in Pregnancy Program Project Grant (PPG) [HD11725]; National Institutes of Health, U.S. Public Health Service [MO1 RR 08084]; National Center For Advancing Translational Sciences of the National Institutes of Health [UL1 TR001425] FX This study was supported in part by the Diabetes in Pregnancy Program Project Grant (PPG), HD11725, funded from 1978 to 1995 by the National Institutes of Health, U.S. Public Health Service grant no. MO1 RR 08084, and by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award no. UL1 TR001425. The content is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 15 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1255 EP 1261 DI 10.1055/s-0036-1585055 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900006 PM 27398699 ER PT J AU Kawakita, T Bowers, K McWhorter, K Rosen, B Adams, M Miodovnik, M Khoury, JC AF Kawakita, Tetsuya Bowers, Katherine McWhorter, Ketrell Rosen, Barak Adams, Michelle Miodovnik, Menachem Khoury, Jane C. TI Characterizing Gestational Weight Gain According to Institute of Medicine Guidelines in Women with Type 1 Diabetes Mellitus: Association with Maternal and Perinatal Outcome SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE gestational weight gain; neonatal hyperbilirubinemia; Institute of Medicine guidelines; macrosomia; type 1 diabetes ID RANDOMIZED CONTROLLED-TRIAL; PREGNANCY OUTCOMES; NEPHROPATHY; PROGRESSION; RISK AB Objective This study aims to evaluate the association between gestational weight gain (GWG) defined by the current Institute of Medicine (IOM) guidelines and pregnancy outcomes in women with type 1 diabetes mellitus (DM). Study design This is a secondary analysis of a cohort of 293 pregnancies of women with type 1 DM between 24 and 41 weeks' gestation. Women were categorized according to GWG per week over the second and third trimester: below, within, and above the IOM guidelines. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for maternal and neonatal outcomes, controlling for covariates and confounders (referent: GWG within the IOM guidelines). Results Of the 293 women, there were 49 women (16.7%) with the GWG below the IOM guidelines, 86 women (29.4%) with the GWG within the IOM guidelines, and 158 women (53.9%) with the GWG above the IOM guidelines. Women with the GWG above the IOM guidelines had a higher risk of macrosomia and neonatal hyperbilirubinemia (aOR: 2.78; 95% CI: 1.23-6.30 and 2.31; 1.22-4.35, respectively). Conclusion GWG above the IOM guidelines is associated with an increased risk of macrosomia and neonatal hyperbilirubinemia. Maintaining GWG within the IOM guidelines may decrease the risk of excessive fetal growth and neonatal hyperbilirubinemia in infants of women with type 1 DM. C1 [Kawakita, Tetsuya] MedStar Washington Hosp Ctr, Obstet & Gynecol, 101 Irving St,NW,5B63, Washington, DC 20010 USA. [Bowers, Katherine; McWhorter, Ketrell; Khoury, Jane C.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [McWhorter, Ketrell] Univ Cincinnati, Dept Environm Hlth, Div Epidemiol, Cincinnati, OH USA. [Rosen, Barak] Mt Sinai West Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY USA. [Adams, Michelle] Cincinnati Childrens Hosp Med Ctr, Off Clin & Translat Res, Cincinnati, OH 45229 USA. [Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Khoury, Jane C.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. RP Kawakita, T (reprint author), MedStar Washington Hosp Ctr, Obstet & Gynecol, 101 Irving St,NW,5B63, Washington, DC 20010 USA. EM tetsuya.x.kawakita@gmail.com FU Diabetes in Pregnancy Program Project Grant [HD11725]; National Institutes of Health (NIH), National Institute of Child Health and Human Development, United States Public Health Service [MO1 RR 08084]; National Center for Advancing Translational Sciences of the NIH [UL1 TR001425] FX This study was supported in part by Diabetes in Pregnancy Program Project Grant, HD11725, funded between 1978 and 1995 by the National Institutes of Health (NIH), National Institute of Child Health and Human Development, United States Public Health Service (Grant no: MO1 RR 08084), and the National Center for Advancing Translational Sciences of the NIH under Award no: UL1 TR001425. NR 22 TC 0 Z9 0 U1 6 U2 6 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1266 EP 1272 DI 10.1055/s-0036-1585420 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900008 PM 27398703 ER PT J AU Szczesniak, RD Li, D Duan, LL Altaye, M Miodovnik, M Khoury, JC AF Szczesniak, Rhonda D. Li, Dan Duan, Leo L. Altaye, Mekibib Miodovnik, Menachem Khoury, Jane C. TI Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE blood pressure variability; curve shape; functional data analysis; functional principal component analysis; glucose control; glucose variability; insulin variability; medical monitoring; sparse longitudinal data AB Objective To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. C1 [Szczesniak, Rhonda D.; Altaye, Mekibib; Khoury, Jane C.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Szczesniak, Rhonda D.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Med, Cincinnati, OH 45229 USA. [Li, Dan; Duan, Leo L.] Univ Cincinnati, Dept Math Sci, Cincinnati, OH USA. [Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA. [Khoury, Jane C.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. RP Szczesniak, RD (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol MLC 5041, Cincinnati, OH 45229 USA. EM Rhonda.Szczesniak@cchmc.org FU National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) [K25 HL125954]; Diabetes in Pregnancy Program Project Grant [HD11725]; NIH, U.S.P.H.S. [MO1 RR 08084]; General Clinical Research Centers Program, National Center for Research Resources (NCRR); Institutional Clinical and Translational Science Award, NIH/NCRR [5UL1RR026314] FX The authors are grateful to the reviewers for their thoughtful comments and recommendations, which have substantially improved the clarity and message of the article. A portion of the abstract was presented at the 14th Biennial Meeting of the Diabetes in Pregnancy Study Group of North America. Dr. Szczesniak received partial support for this work from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (grant no. K25 HL125954). Supported in part by Diabetes in Pregnancy Program Project Grant, HD11725, funded from 1978 to 1995 by the NIH, U.S.P.H.S. grant no. MO1 RR 08084, General Clinical Research Centers Program, National Center for Research Resources (NCRR), and by an Institutional Clinical and Translational Science Award, NIH/NCRR grant no. 5UL1RR026314. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 24 TC 1 Z9 1 U1 2 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1282 EP 1290 DI 10.1055/s-0036-1586507 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900010 PM 27490775 ER PT J AU Kawakita, T Bowers, K Coviello, E Miodovnik, M Ehrlich, S Rosenn, B Khoury, JC AF Kawakita, T. Bowers, K. Coviello, E. Miodovnik, M. Ehrlich, S. Rosenn, B. Khoury, J. C. TI Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE prepregnancy weight; preterm delivery; spontaneous abortion; type 1 diabetes; low BMI; high BMI ID BODY-MASS INDEX; MATERNAL UNDERWEIGHT; PRETERM DELIVERY; RISK; OBESITY; BIRTH; NEPHROPATHY; MANAGEMENT; GAIN AB Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m(2)), normal BMI (20 to < 25 kg/m(2)), and high BMI (>= 25 kg/m(2)). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin Al concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A(1) was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI). C1 [Kawakita, T.; Coviello, E.] MedStar Washington Hosp Ctr, Dept Obstet & Gynecol, Washington, DC USA. [Bowers, K.; Ehrlich, S.; Khoury, J. C.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, MLC 5041,3333 Burnet Ave, Cincinnati, OH 45229 USA. [Miodovnik, M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Rosenn, B.] Mt Sinai West Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY USA. [Khoury, J. C.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. RP Khoury, JC (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, MLC 5041,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Jane.khoury@cchmc.org FU Diabetes in Pregnancy Program Project Grant (PPG) [HD11725]; National Institutes of Health (NIH), U.S.P.H.S. [MO1 RR 08084]; General Clinical Research Centers Program, National Center for Research Resources (NCRR); Institutional Clinical and Translational Science Award, NIH/NCRR [5UL1RR026314] FX This study was supported in part by Diabetes in Pregnancy Program Project Grant (PPG), HD11725, funded from 1978 to 1995 by the National Institutes of Health (NIH), U.S.P.H.S. grant no. MO1 RR 08084, General Clinical Research Centers Program, National Center for Research Resources (NCRR), and by an Institutional Clinical and Translational Science Award, NIH/NCRR grant no. 5UL1RR026314. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 23 TC 0 Z9 0 U1 2 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2016 VL 33 IS 13 BP 1300 EP 1305 DI 10.1055/s-0036-1586506 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA2DV UT WOS:000386403900012 PM 27487228 ER PT J AU Blair, JR AF Blair, James R. TI The Neurobiology of Disruptive Behavior Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID REWARD ANTICIPATION; CONDUCT PROBLEMS; EXPECTED VALUE; YOUTHS C1 [Blair, James R.] NIH, Sect Affect & Cognit Neurosci, Bldg 10, Bethesda, MD 20892 USA. RP Blair, JR (reprint author), NIH, Sect Affect & Cognit Neurosci, Bldg 10, Bethesda, MD 20892 USA. EM jamesblair@mail.nih.gov NR 10 TC 0 Z9 0 U1 6 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2016 VL 173 IS 11 BP 1073 EP 1074 DI 10.1176/appi.ajp.2016.16080971 PG 2 WC Psychiatry SC Psychiatry GA EA2LE UT WOS:000386423000003 PM 27799002 ER PT J AU LeDoux, JE Pine, DS AF LeDoux, Joseph E. Pine, Daniel S. TI Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID PREFRONTAL CORTEX FUNCTION; HUMAN AMYGDALA; GENERALIZED ANXIETY; EXPOSURE THERAPY; WORKING-MEMORY; HUMAN-BRAIN; EMOTIONAL STIMULI; COGNITIVE CONTROL; PANIC DISORDER; EXTINCTION AB Tremendous progress has been made in basic neuroscience in recent decades. One area that has been especially successful is research on how the brain detects and responds to threats. Such studies have demonstrated comparable patterns of brain-behavior relationships underlying threat processing across a range of mammalian species, including humans. This would seem to be an ideal body of information for advancing our understanding of disorders in which altered threat processing is a key factor, namely, fear and anxiety disorders. But research on threat processing has not led to significant improvements in clinical practice. The authors propose that in order to take advantage of this progress for clinical gain, a conceptual reframing is needed. Key to this conceptual change is recognition of a distinction between circuits underlying two classes of responses elicited by threats: 1) behavioral responses and accompanying physiological changes in the brain and body and 2) conscious feeling states reflected in self-reports of fear and anxiety. This distinction leads to a "two systems" view of fear and anxiety. The authors argue that failure to recognize and consistently emphasize this distinction has impeded progress in understanding fear and anxiety disorders and hindered attempts to develop more effective pharmaceutical and psychological treatments. The two-system view suggests a new way forward. C1 [LeDoux, Joseph E.] NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Dept Psychol, 6 Washington Pl, New York, NY 10003 USA. NYU, Dept Psychiat, 550 1St Ave, New York, NY 10016 USA. NYU, Dept Child & Adolescent Psychiat, New York, NY USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP LeDoux, JE (reprint author), NYU, Ctr Neural Sci, New York, NY 10003 USA. EM ledoux@cns.nyu.edu FU NIMH Intramural Research Program [1ZIAMH002781] FX Supported by NIMH Intramural Research Program Project 1ZIAMH002781 NR 150 TC 4 Z9 4 U1 23 U2 23 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2016 VL 173 IS 11 BP 1083 EP 1093 DI 10.1176/appi.ajp.2016.16030353 PG 11 WC Psychiatry SC Psychiatry GA EA2LE UT WOS:000386423000007 PM 27609244 ER PT J AU Skovbakke, SL Winther, M Gabl, M Holdfeldt, A Linden, S Wang, JM Dahlgren, C Franzyk, H Forsman, H AF Skovbakke, Sarah Line Winther, Malene Gabl, Michael Holdfeldt, Andre Linden, Sara Wang, Ji Ming Dahlgren, Claes Franzyk, Henrik Forsman, Huamei TI The peptidomimetic Lau-(Lys-beta NSpe)(6)-NH2 antagonizes formyl peptide receptor 2 expressed in mouse neutrophils SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Receptor antagonism; Anti-inflammatory; GPCR; NADPH-oxidase; Reactive oxygen species ID PROTEIN-COUPLED RECEPTORS; N-FORMYLPEPTIDE RECEPTOR; LIPOXIN A(4); STAPHYLOCOCCUS-AUREUS; RESPIRATORY BURST; CYCLOSPORINE-H; BONE-MARROW; ACTIVATION; FPR; LIGAND AB The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the human and murine FPR family members is required. Compared to FPR1 and FPR2 expressed by human neutrophils, very little is known about agonist/antagonist recognition patterns for their murine orthologues, but now we have identified two potent and selective formylated peptide agonists (fMIFL and PSM alpha 2) for Fpr1 and Fpr2, respectively. These peptides were used to determine the inhibition profile of a set of antagonists with known specificities for the two FPRs in relation to the corresponding murine receptors. Some of the most potent and selective antagonists for the human receptors proved to be devoid of effect on their murine orthologues as determined by their inability to inhibit superoxide release from murine neutrophils upon stimulation with receptor-specific agonists. The Boc-FLFLF peptide was found to be a selective antagonist for Fpr1, whereas the lipidated peptidomimetic Lau-(Lys-beta INSpe)(6)-NH2 and the hexapeptide WRW4 were identified as Fpr2-selective antagonists. (C) 2016 Elsevier Inc. All rights reserved. C1 [Skovbakke, Sarah Line; Winther, Malene; Gabl, Michael; Holdfeldt, Andre; Dahlgren, Claes; Forsman, Huamei] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. [Skovbakke, Sarah Line; Franzyk, Henrik] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-1168 Copenhagen, Denmark. [Linden, Sara] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Biochem & Cell Biol, Gothenburg, Sweden. [Wang, Ji Ming] Frederick Natl Lab Canc Res, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD USA. RP Dahlgren, C (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. EM Claes.Dahlgren@microbio.gu.se FU Department of Drug Design and Pharmacology, University of Copenhagen; Aase and Ejnar Danielsens foundation; King Christian 10th foundation; Swedish Research Council; King Gustaf the Vth 80-year foundation; IngaBritt and Arne Lundbergs foundation; Sahlgrenska University Hospital, Gothenburg, Sweden FX We thank the members of the Phagocyte Research Group at the Sahlgrenska Academy for critically discussing the results and the manuscript. Sarah Line Skovbakke is supported by research grants from Department of Drug Design and Pharmacology, University of Copenhagen, Aase and Ejnar Danielsens foundation and King Christian 10th foundation. The Gothenburg group was supported by grants from the Swedish Research Council, The King Gustaf the Vth 80-year foundation, IngaBritt and Arne Lundbergs foundation and, the Sahlgrenska University Hospital, Gothenburg, Sweden through the national ALF-agreement. The funding agencies had no influence on the study design, data collection and analysis, or writing and submission of the report. NR 42 TC 1 Z9 1 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 1 PY 2016 VL 119 BP 56 EP 65 DI 10.1016/j.bcp.2016.09.004 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DZ9KF UT WOS:000386193300006 PM 27614010 ER PT J AU Gao, XX Xie, C Wang, YY Luo, YH Yagai, T Sun, DX Qin, XM Krausz, KW Gonzalez, FJ AF Gao, Xiaoxia Xie, Cen Wang, Yuanyuan Luo, Yuhong Yagai, Tomoki Sun, Dongxue Qin, Xuemei Krausz, Kristopher W. Gonzalez, Frank J. TI The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Flutamide; Aryl hydrocarbon receptor; Bile acid homeostasis; ABCC4; Metabolomics ID SALT EXPORT PUMP; HUMAN LIVER-MICROSOMES; AH RECEPTOR; TOXICITY; DRUG; BINDING; HEPATOTOXICITY; METABOLISM; ACTIVATION; INHIBITION AB Flutamide (FLU), an oral, nonsteroidal antiandrogen drug used in the treatment of prostate cancer, is associated with idiosyncratic hepatotoxicity that sometimes causes severe liver damage, including cholestasis, jaundice, and liver necrosis. To understand the mechanism of toxicity, a combination of aryl hydrocarbon receptor (Ahr)-deficient (Ahr(-/-)) mice, primary hepatocytes, luciferase reporter gene assays, in silica ligand docking and ultra-performance chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics was used. A significant increase of liver weights, and liver and serum bile acid levels was observed after FLU treatment, indicating hepatomegaly and disrupted bile acid homeostasis. Expression of the AhR gene battery was markedly increased in livers of wild-type mice Ahr(+/+) treated with FLU, while no change was noted in Ahr(-/-) mice. Messenger RNAs encoded by AhR target genes were induced in primary mouse hepatocytes cultured with FLU, which confirmed the in vivo results. Ligand-docking analysis further predicted that FLU is an AhR agonist ligand which was confirmed by luciferase reporter gene assays. Multivariate data analysis showed that bile acids were responsible for the separation of vehicle- and FLU-treated Ahr(+/+) mice, while there was no separation in Ahr(-/-) mice. Expression of mRNA encoding the bile acid transporter ABCC4 was increased and farnesoid X receptor signaling was inhibited in the livers of Ahr(+/+) mice, but not in Ahr(-/-) mice treated with FLU, in agreement with the observed downstream metabolic alterations. These findings provide new insights into the mechanism of liver injury caused by FLU treatment involving activation of AhR and the alterations of bile acid homeostasis, which could guide clinical application. Published by Elsevier Inc. C1 [Gao, Xiaoxia; Qin, Xuemei] Shanxi Univ, Modern Res Ctr Tradit Chinese Med, Taiyuan 030006, Shanxi, Peoples R China. [Gao, Xiaoxia; Xie, Cen; Luo, Yuhong; Yagai, Tomoki; Sun, Dongxue; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wang, Yuanyuan] Univ Tennessee, Hlth Sci Ctr, Biosci Res Dept, 875 Union Ave, Memphis, TN 38163 USA. [Sun, Dongxue] Shenyang Pharmaceut Univ, Coll Tradit Chinese Med, Shenyang 110016, Liaoning, Peoples R China. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gaoxiaoxia@sxu.edu.cn; cen.xie@nih.gov; ywang197@uthsc.edu; yuhong.luo@nih.gov; tomoki.yagai@nih.gov; dongxue.sun@nih.gov; qinxm@sxu.edu.cn; krauszk@intra.nci.nih.gov; gonzalef@mail.nih.gov FU National Cancer Institute Intramural Research Program; National Natural Science Foundation of China [81473415, 81373040]; Shanxi University FX This study was supported by the National Cancer Institute Intramural Research Program and the National Natural Science Foundation of China [Grant No. 81473415 and 81373040]. X.G. was supported by Shanxi University. We thank Linda G. Byrd for assistance with the mouse studies. NR 47 TC 0 Z9 0 U1 10 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 1 PY 2016 VL 119 BP 93 EP 104 DI 10.1016/j.bcp.2016.08.021 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DZ9KF UT WOS:000386193300010 PM 27569425 ER PT J AU Kulminski, AM Raghavachari, N Arbeev, KG Culminskaya, I Arbeeva, L Wu, DQ Ukraintseva, SV Christensen, K Yashin, AI AF Kulminski, Alexander M. Raghavachari, Nalini Arbeev, Konstantin G. Culminskaya, Irina Arbeeva, Liubov Wu, Deqing Ukraintseva, Svetlana V. Christensen, Kaare Yashin, Anatoliy I. TI Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study SO BIOGERONTOLOGY LA English DT Article DE ApoE; Health span; Life span ID MACULAR DEGENERATION; E GENOTYPES; DIABETIC-NEPHROPATHY; RENAL-DISEASE; LONGEVITY; RISK; METAANALYSIS; ASSOCIATION; CANCER; PROGRESSION AB The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the epsilon 2 allele with lower LDL-C levels, lower risks of HD, and better survival. The epsilon 2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (beta = -7.1, p = 6.6 x 10(-44)). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 x 10(-6)) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 x 10(-2)). These results show that epsilon 2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking epsilon 2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine. C1 [Kulminski, Alexander M.; Arbeev, Konstantin G.; Culminskaya, Irina; Arbeeva, Liubov; Wu, Deqing; Ukraintseva, Svetlana V.; Yashin, Anatoliy I.] Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA. [Raghavachari, Nalini] NIA, 31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA. [Christensen, Kaare] Univ Southern Denmark, Danish Aging Res Ctr, DK-5000 Odense C, Denmark. [Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. [Christensen, Kaare] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark. RP Kulminski, AM (reprint author), Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA. EM Alexander.Kulminski@duke.edu OI Kulminski, Alexander/0000-0002-0205-8228 FU National Institute on Aging [U01AG023749, U01AG023744, U01AG023712, U01 AG023712, P01 AG043352, R01 AG047310] FX The Long Life Family Study is funded by U01AG023749, U01AG023744 and U01AG023712 from the National Institute on Aging. This work was supported by the National Institute on Aging (Grant Numbers U01 AG023712, P01 AG043352, R01 AG047310). NR 54 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 EI 1573-6768 J9 BIOGERONTOLOGY JI Biogerontology PD NOV PY 2016 VL 17 IS 5-6 BP 893 EP 905 DI 10.1007/s10522-016-9659-3 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA EA1VX UT WOS:000386381300009 PM 27447179 ER PT J AU Miyazaki, T Lin, TY Suzuki, E Lee, C Stopfer, M Ito, K AF Miyazaki, Takaaki Lin, Tzu-Yang Suzuki, Emiko Lee, Chi-hon Stopfer, Mark Ito, Kei TI Genetic identification of candidate gustatory second-order neurons that convey appetitive taste information to the motor/reward systems SO CHEMICAL SENSES LA English DT Meeting Abstract CT 17th International Symposium on Olfaction and Taste (ISOT) CY JUN 05-09, 2016 CL Yokohama, JAPAN C1 [Miyazaki, Takaaki; Lin, Tzu-Yang; Lee, Chi-hon; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA. [Miyazaki, Takaaki; Ito, Kei] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. [Miyazaki, Takaaki; Suzuki, Emiko] Natl Inst Genet, Shizuoka, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X EI 1464-3553 J9 CHEM SENSES JI Chem. Senses PD NOV PY 2016 VL 41 IS 9 MA P2-096 BP E222 EP E223 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA DZ8NB UT WOS:000386126000313 ER PT J AU Pallotto, M Briggman, KL AF Pallotto, Marta Briggman, Kevin L. TI Functional connectivity of perinatal and adult born granule cells following localized optogenetic stimulation in the mouse olfactory bulb SO CHEMICAL SENSES LA English DT Meeting Abstract CT 17th International Symposium on Olfaction and Taste (ISOT) CY JUN 05-09, 2016 CL Yokohama, JAPAN C1 [Pallotto, Marta; Briggman, Kevin L.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X EI 1464-3553 J9 CHEM SENSES JI Chem. Senses PD NOV PY 2016 VL 41 IS 9 MA P3-012 BP E241 EP E241 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA DZ8NB UT WOS:000386126000364 ER PT J AU Jung, J Goldstein, RB Grant, BF AF Jung, Jeesun Goldstein, Rise B. Grant, Bridget F. TI Association of respondent psychiatric comorbidity with family history of comorbidity: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ADVERSE CHILDHOOD EXPERIENCES; SUBSTANCE USE DISORDERS; ANTISOCIAL PERSONALITY-DISORDER; INTER-INFORMANT AGREEMENT; GENERAL-POPULATION SAMPLE; ANXIETY DISORDERS; PANIC DISORDER; SOCIAL PHOBIA; PROCEDURAL VALIDITY; DIAGNOSTIC-CRITERIA AB Objective: Substance use disorders and major psychiatric disorders are common, highly comorbid with each other, and familial. However, the extent to which comorbidity is itself familial remains unclear. The purpose of this study is to investigate associations between comorbidity among respondents with family history of comorbidity. Methods: We analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions-III to study the associations of family history (FH) of comorbidity among alcoholism, drug problems, depression, antisocial behavior, and anxiety disorders in parents and maternal and paternal grandparents with corresponding DSM-5 diagnostic comorbidity among respondents. We utilized multivariable multinomial logistic regression models controlling for age, sex, race, education, family income, marital status, and adverse childhood experiences (ACEs). Results: All comorbid associations of any two disorders with FH were statistically significant; almost all adjusted odds ratios (ORs) for respondent comorbidity in the presence of FH of the parallel comorbidity exceeded 10. ORs involving antisocial behavior in relatives and antisocial personality disorder in respondents were consistently larger than those for any other pairs of disorders. After further adjustment for ACEs, most patterns of association were similar but the ORs were reduced twofold to threefold. ACEs may be mediators in relationships between familial and respondent comorbidities. Conclusion: Further investigations of relationships among familial comorbidity, ACEs, and respondents' diagnoses may improve understanding of comorbidity. Published by Elsevier Inc. C1 [Jung, Jeesun; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,Room 3064, Rockville, MD 20852 USA. RP Jung, J (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,Room 3064, Rockville, MD 20852 USA. EM jeesun.jung@nih.gov; goldster@mail.nih.gov; bgrant@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Program of the National Institutes of Health, NIAAA FX The National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, NIAAA. NR 44 TC 0 Z9 0 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV PY 2016 VL 71 BP 49 EP 56 DI 10.1016/j.comppsych.2016.08.003 PG 8 WC Psychiatry SC Psychiatry GA EA5ET UT WOS:000386642900007 PM 27622994 ER PT J AU Cruz, CRY Andreeff, M Barrett, J AF Cruz, C. Russell Y. Andreeff, Michael Barrett, John TI Untitled SO CYTOTHERAPY LA English DT Editorial Material C1 [Cruz, C. Russell Y.] Childrens Natl Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Washington, DC 20010 USA. [Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. [Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Cruz, CRY (reprint author), Childrens Natl Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Washington, DC 20010 USA. EM CCruz@childrensnational.org NR 12 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD NOV PY 2016 VL 18 IS 11 BP 1349 EP 1350 DI 10.1016/j.jcyt.2016.09.004 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA EA0YT UT WOS:000386316200001 PM 27686830 ER PT J AU Tanamas, SK Saulnier, PJ Fufaa, GD Wheelock, KM Weil, EJ Hanson, RL Knowler, WC Bennett, PH Nelsons, RG AF Tanamas, Stephanie K. Saulnier, Pierre-Jean Fufaa, Gudeta D. Wheelock, Kevin M. Weil, E. Jennifer Hanson, Robert L. Knowler, William C. Bennett, Peter H. Nelsons, Robert G. TI Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; PIMA-INDIANS; BLOOD-PRESSURE; RENAL-FUNCTION; NEPHROPATHY; MELLITUS; PROGRESSION; IRBESARTAN; MORTALITY; BLOCKADE AB OBJECTIVE To determine whether early administration of losartan slows progression of diabetic kidney disease over an extended period. RESEARCH DESIGN AND METHODS We conducted a 6-year clinical trial in 169 American Indians with type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants were randomly assigned to receive losartan and 85 to placebo. Primary outcome was a decline in glomerular filtration rate (GFR; iothalamate) to <= 60 mL/min or to half the baseline value in persons who entered with GFR <120 mL/min. At enrollment, GFR averaged 165 mL/min (interquartile range 49-313 mL/min). During the trial, nine persons reached the primary outcome with a hazard ratio (HR; losartan vs. placebo) of 0.50 (95% CI 0.12-1.99). Participants were then followed posttrial for up to 12 years, with treatment managed outside the study. The effect of losartan on the primary GFR outcome was then reanalyzed for the entire study period, including the clinical trial and posttrial follow-up. RESULTS After completion of the clinical trial, treatment with renin-angiotensin system inhibitors was equivalent in both groups. During a median of 13.5 years following randomization, 29 participants originally assigned to losartan and 35 to placebo reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44-1.18). CONCLUSIONS Long-term risk of GFR decline was not significantly different between persons randomized to early treatment with losartan and those randomized to placebo. Accordingly, we found no evidence of an extended benefit of early losartan treatment on slowing GFR decline in persons with type 2 diabetes. C1 [Tanamas, Stephanie K.; Saulnier, Pierre-Jean; Fufaa, Gudeta D.; Wheelock, Kevin M.; Weil, E. Jennifer; Hanson, Robert L.; Knowler, William C.; Bennett, Peter H.; Nelsons, Robert G.] NIDDKD, NIH, Phoenix, AZ USA. [Saulnier, Pierre-Jean] Ctr Hosp Univ Poitiers, INSERM, Clin Invest Ctr CIC1402, Poitiers, France. RP Nelsons, RG (reprint author), NIDDKD, NIH, Phoenix, AZ USA. EM rnelson@nih.gov FU American Diabetes Association [1-08-CR-42] FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association (Clinical Science Award 1-08-CR-42), and Merck, which provided the study drug and placebo tablets. NR 25 TC 0 Z9 0 U1 2 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2016 VL 39 IS 11 BP 2004 EP 2010 DI 10.2337/dc16-0795 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA1BZ UT WOS:000386328800032 PM 27612501 ER PT J AU Klein, OL Aviles-Santa, L Cai, LW Collard, HR Kanaya, AM Kaplan, RC Kinney, GL Mendes, E Smith, L Talavera, G Wu, DH Daviglus, M AF Klein, Oana L. Aviles-Santa, Larissa Cai, Lianwen Collard, Harold R. Kanaya, Alka M. Kaplan, Robert C. Kinney, Gregory L. Mendes, Eliana Smith, Lewis Talavera, Gregory Wu, Donghong Daviglus, Martha TI Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) SO DIABETES CARE LA English DT Article ID LUNG-FUNCTION; INSULIN-RESISTANCE; HEART-FAILURE; MELLITUS; INFLAMMATION; RISK; ATHEROSCLEROSIS; ASSOCIATION; SPIROMETRY; DIFFUSION AB OBJECTIVE Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored. RESEARCH DESIGN AND METHODS The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEND, forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses. RESULTS Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEVi 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEVi (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/ Latinos with lung disease. CONCLUSIONS Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further. C1 [Klein, Oana L.; Collard, Harold R.; Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Aviles-Santa, Larissa] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Cai, Lianwen] UNC Gillings Sch Publ Hlth, Chapel Hill, NC USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Kinney, Gregory L.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Mendes, Eliana] Univ Miami, Dept Med, Miami, FL USA. [Smith, Lewis; Wu, Donghong] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Smith, Lewis; Wu, Donghong] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Talavera, Gregory] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Daviglus, Martha] Univ Illinois, Inst Minor Hlth Res, Chicago, IL USA. RP Klein, OL (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA USA. EM oklein@medicine.ucsf.edu FU National Heart, Lung, and Blood Institute [N01-HC 65233]; University of Miami [N01-HC-65234]; Albert Einstein College of Medicine [N01-HC-65235]; Northwestern University [N01-HC-65236]; San Diego State University [N01-HC-65237]; National Institute on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; Office of Dietary Supplements FX The HCHS/SOL was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute to the University of North Carolina (N01-HC 65233), University of Miami (N01-HC-65234), Albert Einstein College of Medicine (N01-HC-65235), Northwestern University (N01-HC-65236), and San Diego State University (N01-HC-65237). The following National Institutes of Health institutes/offices collaborated and cofunded the study: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and Office of Dietary Supplements. NR 33 TC 0 Z9 0 U1 3 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2016 VL 39 IS 11 BP 2051 EP 2057 DI 10.2337/dc16-1170 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA1BZ UT WOS:000386328800038 PM 27612502 ER PT J AU Zamoiski, RD Freedman, DM Linet, MS Kitahara, CM Liu, W Cahoon, EK AF Zamoiski, Rachel D. Freedman, D. Michal Linet, Martha S. Kitahara, Cari M. Liu, Wayne Cahoon, Elizabeth K. TI Prospective study of ultraviolet radiation exposure and risk of breast cancer in the United States SO ENVIRONMENTAL RESEARCH LA English DT Article DE Breast cancer; Ultraviolet radiation; Sunlight; Vitamin D; Cancer epidemiology ID DIETARY VITAMIN-D; RADIOLOGIC TECHNOLOGISTS; SUN EXPOSURE; FOLLOW-UP; SUNLIGHT; HEALTH; WOMEN; POLYMORPHISMS; POPULATION; US AB Although there are few environmental risk factors for breast cancer, some epidemiologic studies found that exposure to solar UV radiation (UVR) may lower risk. Prior epidemiologic studies are limited by narrow ambient UVR ranges and lack lifetime exposure assessment. To address these issues, we studied a cohort with residences representing a wide range of ambient UVR. Using the nationwide U.S. Radiologic Technologists study (USRT), we examined the association between breast cancer risk and UVR based on ambient UVR, time outdoors, a combined variable of ambient UVR and time outdoors (combined UVR), and sun susceptibility factors. Participants reported location of residence and hours spent outdoors during five age periods. Ambient UVR was derived by linking satellite-based annual UVR estimates to self-reported residences. Lifetime values were calculated by averaging these measures accounting for years spent in that location. We examined the risk of breast cancer among 36,725 participants (n=716 cases) from baseline questionnaire completion (2003-2005) through 2012-2013 using Cox proportional hazards models. Breast cancer risk was unrelated to ambient UVR (HR for lifetime 5th vs 1st quintile = 1.22, 95% CI: 0.95-1.56, p-trend = 0.36), time outdoors (HR for lifetime 5th vs 1st quintile=0.87, 95% confidence interval (CI): 0.68-1.10, p-trend = 0.46), or combined UVR (HR lifetime 5th vs 1st quintile = 0.85, 95% CI: 0.67-1.08, p-trend = 0.46). Breast cancer risk was not associated with skin complexion, eye or hair color, or sunburn history. This study does not support the hypothesis that UVR exposure lowers breast cancer risk. Published by Elsevier Inc. C1 [Zamoiski, Rachel D.; Freedman, D. Michal; Linet, Martha S.; Kitahara, Cari M.; Liu, Wayne; Cahoon, Elizabeth K.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Zamoiski, RD (reprint author), 9609 Med Ctr Dr,Room 7E512, Rockville, MD 20850 USA. EM rachel.zamoiski@nih.gov RI Kitahara, Cari/R-8267-2016 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda MD FX This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda MD. NR 35 TC 2 Z9 2 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2016 VL 151 BP 419 EP 427 DI 10.1016/j.envres.2016.08.013 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA EA2HO UT WOS:000386413600045 PM 27544330 ER PT J AU Pollack, AZ Perkins, NJ Sjaarda, L Mumford, SL Kannan, K Philippat, C Wactawski-Wende, J Schisterman, EF AF Pollack, Anna Z. Perkins, Neil J. Sjaarda, Lindsey Mumford, Sunni L. Kannan, Kurunthachalam Philippat, Claire Wactawski-Wende, Jean Schisterman, Enrique F. TI Variability and exposure classification of urinary phenol and paraben metabolite concentrations in reproductive-aged women SO ENVIRONMENTAL RESEARCH LA English DT Article DE Benzophenone-3; Bisphenol A; Dichlorophenol; Intra-individual variability; Parabens; Reliability, Triclosan ID BISPHENOL-A CONCENTRATIONS; PERSONAL CARE PRODUCTS; UNITED-STATES; PHTHALATE METABOLITE; TEMPORAL VARIABILITY; POSTMENOPAUSAL WOMEN; MENSTRUAL-CYCLE; PREGNANT-WOMEN; HUMAN HEALTH; PREDICTORS AB Background: Human exposure to phenols and parabens is widespread. Within-person variability of urinary concentrations in healthy women is not well characterized. Objectives: To characterize the variability of urinary phenol and paraben concentrations across two months and evaluate the ability of a single spot urine sample to characterize exposure. Methods: 143 women provided 509 spot urine samples collected across two months of study (3-5 samples/woman). We measured urinary concentrations of 8 phenols: bisphenol A (BPA), benzophenone-3 (BP-3), benzophenone-1 (BP-1), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-trichlorophenol (2,4,6-TCP), triclosan (TCS); and 8 parabens and their metabolites (benzyl (BzP), butyl (BuP), ethyl (EtP), heptyl (HeP), methyl (MeP), propyl (PrP), 4-hydroxybenzoic acid (4-HB), 3,4-dihydroxybenzoic acid (3,4-DHB)). Biomarker variability was characterized using the intraclass correlation coefficient (ICC) and surrogate category analyses were conducted. Results: ICCs ranged from very low for BPA (0.04) to moderate for BP-3, BP-1, TCS, BzP, and MeP (0.66, 0.58, 0.55, 0.54, and 0.62, respectively). Surrogate analyses suggested that BP-1, BP-3, TCS, 2,4-DCP, BuP, and PrP may be characterized by a single spot sample (sensitivity range 0.76-0.86) but that additional samples were necessary for BPA, HeP, 4-HB, and 3,4-DHB (sensitivity range 0.47-0.61). Conclusions: Urinary phenol and paraben metabolite concentrations were variable across two months in healthy women but the degree of reliability differed by the specific biomarker. A small number of samples may sufficiently characterize typical concentrations for BP-3, BP-1, TCS, BuP, and PrP; but additional biospecimens may be necessary to characterize exposure for other compounds, including BPA. (C) 2016 Elsevier Inc. All rights reserved. C1 [Pollack, Anna Z.] George Mason Univ, Coll Hlth & Human Serv, Dept Global & Community Hlth, 4400 Univ Dr,MS5B7, Fairfax, VA 22030 USA. [Perkins, Neil J.; Sjaarda, Lindsey; Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Rockville, MD 20852 USA. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. [Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Empire State Plaza,POB 509, Albany, NY 12201 USA. [Philippat, Claire] Univ Grenoble Alpes, IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, F-38000 Grenoble, France. [Philippat, Claire] INSERM, IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, F-38000 Grenoble, France. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, 410 Kimball Hall, Buffalo, NY 14214 USA. RP Pollack, AZ (reprint author), George Mason Univ, Coll Hlth & Human Serv, Dept Global & Community Hlth, 4400 Univ Dr,MS5B7, Fairfax, VA 22030 USA. EM apollac2@gmu.edu; perkinsn@mail.nih.gov; lindsey.sjaarda@nih.gov; mumfords@mail.nih.gov; kurunthachalam.kannan@health.ny.gov; Claire.philippat@inserm.fr; jww@buffalo.edu; schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Sjaarda, Lindsey/0000-0003-0539-8110; Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States [HHSN275200403394C, HHSN275201100001I, Task 3 HHSN27500003] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States (Contract Numbers: HHSN275200403394C, HHSN275201100001I, and Task 3 HHSN27500003). The authors thank the investigators and staff at the Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and at the University at Buffalo for their respective roles in the study and the study participants for their commitment to the study. We acknowledge the George Mason University Microbiome Analysis Center (MBAC) Metabiome Portal for assistance with the correlation figure using Cytoscape. NR 51 TC 0 Z9 0 U1 14 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2016 VL 151 BP 513 EP 520 DI 10.1016/j.envres.2016.08.016 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA EA2HO UT WOS:000386413600055 PM 27567355 ER PT J AU Zijlema, W Cai, YT Doiron, D Mbatchou, S Fortier, I Gulliver, J de Hoogh, K Morley, D Hodgson, S Elliott, P Key, T Kongsgard, H Hveem, K Gaye, A Burton, P Hansell, A Stolk, R Rosmalen, J AF Zijlema, Wilma Cai, Yutong Doiron, Dany Mbatchou, Stephan Fortier, Isabel Gulliver, John de Hoogh, Kees Morley, David Hodgson, Susan Elliott, Paul Key, Timothy Kongsgard, Havard Hveem, Kristian Gaye, Amadou Burton, Paul Hansell, Anna Stolk, Ronald Rosmalen, Judith TI Road traffic noise, blood pressure and heart rate: Pooled analyses of harmonized data from 88,336 participants SO ENVIRONMENTAL RESEARCH LA English DT Article DE Blood pressure; Heart rate; Noise; Air pollution; Epidemiology; Meta-analysis ID LONG-TERM EXPOSURE; AIR-POLLUTION; EPIC-OXFORD; BRITISH VEGETARIANS; DATASHAPER APPROACH; PRESCHOOL-CHILDREN; MEAT-EATERS; HYPERTENSION; ASSOCIATIONS; COHORT AB Introduction: Exposure to road traffic noise may increase blood pressure and heart rate. It is unclear to what extent exposure to air pollution may influence this relationship. We investigated associations between noise, blood pressure and heart rate, with harmonized data from three European cohorts, while taking into account exposure to air pollution. Methods: Road traffic noise exposure was assessed using a European noise model based on the Common Noise Assessment Methods in Europe framework (CNOSSOS-EU). Exposure to air pollution was estimated using a European-wide land use regression model. Blood pressure and heart rate were obtained by trained clinical professionals. Pooled cross-sectional analyses of harmonized data were conducted at the individual level and with random-effects meta-analyses. Results: We analyzed data from 88,336 participants, across the three participating cohorts (mean age 47.0 (+/- 13.9) years). Each 10 dB(A) increase in noise was associated with a 0.93 (95% CI 0.76;1.11) bpm increase in heart rate, but with a decrease in blood pressure of 0.01 (95% CI -0.24;0.23) mmHg for systolic and 0.38 (95% CI -0.53; -0.24) mmHg for diastolic blood pressure. Adjustments for PM10 or NO2 attenuated the associations, but remained significant for DBP and HR. Results for BP differed by cohort, with negative associations with noise in LifeLines, no significant associations in EPIC-Oxford, and positive associations with noise > 60 dB(A) in HUNT3. Conclusions: Our study suggests that road traffic noise may be related to increased heart rate. No consistent evidence for a relation between noise and blood pressure was found. C1 [Zijlema, Wilma; Stolk, Ronald] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Zijlema, Wilma; Hansell, Anna] Univ Pompeu Fabra UPF, Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain. [Cai, Yutong; Gulliver, John; de Hoogh, Kees; Morley, David; Hodgson, Susan; Elliott, Paul] Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England. [Doiron, Dany; Mbatchou, Stephan; Fortier, Isabel] McGill Univ, Hlth Ctr RI MUHC, Res Inst, Montreal, PQ, Canada. [Doiron, Dany; de Hoogh, Kees] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Doiron, Dany; de Hoogh, Kees] Univ Basel, Basel, Switzerland. [Key, Timothy] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England. [Kongsgard, Havard; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway. [Gaye, Amadou] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, Bethesda, MD 20892 USA. [Burton, Paul] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Hansell, Anna] Imperial Coll Healthcare NHS Trust, London, England. [Rosmalen, Judith] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Rosmalen, Judith] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Zijlema, Wilma] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain. RP Zijlema, W (reprint author), ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona Biomed Res Pk PRBB,Doctor Aiguader 88, Barcelona 08003, Spain. EM wilma.zijlema@isglobal.org OI Zijlema, Wilma/0000-0002-6257-5091; Gaye, Amadou/0000-0002-1180-2792 FU European Union [261433]; MRC; Wellcome Trust underpinning the ALSPAC project (Wellcome/MRC strategic award) [092731]; Welsh Institute - MRC; Scottish Farr Institute - MRC; BBMRI-LPC (EU FP7, I3 grant); FES (Fonds Economische Structuurversterking); SNN (Samenwerkingsverband Noord Nederland); REP (Ruimtelijk Economisch Programma); Cancer Research UK [C8221/A19170]; UK Medical Research Council [MR/M012190]; Imperial College Healthcare NHS Trust; Imperial College Biomedical Research Centre - National Institute for Health Research (NIHR); Medical Research Council; Public Health England (MRC-PHE) Centre for Environment and Health [MR/L01341X/1]; NIHR Health Protection Research Unit on Health Impact of Environmental Hazards [HPRU-2012-10030-KCL] FX The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261433 (Biobank Standardisation and Harmonization for Research Excellence in the European Union BioSHaRE-EU). DataSHIELD development has also been partly funded under a strategic award from MRC and Wellcome Trust underpinning the ALSPAC project (Wellcome/MRC strategic award 092731); and the Welsh and Scottish Farr Institutes funded by MRC, BBMRI-LPC (EU FP7, I3 grant). BioSHaRE, and the involved cohorts LifeLines (BRIF 4568) and HUNT3 (BRIF 2365) are engaged in a Bioresource Research Impact Factor (BRIF) policy pilot study, details of which can be found at https://www.bioshare.eu/content/bioresource-impact-factor.; The Lifelines Biobank initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijk Economisch Programma). LifeLines is a facility that is open for all researchers. Information on application and data access procedure is summarized on www.lifelines.net. We thank all the participants of EPIC-Oxford and data collection teams for generously helping us in this research. EPIC-Oxford is supported by Cancer Research UK (C8221/A19170), and the UK Medical Research Council (MR/M012190). The Nord-Trondelag Health Study (The HUNT Study) is collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology NTNU), Nord-Trondelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. P.E. is supported by the Imperial College Healthcare NHS Trust and Imperial College Biomedical Research Centre funded by the National Institute for Health Research (NIHR), the Medical Research Council and Public Health England (MRC-PHE) Centre for Environment and Health (MR/L01341X/1), the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards (HPRU-2012-10030-KCL) and he is an NIHR Senior Investigator. NR 44 TC 1 Z9 1 U1 11 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2016 VL 151 BP 804 EP 813 DI 10.1016/j.envres.2016.09.014 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA EA2HO UT WOS:000386413600087 PM 27692672 ER PT J AU Goetzl, EJ Mustapic, M Kapogiannis, D Eitan, E Lobach, IV Goetzl, L Schwartz, JB Miller, BL AF Goetzl, Edward J. Mustapic, Maja Kapogiannis, Dimitrios Eitan, Erez Lobach, Irina V. Goetzl, Laura Schwartz, Janice B. Miller, Bruce L. TI Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease SO FASEB JOURNAL LA English DT Article DE dementia; amyloid; tau; biomarkers ID BETA-SECRETASE; TRANSCRIPTIONAL REGULATION; EXTRACELLULAR VESICLES; OXIDATIVE STRESS; CLINICAL-TRIALS; NERVOUS-SYSTEM; BLOOD EXOSOMES; ADAS-COG; A-BETA; NEURONS AB Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway. The capacity to isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing neuron-specific cargo, has permitted characterization of CNS-derived exosomes in living humans. Constituents of the amyloid -peptide (A)42-generating system now are examined in 2 distinct sets of human neural cells by quantification in astrocyte-derived exosomes (ADEs) and NDEs, enriched separately from plasmas of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) and matched cognitively normal controls. ADE levels of -site amyloid precursor protein-cleaving enzyme 1 (BACE-1), -secretase, soluble A42, soluble amyloid precursor protein (sAPP), sAPP, glial-derived neurotrophic factor (GDNF), P-T181-tau, and P-S396-tau were significantly (3- to 20-fold) higher than levels in NDEs for patients and controls. BACE-1 levels also were a mean of 7-fold higher in ADEs than in NDEs from cultured rat type-specific neural cells. Levels of BACE-1 and sAPP were significantly higher and of GDNF significantly lower in ADEs of patients with AD than in those of controls, but not significantly different in patients with FTD than in controls. Abundant proteins of the A42 peptide-generating system in ADEs may sustain levels in neurons. ADE cargo proteins may be useful for studies of mechanisms of cellular interactions and effects of BACE-1 inhibitors in AD.Goetzl, E. J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., Miller, B. L. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease. C1 [Goetzl, Edward J.; Schwartz, Janice B.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Lobach, Irina V.] Univ Calif San Francisco, Clin Translat Sci Inst, San Francisco, CA 94143 USA. [Schwartz, Janice B.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Goetzl, Edward J.; Schwartz, Janice B.] Jewish Home San Francisco, Geriatr Res Ctr, San Francisco, CA USA. [Mustapic, Maja; Kapogiannis, Dimitrios; Eitan, Erez] NIA, Lab Neurosci, NIH, Baltimore, MD 21224 USA. [Goetzl, Laura] Temple Univ, Dept Obstet Gynecol & Reprod Sci, Philadelphia, PA 19122 USA. RP Goetzl, EJ (reprint author), Geriatr Res Ctr, 1719 Broderick St, San Francisco, CA 94115 USA. EM edward.goetzl@ucsf.edu FU Biomarkers Across Neurodegenerative Diseases 2 program of the Michael J. Fox Foundation for Parkinson's Research; Alzheimer's Association; Alzheimer's Research UK; Weston Brain Institute; U.S. National Institues of Health (NIH) National Institute on Aging (NIA) Intramural Program; NIH/NIA [P30 AG028383] FX This work was supported by a grant from the Biomarkers Across Neurodegenerative Diseases 2 program of the Michael J. Fox Foundation for Parkinson's Research, the Alzheimer's Association, Alzheimer's Research UK and the Weston Brain Institute, the U.S. National Institues of Health (NIH) National Institute on Aging (NIA) Intramural Program (to M.M., D.K. and E.E.), and NIH/NIA grant P30 AG028383 (to E.L.A.). The authors thank Judith H. Goetzl (Jewish Home of San Francisco) for expert preparation of the illustrations. E.J.G. has filed a provisional patent application with the U.S. Patent Office for the methodology of immunochemical isolation and analytical applications of astrocyte-derived exosomes. The remaining authors declare no competing financial interests. NR 39 TC 0 Z9 0 U1 9 U2 9 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD NOV PY 2016 VL 30 IS 11 BP 3853 EP 3859 DI 10.1096/fj.201600756R PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA EA3BY UT WOS:000386474700019 PM 27511944 ER PT J AU Park, H Sha, MM Willis, G AF Park, Hyunjoo Sha, M. Mandy Willis, Gordon TI Influence of English-language Proficiency on the Cognitive Processing of Survey Questions SO FIELD METHODS LA English DT Review AB When recruiting respondents for cognitive interviews testing translated survey questionnaires, researchers often recommend interviewing monolingual non-English speakers because they are the likely users of the translations. However, these individuals are hard to recruit, and there is no standard definition of monolingual. Using cognitive interview data collected from pretesting of Chinese and Korean translations of the American Community Survey Language Assistance Guide, we investigated whether there were differences in respondents' understanding of survey questions according to their level of English proficiency and if such differences remained after considering demographic characteristics. We found that the types of issues reported by monolingual speakers and partially bilingual speakers were similar and that differences seemed to be driven by different demographic characteristics and not necessarily by language proficiency. Our findings suggest the value of evaluating translated questionnaires with individuals having diverse demographic characteristics and recruiting both monolingual speakers and partially bilingual speakers as research participants. C1 [Park, Hyunjoo] RTI Int, Ctr Survey Methodol, Survey Res Div, 351 Calif St,Suite 500, San Francisco, CA 94104 USA. [Sha, M. Mandy] RTI Int, Ctr Survey Methodol, Survey Res Div, Chicago, IL USA. [Willis, Gordon] NCI, NIH, Bethesda, MD 20892 USA. RP Park, H (reprint author), RTI Int, Ctr Survey Methodol, Survey Res Div, 351 Calif St,Suite 500, San Francisco, CA 94104 USA. EM mpark@rti.org NR 17 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1525-822X EI 1552-3969 J9 FIELD METHOD JI Field Methods PD NOV PY 2016 VL 28 IS 4 BP 415 EP 430 DI 10.1177/1525822X16630262 PG 16 WC Anthropology; Social Sciences, Interdisciplinary SC Anthropology; Social Sciences - Other Topics GA DZ6ZB UT WOS:000386011000006 ER PT J AU Rand, MS Baldwin, KS Bangma, J Barbeau, T Bermudez, DS Bernhard, M Botha, H Bowden, JA Brock, JW Cantu, T Crain, DA Davis, E Doheny, B Edwards, TM Girling, J Gunderson, MP Hamlin, HJ Kohno, S Larkin, IV Martinot, A Masson, GR Matter, J McCoy, KA McNabb, NA Milnes, MR Moore, BC Nilsen, FM Orlando, EF Palmer, B Parrott, BB Rainwater, TR Roark, AM Rooney, AA Tubbs, CW Wenzel, AG Williams, CE AF Rand, Matthew S. Baldwin, Kevin S. Bangma, Jacqueline Barbeau, Tamatha Bermudez, Dieldrich S. Bernhard, Melissa Botha, Hannes Bowden, John A. Brock, John W. Cantu, Theresa Crain, D. Andrew Davis, Elizabeth Doheny, Brenna Edwards, Thea M. Girling, Jane Gunderson, Mark P. Hamlin, Heather J. Kohno, Satomi Larkin, Iske V. Martinot (Jezek), Amanda Masson, Greg R. Matter, John McCoy, Krista A. McNabb, Nicole A. Milnes, Matthew R. Moore, Brandon C. Nilsen, Frances M. Orlando, Edward F. Palmer, Brent Parrott, Benjamin B. Rainwater, Thomas R. Roark, Alison M. Rooney, Andrew A. Tubbs, Christopher W. Wenzel, Abby G. Williams, Cameron E. TI In memory of Professor Louis J. Guillette, Jr. In Memoriam SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Biographical-Item C1 [Rand, Matthew S.] Carleton Coll, Northfield, MN 55057 USA. [Baldwin, Kevin S.] Monmouth Coll, Monmouth, IL USA. [Bangma, Jacqueline; Doheny, Brenna; Kohno, Satomi; Nilsen, Frances M.; Parrott, Benjamin B.] Med Univ South Carolina, Hollings Marine Lab, Charleston, SC USA. [Barbeau, Tamatha] Francis Marion Univ, Florence, SC USA. [Bermudez, Dieldrich S.] SC Johnson, Racine, WI USA. [Bernhard, Melissa] Mote Marine Lab, Sarasota, FL 34236 USA. [Botha, Hannes] Univ Limpopo, Mpumalanga Tourism & Parks Agcy, Polokwane, South Africa. [Bowden, John A.] NIST, Charleston, SC USA. [Brock, John W.] Univ N Carolina, Asheville, NC USA. [Cantu, Theresa] Med Univ South Carolina, Charleston, SC USA. [Crain, D. Andrew] Maryville Coll, Maryville, TN USA. [Davis, Elizabeth] Butler Univ, Indianapolis, IN 46208 USA. [Edwards, Thea M.; Moore, Brandon C.] Univ South, Sewanee, TN USA. [Girling, Jane] Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic 3010, Australia. [Gunderson, Mark P.] Coll Idaho, Caldwell, ID USA. [Hamlin, Heather J.] Univ Maine, Orono, ME 04469 USA. [Larkin, Iske V.] Univ Florida, Coll Vet Med, Gainesville, FL 32611 USA. [Martinot (Jezek), Amanda] Harvard Med Sch, Boston, MA USA. [Masson, Greg R.] US Fish & Wildlife Serv, Brunswick, ME USA. [Matter, John] Juniata Coll, Huntingdon, PA 16652 USA. [McCoy, Krista A.] East Carolina Univ, Greenville, NC 27858 USA. [McNabb, Nicole A.] Coll Charleston, Hollings Marine Lab, Charleston, SC USA. Mars Hill Univ, Mars Hill, NC USA. [Orlando, Edward F.] Univ Maryland, College Pk, MD 20742 USA. [Palmer, Brent] Univ Kentucky, Lexington, KY 40506 USA. [Rainwater, Thomas R.] Clemson Univ, Clemson, SC 29631 USA. [Roark, Alison M.] Furman Univ, Greenville, SC 29613 USA. [Rooney, Andrew A.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Tubbs, Christopher W.] San Diego Zoo Global Inst Conservat Res, Escondido, CA USA. [Wenzel, Abby G.] Med Univ South Carolina, Charleston, SC USA. [Williams, Cameron E.] Coll Charleston, Charleston, SC USA. RP Rand, MS (reprint author), Carleton Coll, Northfield, MN 55057 USA. EM mrand@carleton.edu NR 1 TC 0 Z9 0 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 EI 1095-6840 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD NOV 1 PY 2016 VL 238 BP 1 EP 3 DI 10.1016/j.ygcen.2016.02.014 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ9KW UT WOS:000386195000001 ER PT J AU Derkach, A Chatterjee, N AF Derkach, Andriy Chatterjee, Nilanjan TI Simplified Power Calculations for Rare Variant Association Tests and Implications for Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Derkach, Andriy] NCI, Rockville, MD USA. [Chatterjee, Nilanjan] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 11 BP 612 EP 612 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800018 ER PT J AU Sallah, N Carstensen, T Wakeham, K Bagni, R Labo, N Pollard, MO Gurdasani, D Ekoru, K Fatumo, S Pomilla, C Young, EH Asiki, G Kamali, A Sandhu, M Kellam, P Whitby, D Newton, R Barroso, I AF Sallah, Neneh Carstensen, Tommy Wakeham, Katie Bagni, Rachel Labo, Nazzarena Pollard, Martin O. Gurdasani, Deepti Ekoru, Kenneth Fatumo, Segun Pomilla, Cristina Young, Elizabeth H. Asiki, Gershim Kamali, Anatoli Sandhu, Manjinder Kellam, Paul Whitby, Denise Newton, Robert Barroso, Ines TI Novel Genome-Wide Sequence Variants Influence Antibody Response to Epstein-Barr Virus in an African Population SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Sallah, Neneh; Carstensen, Tommy; Pollard, Martin O.; Gurdasani, Deepti; Ekoru, Kenneth; Fatumo, Segun; Pomilla, Cristina; Young, Elizabeth H.; Sandhu, Manjinder; Barroso, Ines] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England. [Sallah, Neneh; Kellam, Paul] Wellcome Trust Sanger Inst, Virus Genom, Hinxton, England. [Carstensen, Tommy; Pollard, Martin O.; Gurdasani, Deepti; Ekoru, Kenneth; Fatumo, Segun; Pomilla, Cristina; Young, Elizabeth H.; Sandhu, Manjinder] Univ Cambridge, Dept Med, Cambridge, England. [Wakeham, Katie; Asiki, Gershim; Kamali, Anatoli; Newton, Robert] MRC Uganda Virus Res Inst, Uganda Res Unit AIDS, Entebbe, Uganda. [Bagni, Rachel] Frederick Natl Lab Canc Res, Prot Express Lab, Frederick, MD USA. [Labo, Nazzarena; Whitby, Denise] Frederick Natl Lab Canc Res, Viral Oncol Sect, Aids & Canc Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 26 BP 618 EP 618 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800033 ER PT J AU Bailey-Wilson, JE Musolf, AM Simpson, CL de Andrade, M Mandal, D Gaba, C Yang, P You, M Kupert, EY Anderson, MW Schwartz, AG Pinney, SM Amos, CI AF Bailey-Wilson, Joan E. Musolf, Anthony M. Simpson, Claire L. de Andrade, Mariza Mandal, Diptasri Gaba, Colette Yang, Ping You, Ming Kupert, Elena Y. Anderson, Marshall W. Schwartz, Ann G. Pinney, Susan M. Amos, Christopher I. TI Linkage Analyses Reveal Significant Signals on Multiple Chromosomes for Familial Lung Cancer SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Bailey-Wilson, Joan E.; Musolf, Anthony M.; Simpson, Claire L.] NHGRI, NIH, Baltimore, MD USA. [de Andrade, Mariza; Yang, Ping] Mayo Clin, Rochester, MN USA. [Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Gaba, Colette] Univ Toledo, Dana Canc Ctr, Toledo, OH 43606 USA. [You, Ming; Kupert, Elena Y.; Anderson, Marshall W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Pinney, Susan M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 38 BP 622 EP 622 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800045 ER PT J AU Chen, TH Shi, JX Chatterjee, N AF Chen, Ting-Huei Shi, Jianxin Chatterjee, Nilanjan TI A New Statistical Method for Polygenic Risk Modelling to Incorporate LD and Functional Information of SNPs using GWAS Summary-Level Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Chen, Ting-Huei] Univ Laval, Dept Math & Stat, Quebec City, PQ, Canada. [Shi, Jianxin] NCI DCEG, Biostat Branch, Bethesda, MD USA. [Chatterjee, Nilanjan] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Chatterjee, Nilanjan] Johns Hopkins Univ, Dept Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chatterjee, Nilanjan] Johns Hopkins Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 55 BP 629 EP 629 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800062 ER PT J AU Darst, BF Bilgel, M Koscik, RL Hermann, BP Jedynak, BM Johnson, SC Engelman, CD AF Darst, Burcu F. Bilgel, Murat Koscik, Rebecca L. Hermann, Bruce P. Jedynak, Bruno M. Johnson, Sterling C. Engelman, Corinne D. TI Using LASSO Regression to Identify Gene-Gene and Gene-Environment Interactions Influencing Cognitive Function in those with Increased Alzheimer's Risk SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Darst, Burcu F.; Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Bilgel, Murat] Johns Hopkins Univ, Sch Engn, Dept Biomed Engn, Baltimore, MD USA. [Bilgel, Murat] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Koscik, Rebecca L.; Hermann, Bruce P.; Johnson, Sterling C.; Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI USA. [Hermann, Bruce P.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Hermann, Bruce P.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Jedynak, Bruno M.] Portland State Univ, Dept Math & Stat, Portland, OR 97207 USA. [Johnson, Sterling C.; Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 59 BP 630 EP 631 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800066 ER PT J AU Gong, JF Baskurt, Z Derkach, A Pesevski, A Strug, LJ AF Gong, Jiafen Baskurt, Zeynep Derkach, Andriy Pesevski, Angelina Strug, Lisa J. TI RVS: An R Package to Integrate Next Generation Sequencing (NGS) Data Across Cohorts for Association Analysis SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Gong, Jiafen; Baskurt, Zeynep; Pesevski, Angelina; Strug, Lisa J.] Hosp Sick Children, Res Inst, Program Genet & Genome Biol, Toronto, ON, Canada. [Derkach, Andriy] NCI, Biostat Branch, 9609 Med Ctr Dr, Rockville, MD USA. [Strug, Lisa J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Biostat, Toronto, ON M5S 1A1, Canada. [Strug, Lisa J.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 80 BP 638 EP 638 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800087 ER PT J AU Holzinger, E Szymcak, S Malley, J Dasgupta, A Li, Q Bailey-Wilson, J AF Holzinger, Emily Szymcak, Silke Malley, James Dasgupta, Abhijit Li, Qing Bailey-Wilson, Joan TI A Novel Phenotype Permutation Method to Optimize Threshold selection in Random Forests SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Holzinger, Emily; Li, Qing; Bailey-Wilson, Joan] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. [Szymcak, Silke] Univ Kiel, Inst Med Informat & Stat, Kiel, Germany. [Malley, James] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Dasgupta, Abhijit] NIAMSD, Clin Trials & Outcomes Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 89 BP 641 EP 642 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800096 ER PT J AU Lewis, DD Simpson, CL Musolf, AM Long, K Portas, L Murgia, F Stambolian, D Bailey-Wilson, JE AF Lewis, Deyana D. Simpson, Claire L. Musolf, Anthony M. Long, Kyle Portas, Laura Murgia, Federico Stambolian, Dwight Bailey-Wilson, Joan E. TI Family-Based Rare Variant Association Study of Familial Myopia in Amish and Ashkenazi Jewish families SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Lewis, Deyana D.; Musolf, Anthony M.; Portas, Laura; Murgia, Federico; Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, NIH, Computat & Stat Genom Branch, Baltimore, MD USA. [Simpson, Claire L.] Univ Tennessee, Hlth Sci Ctr, Genet Genom & Informat, Memphis, TN USA. [Long, Kyle] Univ Texas El Paso, El Paso, TX 79968 USA. [Stambolian, Dwight] Univ Penn, Perelman Sch Med, Ophthalmol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 111 BP 649 EP 649 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800117 ER PT J AU Li, Q Holzinger, E Marazita, ML Beaty, TH Bailey-Wilson, JE AF Li, Qing Holzinger, Emily Marazita, Mary L. Beaty, Terri H. Bailey-Wilson, Joan E. TI Modified Random Forest (RF) for Trio Data with Alternative Splitting Criterion to Allow for Missing Genotypes SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Li, Qing; Holzinger, Emily; Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Pittsburgh, PA USA. [Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 114 BP 650 EP 651 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800120 ER PT J AU Middlebrooks, CD Simpson, CL Musolf, AM Portas, L Murgia, F Stambolian, D Bailey-Wilson, JE AF Middlebrooks, Candace D. Simpson, Claire L. Musolf, Anthony M. Portas, Laura Murgia, Federico Stambolian, Dwight Bailey-Wilson, Joan E. TI Association Analyses of Myopia in Multiplex African American Families using FBAT and a Rare Variant FBAT with Exome Chip Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Middlebrooks, Candace D.; Musolf, Anthony M.; Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, Baltimore, MD USA. [Simpson, Claire L.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Portas, Laura] Univ Verona, Cagliari Area, Italy. [Murgia, Federico] Natl Res Council Italy, Inst Populat Genet, Cagliari Area, Italy. [Stambolian, Dwight] Penn Presbyterian Med Ctr, Scheie Eye Inst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 120 BP 653 EP 653 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800126 ER PT J AU Musolf, AM Bailey-Wilson, JE AF Musolf, Anthony M. Bailey-Wilson, Joan E. TI False Positive Rate Inflation and Admixed Populations in the Quantitative Transmission Disequilibrium Test SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Musolf, Anthony M.; Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 124 BP 654 EP 654 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800130 ER PT J AU Page, SJ Rivera, M Kleiner, DE Zhao, X Auh, S Remmers, EF Heller, T AF Page, Sandra J. Rivera, Maria Kleiner, David E. Zhao, Xiongce Auh, Sungyoung Remmers, Elaine F. Heller, Theo TI Polymorphisms in the NADPH Oxidase Complex are Associated with Hepatitis C-induced Fibrosis and Inflammation SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Page, Sandra J.; Rivera, Maria; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Zhao, Xiongce] FDA, Ctr Vet Med, Rockville, MD USA. [Auh, Sungyoung] NIDDK, Off Clin Director, Liver Dis Branch, Bethesda, MD 20892 USA. [Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 126 BP 655 EP 655 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800132 ER PT J AU Shriner, D Rotimi, CN AF Shriner, Daniel Rotimi, Charles N. TI Admixture Mapping using Linear Mixed Models SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Shriner, Daniel; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 141 BP 661 EP 661 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800147 ER PT J AU Sorant, AJM Sabourin, JA Sung, HJ Wilson, AF AF Sorant, Alexa J. M. Sabourin, Jeremy A. Sung, Heejong Wilson, Alexander F. TI The Power and Type I Error of Tiled Regression Analysis Depend on the Selection Criteria at all Stages SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Sorant, Alexa J. M.; Sabourin, Jeremy A.; Sung, Heejong; Wilson, Alexander F.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 147 BP 663 EP 664 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800153 ER PT J AU Sung, H Sampson, M Lewis, K Ng, D Gonsalves, SG Mullikin, JC Remaley, A Biesecker, LG Wilson, AF AF Sung, Heejong Sampson, Maureen Lewis, Katie Ng, David Gonsalves, Stephen G. Mullikin, James C. Remaley, Alan Biesecker, Leslie G. Wilson, Alexander F. CA NISC Comparative Sequencing Progr TI Replication of a Single Nucleotide Polymorphism Variant in CETP Gene Associated with Large-HDL Particle in the ClinSeq (R) Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 24-26, 2016 CL Toronto, CANADA SP Int Genet Epidemiol Soc C1 [Sung, Heejong; Wilson, Alexander F.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. [Sampson, Maureen] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Lewis, Katie; Ng, David; Gonsalves, Stephen G.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; NISC Comparative Sequencing Progr] NIH, Intramural Sequencing Ctr NISC, Natl Human Genome Res Branch, Bldg 10, Bethesda, MD 20892 USA. [Mullikin, James C.] NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA. [Remaley, Alan] NHLBI, Lipoprot Metab Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2016 VL 40 IS 7 MA 152 BP 665 EP 666 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DZ7HF UT WOS:000386034800158 ER PT J AU Whelton, PK Einhorn, PT Muntner, P Appel, LJ Cushman, WC Roux, AVD Ferdinand, KC Rahman, M Taylor, HA Ard, J Arnett, DK Carter, BL Davis, BR Freedman, BI Cooper, LA Cooper, R Desvigne-Nickens, P Gavini, N Go, AS Hyman, DJ Kimmel, PL Margolis, KL Miller, ER Mills, KT Mensah, GA Navar, AM Ogedegbe, G Rakotz, MK Thomas, G Tobin, JN Wright, JT Yoon, SS Cutler, JA AF Whelton, Paul K. Einhorn, Paula T. Muntner, Paul Appel, Lawrence J. Cushman, William C. Roux, Ana V. Diez Ferdinand, Keith C. Rahman, Mahboob Taylor, Herman A. Ard, Jamy Arnett, Donna K. Carter, Barry L. Davis, Barry R. Freedman, Barry I. Cooper, Lisa A. Cooper, Richard Desvigne-Nickens, Patrice Gavini, Nara Go, Alan S. Hyman, David J. Kimmel, Paul L. Margolis, Karen L. Miller, Edgar R., III Mills, Katherine T. Mensah, George A. Navar, Ann M. Ogedegbe, Gbenga Rakotz, Michael K. Thomas, George Tobin, Jonathan N. Wright, Jackson T. Yoon, Sung Sug (Sarah) Cutler, Jeffrey A. CA Natl Heart Lung Blood Inst Working TI Research Needs to Improve Hypertension Treatment and Control in African Americans SO HYPERTENSION LA English DT Review ID HIGH BLOOD-PRESSURE; LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; INFLUENCING ANTIHYPERTENSIVE RESPONSE; GENOMIC ASSOCIATION ANALYSIS; RANDOMIZED CLINICAL-TRIAL; CHRONIC KIDNEY-DISEASE; TEAM-BASED CARE; CARDIOVASCULAR-DISEASE; HIGH-RISK C1 [Whelton, Paul K.; Ferdinand, Keith C.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 8318,1440 Canal St,Room 2018, New Orleans, LA 70112 USA. [Whelton, Paul K.; Ferdinand, Keith C.] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Einhorn, Paula T.; Desvigne-Nickens, Patrice; Mensah, George A.; Cutler, Jeffrey A.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. [Gavini, Nara; Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, Bldg 10, Bethesda, MD 20892 USA. [Muntner, Paul] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Appel, Lawrence J.; Cooper, Lisa A.; Miller, Edgar R., III] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Cushman, William C.] Vet Affairs Med Ctr, Prevent Med Sect, Memphis, TN USA. [Roux, Ana V. Diez] Drexel Univ, Dornsife Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rahman, Mahboob; Wright, Jackson T.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Dept Med, Cleveland, OH 44106 USA. [Taylor, Herman A.] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. [Ard, Jamy] Wake Forest Univ, Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Ard, Jamy; Freedman, Barry I.] Wake Forest Univ, Wake Forest Sch Med, Dept Med, Winston Salem, NC 27109 USA. [Arnett, Donna K.] Univ Kentucky, Deans Off, Coll Publ Hlth, Lexington, KY 40506 USA. [Carter, Barry L.] Univ Iowa, Coll Pharm, Dept Pharm Practice & Sci, Iowa City, IA 52242 USA. [Davis, Barry R.] Univ Texas Sch Publ Hlth, Dept Biostat, Houston, TX USA. [Cooper, Richard] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL USA. [Go, Alan S.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Hyman, David J.] Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. [Kimmel, Paul L.] NIDDK, Bethesda, MD 20892 USA. [Margolis, Karen L.] HealthPartners Inst, Minneapolis, MN USA. [Navar, Ann M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Ogedegbe, Gbenga] NYU Sch Med, Dept Populat Hlth, New York, NY USA. [Rakotz, Michael K.] Amer Med Assoc, 515 N State St, Chicago, IL 60610 USA. [Thomas, George] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH USA. [Tobin, Jonathan N.] Clin Directors Network, New York, NY USA. [Tobin, Jonathan N.] Rockefeller Univ, Ctr Clin & Translat Sci, 1230 York Ave, New York, NY 10021 USA. [Yoon, Sung Sug (Sarah)] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Whelton, PK (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 8318,1440 Canal St,Room 2018, New Orleans, LA 70112 USA. EM pkwhelton@gmail.com FU NHLBI; National Institutes of Health (NIH) [T32HL069749-12]; National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the NHLBI with a contribution from the National Institute of Diabetes and Digestive and Kidney Diseases. A.M. Navar was supported by National Institutes of Health (NIH) training grant T32HL069749-12. NR 76 TC 1 Z9 1 U1 9 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD NOV PY 2016 VL 68 IS 5 BP 1066 EP 1072 DI 10.1161/HYPERTENSIONAHA.116.07905 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DZ9VE UT WOS:000386227500003 PM 27620388 ER PT J AU Salehi, E Hedayati, MT Zoll, J Rafati, H Ghasemi, M Doroudinia, A Abastabar, M Tolooe, A Snelders, E van der Lee, HA Rijs, AJMM Verweij, PE Seyedmousavi, S Melchers, WJG AF Salehi, Elham Hedayati, Mohammad T. Zoll, Jan Rafati, Haleh Ghasemi, Maryam Doroudinia, Atosa Abastabar, Mahdi Tolooe, Ali Snelders, Eveline van der Lee, Henrich A. Rijs, Antonius J. M. M. Verweij, Paul E. Seyedmousavi, Seyedmojtaba Melchers, Willem J. G. TI Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB In a retrospective multicenter study, 102 formalin-fixed paraffin-embedded (FFPE) tissue specimens with histopathology results were tested. Two 4-to 5-mu m FFPE tissue sections from each specimen were digested with proteinase K, followed by automated nucleic acid extraction. Multiple real-time quantitative PCR (qPCR) assays targeting the internal transcribed spacer 2 (ITS2) region of ribosomal DNA, using fluorescently labeled primers, was performed to identify clinically important genera and species of Aspergillus, Fusarium, Scedosporium, and the Mucormycetes. The molecular identification was correlated with results from histological examination. One of the main findings of our study was the high sensitivity of the automated DNA extraction method, which was estimated to be 94%. The qPCR procedure that was evaluated identified a range of fungal genera/species, including Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger, Fusarium oxysporum, Fusarium solani, Scedosporium apiospermum, Rhizopus oryzae, Rhizopus microsporus, Mucor spp., and Syncephalastrum. Fusarium oxysporum and F. solani DNA was amplified from five specimens from patients initially diagnosed by histopathology as having aspergillosis. Aspergillus flavus, S. apiospermum, and Syncephalastrum were detected from histopathological mucormycosis samples. In addition, examination of four samples from patients suspected of having concomitant aspergillosis and mucormycosis infections resulted in the identification of two A. flavus isolates, one Mucor isolate, and only one sample having both R. oryzae and A. flavus. Our results indicate that histopathological features of molds may be easily confused in tissue sections. The qPCR assay used in this study is a reliable tool for the rapid and accurate identification of fungal pathogens to the genus and species levels directly from FFPE tissues. C1 [Salehi, Elham] Mazandaran Univ Med Sci, Student Res Comm, Sari, Iran. [Salehi, Elham; Hedayati, Mohammad T.; Abastabar, Mahdi] Mazandaran Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Sari, Iran. [Hedayati, Mohammad T.; Abastabar, Mahdi; Seyedmousavi, Seyedmojtaba] Mazandaran Univ Med Sci, Invas Fungi Res Ctr, Sari, Iran. [Zoll, Jan; Snelders, Eveline; van der Lee, Henrich A.; Rijs, Antonius J. M. M.; Verweij, Paul E.; Seyedmousavi, Seyedmojtaba; Melchers, Willem J. G.] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. [Zoll, Jan; Snelders, Eveline; van der Lee, Henrich A.; Rijs, Antonius J. M. M.; Verweij, Paul E.; Seyedmousavi, Seyedmojtaba; Melchers, Willem J. G.] Radboudumc CWZ, Ctr Expertise Mycol, Nijmegen, Netherlands. [Rafati, Haleh] Erasmus MC, Dept Biochem, Rotterdam, Netherlands. [Ghasemi, Maryam] Mazandaran Univ Med Sci, Sch Med, Dept Pathol, Sari, Iran. [Doroudinia, Atosa] Shahid Beheshti Univ Med Sci, Fac Med, Dept Pathol, Transplantat Res Ctr,Natl Res Inst TB & Lung Dis, Tehran, Iran. [Tolooe, Ali] Univ Tehran, Fac Vet Med, Tehran, Iran. [Seyedmousavi, Seyedmojtaba] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Seyedmousavi, S (reprint author), Mazandaran Univ Med Sci, Invas Fungi Res Ctr, Sari, Iran.; Seyedmousavi, S; Melchers, WJG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands.; Seyedmousavi, S; Melchers, WJG (reprint author), Radboudumc CWZ, Ctr Expertise Mycol, Nijmegen, Netherlands. EM Seyedmousavi@nih.gov; Willem.Melchers@radboudumc.nl RI Hedayati, Mohammad T./E-2304-2017; Abastabar, Mahdi/F-2768-2017 OI Hedayati, Mohammad T./0000-0001-6415-4648; FU Mazandaran University of Medical Sciences (MazUMS) [859]; Mazandaran University of Medical Sciences, Sari, Iran [859] FX This work, including the efforts of Elham Salehi and Mohammad T. Hedayati, was funded by Mazandaran University of Medical Sciences (MazUMS) (859).; This publication was prepared as a collaborative study between the Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran (research project fund no. 859), and the Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands. NR 36 TC 1 Z9 1 U1 6 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2016 VL 54 IS 11 BP 2798 EP 2803 DI 10.1128/JCM.01185-16 PG 6 WC Microbiology SC Microbiology GA DZ8ID UT WOS:000386113200025 PM 27605714 ER PT J AU Finigan-Carr, NM Gielen, A Haynie, DL Cheng, TL AF Finigan-Carr, Nadine M. Gielen, Andrea Haynie, Denise L. Cheng, Tina L. TI Youth Violence: How Gender Matters in Aggression Among Urban Early Adolescents SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE aggression; early adolescence; gender; urban; African American ID AFRICAN-AMERICAN ADOLESCENTS; COMMUNITY VIOLENCE; RELATIONAL AGGRESSION; PARTICIPATION RATES; PARENTAL INFLUENCES; PLANNED BEHAVIOR; REASONED ACTION; SOCIAL SUPPORT; MINORITY YOUTH; RISK-FACTORS AB Although research suggests gender differences in both forms and functions of aggressive behavior, there has been limited research into these types among African American early adolescents. This study examined the types and patterns of aggression in girls and boys in that group. Participants were 452 predominantly African American middle school youth (50.4% girls) aged 11 to 13 (M = 11.97) enrolled in three urban public schools. Students were invited to participate in a school-based intervention designed to prevent aggressive and deviant behaviors. Assessments occurred pre- and post-intervention. Surveys were analyzed to identify gender differences in the levels and types of aggressive behaviors, as well as differences in predictors of aggressive behaviors. Predictors were measured at baseline; aggressive behaviors at follow-up. There were significant gender differences in types of aggressive behaviors and their predictors indicating a need to develop and implement more suitable, gender-tailored prevention and treatment approaches. C1 [Finigan-Carr, Nadine M.] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. [Gielen, Andrea; Cheng, Tina L.] Johns Hopkins Univ, Baltimore, MD USA. [Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Finigan-Carr, NM (reprint author), Univ Maryland, Ruth H Young Ctr Families & Children, Baltimore, MD 21201 USA. EM nfinigan-carr@ssw.umaryland.edu OI Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-HD-2-3344]; NICHD [1K24HD052559-01]; NICHD Intramural Research Program; DC-Baltimore Research Center on Child Health Disparities from the National Institute on Minority Health and Health Disparities [P20 MD00165] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Contract Number N01-HD-2-3344 and NICHD Grant Number 1K24HD052559-01 (Cheng), the NICHD Intramural Research Program (Haynie), and the DC-Baltimore Research Center on Child Health Disparities P20 MD00165 from the National Institute on Minority Health and Health Disparities (Cheng and Finigan-Carr). NR 71 TC 0 Z9 0 U1 22 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 EI 1552-6518 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD NOV PY 2016 VL 31 IS 19 BP 3257 EP 3281 DI 10.1177/0886260515584348 PG 25 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA DZ7FY UT WOS:000386031500008 ER PT J AU Lee, GO Richard, SA Kang, G Houpt, ER Seidman, JC Pendergast, LL Bhutta, ZA Ahmed, T Mduma, ER Lima, AA Bessong, P Jennifer, MS Hossain, MI Chandyo, RK Nyathi, E Lima, IF Pascal, J Soofi, S Ladaporn, B Guerrant, RL Caulfield, LE Black, RE Kosek, MN AF Lee, Gwenyth O. Richard, Stephanie A. Kang, Gagandeep Houpt, Eric R. Seidman, Jessica C. Pendergast, Laura L. Bhutta, Zulfiqar A. Ahmed, Tahmeed Mduma, Estomih R. Lima, Aldo A. Bessong, Pascal Jennifer, Mats Steffi Hossain, Md Iqbal Chandyo, Ram Krishna Nyathi, Emanuel Lima, Ila F. Pascal, John Soofi, Sajid Ladaporn, Bodhidatta Guerrant, Richard L. Caulfield, Laura E. Black, Robert E. Kosek, Margaret N. CA MAL-ED Network Investigators TI A Comparison of Diarrheal Severity Scores in the MAL-ED Multisite Community-Based Cohort Study SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE diarrhea; epidemiology; pediatric ID ROTAVIRUS GASTROENTERITIS; DEVELOPING-COUNTRIES; CHILDREN; DISEASE; SURVEILLANCE; DEFINITION; EPISODES; ISSUES; SCALES AB Objectives:There is a lack of consensus on how to measure diarrheal severity. Within the context of a multisite, prospective cohort study, we evaluated the performance of a modified Vesikari score (MAL-ED), 2 previously published scores (Clark and CODA [a diarrheal severity score (Community DiarrheA) published by Lee et al]), and a modified definition of moderate-to-severe diarrhea (MSD) based on dysentery and health care worker diagnosed dehydration.Methods:Scores were built using maternally reported symptoms or fieldworker-reported clinical signs obtained during the first 7 days of a diarrheal episode. The association between these and the risk of hospitalization were tested using receiver operating characteristic analysis. Severity scores were also related to illness etiology, and the likelihood of the episode subsequently becoming prolonged or persistent.Results:Of 10,159 episodes from 1681 children, 143 (4.0%) resulted in hospitalization. The area under the curve of each score as a predictor of hospitalization was 0.84 (95% confidence interval: 0.81, 0.87) (Clark), 0.85 (0.82, 0.88) (MAL-ED), and 0.87 (0.84, 0.89) (CODA). Severity was also associated with etiology and episode duration. Although families were more likely to seek care for severe diarrhea, approximately half of severe cases never reached the health system.Conclusions:Community-based diarrheal severity scores are predictive of relevant child health outcomes. Because they require no assumptions about health care access or utilization, they are useful in refining estimates of the burden of diarrheal disease, in estimating the effect of disease control interventions, and in triaging children for referral in low- and middle-income countries in which the rates of morbidity and mortality after diarrhea remain high. C1 [Lee, Gwenyth O.; Caulfield, Laura E.; Black, Robert E.; Kosek, Margaret N.] Johns Hopkins Bloomberg Sch Publ Hlth, 615N Wolfe St,Room E5545, Baltimore, MD 21205 USA. [Richard, Stephanie A.; Seidman, Jessica C.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Kang, Gagandeep; Jennifer, Mats Steffi] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Houpt, Eric R.; Guerrant, Richard L.] Univ Virginia, Charlottesville, VA USA. [Pendergast, Laura L.] Temple Univ, Philadelphia, PA 19122 USA. [Bhutta, Zulfiqar A.; Soofi, Sajid] Aga Khan Univ, Karachi, Pakistan. [Ahmed, Tahmeed; Hossain, Md Iqbal] Icddr B, Dhaka, Bangladesh. [Mduma, Estomih R.; Pascal, John] Haydom Lutheran Hosp, Haydom, Manyara Region, Tanzania. [Lima, Aldo A.; Lima, Ila F.] Univ Fed Ceara, Fortaleza, Ceara, Brazil. [Bessong, Pascal; Nyathi, Emanuel] Univ Venda, Thohoyandou, South Africa. [Chandyo, Ram Krishna] Univ Bergen, Ctr Int Hlth, Bergen, Norway. [Chandyo, Ram Krishna] Tribhuvan Univ, Inst Med, Dept Child Hlth, Kathmandu, Nepal. [Ladaporn, Bodhidatta] Armed Forces Res Inst Med Sci, Bangkok, Thailand. RP Kosek, MN (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615N Wolfe St,Room E5545, Baltimore, MD 21205 USA. EM mkosek@jhmi.edu FU Bill & Melinda Gates Foundation; Foundation for the NIH; National Institutes of Health, Fogarty International Center FX The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health, Fogarty International Center. NR 25 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2016 VL 63 IS 5 BP 466 EP 473 DI 10.1097/MPG.0000000000001286 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA EA1KE UT WOS:000386350200016 PM 27347723 ER PT J AU Bavendam, TG Norton, JM Kirkali, Z Mullins, C Kusek, JW Star, RA Rodgers, GP AF Bavendam, Tamara G. Norton, Jenna M. Kirkali, Ziya Mullins, Chris Kusek, John W. Star, Robert A. Rodgers, Griffin P. TI Advancing a Comprehensive Approach to the Study of Lower Urinary Tract Symptoms SO JOURNAL OF UROLOGY LA English DT Review DE behavioral medicine; executive function; lower urinary tract symptoms; psychology; social determinants of health ID COMMUNITY-HEALTH SURVEY; BENIGN PROSTATIC HYPERPLASIA; TREATMENT-SEEKING BEHAVIOR; LIFE-STYLE FACTORS; OVERACTIVE BLADDER; RISK-FACTORS; UROLOGICAL SYMPTOMS; METABOLIC SYNDROME; PHYSICAL-ACTIVITY; OLDER WOMEN AB Purpose: Lower urinary tract symptoms are common in the United States population, leading to significant economic, quality of life and public health issues. The burden will increase as the population ages, and risk factors for lower urinary tract symptoms, including diabetes and obesity, remain highly prevalent. Improving clinical management and establishing the knowledge base to prevent lower urinary tract symptoms will require a comprehensive research approach that examines factors beyond the lower urinary tract. While the study of extra-lower urinary tract factors has increased recently, current urological research does not systematically account for the broad set of potential contributing factors spanning biological, behavioral, psychological/executive function and sociocultural factors. A comprehensive assessment of potential contributors to risk, treatment response and progression is necessary to reduce the burden of this condition in the United States. Materials and Methods: We considered challenges to continuing the predominantly lower urinary tract dysfunction centric approach that has dominated previous research of lower urinary tract symptoms. Results: We developed a new, comprehensive framework for urology research that includes a broader set of potential factors contributing to lower urinary tract symptoms. This framework aims to broaden research to consider a comprehensive set of potential contributing factors and to engage a broad range of researchers in the investigation of as many extra-lower urinary tract factors as possible, with the goal of improving clinical care and prevention. Conclusions: We propose a new framework for future urology research, which should help to reduce the medical and economic burden of lower urinary tract symptoms in the United States population. C1 [Rodgers, Griffin P.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. [Rodgers, Griffin P.] NIDDK, Off Director, NIH, Bethesda, MD USA. RP Bavendam, TG (reprint author), NIDDK, Womens Urol Hlth, NIH, 6707 Democracy Blvd. MSC 5458,Off 615, Bethesda, MD 20817 USA. EM tamara.bavendam@nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 49 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 2016 VL 196 IS 5 BP 1342 EP 1348 DI 10.1016/j.juro.2016.05.117 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DZ6EJ UT WOS:000385954100004 PM 27341750 ER PT J AU Banerjee, A Rapin, N Miller, M Griebel, P Zhou, Y Munster, V Misra, V AF Banerjee, Arinjay Rapin, Noreen Miller, Megan Griebel, Philip Zhou, Yan Munster, Vincent Misra, Vikram TI Generation and Characterization of Eptesicus fuscus (Big brown bat) kidney cell lines immortalized using the Myotis polyomavirus large T-antigen SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Big brown bat; Kidney; Cell-line; MERS-CoV; PED-CoV; VSV; HSV ID IMMUNE-RESPONSES; VIRUS; TRANSFORMATION; IDENTIFICATION; ESTABLISHMENT; TRANSFECTION; FIBROBLASTS; INTERFERON; DIVERSITY; EVOLUTION AB It is speculated that bats are important reservoir hosts for numerous viruses, with 27 viral families reportedly detected in bats. Majority of these viruses have not been isolated and there is little information regarding their biology in bats. Establishing a well-characterized bat cell line supporting the replication of bat-borne viruses would facilitate the analysis of virus-host interactions in an in vitro model. Currently, few bat cell lines have been developed and only Tb1-Lu, derived from Tadarida brasiliensis is commercially available. Here we describe a method to establish and immortalize big brown bat (Eptesicus fuscus) kidney (Efk3) cells using the Myotis polyomavirus T-antigen. Subclones of this cell line expressed both epithelial and fibroblast markers to varying extents. Cell clones expressed interferon beta in response to poly(I:C) stimulation and supported the replication of four different viruses, namely, vesicular stomatitis virus (VSV), porcine epidemic diarrhea coronavirus (PED-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and herpes simplex virus (HSV). To our knowledge, this is the first bat cell line from a northern latitude insectivorous bat developed using a novel technology. The cell line has the potential to be used for isolation of bat viruses and for studying virus-bat interactions in culture. (C) 2016 Elsevier B.V. All rights reserved. C1 [Banerjee, Arinjay; Rapin, Noreen; Misra, Vikram] Univ Saskatchewan, Dept Microbiol, Western Coll Vet Med, Saskatoon, SK, Canada. [Miller, Megan; Munster, Vincent] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. [Griebel, Philip; Zhou, Yan] Univ Saskatchewan, Vaccine & Infect Dis Org Int Vaccine Ctr VIDO Int, Saskatoon, SK, Canada. RP Misra, V (reprint author), Univ Saskatchewan, Dept Microbiol, Western Coll Vet Med, Saskatoon, SK, Canada. EM vikram.misra@usask.ca OI Munster, Vincent/0000-0002-2288-3196 FU Natural Sciences and Engineering Research Council of Canada (NSERC); Integrated Training Program in Infectious Disease, Food Safety and Public Policy - NSERC/CREATE; Department of Veterinary Microbiology, University of Saskatchewan; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Nathalie Berube and Shirley Hauta from VIDO-InterVac for their technical support. Funding for the research was obtained from a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant awarded to Vikram Misra, Integrated Training Program in Infectious Disease, Food Safety and Public Policy funded by NSERC/CREATE and the Department of Veterinary Microbiology, University of Saskatchewan. Vincent Munster and Megan Miller were supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 42 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2016 VL 237 BP 166 EP 173 DI 10.1016/j.jviromet.2016.09.008 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA DZ9JH UT WOS:000386190700027 PM 27639955 ER PT J AU Hanley, DF Thompson, RE Muschelli, J Rosenblum, M McBee, N Lane, K Bistran-Hall, AJ Mayo, SW Keyl, P Gandhi, D Morgan, TC Ullman, N Mould, WA Carhuapoma, JR Kase, C Ziai, W Thompson, CB Yenokyan, G Huang, E Broaddus, WC Graham, RS Aldrich, EF Dodd, R Wijman, C Caron, JL Huang, J Camarata, P Mendelow, AD Gregson, B Janis, S Vespa, P Martin, N Awad, I Zuccarello, M AF Hanley, Daniel F. Thompson, Richard E. Muschelli, John Rosenblum, Michael McBee, Nichol Lane, Karen Bistran-Hall, Amanda J. Mayo, Steven W. Keyl, Penelope Gandhi, Dheeraj Morgan, Tim C. Ullman, Natalie Mould, W. Andrew Carhuapoma, J. Ricardo Kase, Carlos Ziai, Wendy Thompson, Carol B. Yenokyan, Gayane Huang, Emily Broaddus, William C. Graham, R. Scott Aldrich, E. Francois Dodd, Robert Wijman, Cristanne Caron, Jean-Louis Huang, Judy Camarata, Paul Mendelow, A. David Gregson, Barbara Janis, Scott Vespa, Paul Martin, Neil Awad, Issam Zuccarello, Mario CA MISTIE Investigators TI Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial SO LANCET NEUROLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR; CLINICAL-TRIAL; MISSING DATA; STROKE; BLOOD; MANAGEMENT; DETERMINANT; ASPIRATION; GUIDELINES; HEMATOMAS AB Background Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for dot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0.3 mg or 1.0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. Findings Between Feb 2,2006, and April 8,2013,96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9.5%, 95% CI 2.7-22.6] vs eight [14.8%, 6.6-27.1], p=0.542), 7 day mortality (zero [0%, 0-8.4] vs one [1.9%, 0-1-9.9], p=0.562), symptomatic bleeding (one [2.4%, 0.1-12.6] vs five [9.3%, 3.1-20.3], p=0.226), and brain bacterial infections (one [2.4%, 0.1-12.6] vs zero [0%, 0-6.6], p=0.438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22.2%; 95% CI 12.0-35.6] vs three [7.1%; 1.5-19.5]; p=0.051). Interpretation MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. C1 [Hanley, Daniel F.; McBee, Nichol; Lane, Karen; Bistran-Hall, Amanda J.; Keyl, Penelope; Morgan, Tim C.; Ullman, Natalie; Mould, W. Andrew; Carhuapoma, J. Ricardo; Ziai, Wendy] Johns Hopkins Univ, Brain Injury Outcomes Coordinating Ctr, Dept Neurol, Baltimore, MD 21231 USA. [Huang, Emily] Johns Hopkins Univ, Dept Neurosurg, Sch Publ Hlth, Baltimore, MD USA. [Thompson, Richard E.; Muschelli, John; Rosenblum, Michael; Yenokyan, Gayane; Huang, Emily] Johns Hopkins Univ, Dept of Biostat, Sch Publ Hlth, Baltimore, MD USA. [Mayo, Steven W.] Emissary Int, Austin, TX USA. [Gandhi, Dheeraj] Univ Maryland, Dept Neuroradiol, Baltimore, MD 21201 USA. [Aldrich, E. Francois] Univ Maryland, Dept Neurosurg, Baltimore, MD 21201 USA. [Kase, Carlos] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Broaddus, William C.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA. [Graham, R. Scott] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA USA. [Wijman, Cristanne] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Dodd, Robert] Stanford Univ, Dept Neurosurg, Palo Alto, CA 94304 USA. [Caron, Jean-Louis] Univ Texas San Antonio, Dept Neurosurg, San Antonio, TX USA. [Camarata, Paul] Univ Kansas, Dept Neurosurg, Kansas City, KS USA. [Janis, Scott] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Vespa, Paul] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Martin, Neil] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Awad, Issam] Univ Chicago, Dept Neurosurg, Chicago, IL 60637 USA. [Zuccarello, Mario] Univ Cincinnati, Dept Neurosurg, Cincinnati, OH USA. [Mendelow, A. David; Gregson, Barbara] Newcastle Univ, Neurosurg, Newcastle Upon Tyne, Tyne & Wear, England. RP Hanley, DF (reprint author), Johns Hopkins Univ, Brain Injury Outcomes Coordinating Ctr, Dept Neurol, Baltimore, MD 21231 USA. EM dhanley@jhmi.edu FU National Institute of Neurological Disorders and Stroke [R01NS046309] FX This study was supported by grant R01NS046309 awarded to DFH by the National Institute of Neurological Disorders and Stroke. Alteplase was donated by Genentech Catheters and introducers were donated by Codman. We thank the patients and families who volunteered for this study, Rachel Dlugash for her assistance with data summarisation, and Pat Reilly for her guidance. NR 33 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2016 VL 15 IS 12 BP 1226 EP 1235 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA EA0YO UT WOS:000386315700018 ER PT J AU Lee, JC Su, SY Changou, CA Yang, RS Tsai, KS Collins, MT Orwoll, ES Lin, CY Chen, SH Shih, SR Lee, CH Oda, Y Billings, SD Li, CF Nielsen, GP Konishi, E Petersson, F Carpenter, TO Sittampalam, K Huang, HY Folpe, AL AF Lee, Jen-Chieh Su, Sheng-Yao Changou, Chun A. Yang, Rong-Sen Tsai, Keh-Sung Collins, Michael T. Orwoll, Eric S. Lin, Chung-Yen Chen, Shu-Hwa Shih, Shyang-Rong Lee, Cheng-Han Oda, Yoshinao Billings, Steven D. Li, Chien-Feng Nielsen, G. Petur Konishi, Eiichi Petersson, Fredrik Carpenter, Thomas O. Sittampalam, Kesavan Huang, Hsuan-Ying Folpe, Andrew L. TI Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors SO MODERN PATHOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; FRIZZLED-RELATED PROTEIN-4; FACTOR-I; INDUCED OSTEOMALACIA; MITOGENIC ACTIVITY; FGF23 EXPRESSION; BONE; MATRIX; RNA; IDENTIFICATION AB Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1-FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins. C1 [Lee, Jen-Chieh] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept & Grad Inst Pathol, Coll Med, 7 Chung Shan South Rd, Taipei 10002, Taiwan. [Su, Sheng-Yao; Lin, Chung-Yen; Chen, Shu-Hwa] Acad Sinica, Inst Informat Sci, Taipei, Taiwan. [Su, Sheng-Yao] Natl Yang Ming Univ, Acad Sinica, Inst Biomed Informat, Bioinformat Program,Taiwan Int Grad Program, Taipei, Taiwan. [Changou, Chun A.] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan. [Changou, Chun A.] Taipei Med Univ, Grad Inst Translat Med, Integrated Lab, Ctr Translat Med, Taipei, Taiwan. [Yang, Rong-Sen] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Orthoped, Taipei, Taiwan. [Tsai, Keh-Sung; Shih, Shyang-Rong] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. [Collins, Michael T.] NIH, Skeletal Clin Studies Unit, Bldg 10, Bethesda, MD 20892 USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97201 USA. [Lee, Cheng-Han] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Lee, Cheng-Han] Royal Alexandra Hosp, Edmonton, AB, Canada. [Oda, Yoshinao] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka, Japan. [Billings, Steven D.] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA. [Li, Chien-Feng] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Konishi, Eiichi] Kyoto Prefectural Univ Med, Dept Pathol, Kyoto, Japan. [Petersson, Fredrik] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore. [Carpenter, Thomas O.] Yale Univ, Sch Med, Dept Pediat Endocrinol, New Haven, CT USA. [Sittampalam, Kesavan] Singapore Gen Hosp, Pathol Dept, Singapore, Singapore. [Huang, Hsuan-Ying] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung, Taiwan. [Folpe, Andrew L.] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA. RP Lee, JC (reprint author), Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept & Grad Inst Pathol, Coll Med, 7 Chung Shan South Rd, Taipei 10002, Taiwan.; Folpe, AL (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA. EM leejenchieh@ntuh.gov.tw; Folpe.Andrew@mayo.edu OI Lee, Jen-Chieh/0000-0001-7739-5934 FU Ministry of Science and Technology, Taiwan [MOST 104-2628-B-002-003-MY2]; National Taiwan University Hospital, Taipei, Taiwan [NTUH 105-S3041] FX This work was supported by research funds from Ministry of Science and Technology, Taiwan (MOST 104-2628-B-002-003-MY2) and National Taiwan University Hospital, Taipei, Taiwan (NTUH 105-S3041) to Dr Jen-Chieh Lee. We thank Dr Chih-Chien Hung for his assistance in collecting materials; Mr Yung-Chuan Chung, Mr Ren-Wei Wang, Ms Ying-Ying Chuang, and the NTUH sequencing core laboratory for the technical assistance; and Mr Grant Perry for his selfless dedications and generous contributions to this research. URLs for the raw data of RNA-seq: http://www.ncbi.nlm.nih.gov/sra/?term= SRX1560738 (sample PMT-50) http://www.ncbi.nlm.nih.gov/sra/?term= SRX1560739 (sample PMT-16 and -17). NR 46 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2016 VL 29 IS 11 BP 1335 EP 1346 DI 10.1038/nnodpathol.2016.137 PG 12 WC Pathology SC Pathology GA EA2EE UT WOS:000386404800005 PM 27443518 ER PT J AU Kitahara, CM Sosa, JA AF Kitahara, Cari M. Sosa, Julie A. TI The changing incidence of thyroid cancer SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID BODY-MASS INDEX; UNITED-STATES; POOLED ANALYSIS; INCREASING INCIDENCE; BRAF MUTATIONS; PAPILLARY MICROCARCINOMA; RET/PTC REARRANGEMENTS; SUBSEQUENT RISK; INCIDENCE RATES; SHARP INCREASE AB During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue. C1 [Kitahara, Cari M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 7E-536, Bethesda, MD 20892 USA. [Sosa, Julie A.] Duke Univ, Sect Endocrine Surg, Dept Surg, Seeley Mudd Bldg 484,10 Searle Ctr Dr,DUMC 2945, Durham, NC 27710 USA. [Sosa, Julie A.] Duke Clin Res Inst, North Pavil,2400 Pratt St, Durham, NC 27705 USA. RP Kitahara, CM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 7E-536, Bethesda, MD 20892 USA. EM meinholdc@mail.nih.gov RI Kitahara, Cari/R-8267-2016 FU Astra Zeneca; Eli Lilly; GlaxoSmithKline; Novo Nordisk FX C.M.K. declares no competing interests J.A.S. is on the Data Monitoring Committee of the Medullary Thyroid Cancer Consortium Registry, which is sponsored by Astra Zeneca, Eli Lilly, GlaxoSmithKline and Novo Nordisk. NR 107 TC 3 Z9 4 U1 15 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD NOV PY 2016 VL 12 IS 11 BP 646 EP 653 DI 10.1038/nrendo.2016.110 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA1AK UT WOS:000386320500005 PM 27418023 ER PT J AU Joseph, PV Abey, SK Henderson, WA AF Joseph, Paule V. Abey, Sarah K. Henderson, Wendy A. TI Emerging Role of Nutri-Epigenetics in Inflammation and Cancer SO ONCOLOGY NURSING FORUM LA English DT Article DE biology of cancer; epigenetics; nutri-epigenetics; nutrition; DNA methylation ID DNA METHYLATION; PROSTATE-CANCER; COLORECTAL-CANCER; DIALLYL DISULFIDE; COLON-CANCER; CELL; PROGRESSION; METABOLISM; GROWTH; FOLATE AB Nutrition is a factor involved in inflammation and a modulator of risk toward some cancers, and the complexity of linkages between dietary components and epigenetics mechanisms (e.g., DNA methylation, histone modification, chromatin remodeling) may affect the inflammation phenotype and the development of cancer. An increasing number of studies support the role of diet in cancer development, prevention, and treatment. Although current knowledge regarding nutri-epigenetics is expanding, more work is needed, and nurse scientists have the potential to significantly contribute to the expansion of this knowledge. C1 [Joseph, Paule V.; Abey, Sarah K.] NINR, Biobehav Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Henderson, Wendy A.] NINR, Digest Disorder Unit, Biobehav Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Henderson, WA (reprint author), NINR, Digest Disorder Unit, Biobehav Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. EM hendersw@mail.nih.gov NR 35 TC 0 Z9 0 U1 8 U2 8 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2016 VL 43 IS 6 BP 784 EP 788 DI 10.1188/16.ONF.784-788 PG 5 WC Oncology; Nursing SC Oncology; Nursing GA EA1EY UT WOS:000386336500020 PM 27768134 ER PT J AU Galassi, A Kostelecky, B AF Galassi, Annette Kostelecky, Brenda TI Role of Nurses in the Creation of National Cancer Care Plans in Low- and Middle-Income Countries SO ONCOLOGY NURSING FORUM LA English DT Article DE national cancer control planning; nurse leaders; cancer plan; low- and middle-income countries AB A national cancer control plan (NCCP) is a strategic plan that aims to reduce cancer incidence and mortality and improve quality of life by using evidence-based interventions to maximize a country's healthcare resources. NCCPs are essential tools in the global effort to manage the growing burden of noncommunicable diseases. Oncology nurses must understand and participate in the process of NCCP development and implementation to ensure that proposed interventions are acceptable to the target population and that training needs of the healthcare work-force are appropriately addressed, and to effectively deliver interventions from teaching cancer prevention behaviors to administering end-of-life care. C1 [Kostelecky, Brenda] NCI, Canc Control Planning & Policy, Ctr Global Hlth, Rockville, MD 20850 USA. RP Kostelecky, B (reprint author), NCI, Canc Control Planning & Policy, Ctr Global Hlth, Rockville, MD 20850 USA. EM agalassi57@gmail.com NR 13 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2016 VL 43 IS 6 BP 789 EP 792 DI 10.1188/16.ONF.789-792 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA EA1EY UT WOS:000386336500021 ER PT J AU Iwuchukwu, OF Ramirez, AH Shi, YP Bowton, EA Kawai, VK Schildcrout, JS Roden, DM Denny, JC Stein, CM AF Iwuchukwu, Otito F. Ramirez, Andrea H. Shi, Yaping Bowton, Erica A. Kawai, Vivian K. Schildcrout, Jonathan S. Roden, Dan M. Denny, Joshua C. Stein, C. Michael TI Genetic determinants of variability in warfarin response after the dose-titration phase SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE CYP2C9; CYP4F2; dose titration; genetics; GGCX; international normalized ratio variability; international normalized ratio; stable dose; time in therapeutic range; warfarin ID GAMMA-GLUTAMYL CARBOXYLASE; AFRICAN-AMERICANS; ANTICOAGULANT-THERAPY; THROMBOTIC EVENTS; VKORC1; REQUIREMENTS; POLYMORPHISM; CYP2C9; INR; GENOTYPES AB ObjectivesGenetic factors contribute considerably toward variability in warfarin dose requirements and are important in the dose-titration phase; their effects on the stability of anticoagulation later in therapy are not known.MethodsUsing deidentified electronic medical records linked to a DNA-biobank, we studied 140 African-Americans and 943 European-Americans after the warfarin dose-titration phase. We genotyped 12 single nucleotide polymorphisms in genes (CYP2C9, VKORC1, CYP4F2, GGCX, EPHX1, CALU) associated with altered warfarin dose requirements and tested their associations with international normalized ratio variability (INRVAR) and percent time in therapeutic range in European-Americans and African-Americans.ResultsOne allele copy of rs2108622 in CYP4F2 was associated with a 15% [95% confidence interval (CI): 1-26, P=0.03] decrease in the median INRVAR in European-Americans. In African-Americans, GGCX variants rs11676382 and rs699664 were associated with 4.16-fold (95% CI: 1.45-11.97, P=0.009) and 1.50-fold (95% CI: 1.07-2.08, P=0.02) changes in the median INRVAR per variant allele copy, respectively; rs11676382 was also significantly associated with a 23.19% (95% CI: 5.89-40.48, P=0.01) decrease in time in therapeutic range. The total variation in INRVAR explained by both clinical factors and rs2108622 was 5.2% for European-Americans. In African-Americans, the inclusion of GGCX variants rs11676382 and rs699664, and the CYP2C9*8 variant rs7900194 explained approximate to 29% of the variation in INRVAR.ConclusionThe stability of anticoagulation after the warfarin dose-titration phase is differentially affected by variants in CYP4F2 in European-Americans and GGCX loci in African-Americans. C1 [Iwuchukwu, Otito F.; Kawai, Vivian K.; Roden, Dan M.; Stein, C. Michael] Vanderbilt Univ, Sch Med, Dept Med, Div Clin Pharmacol, Nashville, TN 37212 USA. [Shi, Yaping; Schildcrout, Jonathan S.; Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med Bioinformat, Nashville, TN 37212 USA. [Roden, Dan M.; Stein, C. Michael] Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. [Bowton, Erica A.] Vanderbilt Univ, Sch Med, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37212 USA. [Iwuchukwu, Otito F.] Fairleigh Dickinson Univ, Sch Pharm, Div Pharmaceut Sci, Florham Pk, NJ 07932 USA. [Ramirez, Andrea H.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. RP Iwuchukwu, OF (reprint author), Fairleigh Dickinson Univ, Sch Pharm, Div Pharmaceut Sci, Florham Pk, NJ 07932 USA. EM iwuchuof@fdu.edu FU NIH [GM109145, U19HL069757, T32 GM007569, NIH/NIGMS K23 GM117395, NIH/NHLBI 3P01HL56693-17S]; Vanderbilt University Medical Center's BioVU; Vanderbilt CTSA from NCATS/NIH [ULTR000445] FX This work was supported in part by funding by the NIH through grants GM109145, U19HL069757, and T32 GM007569 and Vanderbilt University Medical Center's BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant ULTR000445 from NCATS/NIH. Additional NIH funding source for Vivian K. Kawai - NIH/NIGMS K23 GM117395 and NIH/NHLBI 3P01HL56693-17S. NR 37 TC 1 Z9 1 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1744-6872 EI 1744-6880 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD NOV PY 2016 VL 26 IS 11 BP 510 EP 516 DI 10.1097/FPC.0000000000000244 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA DZ9UU UT WOS:000386226300004 PM 27632229 ER PT J AU Solano, ME Holmes, MC Mittelstadt, PR Chapman, KE Tolosa, E AF Solano, Maria Emilia Holmes, Megan C. Mittelstadt, Paul R. Chapman, Karen E. Tolosa, Eva TI Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Glucocorticoids; Immune ontogeny; Programming of chronic immune diseases ID HEMATOPOIETIC STEM-CELLS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; PITUITARY-ADRENAL AXIS; RECEPTOR GENE-EXPRESSION; PRENATAL MATERNAL STRESS; INDUCED LEUCINE-ZIPPER; LOW-BIRTH-WEIGHT; BETA-HYDROXYSTEROID DEHYDROGENASE; CORTICOTROPIN-RELEASING-FACTOR; HUMAN AMNION FIBROBLASTS AB Endogenous levels of glucocorticoids rise during pregnancy to warrant development and maturation of the fetal organs close to birth. However, during most of the gestation, the fetus is protected from excessive biologically active endogenous glucocorticoids by placental and fetal expression of 11 beta-hydroxysteroid dehydrogenase 2 (11 beta-HSD2). Maternal stress, which may overwhelm placental 11 beta-HSD2 activity with high glucocorticoid levels, or administration of synthetic glucocorticoids to improve the survival chances of the premature newborn, are associated to postnatal increased risk for immune diseases. Fetal exposure to excessive glucocorticoids may underlie this altered postnatal immunity. Here, we revise the role that placental and fetal 11 beta-HSD2, fetal glucocorticoid exposure, and programming of the offspring's the hypothalamic-pituitary-adrenal (HPA) axis play on concerted steps in immune fetal development. We could identify gaps in knowledge about glucocorticoid-induced programming of immune diseases. Finally, based on current evidence about glucocorticoid and HPA axis-mediated immune regulation, we hypothesize on mechanisms that could drive the enhanced risk for atopies, infections, and type I diabetes in offspring that were prenatally exposed to glucocorticoids. C1 [Solano, Maria Emilia] Univ Med Ctr Hamburg Eppendorf, Dept Obstet & Prenatal Med, Hamburg, Germany. [Holmes, Megan C.; Chapman, Karen E.] Univ Edinburgh, Univ BHF Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland. [Mittelstadt, Paul R.] NCI, Lab Immune Regulat, NIH, Bethesda, MD 20892 USA. [Tolosa, Eva] Univ Med Ctr Hamburg Eppendorf, Dept Immunol, Hamburg, Germany. RP Solano, ME (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Obstet & Prenatal Med, Hamburg, Germany. EM e.solano@uke.de OI Chapman, Karen/0000-0001-7777-6817 FU German Research Council (DFG) [KFO296]; British Heart Foundation; Medical Research Council; Wellcome Trust FX Our (MES and ET) research is supported by the German Research Council (DFG), through the KFO296 and by the British Heart Foundation, Medical Research Council and Wellcome Trust (MCH, KEC). We thank D. Riller for excellent graphical work. NR 255 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 EI 1863-2300 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD NOV PY 2016 VL 38 IS 6 BP 739 EP 763 DI 10.1007/s00281-016-0575-z PG 25 WC Immunology; Pathology SC Immunology; Pathology GA EA2MY UT WOS:000386429000010 PM 27465226 ER PT J AU Creed, M Bonci, A Leggio, L AF Creed, Meaghan Bonci, Antonello Leggio, Lorenzo TI Modulating Morphine Context-Induced Drug Memory With Deep Brain Stimulation: More Research Questions by Lowering Stimulation Frequencies? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID NUCLEUS-ACCUMBENS; COCAINE; REINFORCEMENT; CORTEX C1 [Creed, Meaghan] Univ Geneva, Dept Basic Neurosci, Fac Med, Geneva, Switzerland. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Synapt Plast Sect, Baltimore, MD USA. [Bonci, Antonello] NIDA, Synapt Plast Sect, Intramural Res Program, Baltimore, MD USA. [Bonci, Antonello] Solomon H Snyder Neurosci Inst, Baltimore, MD USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Div Intramural Clin & Biol Res, Bethesda, MD USA. [Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Bethesda, MD USA. [Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr,10CRC 15330,MSC 1108,Room 1-5429, Bethesda, MD 20892 USA.; Leggio, L (reprint author), NIDA, NIH, 10 Ctr Dr,10CRC 15330,MSC 1108,Room 1-5429, Bethesda, MD 20892 USA. EM lorenzo.leggio@nih.gov FU Intramural NIH HHS [ZIA AA000218-01, Z99 AA999999] NR 10 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 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2016 VL 80 IS 9 BP 647 EP 649 DI 10.1016/j.biopsych.2016.08.022 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DZ0FA UT WOS:000385511700002 PM 27697154 ER PT J AU Boileau, I Mansouri, E Williams, B Le Foll, B Rusjan, P Mizrahi, R Tyndale, RF Huestis, MA Payer, DE Wilson, AA Houle, S Kish, SJ Tong, JC AF Boileau, Isabelle Mansouri, Esmaeil Williams, Belinda Le Foll, Bernard Rusjan, Pablo Mizrahi, Romina Tyndale, Rachel F. Huestis, Marilyn A. Payer, Doris E. Wilson, Alan A. Houle, Sylvain Kish, Stephen J. Tong, Junchao TI Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [C-11] CURB SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cannabis use disorder; [C-11] CURB; Endocannabinoid; FAAH; Fatty acid amide hydrolase; Positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; MARIJUANA-RELATED PROBLEMS; PROBLEM DRUG-USE; DELTA(9)-TETRAHYDROCANNABINOL-TOLERANT RATS; ENDOCANNABINOID SYSTEM; CEREBROSPINAL-FLUID; ANANDAMIDE LEVELS; AMYGDALA FUNCTION; RECEPTOR-BINDING; C385A VARIANT AB BACKGROUND: One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown. METHODS: Brain FAAH binding was measured with positron emission tomography and [C-11] CURB in 22 healthy control subjects and ten chronic cannabis users during early abstinence. The FAAH genetic polymorphism (rs324420) and blood, urine, and hair levels of cannabinoids and metabolites were determined. RESULTS: In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects (overall Cohen's d = 0.96). Lower binding was negatively correlated with cannabinoid concentrations in blood and urine and was associated with higher trait impulsiveness. CONCLUSIONS: Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids. Further studies are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and whether lower FAAH binding predates drug use. C1 [Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Payer, Doris E.] Ctr Addict & Mental Hlth, Addict Imaging Res Grp, 250 Coll St, Toronto, ON, Canada. [Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Payer, Doris E.; Kish, Stephen J.; Tong, Junchao] Ctr Addict & Mental Hlth, Human Brain Lab, Toronto, ON, Canada. [Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Le Foll, Bernard; Mizrahi, Romina; Tyndale, Rachel F.; Payer, Doris E.; Wilson, Alan A.; Houle, Sylvain; Kish, Stephen J.; Tong, Junchao] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada. [Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Rusjan, Pablo; Mizrahi, Romina; Payer, Doris E.; Wilson, Alan A.; Houle, Sylvain; Kish, Stephen J.] Ctr Addict & Mental Hlth, Res Imaging Ctr, Toronto, ON, Canada. [Le Foll, Bernard; Tyndale, Rachel F.; Kish, Stephen J.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada. [Boileau, Isabelle; Le Foll, Bernard; Rusjan, Pablo; Mizrahi, Romina; Tyndale, Rachel F.; Payer, Doris E.; Kish, Stephen J.; Tong, Junchao] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Boileau, Isabelle; Le Foll, Bernard; Mizrahi, Romina; Kish, Stephen J.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Huestis, Marilyn A.] NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD USA. RP Boileau, I (reprint author), Ctr Addict & Mental Hlth, Addict Imaging Res Grp, 250 Coll St, Toronto, ON, Canada. EM isabelle.boileau@camh.ca FU Canada Foundation for Innovation; Ontario Ministry of Research and Innovation; National Institute of Health; Canadian Institutes of Health Research Grant [TMH109787]; Endowed Chair in Addictions; National Institute of Drug Abuse NIH/NIDA [R21 DA036024] FX This work was supported in part by Canada Foundation for Innovation, the Ontario Ministry of Research and Innovation (SH), the National Institute of Health and National Institute of Drug Abuse NIH/NIDA Grant No. R21 DA036024 (IB), Canadian Institutes of Health Research Grant No. TMH109787 (RFT), and an Endowed Chair in Addictions (Psychiatry Department, RFT). NR 77 TC 1 Z9 1 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2016 VL 80 IS 9 BP 691 EP 701 DI 10.1016/j.biopsych.2016.04.012 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DZ0FA UT WOS:000385511700008 PM 27345297 ER PT J AU Chalhoub, D Orwoll, ES Cawthon, PM Ensrud, KE Boudreau, R Greenspan, S Newman, AB Zmuda, J Bauer, D Cummings, S Cauley, JA AF Chalhoub, Didier Orwoll, Eric S. Cawthon, Peggy M. Ensrud, Kristine E. Boudreau, Robert Greenspan, Susan Newman, Anne B. Zmuda, Joseph Bauer, Douglas Cummings, Steven Cauley, Jane A. CA Osteoporotic Fractures Men MrOS St TI Areal and volumetric bone mineral density and risk of multiple types of fracture in older men SO BONE LA English DT Article DE Aging; QCT; DXA; Men; Fracture risk assessment ID OSTEOPOROTIC FRACTURES; PROXIMAL FEMUR; FEMORAL-NECK; CORTICAL BONE; HIP FRACTURE; LUMBAR SPINE; ELDERLY-MEN; US ADULTS; MROS; AGE AB Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7 years of follow-up. Men answered questionnaires about fractures every 4 months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR = 1.55) and spine sites (HR = 1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. (C) 2016 Elsevier Inc. All rights reserved. C1 [Chalhoub, Didier] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cawthon, Peggy M.] Calif Pacific Med Ctr, San Francisco, CA USA. [Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA. [Boudreau, Robert; Greenspan, Susan; Newman, Anne B.; Zmuda, Joseph; Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St,Crabtree A510, Pittsburgh, PA 15261 USA. [Bauer, Douglas; Cummings, Steven] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. RP Cauley, JA (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St,Crabtree A510, Pittsburgh, PA 15261 USA. EM dic14@pitt.edu; orwoll@ohsu.edu; pcawthon@sfcc-cpmc.net; ensru001@umn.edu; BoudreauR@edc.pitt.edu; greenspn@pitt.edu; NewmanA@edc.pitt.edu; zmudaj@edc.pitt.edu; dbauer@psg.ucsf.edu; scummings@sfcc-cpmc.net; jcauley@edc.pitt.edu OI Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health; National Institute on Aging (NIA); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128] FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. NR 33 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD NOV PY 2016 VL 92 BP 100 EP 106 DI 10.1016/j.bone.2016.08.014 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ2TC UT WOS:000385693400012 PM 27554426 ER PT J AU Rathbun, AM Shardell, M Orwig, D Hebel, JR Hicks, GE Beck, TJ Magaziner, J Hochberg, MC AF Rathbun, Alan M. Shardell, Michelle Orwig, Denise Hebel, J. Richard Hicks, Gregory E. Beck, Thomas J. Magaziner, Jay Hochberg, Marc C. TI Difference in the trajectory of change in bone geometry as measured by hip structural analysis in the narrow neck, intertrochanteric region, and femoral shaft between men and women following hip fracture SO BONE LA English DT Article DE Aging; DXA; Osteoporosis; Injury/fracture healing; Fracture prevention ID SEMIPARAMETRIC REGRESSION-MODELS; X-RAY ABSORPTIOMETRY; OSTEOPOROTIC FRACTURES; MINERAL DENSITY; PERIOSTEAL APPOSITION; POSTMENOPAUSAL WOMEN; ZOLEDRONIC ACID; ELDERLY-MEN; SEX; STRENGTH AB Prior studies have shown that women have declines in bone structure and strength after hip fracture, but it is unclear whether men sustain similar changes. Therefore, the objective was to examine sex differences in proximal femur geometry following hip fracture. Hip structural analysis was used to derive metrics of bone structure and strength: aerial bone mineral density, cross-sectional bone area (CSA), cortical outer diameter, section modulus (SM), and buckling ratio (BR) from dual-energy x-ray absorptiometry scans performed at baseline (within 22 days of hospital admission), two, six, or twelve months after hip fracture in men and women (n = 282) enrolled in the Baltimore Hip Studies 7th cohort. Weighted estimating equations were used to evaluate sex differences at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS). Men had significantly different one year NN changes compared to women in CSA: -6.33% (-12.47, -020) vs. 1.37% (-331, 6.43), P = 0.049; SM: -4.98% (-11.08, 1.10) vs. 3.94% (-2.51, 10.42), P = 0.042; and BR: 7.50% (0.65, 14.36) vs. -1.20% (-6.41, 4.00), P = 0.044. One year IT changes displayed similar patterns, but the sex differences were not statistically significant for CSA: -4.07% (-10.83, 2.67) vs. 0.41% (-3.41, 4.24), P = 0.252; SM: -4.78% (-12.10,5.53) vs. -0.31 (-4.74, 4.11), P = 0.287; and BR: 4.59% (-0.65, 9.84) vs. 1.52% (-423, 728), P = 0.425. Differences in FS geometric parameters were even smaller in magnitude and not significantly different by sex. Women generally experienced non-significant increases in bone tissue and strength following hip fracture, while men had structural declines that were statistically greater at the NN region. Reductions in the mechanical strength of the proximal femur after hip fracture could put men at higher risk for subsequent fractures of the contralateral hip. (C) 2016 Elsevier Inc. All rights reserved. C1 [Rathbun, Alan M.; Orwig, Denise; Hebel, J. Richard; Magaziner, Jay; Hochberg, Marc C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Shardell, Michelle] NIA, Baltimore, MD 21224 USA. [Hicks, Gregory E.] Univ Delaware, Newark, DE USA. [Beck, Thomas J.] Beck Radiol Innovat, Catonsville, MD USA. RP Rathbun, AM (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Howard Hall Suite 200,660 W Redwood St, Baltimore, MD 21201 USA. EM arathbun@epi.umaryland.edu FU National Institute on Aging [R37 AG009901, R01 AG029315, P30 AG028747, T32 AG000262] FX This research was supported by grants from the National Institute on Aging (R37 AG009901, R01 AG029315, P30 AG028747, and T32 AG000262). The funding sponsor had no role in study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. We also acknowledge the cooperation of the hospitals, DXA facilities, residents, and families participating in this project. NR 51 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 8756-3282 EI 1873-2763 J9 BONE JI Bone PD NOV PY 2016 VL 92 BP 124 EP 131 DI 10.1016/j.bone.2016.08.020 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ2TC UT WOS:000385693400015 PM 27569519 ER PT J AU Ellis, A Grace, PM Wieseler, J Favret, J Springer, K Skarda, B Ayala, M Hutchinson, MR Falci, S Rice, KC Maier, SF Watkins, LR AF Ellis, Amanda Grace, Peter M. Wieseler, Julie Favret, Jacob Springer, Kendra Skarda, Bryce Ayala, Monica Hutchinson, Mark R. Falci, Scott Rice, Kenner C. Maier, Steven F. Watkins, Linda R. TI Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE TLR4; Inflammasome; Proinflammatory cytokines; (+)-Naltrexone; Interleukin-1 beta; NLRP3; Tumor necrosis factor; Neuropathic pain; Rats ID CENTRAL NEUROPATHIC PAIN; OPIOID ANALGESIA; ACTIVATION; REMIFENTANIL; INFLAMMATION; RECEPTORS; RECOVERY; SURGERY; CELLS AB Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 h after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1 beta, and NLRP3, as well as IL-1 beta protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury. (C) 2016 Elsevier Inc. All rights reserved. C1 [Ellis, Amanda; Grace, Peter M.; Wieseler, Julie; Favret, Jacob; Springer, Kendra; Skarda, Bryce; Ayala, Monica; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Ctr Neurosci, Campus Box 345, Boulder, CO 80309 USA. [Grace, Peter M.; Hutchinson, Mark R.] Univ Adelaide, Sch Med, Adelaide, SA, Australia. [Hutchinson, Mark R.] Australian Res Council, Ctr Excellence Nanoscale BioPhoton, Canberra, ACT, Australia. [Falci, Scott] Craig Hosp, Englewood, CO USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA. RP Watkins, LR (reprint author), Univ Colorado, Dept Psychol & Neurosci, Campus Box 345, Boulder, CO 80309 USA. EM linda.watkins@colorado.edu OI Grace, Peter/0000-0002-8999-1220; Hutchinson, Mark/0000-0003-2154-5950 FU NIH (USA) [DE021966, DA023132]; NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA); National Institute of Alcohol Abuse and Alcoholism (NIAAA); NHMRC (Australia) [1054091, 465423] FX This work was supported by NIH (USA) grants DE021966 and DA023132 (LRW). Synthesis and purification of (+)-naltrexone 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). Peter M Grace was a NHMRC (Australia) CJ Martin Fellow [ID: 1054091] and American Australian Association Sir Keith Murdoch Fellow. Mark R. Hutchinson was a NHMRC (Australia) CJ Martin Fellow (ID 465423; 2007-2010) and an Australian Research Council Research Fellow (DP110100297). Watkins is a co-founder of Xalud Therapeutics, which is exploring development of (+)-naltrexone for potential future clinical trials. The remaining authors have no conflicting interests. NR 34 TC 2 Z9 2 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD NOV PY 2016 VL 58 BP 348 EP 356 DI 10.1016/j.bbi.2016.08.004 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA DZ5MG UT WOS:000385905600038 PM 27519154 ER PT J AU Pinal-Fernandez, I Mammen, AL AF Pinal-Fernandez, Iago Mammen, Andrew L. TI Spectrum of immune-mediated necrotizing myopathies and their treatments SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoantibody; autoimmunity; 3-hydroxy-3-methylglutaryl-CoA reductase; immune-mediated necrotizing myopathy; myositis; signal recognition particle ID SIGNAL RECOGNITION PARTICLE; IDIOPATHIC INFLAMMATORY MYOPATHIES; AUTOIMMUNE MYOPATHY; CASE SERIES; REDUCTASE; AUTOANTIBODIES; ANTIBODIES; STATIN; MYOSITIS; FEATURES AB Purpose of reviewThis review aims to describe the spectrum of clinical, histological, and serological features in patients with immune-mediated necrotizing myopathies (IMNMs).Recent findingsAutoantibodies recognizing the signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) define two unique subtypes of necrotizing myositis patient with distinct clinical features. For example, the major histocompatibility class II human leukocyte antigen allele DRB111:01 is a strong immunogenetic risk factor for developing anti-HMGCR autoantibodies whereas B5001 and DQA10104 are over-represented in patients with anti-SRP autoantibodies. Furthermore, statin exposure is a risk factor only for anti-HMGCR autoantibodies. And while skeletal muscle involvement is predominant in most patients with both autoantibodies, lung involvement appears in approximate to 20% of anti-SRP-positive patients but is more rare in anti-HMGCR-positive patients. Of note, approximate to 20% of anti-SRP and anti-HMGCR positive patients have significant lymphocytic infiltrates on muscle biopsy and thus would not be formally categorized as having IMNM; aside from this, these patients are clinically indistinguishable from other patients with the same autoantibody profile.SummaryAnti-SRP and anti-HMGCR autoantibodies define unique populations of IMNM patients. It may be more appropriate to subtype myositis patients based on these autoantibodies than on their muscle biopsy features. C1 [Pinal-Fernandez, Iago; Mammen, Andrew L.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Mammen, Andrew L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Mammen, AL (reprint author), NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, 50 South Dr,Room 1141,Bldg 50,MSC 8024, Bethesda, MD 20892 USA. EM andrew.mammen@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 38 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD NOV PY 2016 VL 28 IS 6 BP 619 EP 624 DI 10.1097/BOR.0000000000000335 PG 6 WC Rheumatology SC Rheumatology GA DZ0LL UT WOS:000385530800008 PM 27607340 ER PT J AU Lin, B Dutta, B Oh, KS Fraser, I AF Lin, B. Dutta, B. Oh, K. -S. Fraser, I. TI DISCOVERY OF A NOVEL TRANSCRIPTIONAL REGULATOR OF SUSTAINING TLR-MEDIATED INFLAMMATORY RESPONSES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Lin, B.; Dutta, B.; Oh, K. -S.; Fraser, I.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA O001 BP 46 EP 46 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100007 ER PT J AU St Leger, AJ Desai, J Drummond, R Almaghrabi, F Silver, P Lionakis, M Caspi, R AF St Leger, A. J. Desai, J. Drummond, R. Almaghrabi, F. Silver, P. Lionakis, M. Caspi, R. TI MICROBIOME-DEPENDENT MODULATION OF MUCOSAL IMMUNITY AT THE OCULAR SURFACE SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [St Leger, A. J.; Almaghrabi, F.; Silver, P.; Caspi, R.] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Desai, J.; Drummond, R.; Lionakis, M.] NIAID, Fungal Pathogenesis Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA O004 BP 47 EP 48 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100010 ER PT J AU Durum, S Hixon, J Senkevitch, E Cramer, S Barata, J Walsh, S Li, W AF Durum, S. Hixon, J. Senkevitch, E. Cramer, S. Barata, J. Walsh, S. Li, W. TI TARGETING THE IL-7R PATHWAY IN LEUKEMIA WITH JAK INHIBITORS AND MABS. SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Durum, S.; Hixon, J.; Senkevitch, E.; Cramer, S.; Li, W.] NCI, Frederick, MD 21701 USA. [Barata, J.] Univ Lisbon, Lisbon, Portugal. [Walsh, S.] Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA O008 BP 49 EP 49 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100014 ER PT J AU Villarino, A Sciume, G Robinson, G Hennighausen, L O'Shea, J AF Villarino, A. Sciume, G. Robinson, G. Hennighausen, L. O'Shea, J. TI HOMEOSTATIC STAT5 SIGNALING DRIVES ACCUMULATION AND FUNCTION OF INNATE LYMPHOCYTES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Villarino, A.; Sciume, G.; O'Shea, J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Robinson, G.; Hennighausen, L.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA O024 BP 55 EP 56 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100030 ER PT J AU Obajemu, A Onabajo, OO Rao, N Banday, R Prokunina-Olsson, L AF Obajemu, A. Onabajo, O. O. Rao, N. Banday, R. Prokunina-Olsson, L. TI IFN-lambda 4 HAS A POTENT ANTIPROLIFERATIVE ACTIVITY IN B-CELL LYMPHOMA AND HEPATOMA CELL LINES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Obajemu, A.; Onabajo, O. O.; Rao, N.; Banday, R.; Prokunina-Olsson, L.] NCI, DCEG, LTG, NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P001 BP 58 EP 58 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100035 ER PT J AU Fernandez, DJ Fu, J Nag, ML AF Fernandez, D. J. Fu, J. Nag, M. Lal TI DISRUPTION OF PD-1/PD-L1 SIGNALING IN 2D VS. 3D COLORECTAL CANCER COCULTURE MODEL REVEALED BY RNAI HIGH THROUGHPUT SCREEN SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Fernandez, D. J.; Fu, J.; Nag, M. Lal] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 2 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P008 BP 61 EP 61 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100041 ER PT J AU Wang, F Onabajo, OO Prokunina-Olsson, L AF Wang, F. Onabajo, O. O. Prokunina-Olsson, L. TI EXPLORATION OF IFNLR1-DEPENDENT AND INDEPENDENT CANCER-RELATED FUNCTIONS OF IFN-E4 IN A HEPATOMA CELL LINE SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Wang, F.; Onabajo, O. O.; Prokunina-Olsson, L.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P014 BP 64 EP 64 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100047 ER PT J AU Young, H Leung, P Tsuneyama, K Valencia, J Hodge, D Kim, S Back, T Karwan, M Merchant, A Baba, N Feng, D Park, O Gao, B Yang, GX Gershwin, ME Bae, H AF Young, H. Leung, P. Tsuneyama, K. Valencia, J. Hodge, D. Kim, S. Back, T. Karwan, M. Merchant, A. Baba, N. Feng, D. Park, O. Gao, B. Yang, G. -X. Gershwin, M. E. Bae, H. TI THE SEX BIAS OBSERVED IN A MURINE MODEL OF LIVER AUTOIMMUNITY INVOLVES CD4+T CELLS AND THE INTERPLAY OF TYPE I AND TYPE II INTERFERONS SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Young, H.; Valencia, J.; Kim, S.; Back, T.; Karwan, M.; Merchant, A.; Bae, H.] NCI Frederick, Frederick, MD USA. [Leung, P.; Yang, G. -X.; Gershwin, M. E.] Univ Calif Davis, Davis, CA 95616 USA. [Tsuneyama, K.] Univ Tokushima, Tokushima, Japan. [Hodge, D.] NIH, CNR, Bldg 10, Bethesda, MD 20892 USA. [Baba, N.] Kagawa Prefectural Cent Hosp, Takamatsau, Japan. [Feng, D.] NIA, NIH, Bethesda, MD 20892 USA. [Park, O.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Gao, B.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P047 BP 79 EP 79 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100080 ER PT J AU Bergamaschi, C Ng, SSM Nagy, BA Jensen, SM Hui, X Alicea, C Fox, BA Felber, BK Pavlakis, GN AF Bergamaschi, C. Ng, S. S. M. Nagy, B. A. Jensen, S. M. Hui, X. Alicea, C. Fox, B. A. Felber, B. K. Pavlakis, G. N. TI HETERODIMERIC IL-15 ENHANCES TUMOR INFILTRATION, PERSISTENCE AND EFFECTOR FUNCTIONS OF ADOPTIVELY TRANSFERRED TUMOR-SPECIFIC T CELLS IN THE ABSENCE OF LYMPHODEPLETION SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Bergamaschi, C.; Ng, S. S. M.; Nagy, B. A.; Hui, X.; Alicea, C.; Felber, B. K.; Pavlakis, G. N.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Jensen, S. M.; Fox, B. A.] Providence Canc Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P079 BP 93 EP 94 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100112 ER PT J AU Ren, M Liao, W Zheng, M Peltz, G Leonard, J AF Ren, M. Liao, W. Zheng, M. Peltz, G. Leonard, J. TI MSX2-INTERACTING NUCLEAR TARGET PROTEIN (MINT) IS A NOVEL REGULATOR OF TH9 DIFFERENTIATION SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Ren, M.; Liao, W.; Leonard, J.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Zheng, M.; Peltz, G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P095 BP 100 EP 101 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100128 ER PT J AU Ozato, K AF Ozato, K. TI BRD4 SETS CHROMATIN LANDSCAPE TO REGULATE CYTOKINE TRANSCRIPTION AND INFLAMMATORY DISEASES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Ozato, K.] NICHD, PGD, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P119 BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100152 ER PT J AU Chen, J Waldmann, T AF Chen, J. Waldmann, T. TI FUNCTIONAL DISORDERS AND ACTIVATING JAK/STAT MUTATIONS IN T-CELL LEUKEMIA/LYMPHOMA SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Chen, J.; Waldmann, T.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P131 BP 116 EP 116 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100164 ER PT J AU John, SP Sun, J Fraser, I AF John, S. P. Sun, J. Fraser, I. TI IFIT1 REGULATES PROINFLAMMATORY AND ANTIVIRAL GENE PROGRAMS IN LPS-STIMULATED MACROPHAGES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [John, S. P.; Sun, J.; Fraser, I.] NIAID, Lab Syst Biol, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P150 BP 124 EP 125 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100183 ER PT J AU Chiramel, A Meyerson, N Montoya, V McNally, K Robertson, S Sturdevant, G Taylor, T Sawyer, S Best, S AF Chiramel, A. Meyerson, N. Montoya, V. McNally, K. Robertson, S. Sturdevant, G. Taylor, T. Sawyer, S. Best, S. TI MOVE OVER RETROVIRUSES:TRIM5 IS A POTENT RESTRICTION FACTOR FOR TICK-BORNE FLAVIVIRUSES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Chiramel, A.; Montoya, V.; McNally, K.; Robertson, S.; Sturdevant, G.; Best, S.] NIAID, Hamilton, MT USA. [Meyerson, N.] Univ Colorado, Boulder, CO 80309 USA. [Taylor, T.] Univ Toledo, 2801 W Bancroft St, Toledo, OH 43606 USA. [Sawyer, S.] NIAID, Boulder, CO USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P151 BP 125 EP 125 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100184 ER PT J AU Ha, H Wang, H Claudio, E Tang, W Siebenlist, U AF Ha, H. Wang, H. Claudio, E. Tang, W. Siebenlist, U. TI IL-17 DRIVES PSORIATIC INFLAMMATION VIA DISTINCT, TARGET CELL-SPECIFIC MECHANISMS SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Ha, H.; Wang, H.; Claudio, E.; Tang, W.; Siebenlist, U.] NIAID, Immune Activat Sect, LMI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P189 BP 141 EP 141 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100222 ER PT J AU Onabajo, OO Rao, N Obajemu, AA Kari, DA Sheikh, F Donnelly, R Shabman, RS Prokunina-Olsson, L AF Onabajo, O. O. Rao, N. Obajemu, A. A. Kari, D. A. Sheikh, F. Donnelly, R. Shabman, R. S. Prokunina-Olsson, L. TI IFNL4 INDUCES A FASTER BUT MORE TRANSIENT ANTIVIRAL RESPONSE COMPARED TO OTHER TYPE III INTERFERONS SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Onabajo, O. O.; Rao, N.; Obajemu, A. A.; Prokunina-Olsson, L.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kari, D. A.; Shabman, R. S.] J Craig Venter Inst, Virol Grp, Rockville, MD USA. [Sheikh, F.; Donnelly, R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P193 BP 143 EP 143 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100226 ER PT J AU Chong, WP Horai, R Silver, PB Jittayasothorn, Y Chan, CC Caspi, RR AF Chong, W. P. Horai, R. Silver, P. B. Jittayasothorn, Y. Chan, C. -C. Caspi, R. R. TI IL-17A IS DISPENSABLE FOR AUTOIMMUNE TISSUE DAMAGE IN THE NEURORETINA AND NEGATIVELY REGULATES THE TH17 CYTOKINE PROGRAM SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Chong, W. P.; Horai, R.; Silver, P. B.; Jittayasothorn, Y.; Chan, C. -C.; Caspi, R. R.] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P210 BP 151 EP 151 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100243 ER PT J AU Rochman, Y Leonard, WJ Singh, H AF Rochman, Y. Leonard, W. J. Singh, H. TI TSLP SIGNALING IN CD4 T CELLS PRIMES PATHOGENIC TH2 RESPONSES SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Rochman, Y.; Singh, H.] Cincinnati Childrens Hosp Med Ctr, Immunobiol, Cincinnati, OH 45229 USA. [Rochman, Y.; Singh, H.] Cincinnati Childrens Hosp Med Ctr, Ctr Syst Immunol, Cincinnati, OH 45229 USA. [Rochman, Y.; Singh, H.] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA. [Leonard, W. J.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Leonard, W. J.] NHLBI, Blood Inst, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P213 BP 152 EP 152 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100246 ER PT J AU Wilhelm, C Harrison, O Schmitt, V Pelletier, M Spencer, S Urban, J Siegel, R Belkaid, Y AF Wilhelm, C. Harrison, O. Schmitt, V. Pelletier, M. Spencer, S. Urban, J. Siegel, R. Belkaid, Y. TI FATTY ACID METABOLISM SUSTAINS ILC2 MEDIATED BARRIER IMMUNITY DURING INFECTION AND MALNUTRITION SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Wilhelm, C.; Schmitt, V.] Univ Bonn, Bonn, Germany. [Harrison, O.; Spencer, S.; Siegel, R.; Belkaid, Y.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Pelletier, M.] Univ Laval, Quebec City, PQ, Canada. [Urban, J.] USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA 3P214 BP 152 EP 152 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100247 ER PT J AU Du, N Lin, JX Li, P Spolski, R Leonard, WJ AF Du, N. Lin, J. -X. Li, P. Spolski, R. Leonard, W. J. TI ESSENTIAL ROLES OF STAT5 TETRAMERS IN THE MATURATION AND SURVIVAL OF NATURAL KILLER CELLS SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Du, N.; Lin, J. -X.; Li, P.; Spolski, R.; Leonard, W. J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P215 BP 153 EP 153 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100248 ER PT J AU Furumoto, Y Smith, CK Blanco, L Zhao, W Tsai, WL Hoffmann, V Nunez, L Sciume, G Thaker, SG Remaley, AT O'Shea, JJ Kaplan, MJ Gadina, M AF Furumoto, Y. Smith, C. K. Blanco, L. Zhao, W. Tsai, W. L. Hoffmann, V. Nunez, L. Sciume, G. Thaker, S. G. Remaley, A. T. O'Shea, J. J. Kaplan, M. J. Gadina, M. TI TOFACITINIB REDUCES CIRCULATING CYTOKINES, EXPRESSION OF INTERFERON-DEPENDENT GENES AND VASCULAR DAMAGE IN MURINE LUPUS SO CYTOKINE LA English DT Meeting Abstract CT 4th Annual Meeting of The International-Cytokine-and-Interferon-Society (ICIS) CY OCT 16-19, 2016 CL San Francisco, CA SP Int Cytokine & Interferon Soc C1 [Furumoto, Y.; Tsai, W. L.; Nunez, L.; Gadina, M.] NIAMS, Off Sci & Technol, Bethesda, MD USA. [Smith, C. K.; Blanco, L.; Zhao, W.; Kaplan, M. J.] NIAMS, Syst Autoimmun Branch, Bethesda, MD USA. [Hoffmann, V.] ORS, Div Vet Resources, Bethesda, MD USA. [Sciume, G.; O'Shea, J. J.] NIAMS, Mol Immunol & Inflammat Branch, Bethesda, MD USA. [Thaker, S. G.; Remaley, A. T.] NHLBI, Lipoprot Metab Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD NOV PY 2016 VL 87 MA P221 BP 155 EP 156 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA DY7PH UT WOS:000385321100254 ER PT J AU Barentsz, JO Choyke, PL Cornud, F Haider, MA Macura, KJ Margolis, D Shtern, F Padhani, AR Tempany, CM Thoeny, HC Verma, S Weinreb, JC AF Barentsz, Jelle O. Choyke, Peter L. Cornud, Francois Haider, Masoom A. Macura, Katarzyna J. Margolis, Daniel Shtern, Faina Padhani, Anwar R. Tempany, Clare M. Thoeny, Harriet C. Verma, Sadhna Weinreb, Jeffrey C. TI Reply to Erik Rud and Eduard Baco's Letter to the Editor re: Re: Jeffrey C. Weinreb, Jelle O. Barentsz, Peter L. Choyke, et al. PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol 2016; 69: 16-40 SO EUROPEAN UROLOGY LA English DT Letter C1 [Barentsz, Jelle O.] Radboudumc, Nijmegen, Netherlands. [Choyke, Peter L.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Cornud, Francois] Rene Descartes Univ, Paris, France. [Haider, Masoom A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Macura, Katarzyna J.] Johns Hopkins Univ, Baltimore, MD USA. [Margolis, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA. [Shtern, Faina] AdMeTech Fdn, Boston, MA USA. [Padhani, Anwar R.] Mt Vernon Hosp, Paul Strickland Scanner Ctr, Northwood, Middx, England. [Tempany, Clare M.] Harvard Univ, Boston, MA 02115 USA. [Thoeny, Harriet C.] Univ Hosp Bern, Bern, Switzerland. [Verma, Sadhna] Univ Cincinnati, Cincinnati, OH USA. [Weinreb, Jeffrey C.] Yale Sch Med, New Haven, CT USA. RP Barentsz, JO (reprint author), Radboudumc, Nijmegen, Netherlands. EM jelle.barentsz@radboudumc.nl NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD NOV PY 2016 VL 70 IS 5 BP E137 EP E138 DI 10.1016/j.eururo.2016.04.016 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA DZ0GN UT WOS:000385515600051 PM 27130148 ER PT J AU Nakajima, S Harrison, O Merrill, D Linehan, J Belkaid, Y AF Nakajima, S. Harrison, O. Merrill, D. Linehan, J. Belkaid, Y. TI The role of Candida albicans in the pathogenesis of psoriasis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 2nd Inflammatroy Skin Disease Summit CY NOV 16-19, 2016 CL New York, NY C1 [Nakajima, S.; Harrison, O.; Merrill, D.; Linehan, J.; Belkaid, Y.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2016 VL 25 SU S4 MA P075 BP 31 EP 31 PG 1 WC Dermatology SC Dermatology GA DY8BR UT WOS:000385353900075 ER PT J AU Bhattacharya, S Kim, JC Nakato, G Ogawa, Y Kellet, M Udey, MC Morasso, MI AF Bhattacharya, S. Kim, J. -C. Nakato, G. Ogawa, Y. Kellet, M. Udey, M. C. Morasso, M. I. TI The epithelial DLX3-dependent transcriptome regulates skin immune homeostasis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 2nd Inflammatroy Skin Disease Summit CY NOV 16-19, 2016 CL New York, NY C1 [Bhattacharya, S.; Kim, J. -C.; Kellet, M.; Morasso, M. I.] NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. [Nakato, G.; Ogawa, Y.; Udey, M. C.] Ctr Canc Res, Dermatol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2016 VL 25 SU S4 MA P111 BP 43 EP 44 PG 2 WC Dermatology SC Dermatology GA DY8BR UT WOS:000385353900111 ER PT J AU Laranjeira, ABA Yang, SX AF Laranjeira, Angelo B. A. Yang, Sherry X. TI Therapeutic target discovery and drug development in cancer stem cells for leukemia and lymphoma: from bench to the clinic SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE Cancer stem cells (CSCs); Notch; Hedgehog (Hh); Wnt; -catenin; leukemia; lymphoma ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEDGEHOG SIGNALING PATHWAY; SELF-RENEWAL CAPACITY; GAMMA-SECRETASE; SONIC HEDGEHOG; INITIATING CELLS; PROGENITOR CELLS; NEURAL-TUBE; T-ALL AB Introduction: Cancer stem cells (CSCs), also known as tumor initialing cells, have self-renewal capacity and are believed to play an important role in residual disease or tumor relapse. CSCs exhibit characteristic slow growth rate and are resistant to conventional chemotherapy/radiotherapy in experimental models. The type of cells commonly employs aberrant activity of the embryonic signal transduction pathways - Notch, Hedgehog (Hh), and Wnt - for uncontrolled proliferation and survival.Areas covered: The following article discusses key genetic and molecular alterations in Notch, Hh and Wnt pathways and drugs targeting the alterations for the treatment of leukemia and lymphoma.Expert opinion: Early signs of signal agent activity have been observed in certain types of leukemia and lymphoma with experimental therapeutics targeting the embryonic pathways in the CSC signaling network. However, clinical development of agents that inhibit the Wnt/-catenin, Notch and Hh signaling appear to be more complex in relapsed or refractory malignancies. A strategy to effectively target signaling may rely on early application of biomarkers representative of the active signaling nodes companion to the molecularly targeted agents. Biomarkers for efficacy could potentially guide selective treatment of hematological malignancies or cancer with drugs that target the embryonic pathways. C1 [Laranjeira, Angelo B. A.; Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Yang, SX (reprint author), Bldg 37 Rm 1048,37 Convent Dr, Bethesda, MD 20892 USA. EM Sherry.Yang@nih.gov FU Division of Cancer Treatment and Diagnosis, the National Cancer Institute, National Institutes of Health, USA FX This paper is in part supported by the Division of Cancer Treatment and Diagnosis, the National Cancer Institute, National Institutes of Health, USA. NR 81 TC 0 Z9 0 U1 7 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD NOV PY 2016 VL 11 IS 11 SI SI BP 1071 EP 1080 DI 10.1080/17460441.2016.1236785 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DZ5XT UT WOS:000385936200006 PM 27626707 ER PT J AU Yang, XHR Rotunno, M Xiao, YZ Ingvar, C Helgadottir, H Pastorino, L van Doorn, R Bennett, H Graham, C Sampson, JN Malasky, M Vogt, A Zhu, B Bianchi-Scarra, G Bruno, W Queirolo, P Fornarini, G Hansson, J Tuominen, R Burdett, L Hicks, B Hutchinson, A Jones, K Yeager, M Chanock, SJ Landi, MT Hoiom, V Olsson, H Gruis, N Ghiorzo, P Tucker, MA Goldstein, AM AF Yang, Xiaohong R. Rotunno, Melissa Xiao, Yanzi Ingvar, Christian Helgadottir, Hildur Pastorino, Lorenza van Doorn, Remco Bennett, Hunter Graham, Cole Sampson, Joshua N. Malasky, Michael Vogt, Aurelie Zhu, Bin Bianchi-Scarra, Giovanna Bruno, William Queirolo, Paola Fornarini, Giuseppe Hansson, Johan Tuominen, Rainer Burdett, Laurie Hicks, Belynda Hutchinson, Amy Jones, Kristine Yeager, Meredith Chanock, Stephen J. Landi, Maria Teresa Hoiom, Veronica Olsson, Hakan Gruis, Nelleke Ghiorzo, Paola Tucker, Margaret A. Goldstein, Alisa M. TI Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations SO HUMAN GENETICS LA English DT Article ID POSITIVE MELANOMA FAMILIES; DATABASE; KINDREDS; BRCA1; SNPS AB The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequencing data to examine 24 putative PC-related genes in 43 PC patients with and 23 PC patients without germline CDKN2A mutations and 1001 controls. For each gene and the four pathways in which they occurred, we tested whether PC patients (overall or CDKN2A+ and CDKN2A- cases separately) had an increased number of rare nonsynonymous variants. Overall, we identified 35 missense variants in PC patients, 14 in CDKN2A+ and 21 in CDKN2A- PC cases. We found nominally significant associations for mismatch repair genes (MLH1, MSH2, MSH6, PMS2) in all PC patients and for ATM, CPA1, and PMS2 in CDKN2A- PC patients. Further, nine CDKN2A+ and four CDKN2A- PC patients had rare potentially deleterious variants in multiple PC-related genes. Loss-of-function variants were only observed in CDKN2A- PC patients, with ATM having the most pathogenic variants. Also, ATM variants (n = 5) were only observed in CDKN2A- PC patients with a family history that included digestive system tumors. Our results suggest that a subset of PC patients may have increased risk because of germline mutations in multiple PC-related genes. C1 [Yang, Xiaohong R.; Rotunno, Melissa; Xiao, Yanzi; Bennett, Hunter; Graham, Cole; Sampson, Joshua N.; Malasky, Michael; Vogt, Aurelie; Zhu, Bin; Burdett, Laurie; Hicks, Belynda; Hutchinson, Amy; Jones, Kristine; Yeager, Meredith; Chanock, Stephen J.; Landi, Maria Teresa; Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Rotunno, Melissa] NCI, Div Canc Control & Populat Studies, NIH, Bethesda, MD 20892 USA. [Ingvar, Christian] Univ Lund Hosp, Dept Surg, Lund, Sweden. [Helgadottir, Hildur; Hansson, Johan; Tuominen, Rainer; Hoiom, Veronica] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Helgadottir, Hildur; Hansson, Johan; Tuominen, Rainer; Hoiom, Veronica] Karolinska Univ Hosp, Stockholm, Sweden. [Pastorino, Lorenza; Bianchi-Scarra, Giovanna; Bruno, William; Ghiorzo, Paola] Univ Genoa, Dept Internal Med & Med Specialties, Genoa, Italy. [van Doorn, Remco; Gruis, Nelleke] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. [Malasky, Michael; Vogt, Aurelie; Zhu, Bin; Burdett, Laurie; Hicks, Belynda; Hutchinson, Amy; Jones, Kristine; Yeager, Meredith] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD USA. [Queirolo, Paola; Fornarini, Giuseppe] IRCCS AOU San Martino IST, Med Oncol Unit, Genoa, Italy. [Olsson, Hakan] Univ Lund Hosp, Dept Oncol, Lund, Sweden. [Goldstein, Alisa M.] 9609 Med Ctr Dr, Bethesda, MD 20892 USA. [Pastorino, Lorenza; Bianchi-Scarra, Giovanna; Bruno, William; Ghiorzo, Paola] IRCCS AOU San Martino IST, Genet Rare Canc, Genoa, Italy. RP Goldstein, AM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.; Goldstein, AM (reprint author), 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM goldstea@mail.nih.gov RI Queirolo, Paola/K-6778-2016 OI Queirolo, Paola/0000-0002-9917-6633 FU Intramural Research Program of the National Cancer Institute, the National Institutes of Health, the Division of Cancer Epidemiology and Genetics; Swedish Cancer Society; Kamprad Foundation; Gunnar Nilsson Foundation; ERC [294576]; Swedish Medical Research Council; Radiumhemmets research funds; Stockholm County Council (ALF-project); Karolinska Institutet Research funds; Paulsson Trust (Lund); AIRC [IG 15460]; Italian Ministry of Health; Dutch Cancer Society [UL 2012-5489] FX This work was supported by the Intramural Research Program of the National Cancer Institute, the National Institutes of Health, the Division of Cancer Epidemiology and Genetics. This work was also supported in part by the Swedish Cancer Society, Kamprad Foundation, Gunnar Nilsson Foundation and the ERC advanced Grant 294576-risk factors cancer; the Swedish Medical Research Council, the Swedish Cancer Society, Radiumhemmets research funds, the Stockholm County Council (ALF-project), Karolinska Institutet Research funds; The Paulsson Trust (Lund); AIRC IG 15460 to PG, Italian Ministry of Health 5 x 1000 to IRCCS AOU San Martino-IST to PG and GBS; the work of NAG and RvD was in part supported by the Dutch Cancer Society (UL 2012-5489). NR 29 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD NOV PY 2016 VL 135 IS 11 BP 1241 EP 1249 DI 10.1007/s00439-016-1715-1 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DY7YK UT WOS:000385345000004 PM 27449771 ER PT J AU Maglic, D Stephen, J Malicdan, MCV Guo, J Fischer, R Konzman, D Mullikin, JC Gahl, WA Vilboux, T Gunay-Aygun, M AF Maglic, Dino Stephen, Joshi Malicdan, May Christine V. Guo, Jennifer Fischer, Roxanne Konzman, Daniel Mullikin, James C. Gahl, William A. Vilboux, Thierry Gunay-Aygun, Meral CA NISC Comparative Sequencing TI TMEM231 Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family SO HUMAN MUTATION LA English DT Article DE TMEM231; whole exome sequencing; translocation; gene conversion; cilia ID MUTATIONS; DISEASES; CILIOPATHIES; BIOLOGY; MODEL AB Joubert and Meckel-Gruber syndromes (JS and MGS) are ciliopathies with overlapping features. JS patients manifest the molar tooth sign on brain imaging and variable eye, kidney, and liver disease. MGS presents with polycystic kidneys, occipital encephalocele, and polydactyly; it is typically perinatally fatal. Both syndromes are genetically heterogeneous; some genes cause either syndrome. Here, we report two brothers married to unrelated women. The first brother had three daughters with JS and a son with polycystic kidneys who died at birth. The second brother's wife had a fetal demise due to MGS. Whole exome sequencing identified TMEM231 NM_001077416.2: c.784G>A; p.(Asp262Asn) in all children and the wife of the first brother; the second brother's wife had a c.406T>G;p.(Trp136Gly) change. In-depth analysis uncovered a rare gene conversion event in TMEM231, leading to loss of exon 4, in all the affected children of first brother. We believe that the combination of this gene conversion with different missense mutations led to a spectrum of phenotypes that span JS and MGS. C1 [Maglic, Dino; Stephen, Joshi; Malicdan, May Christine V.; Guo, Jennifer; Fischer, Roxanne; Konzman, Daniel; Gahl, William A.; Vilboux, Thierry; Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Maglic, Dino; Malicdan, May Christine V.; Gahl, William A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA. [Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; NISC Comparative Sequencing] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Vilboux, Thierry] Inova Translat Med Inst, Falls Church, VA USA. RP Gunay-Aygun, M (reprint author), NHGRI, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (NIH); NIH Medical Research Scholars Program; Pfizer Inc.; Doris Duke Charitable Foundation; Newport Foundation; American Association for Dental Research; Howard Hughes Medical Institute; Colgate-Palmolive Company FX Contract Grant Sponsors: Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (NIH); NIH Medical Research Scholars Program; Pfizer Inc.; The Doris Duke Charitable Foundation; The Newport Foundation; The American Association for Dental Research; The Howard Hughes Medical Institute; Colgate-Palmolive Company; other private donors. NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2016 VL 37 IS 11 BP 1144 EP 1148 DI 10.1002/humu.23054 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA DZ4BZ UT WOS:000385804100003 PM 27449316 ER PT J AU Reading, NS Shooter, C Song, JH Miller, R Agarwal, A Lanikova, L Clark, B Thein, SL Divoky, V Prchal, JT AF Reading, N. Scott Shooter, Claire Song, Jihyun Miller, Robin Agarwal, Archana Lanikova, Lucie Clark, Barnaby Thein, Swee Lay Divoky, Vladimir Prchal, Josef T. TI Loss of Major DNase I Hypersensitive Sites in Duplicated -globin Gene Cluster Incompletely Silences HBB Gene Expression SO HUMAN MUTATION LA English DT Article DE globin genes; regulation; sickle cell disease; HBB duplication ID LOCUS-CONTROL REGION; ACTIVATION; TRANSCRIPTION; LCR; DELETION; ELEMENTS AB We report an infant with sickle cell disease phenotype by biochemical analysis whose -globin gene (HBB) sequencing showed sickle cell mutation (HBBS) heterozygosity. The proband has a unique head-to-tail duplication of the -globin gene cluster having wild-type (HBBA) and HBBS alleles inherited from her father; constituting her HBBS/HBBS-HBBA genotype. Further analyses revealed that proband's duplicated -globin gene cluster (approximate to 650kb) encompassing HBBA does not include the immediate upstream locus control region (LCR) or 3 DNase I hypersensitivity (HS) element. The LCR interacts with -globin gene cluster involving long range DNA interactions mediated by various transcription factors to drive the regulation of globin genes expression. However, a low level of HBBA transcript was clearly detected by digital PCR. In this patient, the observed transcription from the duplicated, distally displaced HBBA cluster demonstrates that the loss of LCR and flanking 3HS sites do not lead to complete silencing of HBB transcription. C1 [Reading, N. Scott; Agarwal, Archana; Prchal, Josef T.] ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Reading, N. Scott; Song, Jihyun; Lanikova, Lucie; Prchal, Josef T.] Univ Utah, Sch Med, Dept Internal Med, Div Hematol, Salt Lake City, UT USA. [Reading, N. Scott; Agarwal, Archana; Prchal, Josef T.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Shooter, Claire; Clark, Barnaby; Thein, Swee Lay] Kings Coll London, Div Canc Studies, Mol Haematol, Fac Life Sci & Med, London, England. [Miller, Robin] Nemours El Dupont Hosp Children, Ctr Canc & Blood Disorders, Wilmington, DE USA. [Lanikova, Lucie] Acad Sci Czech Republic, Inst Mol Genet, Dept Cell & Dev Biol, Prague, Czech Republic. [Clark, Barnaby] Viapath Kings Coll Hosp NHS Fdn Trust, Dept Mol Pathol, London, England. [Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Divoky, Vladimir] Palacky Univ, Fac Med & Dent, Dept Biol, Olomouc 77515, Czech Republic. [Divoky, Vladimir] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic. RP Divoky, V (reprint author), Palacky Univ, Fac Med & Dent, Dept Biol, Olomouc 77515, Czech Republic.; Prchal, JT (reprint author), Univ Utah, Sch Med, Hematol, Salt Lake City, UT 84132 USA. EM vladimir.divoky@upol.cz; josef.prchal@hsc.utah.edu FU Czech Republic Program KON-TAKT II [LH15223]; SLT - King's College Hospital Charity [KCH 96076] FX Contract Grant Sponsor: LL, VD were supported by Czech Republic Program KON-TAKT II (LH15223); CS was supported by a studentship grant to SLT - King's College Hospital Charity [KCH 96076]. NR 20 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2016 VL 37 IS 11 BP 1153 EP 1156 DI 10.1002/humu.23061 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA DZ4BZ UT WOS:000385804100005 PM 27492747 ER PT J AU Coleman, CN AF Coleman, C. Norman TI Masters of Our Destiny: From Jazz Quartet to Symphony Orchestra SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2016 VL 96 IS 3 BP 511 EP 513 DI 10.1016/j.ijrobp.2016.07.006 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DZ0IX UT WOS:000385522900004 PM 27681746 ER PT J AU Jansson, LM Spencer, N McConnell, K Velez, M Tuten, M Harrow, CA Jones, HE Swortwood, MJ Barnes, AJ Scheidweiler, KB Huestis, MA AF Jansson, Lauren M. Spencer, Nancy McConnell, Krystle Velez, Martha Tuten, Michelle Harrow, Cheryl A. Jones, Hendree E. Swortwood, Madeleine J. Barnes, Allan J. Scheidweiler, Karl B. Huestis, Marilyn A. TI Maternal Buprenorphine Maintenance and Lactation SO JOURNAL OF HUMAN LACTATION LA English DT Article DE breastfeeding; chemically dependent women; drug-exposed infants; substance abuse ID NEONATAL ABSTINENCE SYNDROME; TANDEM MASS-SPECTROMETRY; BREAST-MILK; METHADONE-MAINTENANCE; NORBUPRENORPHINE; METABOLITE; GUIDELINES; EXPOSURE; INFANTS; PLASMA AB Background: In addition to the well-known benefits of human milk and breastfeeding for the mother and infant, breastfeeding may mitigate neonatal abstinence syndrome severity in prenatally opioid-exposed infants. However, lack of conclusive data regarding the extent of the presence of buprenorphine and active metabolites in human milk makes the recommendation of breastfeeding for buprenorphine-maintained women difficult for many providers. Objective: This study seeks to determine the concentrations of buprenorphine and its active metabolites (norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide) in human milk, maternal plasma, and infant plasma of buprenorphine-maintained women and their infants. Methods: Up to 10 buprenorphine-maintained women provided paired breast milk and plasma samples at 2, 3, 4, 14, and 30 days postdelivery, and 9 infants provided plasma samples on day 14 of life. All samples were analyzed via liquid chromatography tandem mass spectrometry to determine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide by a fully validated method. Results: Concentrations of buprenorphine and metabolites are low in human milk and maternal plasma. Breastfed infant plasma concentrations of buprenorphine were low or undetectable and metabolite concentrations undetectable at 14 days of infant age. There were significant correlations between maternal buprenorphine dose and maternal plasma and human milk buprenorphine concentrations. Conclusion: These data find low concentrations of buprenorphine and metabolites in human milk and lend support to the recommendation for lactation among stable buprenorphine-maintained women. However, the correlation between maternal dose and maternal plasma and human milk buprenorphine concentrations bears further study. C1 [Jansson, Lauren M.; McConnell, Krystle; Velez, Martha] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Spencer, Nancy; Harrow, Cheryl A.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Tuten, Michelle] Univ Maryland, Baltimore, MD 21201 USA. [Jones, Hendree E.] Univ N Carolina, Chapel Hill, NC USA. [Swortwood, Madeleine J.; Barnes, Allan J.; Scheidweiler, Karl B.] NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Huestis, Marilyn A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Jansson, LM (reprint author), Johns Hopkins Univ, Sch Med, Ctr Addict & Pregnancy, 4940 Eastern Ave,D4E, Baltimore, MD 21224 USA. EM ljansson@jhmi.edu FU NIH/NIDA [RO1DA031689] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by a NIH/NIDA supplement to RO1DA031689, awarded to the first author. NR 23 TC 0 Z9 0 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-3344 EI 1552-5732 J9 J HUM LACT JI J. Hum. Lact. PD NOV PY 2016 VL 32 IS 4 BP 675 EP 681 DI 10.1177/0890334416663198 PG 7 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA DZ2ZF UT WOS:000385710900018 PM 27563013 ER PT J AU Kahn, JA Rudy, BJ Xu, JH Kapogiannis, B Secord, E Gillison, M AF Kahn, Jessica A. Rudy, Bret J. Xu, Jiahong Kapogiannis, Bill Secord, Elizabeth Gillison, Maura TI Prevalence and Risk Factors for Oral DNA Tumor Viruses in HIV-Infected Youth SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE human immunodeficiency virus; human papillomavirus; Epstein-Barr virus; kaposi sarcoma-associated herpesvirus (human herpesvirus 8) ID EPSTEIN-BARR-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; HPV INFECTION; NATURAL-HISTORY; UNITED-STATES; NECK CANCERS; WOMEN; MEN; MUCOSA AB Human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpes virus (KSHV) may promote oral cancers, especially among immunosuppressed individuals. The aims of this study were to examine whether demographic characteristics, medical history, sexual behaviors, substance use, CD4+ T-cell count, HIV viral load, and HPV vaccination were associated with HPV, EBV, and KSHV infection and viral load. Multivariable modeling using logistic or linear regression examined associations between independent variables and infection or viral load, respectively. Among 272 HIV-infected 12-24-year-old youth, 19.5% were positive for oral HPV, 88.2% for EBV, and 11.8% for KSHV. In multivariable models, recent marijuana use (OR 1.97, 95% CI 1.02-3.82) and lower CD4+ T-cell count (<350 vs. >= 350 cells/mm(3) : OR 1.92, 95% CI 1.003-3.69) were associated with HPV infection; lifetime tobacco use (estimated coefficient [EC] 1.55, standard error [SE] 0.53, P = 0.0052) with HPV viral load; recent tobacco use (OR 2.90, 95% CI 1.06-7.97), and higher HIV viral load (>400 vs. <400 copies/ml: OR 3.98, 95% CI 1.84-8.74) with EBV infection; Black versus White race (EC 1.18, SE 0.37, P = 0.0023), and lower CD4+ T-cell count (EC 0.70, SE 0.28, P = 0.017) with EBV viral load, male versus female gender (OR 10, 95% CI 1.32-100) with KSHV infection, and younger age at HIV diagnosis (1-14 vs. 18-20 years: EC 0.33, SE 0.16, P = 0.049; 15-17 vs. 18-20 years: EC 0.35, SE 0.13, P = 0.0099) with KSHV viral load. In conclusion, substance use and immunosuppression are associated with oral DNA tumor viruses in HIV-infected youth. (C) 2016 Wiley Periodicals, Inc. C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 4000, Cincinnati, OH 45229 USA. [Kahn, Jessica A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Rudy, Bret J.] NYU, Sch Med, New York, NY USA. [Xu, Jiahong] Westat Corp, Rockville, MD USA. [Kapogiannis, Bill] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Rockville, MD USA. [Secord, Elizabeth] Wayne State Univ, Detroit, MI USA. [Gillison, Maura] Ohio State Univ, Columbus, OH 43210 USA. RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent & Transit Med, 3333 Burnet Ave,MLC 4000, Cincinnati, OH 45229 USA. EM jessica.kahn@cchmc.org FU Adolescent Trials Network for HIV/AIDS Interventions from the National Institutes of Health [U01 HD 040533, U01 HD 040474]; National Institute of Child Health and Human Development; National Institutes of Drug Abuse and Mental Health; Viral Oncology Program, Ohio State University Comprehensive Cancer Center; Merck, Inc. FX Grant sponsor: Adolescent Trials Network for HIV/AIDS Interventions from the National Institutes of Health; Grant numbers: U01 HD 040533; U01 HD 040474; Grant sponsor: National Institute of Child Health and Human Development; Grant sponsor: National Institutes of Drug Abuse and Mental Health; Grant sponsor: Viral Oncology Program, Ohio State University Comprehensive Cancer Center; Grant sponsor: Merck, Inc. NR 55 TC 0 Z9 0 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 EI 1096-9071 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 2016 VL 88 IS 11 BP 1944 EP 1952 DI 10.1002/jmv.24555 PG 9 WC Virology SC Virology GA DZ3CX UT WOS:000385723000015 PM 27096166 ER PT J AU Lindblad, R Hu, L Oden, N Wakim, P Rosa, C VanVeldhuisen, P AF Lindblad, Robert Hu, Lian Oden, Neal Wakim, Paul Rosa, Carmen VanVeldhuisen, Paul TI Mortality Rates Among Substance Use Disorder Participants in Clinical Trials: Pooled Analysis of Twenty-Two Clinical Trials Within the National Drug Abuse Treatment Clinical Trials Network SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Substance use disorder; Clinical trial; Standardized mortality rate; Standardized mortality ratio; Pooled analysis ID BUPRENORPHINE-NALOXONE; CONFIDENCE-INTERVALS; TREATMENT PROGRAMS; SEEKING TREATMENT; RANDOMIZED-TRIAL; MULTISITE TRIAL; DEATH RATES; FOLLOW-UP; IMPACT; COHORT AB Background: Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. Objective: The aim of this study is to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Participants: Drug and or alcohol users (N = 9866) who sought treatment and participated in one of the twenty-two CTN trials. Measurements: Data were collected through randomized clinical trials in national community treatment programs for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rate(s) (SM rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared to the U.S. general population. Results: The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio = 5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants, it was over three times (SM ratio = 3.39, 95% CI: 2.25-4.90) higher than their gender comparable peers in the U.S. general population. Conclusions: Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment seeking clinical trial participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trial participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates, especially within subgroups based on primary substance of abuse. These SUD mortality rates can be used to facilitate safety monitoring within SUD clinical trials. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lindblad, Robert; Hu, Lian; Oden, Neal; VanVeldhuisen, Paul] Emmes Corp, Rockville, MD 20850 USA. [Wakim, Paul] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Rosa, Carmen] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. RP Lindblad, R (reprint author), Emmes Corp, Rockville, MD 20850 USA. FU National Institute on Drug Abuse, National Drug Abuse Treatment Clinical Trials Network, National Institutes of Health [HHSN271200900034C] FX This research was supported by the National Institute on Drug Abuse, National Drug Abuse Treatment Clinical Trials Network, National Institutes of Health, through Contract No. HHSN271200900034C. NR 43 TC 0 Z9 0 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD NOV PY 2016 VL 70 BP 73 EP 80 DI 10.1016/j.jsat.2016.08.010 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA DY7UX UT WOS:000385335900011 PM 27692192 ER PT J AU Li, QX Fischer, E Cohen, JI AF Li, Qingxue Fischer, Elizabeth Cohen, Jeffrey I. TI Cell Surface THY-1 Contributes to Human Cytomegalovirus Entry via a Macropinocytosis-Like Process SO JOURNAL OF VIROLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; SIMPLEX-VIRUS ENTRY; CLATHRIN-INDEPENDENT ENDOCYTOSIS; EPITHELIAL TIGHT JUNCTIONS; DISINTEGRIN-LIKE DOMAIN; GROWTH-FACTOR RECEPTOR; GPI-ANCHORED PROTEINS; ENDOTHELIAL-CELLS; GLYCOPROTEIN-B; LIPID RAFTS AB Previously we showed that THY-1 has a critical role in the initial stage of infection of certain cell types with human cytomegalovirus (HCMV) and that THY-1 is important for HCMV-mediated activation of phosphatidylinositol 3-kinase (PI3K)/Akt during virus entry. THY-1 is known to interact with integrins and is a major cargo protein of clathrin-independent endocytic vesicles. Since macropinocytosis involves integrin signaling, is PI3K/Akt dependent, and is a clathrin-independent endocytic process, we determined whether THY-1 has a role in HCMV entry by macropinocytosis. Using electron microscopy in two cell lines that support HCMV infection in a THY-1-dependent manner, we found that HCMV enters these cells by a macropinocytosis-like process. THY-1 associated with HCMV virions on the cell surface and colocalized with virus inside macropinosomes. 5-(N-Ethyl-N-isopropyl) amiloride (EIPA) and soluble THY-1 blocked HCMV infection in the cell lines by >= 80% and 60%, respectively. HCMV entry into the cells triggered increased influx of extracellular fluid, a marker of macropinocytosis, and this increased fluid uptake was inhibited by EIPA and by soluble THY-1. Blocking actin depolymerization, Na+/H+ exchange, PI3K, and Pak1 kinase, which are critical for macropinocytosis, impaired HCMV infection. Neither internalized HCMV virions nor THY-1 in virus-infected cells colocalized with transferrin as determined by confocal microscopy, indicating that clathrin-mediated endocytosis was not involved in THY-1-associated virus entry. These results suggest that HCMV has adapted to utilize THY-1, a cargo protein of clathrin-independent endocytotic vesicles, to facilitate efficient entry into certain cell types by a macropinocytosis-like process. C1 [Li, Qingxue; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA. [Fischer, Elizabeth] NIH, Res Technol Branch, Rocky Mt Labs, Hamilton, MT USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health FX This work was funded by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. NR 107 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 21 BP 9766 EP 9781 DI 10.1128/JVI.01092-16 PG 16 WC Virology SC Virology GA DZ0JW UT WOS:000385525700019 PM 27558416 ER PT J AU Barreto-de-Souza, V Arakelyan, A Zicari, S Margolis, L Vanpouille, C AF Barreto-de-Souza, Victor Arakelyan, Anush Zicari, Sonia Margolis, Leonid Vanpouille, Christophe TI Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human Tissue Ex Vivo SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; SEXUAL TRANSMISSION; HEPARAN-SULFATE; TYPE-1 HIV-1; MACROPHAGES; BLOOD; SEMEN; REPLICATION; ATTACHMENT AB Unprotected sexual intercourse with HIV-infected men is the major cause of new infections. HIV virions are released into semen by various cells of the male genital tract, as well as by infected monocytes and lymphocytes present in semen. Some of these virions may attach to the surfaces of cells, infected or uninfected. We investigated whether cells carrying attached HIV on their surfaces can transmit infection. We addressed this question in a model system of human tissue exposed ex vivo to monocytes and lymphocytes carrying HIV on their surfaces. We gamma irradiated the cells to prevent their productive infection. In spite of comparable amounts of HIV attached to monocytes and lymphocytes, only monocytes were capable of transmitting infection and triggering productive infection in tissue. This HIV-1 transmission was mediated by cell-cell contacts. Our experiments suggest that in vivo, HIV attached to infected or uninfected monocytes, which far outnumber lymphocytes in HIV-infected semen, may contribute to sexual transmission of HIV from men to their partners. C1 [Barreto-de-Souza, Victor; Arakelyan, Anush; Zicari, Sonia; Margolis, Leonid; Vanpouille, Christophe] NICHHD, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM margolil@mail.nih.gov FU NICHD Intramural Program; Brazilian Ministry of Education; Brazilian Ministry of Science and Technology FX This work, including the efforts of Victor Barreto-de-Souza, Anush Arakelyan, Sonia Zicari, Leonid Margolis, and Christophe Vanpouille, was funded by the NICHD Intramural Program. This work, including the efforts of Victor Barreto-de-Souza, was funded by the Brazilian Ministry of Education and the Brazilian Ministry of Science and Technology. NR 41 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 21 BP 9833 EP 9840 DI 10.1128/JVI.00742-16 PG 8 WC Virology SC Virology GA DZ0JW UT WOS:000385525700024 PM 27558419 ER PT J AU Ayala, VI Trivett, MT Barsov, EV Jain, S Piatak, M Trubey, CM Alvord, WG Chertova, E Roser, JD Smedley, J Komin, A Keele, BF Ohlen, C Ott, DE AF Ayala, Victor I. Trivett, Matthew T. Barsov, Eugene V. Jain, Sumiti Piatak, Michael, Jr. Trubey, Charles M. Alvord, W. Gregory Chertova, Elena Roser, James D. Smedley, Jeremy Komin, Alexander Keele, Brandon F. Ohlen, Claes Ott, David E. TI Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8(+) T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID MAURITIAN CYNOMOLGUS MACAQUES; IN-VIVO; EFFECTOR-CELLS; GENE-TRANSFER; VIRAL ESCAPE; LYMPHOCYTES; INFECTION; VACCINE; REPLICATION; ANTIGEN AB AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4(+) T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus. C1 [Ayala, Victor I.; Trivett, Matthew T.; Barsov, Eugene V.; Jain, Sumiti; Piatak, Michael, Jr.; Trubey, Charles M.; Chertova, Elena; Roser, James D.; Smedley, Jeremy; Komin, Alexander; Keele, Brandon F.; Ohlen, Claes; Ott, David E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. [Ayala, Victor I.; Trivett, Matthew T.; Barsov, Eugene V.; Jain, Sumiti; Piatak, Michael, Jr.; Trubey, Charles M.; Chertova, Elena; Roser, James D.; Smedley, Jeremy; Komin, Alexander; Keele, Brandon F.; Ohlen, Claes; Ott, David E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Anim Sci Program, Frederick, MD USA. [Alvord, W. Gregory] Frederick Natl Lab Canc Res, DMS Appl Informat & Management Sci, Baltimore, MD USA. [Ayala, Victor I.] Adv Biosci Labs, Gaithersburg, MD USA. [Barsov, Eugene V.] Intrexton Corp, Germantown, MD USA. [Jain, Sumiti] Juno Therapeut, Seattle, WA USA. [Smedley, Jeremy] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Komin, Alexander] Johns Hopkins Univ, Baltimore, MD USA. RP Ott, DE (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. EM ottde@mail.nih.gov FU HHS \ NIH \ National Cancer Institute (NCI) [HHSN261200800001E] FX This work, including the efforts of Victor I. Ayala, Matthew Trivett, Eugene V. Barsov, Sumiti Jain, Michael Piatak, Charles M. Trubey, W. Gregory Alvord, Elena Chertova, James D. Roser, Jeremy Smedley, Alexander Komin, Brandon F. Keele, Claes Ohlen, and David E. Ott, was funded by HHS vertical bar NIH vertical bar National Cancer Institute (NCI) (HHSN261200800001E). NR 58 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 21 BP 9942 EP 9952 DI 10.1128/JVI.01522-16 PG 11 WC Virology SC Virology GA DZ0JW UT WOS:000385525700033 PM 27558423 ER PT J AU Scherer, J Yaffe, ZA Vershinin, M Enquist, LW AF Scherer, Julian Yaffe, Zachary A. Vershinin, Michael Enquist, Lynn W. TI Dual-Color Herpesvirus Capsids Discriminate Inoculum from Progeny and Reveal Axonal Transport Dynamics SO JOURNAL OF VIROLOGY LA English DT Article ID PSEUDORABIES VIRUS; CYTOPLASMIC DYNEIN; SIMPLEX-VIRUS; MYCALOLIDE-B; PROTEIN; ADENOVIRUS; NEUROINVASION; PARTICLES; COMPONENT; DYNACTIN AB Alphaherpesviruses such as herpes simplex virus and pseudorabies virus (PRV) are neuroinvasive double-stranded DNA (dsDNA) viruses that establish lifelong latency in peripheral nervous system (PNS) neurons of their native hosts. Following reactivation, infection can spread back to the initial mucosal site of infection or, in rare cases, to the central nervous system, with usually serious outcomes. During entry and egress, viral capsids depend on microtubule-based molecular motors for efficient and fast transport. In axons of PNS neurons, cytoplasmic dynein provides force for retrograde movements toward the soma, and kinesins move cargo in the opposite, anterograde direction. The dynamic properties of virus particles in cells can be imaged by fluorescent protein fusions to the small capsid protein VP26, which are incorporated into capsids. However, single-color fluorescent protein tags fail to distinguish the virus inoculum from progeny. Therefore, we established a dual-color system by growing a recombinant PRV expressing a red fluorescent VP26 fusion (PRV180) on a stable cell line expressing a green VP26 fusion (PK15-mNG-VP26). The resulting dual-color virus preparation (PRV180G) contains capsids tagged with both red and green fluorescent proteins, and 97% of particles contain detectable levels of mNeonGreen (mNG)-tagged VP26. After replication in neuronal cells, all PRV180G progeny exclusively contain monomeric red fluorescent protein (mRFP)-VP26-tagged capsids. We used PRV180G for an analysis of axonal capsid transport dynamics in PNS neurons. Fast dual-color total internal reflection fluorescence (TIRF) microscopy, single-particle tracking, and motility analyses reveal robust, bidirectional capsid motility mediated by cytoplasmic dynein and kinesin during entry, whereas egressing progeny particles are transported exclusively by kinesins. C1 [Scherer, Julian; Yaffe, Zachary A.; Enquist, Lynn W.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Scherer, Julian; Yaffe, Zachary A.; Enquist, Lynn W.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA. [Vershinin, Michael] Univ Utah, Dept Phys & Astron, Salt Lake City, UT USA. [Yaffe, Zachary A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Enquist, LW (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.; Enquist, LW (reprint author), Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA. EM lenquist@princeton.edu FU National Science Foundation (NSF) [1563280]; HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [F32 GM112337]; HHS \ NIH \ National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NS033506, RO1 NS060699] FX This work, including the efforts of Michael Vershinin, was funded by National Science Foundation (NSF) (1563280). This work, including the efforts of Julian Scherer, was funded by HHS vertical bar NIH vertical bar National Institute of General Medical Sciences (NIGMS) (F32 GM112337). This work, including the efforts of Lynn W. Enquist, was funded by HHS vertical bar NIH vertical bar National Institute of Neurological Disorders and Stroke (NINDS) (RO1 NS033506 and RO1 NS060699). NR 40 TC 1 Z9 1 U1 4 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 21 BP 9997 EP 10006 DI 10.1128/JVI.01122-16 PG 10 WC Virology SC Virology GA DZ0JW UT WOS:000385525700037 ER PT J AU Liang, B Ngwuta, JO Herbert, R Swerczek, J Dorward, DW Amaro-Carambot, E Mackow, N Kabatova, B Lingemann, M Surman, S Yang, LJ Chen, M Moin, SM Kumar, A McLellan, JS Kwong, PD Graham, BS Schaap-Nutt, A Collins, PL Munir, S AF Liang, Bo Ngwuta, Joan O. Herbert, Richard Swerczek, Joanna Dorward, David W. Amaro-Carambot, Emerito Mackow, Natalie Kabatova, Barbora Lingemann, Matthias Surman, Sonja Yang, Lijuan Chen, Man Moin, Syed M. Kumar, Azad McLellan, Jason S. Kwong, Peter D. Graham, Barney S. Schaap-Nutt, Anne Collins, Peter L. Munir, Shirin TI Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE CANDIDATE; F-PROTEIN; NEWCASTLE-DISEASE; AVIAN INFLUENZA; SENDAI-VIRUS; NEUTRALIZING ANTIBODIES; TRANSMEMBRANE DOMAIN; MUCOSAL IMMUNIZATION; MONOCLONAL-ANTIBODY; YOUNG-CHILDREN AB Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine/human PIV3 (rB/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced "high-quality" RSV-neutralizing antibodies, defined as antibodies that neutralize RSV in vitro without added complement (B. Liang et al., J Virol 89: 9499-9510, 2015, doi: 10.1128/JVI.01373-15). In the present study, we modified RSV F by replacing its cytoplasmic tail (CT) domain or its CT and transmembrane (TM) domains (TMCT) with counterparts from BPIV3 F, with or without pre-F stabilization. This resulted in RSV F being packaged in the rB/HPIV3 particle with an efficiency similar to that of RSV particles. Enhanced packaging was substantially attenuating in hamsters (10- to 100-fold) and rhesus monkeys (100- to 1,000-fold). Nonetheless, TMCT-directed packaging substantially increased the titers of high-quality RSV-neutralizing serum antibodies in hamsters. In rhesus monkeys, a strongly additive immunogenic effect of packaging and pre-F stabilization was observed, as demonstrated by 8- and 30-fold increases of RSV-neutralizing serum antibody titers in the presence and absence of added complement, respectively, compared to pre-F stabilization alone. Analysis of vaccine-induced F-specific antibodies by binding assays indicated that packaging conferred substantial stabilization of RSV F in the pre-F conformation. This provides an improved version of this well-tolerated RSV/HPIV3 vaccine candidate, with potently improved immunogenicity, which can be returned to clinical trials. C1 [Liang, Bo; Amaro-Carambot, Emerito; Mackow, Natalie; Kabatova, Barbora; Lingemann, Matthias; Surman, Sonja; Yang, Lijuan; Schaap-Nutt, Anne; Collins, Peter L.; Munir, Shirin] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Herbert, Richard; Swerczek, Joanna] NIAID, Expt Primate Virol Sect, Comparat Med Branch, NIH, Poolesville, MD USA. [Dorward, David W.] NIAID, Rocky Mt Lab, Microscopy Unit, NIH, Hamilton, MT 59840 USA. [Ngwuta, Joan O.; Chen, Man; Moin, Syed M.; Kumar, Azad; McLellan, Jason S.; Kwong, Peter D.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USA. RP Munir, S (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM munirs@niaid.nih.gov FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) (Intramural Program) FX This work, including the efforts of Peter L. Collins, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (Intramural Program). NR 54 TC 1 Z9 1 U1 8 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2016 VL 90 IS 21 BP 10022 EP 10038 DI 10.1128/JVI.01196-16 PG 17 WC Virology SC Virology GA DZ0JW UT WOS:000385525700039 PM 27581977 ER PT J AU Fiorini, N Harispe, S Ranwez, S Montmain, J Ranwez, V AF Fiorini, Nicolas Harispe, Sebastien Ranwez, Sylvie Montmain, Jacky Ranwez, Vincent TI Fast and reliable inference of semantic clusters SO KNOWLEDGE-BASED SYSTEMS LA English DT Article DE Clustering; Cluster labeling; Semantic indexing; Neighbor joining; Complexity analysis ID GENE-EXPRESSION DATA; PHYLOGENETIC TREES; ONTOLOGY; SIMILARITY; NETWORKS; TOOL; MESH AB Document Indexing is but not limited to summarizing document contents with a small set of keywords or concepts of a knowledge base. Such a compact representation of document contents eases their use in numerous processes such as content-based information retrieval, corpus-mining and classification. An important effort has been devoted in recent years to, (partly) automate semantic indexing, i.e. associating concepts to documents, leading to the availability of large corpora of semantically indexed documents. In this paper we introduce a method that hierarchically clusters documents based on their semantic indices while providing the proposed clusters with semantic labels. Our approach follows a neighbor joining strategy. Starting from a distance matrix reflecting the semantic similarity of documents, it iteratively selects the two closest clusters to merge them in a larger one. The similarity matrix is then updated. This is usually done by conibining similarity of the two merged clusters, e.g. using the average similarity. We propose in this paper an alternative approach where the new cluster is first semantically annotated and the similarity matrix is then updated using the semantic similarity of this new.,annotation with those of the remaining clusters. The hierarchical clustering so obtained is a binary tree with branch lengths that convey semantic distances of clusters. It is then post-processed by using the branch lengths to keep only the most relevant clusters. Such a tool has numerous practical applications as it automates the organization of documents in meaningful clusters (e.g. papers indexed by MeSH terms, bookmarks or pictures indexed by WordNet) which is a tedious everyday task for many people. We assess the quality of the proposed methods using a specific benchmark of annotated clusters of bookmarks that were built manually. Each dataset of this benchmark has been clustered independently by several users. Remarkably, the clusters automatically built by our method are congruent with the clusters proposed by experts. All resources of this work, including source code, jar file, benchmark files and results are available at this address: http://sc.nicolasfiorini.info. (C) 2016 Elsevier B.V. All rights reserved. C1 [Fiorini, Nicolas; Harispe, Sebastien; Ranwez, Sylvie; Montmain, Jacky] Ecole Mines Ales, Res Ctr LGI2P, Site Nimes,Parc Sci G Besse, F-30035 Nimes 1, France. [Ranwez, Vincent] Montpellier SupAgro CIRAD INRA, UMR AGAP, 2 Pl P Viala, F-34060 Montpellier 1, France. RP Fiorini, N (reprint author), Natl Lib Med, NCBI, Bldg 38A Rm 8N811B,8600 Rockville Pike, Bethesda, MD 20894 USA. EM nicolas.fiorini@nih.gov FU AVieSan national program (French Alliance nationale pour les sciences de la Vie et de la Sant); French Agence Nationale de la Recherche [ANR-10-BINF-01 Ancestrome] FX This work was partly supported by a grant from AVieSan national program (French Alliance nationale pour les sciences de la Vie et de la Sant) and by the French Agence Nationale de la Recherche (ANR-10-BINF-01 Ancestrome). NR 53 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0950-7051 EI 1872-7409 J9 KNOWL-BASED SYST JI Knowledge-Based Syst. PD NOV 1 PY 2016 VL 111 BP 133 EP 143 DI 10.1016/j.knosys.2016.08.008 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA DY7TH UT WOS:000385331700011 ER PT J AU Freidlin, RZ Agarwal, HK Sankineni, S Brown, AM Mertan, F Bernardo, M Daar, D Merino, M Citrin, D Wood, BJ Pinto, PA Choyke, PL Turkbey, B AF Freidlin, Raisa Z. Agarwal, Harsh K. Sankineni, Sandeep Brown, Anna M. Mertan, Francesca Bernardo, Marcelino Daar, Dagane Merino, Maria Citrin, Deborah Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. Turkbey, Baris TI Application of an unsupervised multi-characteristic framework for intermediate-high risk prostate cancer localization using diffusion-weighted MRI SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Diffusion-weighted MRI; DWI; Prostate cancer; Tumor localization ID COMPUTER-AIDED DIAGNOSIS; GAUSSIAN WATER DIFFUSION; CONTRAST-ENHANCED MRI; COEFFICIENT VALUES; TISSUES; DIFFERENTIATION; COMBINATION; TRANSITION; PERFUSION; GRADE AB Purpose: The aim of this proof-of-concept work is to propose an unsupervised framework that combines multiple parameters, in "positive-if-all-positive" manner, from different models to localize tumors. Methods: A voxel-by-voxel analysis of the DW-MRI images of whole prostate was performed to obtain parametric maps for D*, D, f, and K using the IVIM and kurtosis models. Ten patients with moderate or high-risk prostate cancer were included in study. The mean age and serum PSA for these 10 patients were 65 years (range 54-78) and 21.9 ng/mL (range 4.84-44.81), respectively. These patients were scanned using a DW spin-echo sequence with echo-planar readout with 16 equidistantly spaced b-values in the range of 0-2000 s/mm(2) (TE = 58 ms; TR = 3990 ins; spatial resolution 2.19 x 2.19 x 2.73 mm(3), slices =26, FOV = 140 x 140mm, slice gap =0.27 mm, NSA = 2). Results: The proposed framework detected 24 lesions of which 14 were true positive with 58% tumor detection rate on lesion-based analysis with sensitivity of 100%. The mpMRI evaluation (PIRADSv2) identified 12 of 14 true positive lesions with sensitivity of 86%; positive predictive value of mpMRI was 92%. The index lesions were visible on all framework maps and were coded as the most suspicious in 9 of 10 patients. Conclusion: Preliminary results of the proposed framework indicate high patient-based sensitivity with 100% detection rate for identifying moderate-high risk aggressive index lesions. Published by Elsevier Inc. C1 [Freidlin, Raisa Z.] NIH, Div Computat Biosci, CIT, Bldg 10, Bethesda, MD 20892 USA. [Agarwal, Harsh K.; Sankineni, Sandeep; Brown, Anna M.; Mertan, Francesca; Bernardo, Marcelino; Daar, Dagane; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Agarwal, Harsh K.] Philips Res North Amer, Briarcliff Manor, NY USA. [Brown, Anna M.] Duke Univ, Sch Med, Durham, NC USA. [Bernardo, Marcelino; Daar, Dagane] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Merino, Maria] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Citrin, Deborah] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Freidlin, RZ (reprint author), NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, 12 South Dr,Bldg 12A,Room 2023, Bethesda, MD 20892 USA. EM raisa@mail.nih.gov FU NIH; Doris Duke Charitable Foundation; Newport Foundation; American Association for Dental Research; The Howard Hughes Medical Institute; Colgate-Palmolive Company FX This research was made possible through 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 Newport Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/medical-research-scholars-prog ram. NR 36 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X EI 1873-5894 J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD NOV PY 2016 VL 34 IS 9 BP 1227 EP 1234 DI 10.1016/j.mri.2016.06.004 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY7UN UT WOS:000385334900001 PM 27451403 ER PT J AU Yadav, VR Hong, KL Zeldin, DC Nayeem, MA AF Yadav, Vishal R. Hong, Ka L. Zeldin, Darryl C. Nayeem, Mohammed A. TI Vascular endothelial over-expression of soluble epoxide hydrolase (Tie2-sEH) enhances adenosine A(1) receptor-dependent contraction in mouse mesenteric arteries: role of ATP-sensitive K+ channels SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE sEH; A(1)AR; K-ATP channel; Mesenteric artery; Contraction; Relaxation ID SMOOTH-MUSCLE CONTRACTION; PROTEIN-KINASE-C; EPOXYEICOSATRIENOIC ACIDS; CYP-EPOXYGENASES; POTASSIUM CHANNELS; ARACHIDONIC-ACID; PPAR-GAMMA; MAP KINASE; MICE; SENSITIZATION AB Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids. Previously, we reported a decrease in adenosine A(1) receptor (A(1)AR) protein levels in sEH knockout (sEH(-/-)) and an increase in sEH and A(1)AR protein levels in A(2A)AR(-/-) mice. Additionally, K-ATP channels are involved in adenosine receptor (AR)-dependent vascular relaxation. Thus, we hypothesize that a potential relationship may exist among sEH over-expression, A(1)AR upregulation, inactivation of K-ATP channels, and increased in vascular tone. We performed DMT myograph muscle tension measurements and western blot analysis in isolated mouse mesenteric arteries (MAs) from wild-type (WT) and endothelial over-expression of sEH (Tie2-sEH Tr) mice. Our data revealed that NECA (a non-selective adenosine receptors agonist)-induced relaxation was significantly reduced in Tie2-sEH Tr mice, and CCPA (A(1)AR agonist)-induced contraction was increased in Tie2-sEH Tr mice. A(1)AR-dependent contraction in Tie2-sEH Tr mice was significantly attenuated by pharmacological inhibition of CYP4A (HET0016, 10 A mu M), PKC alpha (GO6976, 1 A mu M), and ERK1/2 (PD58059, 1 A mu M). Our western blot analysis revealed significantly higher basal protein expression of CYP4A, A(1)AR, and reduced p-ERK in MAs of Tie2-sEH Tr mice. Notably, pinacidil (K-ATP channel opener)-induced relaxation was also significantly reduced in MAs of Tie2-sEH Tr mice. Furthermore, K-ATP channel-dependent relaxation in MAs was enhanced by inhibition of PKC alpha and ERK1/2 in WT but not Tie2-sEH Tr mice. In conclusion, our data suggest that over-expression of sEH enhances A(1)AR-dependent contraction and reduces K-ATP channel-dependent relaxation in MAs. These results suggest a possible interaction between sEH, A(1)AR, and K-ATP channels in regulating vascular tone. C1 [Yadav, Vishal R.] West Virginia Univ, Dept Physiol & Pharmacol, Coll Med, Morgantown, WV 26506 USA. [Hong, Ka L.; Nayeem, Mohammed A.] West Virginia Univ, Ctr Basic & Translat Stroke Res, Hlth Sci Ctr North, Dept Pharmaceut Sci,Sch Pharm, Biomed Res Bldg,2nd Floor,Room 220,1 Med Ctr Dr, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Nayeem, MA (reprint author), West Virginia Univ, Ctr Basic & Translat Stroke Res, Hlth Sci Ctr North, Dept Pharmaceut Sci,Sch Pharm, Biomed Res Bldg,2nd Floor,Room 220,1 Med Ctr Dr, Morgantown, WV 26506 USA. EM mnayeem@hsc.wvu.edu RI Nayeem, Mohammed/A-3949-2017 OI Nayeem, Mohammed/0000-0002-7827-4760 FU [HL-114559]; [z01-ES025034] FX This study was supported by HL-114559 (to Mohammed Nayeem, PhD.) and z01-ES025034 (Darryl Zeldin, M.D.). The authors would like to thank Jamal Mustafa, PhD. for allowing Vishal Yadav, PhD. (Postdoctoral Fellow in his lab) to work in this project. The authors appreciate the help provided by Sherry Xie for western blot experiment. NR 39 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2016 VL 422 IS 1-2 BP 197 EP 206 DI 10.1007/s11010-016-2821-z PG 10 WC Cell Biology SC Cell Biology GA DY6BY UT WOS:000385192200019 PM 27629787 ER PT J AU Di Tomasso, G Jenkins, LMM Legault, P AF Di Tomasso, Genevieve Jenkins, Lisa M. Miller Legault, Pascale TI ARiBo pull-down for riboproteomic studies based on label-free quantitative mass spectrometry SO RNA LA English DT Article DE RNA pull-down; proteomics; RNA protein interactions; pre-miRNA; let-7 biogenesis ID RNA-BINDING PROTEINS; AFFINITY PURIFICATION; RIBONUCLEOPROTEIN COMPLEXES; MICRORNA BIOGENESIS; MESSENGER-RNAS; STEM-CELLS; QUALITY-CONTROL; LIN28; IDENTIFICATION; TRANSCRIPTS AB As part of their normal life cycle, most RNA molecules associate with several proteins that direct their fate and regulate their function. Here, we describe a novel method for identifying proteins that associate with a target RNA. The procedure is based on the ARiBo method for affinity purification of RNA, which was originally developed to quickly purify RNA with high yields and purity under native conditions. The ARiBo method was further optimized using in vitro transcribed RNA to capture RNA associating proteins from cellular extracts with high yields and low background protein contamination. For these RNA pull downs, stem-loops present in the immature forms of let-7 miRNAs (miRNA stem loops) were used as the target RNAs. Label free quantitative mass spectrometry analysis allowed for the reliable identification of proteins that are specific to the stem-loops present in the immature forms of two miRNAs, let-7a-1 and let-7g. Several proteins known to bind immature forms of these let-7 miRNAs were identified, but with an improved coverage compared to previous studies. In addition, several novel proteins were identified that better define the protein interactome of the let-7 miRNA stem-loops and further link let-7 biogenesis to important biological processes such as development and tumorigenesis. Thus, combining the ARiBo pull-down method with label-free quantitative mass spectrometry provides an effective proteomic approach for identification of proteins that associate with a target RNA. C1 [Di Tomasso, Genevieve; Legault, Pascale] Univ Montreal, Dept Biochim & Med Mol, Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. [Jenkins, Lisa M. Miller] NCI, Lab Cell Biol, Bethesda, MD 20892 USA. RP Legault, P (reprint author), Univ Montreal, Dept Biochim & Med Mol, Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM pascale.legault@umontreal.ca FU Canadian Institutes of Health Research (CIHR) [PPP-122895]; Natural Sciences and Engineering Research Council of Canada [RGPIN-2015-04231]; Parkinson Society of Canada; Intramural Research Program of the National Cancer Institute FX This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (PPP-122895), the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-04231), and the Parkinson Society of Canada to P.L. This work was also supported in part by the Intramural Research Program of the National Cancer Institute (L.M.M.J.). The authors thank Luc DesGroseillers, James G. Omichinski, and all members of the Legault laboratory for critical reading of the manuscript. NR 73 TC 0 Z9 0 U1 4 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA PD NOV PY 2016 VL 22 IS 11 BP 1760 EP 1770 DI 10.1261/rna.057513.116 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DZ5NA UT WOS:000385907600011 PM 27659051 ER PT J AU Galanternik, MV Stratman, AN Jung, HM Butler, MG Weinstein, BM AF Galanternik, Marina Venero Stratman, Amber N. Jung, Hyun Min Butler, Matthew G. Weinstein, Brant M. TI Building the drains: the lymphatic vasculature in health and disease SO WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY LA English DT Review ID GROWTH-FACTOR-C; AVIAN CHORIOALLANTOIC MEMBRANE; CHEMOKINE RECEPTOR CCR7; ENDOTHELIAL-CELL FATE; IN-VIVO; VEGF-C; NODE METASTASIS; EMBRYONIC LYMPHANGIOGENESIS; TRANSCRIPTION FACTOR; PRIMARY LYMPHEDEMA AB The lymphatic vasculature is comprised of a network of endothelial vessels found in close proximity to but separated from the blood vasculature. An essential tissue component of all vertebrates, lymphatics are responsible for the maintenance of fluid homeostasis, dissemination of immune cells, and lipid reabsorption under healthy conditions. When lymphatic vessels are impaired due to invasive surgery, genetic disorders, or parasitic infections, severe fluid build-up accumulates in the affected tissues causing a condition known as lymphedema. Malignant tumors can also directly activate lymphangiogenesis and use these vessels to promote the spread of metastatic cells. Although their first description goes back to the times of Hippocrates, with subsequent anatomical characterization at the beginning of the 20th-century, the lack of identifying molecular markers and tools to visualize these translucent vessels meant that investigation of lymphatic vessels fell well behind research of blood vessels. However, after years under the shadow of the blood vasculature, recent advances in imaging technologies and new genetic and molecular tools have accelerated the pace of research on lymphatic vessel development. These new tools have facilitated both work in classical mammalian models and the emergence of new powerful vertebrate models like zebrafish, quickly driving the field of lymphatic development back into the spotlight. In this review, we summarize the highlights of recent research on the development and function of the lymphatic vascular network in health and disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. C1 [Galanternik, Marina Venero; Stratman, Amber N.; Jung, Hyun Min; Butler, Matthew G.; Weinstein, Brant M.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM bw96w@nih.gov NR 198 TC 1 Z9 1 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1759-7684 EI 1759-7692 J9 WIRES DEV BIOL JI Wiley Interdiscip. Rev.-Dev. Biol. PD NOV-DEC PY 2016 VL 5 IS 6 BP 689 EP 710 DI 10.1002/wdev.246 PG 22 WC Developmental Biology SC Developmental Biology GA DZ0JI UT WOS:000385524200003 ER PT J AU Wahl, D Cogger, VC Solon-Biet, SM Waern, RVR Gokarn, R Pulpitel, T de Cabo, R Mattson, MP Raubenheimer, D Simpson, SJ Le Couteur, DG AF Wahl, Devin Cogger, Victoria C. Solon-Biet, Samantha M. Waern, Rosilene V. R. Gokarn, Rahul Pulpitel, Tamara de Cabo, Rafael Mattson, Mark P. Raubenheimer, David Simpson, Stephen J. Le Couteur, David G. TI Nutritional strategies to optimise cognitive function in the aging brain SO AGEING RESEARCH REVIEWS LA English DT Article DE Aging; Cognition; Geometric framework; Macronutrients; Intermittent fasting ID GENETICALLY HETEROGENEOUS MICE; RANDOMIZED CONTROLLED-TRIAL; DIETARY ENERGY-INTAKE; EXTENDS LIFE-SPAN; ALZHEIMERS-DISEASE; CALORIE RESTRICTION; MEDITERRANEAN DIET; OXIDATIVE STRESS; MOUSE MODEL; PREFRONTAL CORTEX AB Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. (C) 2016 Elsevier B.V. All rights reserved. C1 [Wahl, Devin; Cogger, Victoria C.; Solon-Biet, Samantha M.; Waern, Rosilene V. R.; Gokarn, Rahul; Pulpitel, Tamara; Raubenheimer, David; Simpson, Stephen J.; Le Couteur, David G.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia. [Wahl, Devin; Cogger, Victoria C.; Solon-Biet, Samantha M.; Gokarn, Rahul; Le Couteur, David G.] Sydney Med Sch, Concord Clin Sch, Aging & Alzheimers Inst, ANZAC Res Inst, Concord 2139, Australia. [de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Mattson, Mark P.] NIA, Lab Neurosci, NIH, Baltimore, MD USA. [Raubenheimer, David] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. [Waern, Rosilene V. R.; Raubenheimer, David; Simpson, Stephen J.] Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia. RP Le Couteur, DG (reprint author), Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia. EM david.lecouteur@sydney.edu.au OI Wahl, Devin/0000-0003-2794-0185 FU Aging and Alzheimers Research Institute, National Health and Research Council of Australia (NHMRC) [571328, 1084267]; Intramural Program of the National Institute on Aging, NIH; NHMRC [1110098] FX Funding was provided from the Aging and Alzheimers Research Institute, National Health and Research Council of Australia (NHMRC) grants #571328 and #1084267 and our co-authors in studies cited in this review. RdC and MPM are funded by the Intramural Program of the National Institute on Aging, NIH. SMS-B is supported by the NHMRC Peter Doherty Early Career Fellowship (Grant 1110098). NR 188 TC 1 Z9 1 U1 58 U2 58 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 EI 1872-9649 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2016 VL 31 BP 80 EP 92 DI 10.1016/j.arr.2016.06.006 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DY1NT UT WOS:000384862400006 PM 27355990 ER PT J AU O'Sullivan, CC Lindenberg, M Bryla, C Patronas, N Peer, CJ Amiri-Kordestani, L Davarpanah, N Gonzalez, EM Burotto, M Choyke, P Steinberg, SM Liewehr, DJ Figg, WD Fojo, T Balasubramaniam, S Bates, SE AF O'Sullivan, C. C. Lindenberg, M. Bryla, C. Patronas, N. Peer, C. J. Amiri-Kordestani, L. Davarpanah, N. Gonzalez, E. M. Burotto, M. Choyke, P. Steinberg, S. M. Liewehr, D. J. Figg, W. D. Fojo, T. Balasubramaniam, S. Bates, S. E. TI ANG1005 for breast cancer brain metastases: correlation between F-18-FLT-PET after first cycle and MRI in response assessment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer brain metastases; ANG1005; F-18-FLT-PET; MRI brain ID POSITRON-EMISSION-TOMOGRAPHY; DELIVERY VECTOR ANGIOPEP-2; CELL LUNG-CANCER; F-18-FDG PET; SOLID TUMORS; PROLIFERATION; GLIOMA; PSEUDOPROGRESSION; QUANTIFICATION; PACLITAXEL AB Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate F-18-FLT-PET for response assessment. Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m(2) IV every 21 days. Before and after cycle 1, patients underwent PET imaging with F-18-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20 % change in uptake after one cycle of ANG1005 was deemed significant. Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5 % (n = 10 patients, lower, upper quartiles: -25.5, -4.8 %) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52 %) and 12/20 nontarget lesions (60 %) showed a aeyen20 % decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95 % CI: 0.19, 2.61). The median percentage change in SUVmax was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV80 was also -20.9 % (n = 29; lower, upper quartiles: -49.0, 0.0 %). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles. ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and F-18-FLT-PET imaging. C1 [O'Sullivan, C. C.; Lindenberg, M.; Bryla, C.; Patronas, N.; Peer, C. J.; Amiri-Kordestani, L.; Davarpanah, N.; Gonzalez, E. M.; Burotto, M.; Choyke, P.; Steinberg, S. M.; Liewehr, D. J.; Figg, W. D.; Fojo, T.; Balasubramaniam, S.; Bates, S. E.] NCI, Bethesda, MD 20892 USA. [O'Sullivan, C. C.] Dept Med Oncol, Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. [Burotto, M.] Pontificia Univ Catolica Chile, Santiago, Chile. [Fojo, T.; Bates, S. E.] Columbia Univ, New York, NY USA. RP O'Sullivan, CC (reprint author), NCI, Bethesda, MD 20892 USA.; O'Sullivan, CC (reprint author), Dept Med Oncol, Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM osullivan.ciara@mayo.edu; maria.lindenberg@nih.gov; christine.bryla@nih.gov; npatronas@cc.nih.gov; cody.peer@nih.gov; laleh.amirikordestani@fda.hhs.gov; nicole.davarpanah@nih.gov; edith.gonzalez@fda.hhs.edu; mburotto@alemana.cl; pchoyke@mail.nih.gov; steinbes@mail.nih.gov; liewehrd@mail.nih.gov; wf13e@nih.gov; atf2116@cumc.columbia.edu; sanjeeve.balasubramaniam@fda.hhs.gov; seb2227@cumc.columbia.edu NR 39 TC 0 Z9 0 U1 6 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2016 VL 160 IS 1 BP 51 EP 59 DI 10.1007/s10549-016-3972-z PG 9 WC Oncology SC Oncology GA DY5WU UT WOS:000385175900005 PM 27620882 ER PT J AU Vargas, JNS Kar, AN Kowalak, JA Gale, JR Aschrafi, A Chen, CY Gioio, AE Kaplan, BB AF Vargas, Jose Norberto S. Kar, Amar N. Kowalak, Jeffrey A. Gale, Jenna R. Aschrafi, Armaz Chen, Cai-Yun Gioio, Anthony E. Kaplan, Barry B. TI Axonal localization and mitochondrial association of precursor microRNA 338 SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Subcellular localization; Sympathetic neuron; Superior cervical ganglion; Mitochondrial translation; RNP granule; Proteomics; Local translation; Post-transcriptional regulation ID LOCAL PROTEIN-SYNTHESIS; ADULT-MOUSE FOREBRAIN; LARGE GENE LISTS; SYMPATHETIC NEURONS; RNA INTERFERENCE; MESSENGER-RNAS; DISTAL AXONS; TRANSLATION; IDENTIFICATION; EXPRESSION AB MicroRNAs (miRNAs) selectively localize to subcompartments of the neuron, such as dendrites, axons, and presynaptic terminals, where they regulate the local protein synthesis of their putative target genes. In addition to mature miRNAs, precursor miRNAs (pre-miRNAs) have also been shown to localize to somatodendritic and axonal compartments. miRNA-338 (miR-338) regulates the local expression of several nuclear-encoded mitochondrial mRNAs within axons of sympathetic neurons. Previous work has shown that precursor miR-338 (pre-miR-338) introduced into the axon can locally be processed into mature miR-338, where it can regulate local ATP synthesis. However, the mechanisms underlying the localization of pre-miRNAs to the axonal compartment remain unknown. In this study, we investigated the axonal localization of pre-miR-338. Using proteomic and biochemical approaches, we provide evidence for the localization of pre-miR-338 to distal neuronal compartments and identify several constituents of the pre-miR-338 ribonucleoprotein complex. Furthermore, we found that pre-miR-338 is associated with the mitochondria in axons of superior cervical ganglion (SCG) neurons. The maintenance of mitochondrial function within axons requires the precise spatiotemporal synthesis of nuclear-encoded mRNAs, some of which are regulated by miR-338. Therefore, the association of pre-miR-338 with axonal mitochondria could serve as a reservoir of mature, biologically active miRNAs, which could coordinate the intra-axonal expression of multiple nuclear-encoded mitochondrial mRNAs. C1 [Vargas, Jose Norberto S.; Kar, Amar N.; Gale, Jenna R.; Aschrafi, Armaz; Chen, Cai-Yun; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Neurobiol Sect, Mol Biol Lab, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. [Kowalak, Jeffrey A.] NINDS, NIMH, Clin Prote Unit, Div Intramural Res Programs,NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Neurobiol Sect, Mol Biol Lab, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. EM kaplanb@mail.nih.gov FU Division of Intramural Research Programs of the National Institute of Mental Health [MH002768] FX The work was supported by the Division of Intramural Research Programs of the National Institute of Mental Health (MH002768). The authors would like to thank Mrs. Ching-Yu Sun, Ms. Miranda Tompkins, Dr. Noreen Gervasi, Mr. Shane Scott, and Ms. Anna-Leigh Brown for their scientific insights and engaging conversations, which contributed to the fruition of this work. NR 38 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2016 VL 73 IS 22 BP 4327 EP 4340 DI 10.1007/s00018-016-2270-6 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DY5SO UT WOS:000385163300012 PM 27229124 ER PT J AU Wattenberg, MM Fong, L Madan, RA Gulley, JL AF Wattenberg, Max M. Fong, Lawrence Madan, Ravi A. Gulley, James L. TI Immunotherapy in genitourinary malignancies SO CURRENT OPINION IN UROLOGY LA English DT Review DE bladder cancer; cytotoxic T lymphocyte-associated antigen 4; programmed death 1; programmed death ligand 1; prostate cancer; renal cell carcinoma; transitional cell carcinoma; vaccines ID RESISTANT PROSTATE-CANCER; DOSE-ESCALATION TRIAL; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; INDUCED IMMUNOGENIC MODULATION; IPILIMUMAB PLUS DACARBAZINE; RENAL-CELL CARCINOMA; SIPULEUCEL-T; CTLA-4 BLOCKADE; METASTATIC MELANOMA; RECEIVED IPILIMUMAB AB Purpose of review Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary malignancies including prostate cancer, renal cell carcinoma, and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of genitourinary malignancies are highlighted in this review. Recent findings Dramatic responses to checkpoint inhibitor therapy have been demonstrated in renal cell carcinoma and bladder cancer with recent Food and Drug Administration approvals in both indications. No benefit to checkpoint inhibitor therapy has yet been shown for the management of prostate cancer. Therapeutic cancer vaccines have also shown benefit in the treatment of genitourinary malignancies, specifically in the treatment of prostate cancer. Despite advances in these therapeutic modalities, benefit is limited to a subset of patients. Summary Current evidence supports the use of immune checkpoint inhibitor therapy and therapeutic cancer vaccines for the management of genitourinary malignancies. Further development of biomarkers for predicting response and study of combination therapy is required to achieve optimal efficacy with these therapeutic interventions. C1 [Wattenberg, Max M.; Fong, Lawrence] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Madan, Ravi A.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), 10 Ctr Dr,12N226, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov FU Intramural NIH HHS [Z01 BC010666-04] NR 51 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD NOV PY 2016 VL 26 IS 6 BP 501 EP 507 DI 10.1097/MOU.0000000000000331 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DY1FF UT WOS:000384839600002 PM 27471994 ER PT J AU Wolfe, K O'hUigin, C AF Wolfe, Ken O'hUigin, Colm TI Significance of positive selection and gene duplication in adaptive evolution: in memory of Austin L. Hughes SO IMMUNOGENETICS LA English DT Review DE Selection; Duplication; Evolution ID MAJOR HISTOCOMPATIBILITY COMPLEX; REGIONS; SUBSTITUTION; POLYMORPHISM; DIVERGENCE; ANTIGEN AB In this minireview, we highlight the contributions of the late Austin L. Hughes to two areas of molecular evolution: the role of positive (Darwinian) selection, and the impact of gene duplications during genome evolution. C1 [Wolfe, Ken] Univ Coll Dublin, UCD Conway Inst & Sch Med, Dublin 4, Ireland. [O'hUigin, Colm] Leidos Frederick Inc, Canc Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Wolfe, K (reprint author), Univ Coll Dublin, UCD Conway Inst & Sch Med, Dublin 4, Ireland. EM kenneth.wolfe@ucd.ie NR 29 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD NOV PY 2016 VL 68 IS 10 BP 749 EP 753 DI 10.1007/s00251-016-0937-7 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA DY5KI UT WOS:000385138100001 PM 27461477 ER PT J AU Hankins, RA Walton-Diaz, A Truong, H Shih, J Bratslavsky, G Pinto, PA Linehan, WM Metwalli, AR AF Hankins, Ryan A. Walton-Diaz, Annerleim Hong Truong Shih, Joanna Bratslavsky, Gennady Pinto, Peter A. Linehan, W. Marston Metwalli, Adam R. TI Renal functional outcomes after robotic multiplex partial nephrectomy: the National Cancer Institute experience with robotic partial nephrectomy for 3 or more tumors in a single kidney SO INTERNATIONAL UROLOGY AND NEPHROLOGY LA English DT Article DE Kidney cancer; Partial nephrectomy; Robotic surgery; Multiplex partial nephrectomy; Multifocal renal tumors ID PARENCHYMAL SPARING SURGERY; MULTIINSTITUTIONAL ANALYSIS; CELL CARCINOMA AB To identify renal function outcomes after robotic multiplex partial nephrectomy (RMxPNx), we reviewed our institutional database at the National Institutes of Health, National Cancer Institute. To our knowledge, we present the largest series of RMxPNx renal function outcomes to date. Robotic partial nephrectomy has been employed for oncologic control and to prevent dialysis dependence in hereditary multifocal renal cell carcinoma conditions. We have termed robotic surgery on a single kidney with three or more lesions a RMxPNx. We evaluated patients from a prospectively maintained database at a single institution (NIH/NCI) that underwent RMxPNx from 2007 to 2013. Demographic and operative data were compiled with statistical analysis with T test performed to determine renal function outcomes. A total of 54 patients underwent RMxPNx. Mean number of tumors removed was 8.63 (range 3-52). Mean preoperative creatinine and eGFR were 1.02 +/- 0.26 mg/dL and 85.4 +/- 21.5 mL/min, respectively. Postoperatively, creatinine increased from baseline by 0.45 mg/dL (p < 0.001). Similarly, a mean decrease in eGFR by 24.6 mL/min was observed (p < 0.001). At 3-month follow-up, the creatinine increase from baseline was 0.05 mg/dL (p = 0.10) and mean decrease in eGFR was 3.01 mL/min (p = 0.21). When stratifying based on preoperative CKD stages I-III, similar results were observed. Robotic multiplex partial nephrectomy is a safe and feasible approach to patients with multifocal renal masses. These complex surgeries have a demonstrated learning curve, but this minimally invasive approach for nephron-sparing surgery allows patients to preserve renal function where they would otherwise require open surgery or a radical nephrectomy. C1 [Hankins, Ryan A.; Walton-Diaz, Annerleim; Hong Truong; Shih, Joanna; Bratslavsky, Gennady; Pinto, Peter A.; Linehan, W. Marston; Metwalli, Adam R.] NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10,Room 2 W-5940,10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA. RP Metwalli, AR (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10,Room 2 W-5940,10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA. EM adam.metwalli@nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Institutes of Health [ZIA1BC011028-05, ZIA BC011038-05, ZIA BC011043-05, ZID BC011089-05, ZIE BC 011023-05] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and supported by Grant Nos. ZIA1BC011028-05, ZIA BC011038-05, ZIA BC011043-05, ZID BC011089-05 and ZIE BC 011023-05 from the National Institutes of Health. NR 15 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-1623 EI 1573-2584 J9 INT UROL NEPHROL JI Int. Urol. Nephrol. PD NOV PY 2016 VL 48 IS 11 BP 1817 EP 1821 DI 10.1007/s11255-016-1392-y PG 5 WC Urology & Nephrology SC Urology & Nephrology GA DY5YF UT WOS:000385180000012 PM 27515314 ER PT J AU Tillo, D Mukherjee, S Vinson, C AF Tillo, Desiree Mukherjee, Sanjit Vinson, Charles TI Inheritance of Cytosine Methylation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID TRANSGENERATIONAL EPIGENETIC INHERITANCE; PRIMORDIAL GERM-CELLS; SPERM DNA METHYLATION; EMBRYONIC STEM-CELLS; GENOME-WIDE ANALYSIS; MAMMALIAN DEVELOPMENT; MOUSE SPERMATOZOA; GENE-EXPRESSION; CHROMATIN; DYNAMICS AB There are numerous examples of parental transgenerational inheritance that is epigenetic. The informational molecules include RNA, chromatin modifications, and cytosine methylation. With advances in DNA sequencing technologies, the molecular and epigenetic mechanisms mediating these effects are now starting to be uncovered. This mini-review will highlight some of the examples of epigenetic inheritance, the establishment of cytosine methylation in sperm, and recent genomic studies linking sperm cytosine methylation to epigenetic effects on offspring. A recent paper examining changes in diet and sperm cytosine methylation from pools of eight animals each, found differences between a normal diet, a high fat diet, and a low protein diet. However, epivariation between individuals within a group was greater than the differences between groups obscuring any potential methylation changes linked to diet. Learning more about epivariation may help unravel the mechanisms that regulate cytosine methylation. In addition, other experimental and genetic systems may also produce more dramatic changes in the sperm methylome, making it easier to unravel potential transgenerational phenomena. (C) 2016 Wiley Periodicals, Inc. C1 [Tillo, Desiree; Mukherjee, Sanjit; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM vinsonc@mail.nih.gov FU Intramural Research Program of the NIH; Center for Cancer Research; National Cancer Institute FX Contract grant sponsor: Intramural Research Program of the NIH.; Contract grant sponsor: Center for Cancer Research.; Contract grant sponsor: National Cancer Institute. NR 92 TC 1 Z9 1 U1 15 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2016 VL 231 IS 11 BP 2346 EP 2352 DI 10.1002/jcp.25350 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA DY3TU UT WOS:000385018400008 PM 26910768 ER PT J AU Meseroll, RA Cohen-Fix, O AF Meseroll, Rebecca A. Cohen-Fix, Orna TI The Malleable Nature of the Budding Yeast Nuclear Envelope: Flares, Fusion, and Fenestrations SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID SPINDLE POLE BODY; SACCHAROMYCES-CEREVISIAE; PORE COMPLEXES; ENDOPLASMIC-RETICULUM; MEMBRANE-FUSION; VACUOLE JUNCTIONS; FISSION YEAST; CELL-CYCLE; PIECEMEAL MICROAUTOPHAGY; FUNDAMENTAL FUNCTIONS AB In eukaryotes, the nuclear envelope (NE) physically separates nuclear components and activities from rest of the cell. The NE also provides rigidity to the nucleus and contributes to chromosome organization. At the same time, the NE is highly dynamic; it must change shape and rearrange its components during development and throughout the cell cycle, and its morphology can be altered in response to mutation and disease. Here we focus on the NE of budding yeast, Saccharomyces cerevisiae, which has several unique features: it remains intact throughout the cell cycle, expands symmetrically during interphase, elongates during mitosis and, expands asymmetrically during mitotic delay. Moreover, its NE is safely breached during mating and when large structures, such as nuclear pore complexes and the spindle pole body, are embedded into its double membrane. The budding yeast NE lacks lamins and yet the nucleus is capable of maintaining a spherical shape throughout interphase. Despite these eccentricities, studies of the budding yeast NE have uncovered interesting, and likely conserved, processes that contribute to NE dynamics. In particular, we discuss the processes that drive and enable NE expansion and the dramatic changes in the NE that lead to extensions and fenestrations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA C1 [Meseroll, Rebecca A.; Cohen-Fix, Orna] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Meseroll, RA; Cohen-Fix, O (reprint author), 9000 Rockville Pike,Bldg 8,Room 319, Bethesda, MD 20892 USA. EM rebecca.meseroll@nih.gov; ornac@niddk.nih.gov FU NIDDK Intramural [DK057807] FX Contract grant sponsor: NIDDK Intramural;; Contract grant number: DK057807. NR 84 TC 1 Z9 1 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2016 VL 231 IS 11 BP 2353 EP 2360 DI 10.1002/jcp.25355 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA DY3TU UT WOS:000385018400009 PM 26909870 ER PT J AU Smith, SM Goldstein, RB Grant, BF AF Smith, Sharon M. Goldstein, Rise B. Grant, Bridget F. TI The association between post-traumatic stress disorder and lifetime DSM-5 psychiatric disorders among veterans: Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Post-traumatic stress disorder; Veterans; Comorbidity; Epidemiology; Psychiatric disorders ID GENERAL-POPULATION SAMPLE; MENTAL-HEALTH; PROCEDURAL VALIDITY; VIETNAM VETERANS; GUARD SOLDIERS; SUBSTANCE USE; WAR VETERANS; PRIMARY-CARE; PTSD; RELIABILITY AB This study examined the prevalence, correlates and psychiatric comorbidity of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) posttraumatic stress disorder (PTSD) in a nationally representative sample of U.S. veterans using data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (n = 3119 veteran respondents). The overall prevalence of lifetime PTSD was 6.9%. Lifetime PTSD prevalence was higher among veterans who were female (13.2%), aged 18-29 years (15.3%), Native American (24.1%) or Black (11.0%), previously or never married (9.6% and 11.2, respectively), had incomes less than $70,000 (7.2%-10.1%) and had >2 traumatic events (5.2%-14.7%). After adjusting for sociodemographic characteristics, comorbidity between lifetime PTSD and other psychiatric disorders was highest for any personality disorder (adjusted odds ratio [AORI = 11.1, 95% confidence interval [CI], 5.7, 21.5), any mood disorder (AOR = 9.7, 95% CI, 4.6, 20.4) and any anxiety disorder (AOR = 9.6, 95% CI, 5.1, 17.7), followed by nicotine, drug, and alcohol use disorders (AOR = 3.4, 95% CI, 1.8, 6.5; AOR = 3.1, 95% CI, 2.0, 5.9; 2.1, 95% CI, 1.5, 3.1, respectively). Associations remained with any mood, anxiety, and personality disorders after controlling for other psychiatric disorders (AOR = 3.7, 95% CI, 1.2, 10.9; AOR = 3.5, 95% CI, 1.6, 7.4; AOR = 4.5, 95% CI, 2.3, 8.7, respectively). Veterans who sought treatment for PTSD had more comorbid conditions, although treatment was only associated with comorbid drug use disorder (AOR = 2.4, 95% CI, 1.0, 5.7). In U.S. veterans, PTSD is highly comorbid with other psychiatric disorders. Although many veterans remain untreated, comorbidity may influence treatment seeking. Published by Elsevier Ltd. C1 [Smith, Sharon M.; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. RP Smith, SM (reprint author), NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. EM smithsh1@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); intramural program, NIAAA, NIH; NESARC-III FX The NESARC-III was sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), with supplemental support from the National Institute on Drug Abuse. Support is acknowledged from the intramural program, NIAAA, NIH. Sponsors and funders of the NESARC-III had no role in the design and conducted of the study; collection, management analysis, and interrelation of the data; and preparation, review and approval of the manuscript. NR 50 TC 1 Z9 1 U1 10 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2016 VL 82 BP 16 EP 22 DI 10.1016/j.jpsychires.2016.06.022 PG 7 WC Psychiatry SC Psychiatry GA DY1KN UT WOS:000384854000003 PM 27455424 ER PT J AU Park, JM Samuels, JF Grados, MA Riddle, MA Bienvenu, OJ Goes, FS Cullen, B Wang, Y Krasnow, J Murphy, DL Rasmussen, SA McLaughlin, NC Piacentini, J Pauls, DL Stewart, SE Shugart, YY Maher, B Pulver, AE Knowles, JA Greenberg, BD Fyer, AJ McCracken, JT Nestadt, G Geller, DA AF Park, Jennifer M. Samuels, Jack F. Grados, Marco A. Riddle, Mark A. Bienvenu, O. Joseph Goes, Fernando S. Cullen, Bernadette Wang, Ying Krasnow, Janice Murphy, Dennis L. Rasmussen, Steven A. McLaughlin, Nicole C. Piacentini, John Pauls, David L. Stewart, S. Evelyn Shugart, Yin-Yao Maher, Brion Pulver, Ann E. Knowles, James A. Greenberg, Benjamin D. Fyer, Abby J. McCracken, James T. Nestadt, Gerald Geller, Daniel A. TI ADHD and executive functioning deficits in OCD youths who hoard SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Hoarding; Obsessive compulsive disorder; Children; Adolescents; Executive functioning; ADHD ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SYMPTOM DIMENSIONS; NEUROPSYCHOLOGICAL PERFORMANCE; ANXIETY DISORDERS; COLLABORATIVE GENETICS; CHILDREN; SCALE; ADOLESCENTS; VALIDITY AB Hoarding is common among youth with obsessive compulsive disorder (OCD), with up to 26% of OCD youth exhibiting hoarding symptoms. Recent evidence from adult hoarding and OCD cohorts suggests that hoarding symptoms are associated with executive functioning deficits similar to those observed in subjects with attention deficit hyperactivity disorder (ADHD). However, while hoarding behavior often onsets during childhood, there is little information about executive function deficits and ADHD in affected children and adolescents. The study sample included 431 youths (ages 6-17 years) diagnosed with OCD who participated in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study and completed a series of clinician-administered and parent report assessments, including diagnostic interviews and measures of executive functioning (Behavior Rating Inventory of Executive Functioning; BRIEF) and hoarding severity (Hoarding Rating Scale-Interview; HRS-I). 113 youths (26%) had clinically significant levels of hoarding compulsions. Youths with and without hoarding differed significantly on most executive functioning subdomains and composite indices as measured by the parent-rated BRIEF. Groups did not differ in the frequency of full DSM-IV ADHD diagnoses; however, the hoarding group had significantly greater number of inattention and hyperactivity symptoms compared to the non-hoarding group. In multivariate models, we found that overall BRIEF scores were related to hoarding severity, adjusting for age, gender and ADHD symptoms. These findings suggest an association between hoarding and executive functioning deficits in youths with OCD, and assessing executive functioning may be important for investigating the etiology and treatment of children and adolescents with hoarding and OCD. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Park, Jennifer M.] Stanford Univ, Sch Med, Dept Child & Adolescent Psychiatiy, 1195 W Fremont Ave, Sunnyvale, CA 94087 USA. [Samuels, Jack F.; Grados, Marco A.; Riddle, Mark A.; Bienvenu, O. Joseph; Goes, Fernando S.; Cullen, Bernadette; Wang, Ying; Krasnow, Janice; Pulver, Ann E.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 1800 Orleans St, Baltimore, MD 21287 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, 6001 Execut Blvd,Rm 6200,MSC 9663, Bethesda, MD 20892 USA. [Rasmussen, Steven A.; McLaughlin, Nicole C.; Greenberg, Benjamin D.] Brown Med Sch, Dept Psychiat & Human Behav, Box G-A1, Providence, RI 02912 USA. [Piacentini, John; McCracken, James T.] Univ Calif Los Angeles, Los Angeles Sch Med, Dept Psychiat & Biobehav Sci, 757 Westwood Plaza, Los Angeles, CA 90095 USA. [Stewart, S. Evelyn] Univ British Columbia, Fac Med, Dept Psychiat, Detwiller Pavil,2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. [Shugart, Yin-Yao] NIMH, Unit Stat Genom, Div Intramural Res, 6001 Execut Blvd,Rm 6200,MSC 9663, Bethesda, MD 20892 USA. [Maher, Brion] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA. [Knowles, James A.] Univ Southern Calif, Keck Sch Med, 1975 Zonal Ave, Los Angeles, CA 90033 USA. [Fyer, Abby J.] Columbia Univ, Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Fyer, Abby J.] New York State Psychiat Inst & Hosp, Dept Psychiat, 630 W 168th St, New York, NY 10032 USA. [Pauls, David L.; Geller, Daniel A.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Pauls, David L.; Geller, Daniel A.] Harvard Med Sch, Dept Psychiatty, 55 Fruit St, Boston, MA 02114 USA. RP Park, JM (reprint author), Massachusetts Gen Hosp, Child CBT Program, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. EM jmpark05@stanford.edu FU IRP of NIMH FX Dr. Yin-Yao Shugart is supported by the IRP of NIMH. NR 61 TC 1 Z9 1 U1 11 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2016 VL 82 BP 141 EP 148 DI 10.1016/j.jpsychires.2016.07.024 PG 8 WC Psychiatry SC Psychiatry GA DY1KN UT WOS:000384854000018 PM 27501140 ER PT J AU Shen, YL Phan, N Xiao, X Jin, RM Sun, JF Piniewski, B Kil, D Dou, DJ AF Shen, Yelong NhatHai Phan Xiao, Xiao Jin, Ruoming Sun, Junfeng Piniewski, Brigitte Kil, David Dou, Dejing TI Dynamic socialized Gaussian process models for human behavior prediction in a health social network SO KNOWLEDGE AND INFORMATION SYSTEMS LA English DT Article DE Socialized Gaussian process; Dynamic social correlation; Health social network ID RANDOM FORESTS; CLASSIFICATION AB Modeling and predicting human behaviors, such as the level and intensity of physical activity, is a key to preventing the cascade of obesity and helping spread healthy behaviors in a social network. In our conference paper, we have developed a social influence model, named socialized Gaussian process (SGP), for socialized human behavior modeling. Instead of explicitly modeling social influence as individuals' behaviors influenced by their friends' previous behaviors, SGP models the dynamic social correlation as the result of social influence. The SGP model naturally incorporates personal behavior factor and social correlation factor (i.e., the homophily principle: Friends tend to perform similar behaviors) into a unified model. And it models the social influence factor (i.e., an individual's behavior can be affected by his/her friends) implicitly in dynamic social correlation schemes. The detailed experimental evaluation has shown the SGP model achieves better prediction accuracy compared with most of baseline methods. However, a Socialized Random Forest model may perform better at the beginning compared with the SGP model. One of the main reasons is the dynamic social correlation function is purely based on the users' sequential behaviors without considering other physical activity-related features. To address this issue, we further propose a novel "multi-feature SGP model" (mfSGP) which improves the SGP model by using multiple physical activity-related features in the dynamic social correlation learning. Extensive experimental results illustrate that the mfSGP model clearly outperforms all other models in terms of prediction accuracy and running time. C1 [Shen, Yelong; Jin, Ruoming] Kent State Univ, Dept Comp Sci, Kent, OH 44242 USA. [NhatHai Phan; Xiao, Xiao; Dou, Dejing] Univ Oregon, Comp & Informat Sci, Eugene, OR 97403 USA. [Sun, Junfeng] NIH, Bldg 10, Bethesda, MD 20892 USA. [Piniewski, Brigitte] PeaceHlth Labs, Springfield, OR USA. [Kil, David] HealthMant Inc, Austin, TX USA. RP Dou, DJ (reprint author), Univ Oregon, Comp & Informat Sci, Eugene, OR 97403 USA. EM dou@cs.uoregon.edu FU NIH [R01GM103309] FX This work is supported by the NIH grant R01GM103309. The authors appreciate the anonymous reviewers for their extensive and informative comments to help improve the paper. The authors also appreciate the contribution of Nafisa Chowdhury. NR 23 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0219-1377 EI 0219-3116 J9 KNOWL INF SYST JI Knowl. Inf. Syst. PD NOV PY 2016 VL 49 IS 2 BP 455 EP 479 DI 10.1007/s10115-015-0910-z PG 25 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA DY6BG UT WOS:000385190100003 PM 27746515 ER PT J AU Shaham, Y de Wit, H AF Shaham, Yavin de Wit, Harriet TI Lost in Translation: CRFI Receptor Antagonists and Addiction Treatment SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY C1 [Shaham, Yavin] IRP NIDA, Behav Neurosci Branch, NIH, Baltimore, MD USA. [de Wit, Harriet] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. RP Shaham, Y; de Wit, H (reprint author), IRP NIDA, Behav Neurosci Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM yavin.shaham@nih.gov; hdew@uchicago.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2016 VL 41 IS 12 BP 2795 EP 2797 DI 10.1038/npp.2016.94 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DY6JR UT WOS:000385212700001 PM 27312404 ER PT J AU Schwandt, ML Cortes, CR Kwako, LE George, DT Momenan, R Sinha, R Grigoriadis, DE Pich, EM Leggio, L Heilig, M AF Schwandt, Melanie L. Cortes, Carlos R. Kwako, Laura E. George, David T. Momenan, Reza Sinha, Rajita Grigoriadis, Dimitri E. Pich, Emilio Merlo Leggio, Lorenzo Heilig, Markus TI The CRFI Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PLACEBO-CONTROLLED TRIAL; RECEPTOR ANTAGONIST; MAJOR DEPRESSION; CRH1 ANTAGONIST; RELAPSE; STRESS; RELIABILITY; ANXIETY; INSTRUMENT AB Blockade of corticotropin-releasing factor receptor I (CRFI) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRFI antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21-65 years, n = 39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRFI antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRFI antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRFI blockade in stress-induced alcohol craving and relapse. C1 [Schwandt, Melanie L.; Cortes, Carlos R.; Kwako, Laura E.; George, David T.; Momenan, Reza; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Sinha, Rajita] Yale Univ, Dept Psychiat, Sch Med, Yale Stress Ctr, New Haven, CT 06520 USA. [Grigoriadis, Dimitri E.] Neurocrine Biosci, San Diego, CA USA. [Pich, Emilio Merlo] Imperial Coll London, Dept Med, Div Brain Sci, London, England. [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA. [Leggio, Lorenzo] NIDA, NIH, Bethesda, MD 20892 USA. [Cortes, Carlos R.; Heilig, Markus] Linkoping Univ, Ctr Social & Affect Neurosci, Linkoping, Sweden. RP Heilig, M (reprint author), IKE Linkoping Univ, Ctr Social & Affect Neurosci, S-58183 Linkoping, Sweden. EM markus.heilig@liu.se FU NIAAA DICBR FX We want to thank NIAAA staff and NIH Clinical Center nursing staff for technical support. This study was supported by the NIAAA DICBR, and carried out under a Cooperative Research and Development Agreement (CRADA) between the NIAAA and GlaxoSmithKline. NR 55 TC 3 Z9 3 U1 11 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2016 VL 41 IS 12 BP 2818 EP 2829 DI 10.1038/npp.2016.61 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DY6JR UT WOS:000385212700004 PM 27109623 ER PT J AU Augier, E Dulman, RS Rauffenbart, C Augier, G Cross, AJ Heilig, M AF Augier, Eric Dulman, Russell S. Rauffenbart, Caroline Augier, Gaelle Cross, Alan J. Heilig, Markus TI The mGluR2 Positive Allosteric Modulator, AZD8529, and Cue-Induced Relapse to Alcohol Seeking in Rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; VENTRAL TEGMENTAL AREA; AGONIST LY379268; INDUCED REINSTATEMENT; ETHANOL WITHDRAWAL; HEROIN SEEKING; DEPENDENCE; ADDICTION; COCAINE; REINFORCEMENT AB Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may control relapse of alcohol seeking, but previously available Group II agonists were unable to discriminate between mGluR2 and mGluR3. Here we use AZD8529, a novel positive allosteric mGluR2 modulator, to determine the role of this receptor for alcohol-related behaviors in rats. We assessed the effects of AZD8529 (20 and 40 mg/kg s.c.) on male Wistar rats trained to self-administer 20% alcohol and determined the effects of AZD8529 on self-administration, as well as stress-induced and cue-induced reinstatement of alcohol seeking. The on-target nature of findings was evaluated in Indiana P-rats, a line recently shown to carry a mutation that disrupts the gene encoding mGluR2. The behavioral specificity of AZD8529 was assessed using self-administration of 0.2% saccharin and locomotor activity tests. AZD8529 marginally decreased alcohol self-administration at doses that neither affected 0.2% saccharin self-administration nor locomotor activity. More importantly, cue- but not stress-induced alcohol seeking was blocked by the mGluR2 positive allosteric modulator. This effect of AZD8529 was completely absent in P rats lacking functional mGluR2s, demonstrating the receptor specificity of this effect. Our findings provide evidence fora causal role of mGluR2 in cue induced relapse to alcohol seeking. They contribute support for the notion that positive allosteric modulators of mGluR2 block relapse-like behavior across different drug categories. C1 [Augier, Eric; Augier, Gaelle; Heilig, Markus] Linkoping Univ, IKE, Ctr Social & Affect Neurosci, Cell Biol Bldg,Floor 12, S-58183 Linkoping, Sweden. [Dulman, Russell S.; Rauffenbart, Caroline] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Cross, Alan J.] AstraZeneca Neurosci, Innovat Med & Early Dev Biotech Unit, Cambridge, MA USA. RP Augier, E (reprint author), Linkoping Univ, IKE, Ctr Social & Affect Neurosci, Cell Biol Bldg,Floor 12, S-58183 Linkoping, Sweden. EM enc.augier@liu.se FU National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Swedish Research Council FX We thank AstraZeneca for kindly providing AZD8529. This work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism and funding from the Swedish Research Council. AJC is an AstraZeneca employee. All other authors report no biomedical financial interests or potential conflicts of interest. NR 41 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2016 VL 41 IS 12 BP 2932 EP 2940 DI 10.1038/npp.2016.107 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DY6JR UT WOS:000385212700015 PM 27339394 ER PT J AU Estrada-Veras, J Maled, LC Dave, RH O'Brien, K Gahl, W AF Estrada-Veras, Juvianee Maled, Louisa C. Dave, Rahul H. O'Brien, Kevin Gahl, William TI The Neurologic Manifestations of Erdheim Chester-Disease SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Estrada-Veras, Juvianee; Maled, Louisa C.; O'Brien, Kevin; Gahl, William] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Dave, Rahul H.] NINDS, Viral Immunol & Intravital Imaging Sect, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 2 BP S61 EP S62 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DW3ZH UT WOS:000383581100116 ER PT J AU Estrada-Veras, J O'Brien, K Huang, E Gahl, W AF Estrada-Veras, Juvianee O'Brien, Kevin Huang, Emily Gahl, William TI Dabrafenib and Trametinib as Potential Therapy in BRAF V600E Positive Erdheim Chester Disease (ECD): Preliminary Results SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Estrada-Veras, Juvianee; Gahl, William] NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. [O'Brien, Kevin; Huang, Emily; Gahl, William] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2016 VL 63 SU 2 BP S61 EP S61 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DW3ZH UT WOS:000383581100115 ER PT J AU Hartman, RL Brown, TL Milavetz, G Spurgin, A Pierce, RS Gorelick, DA Gaffney, G Huestis, MA AF Hartman, Rebecca L. Brown, Timothy L. Milavetz, Gary Spurgin, Andrew Pierce, Russell S. Gorelick, David A. Gaffney, Gary Huestis, Marilyn A. TI Cannabis effects on driving longitudinal control with and without alcohol SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE cannabis; alcohol; THC; driving; speed; blood ID MOTOR-VEHICLE CRASHES; CONTROLLED SMOKED CANNABIS; FREQUENT SMOKERS; ORAL FLUID; BLOOD; PERFORMANCE; MARIJUANA; DRIVERS; DRUGS; PLASMA AB Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive (9)-tetrahydrocannabinol (THC) blood concentrations. Current occasional (1x/last 3months, 3days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42h) and after (1.4 and 2.3h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright (c) 2016 John Wiley & Sons, Ltd. Cannabis' effects with/without alcohol on driving longitudinal control were evaluated against blood (9)-tetrahydrocannabinol (THC) and breath alcohol concentrations (BrAC) in 18 drivers at the National Advanced Driving Simulator, University of Iowa. THC was associated with decreased speed, increased driving time >10% below the speed limit, and increased following distance during headway maintenance; BrAC, with increased standard deviation (SD) speed and increased time >10% above the speed limit. Cannabis' association with slower driving and greater headway may suggest awareness of impairment, attempt to compensate. C1 [Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd St,200 Rm 05A721, Baltimore, MD USA. [Brown, Timothy L.] Univ Iowa, Natl Adv Driving Simulator, 2401 Oakdale Blvd, Iowa City, IA USA. [Milavetz, Gary; Spurgin, Andrew] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. [Pierce, Russell S.] VariableSolutions, Iowa City, IA USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Gaffney, Gary] Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Huestis, MA (reprint author), Biomed Res Ctr, Suite 200 Room 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health (NIH); US Office of National Drug Control Policy; National Highway Traffic Safety Administration; NIH Clinical and Translational Science Award (CTSA) program [U54TR001013] FX We would like to thank the University of Iowa Clinical Research Unit and National Advanced Driving Simulator staff (especially Cheryl Roe, Jennifer Henderson, Rose Schmitt and Kayla Smith) for their excellent contributions to successful study completion. We also thank Drs. Dereece Smither and Richard Compton, National Highway Traffic Safety Administration (NHTSA) for valuable input and Omar Ahmad for technical assistance. Volcano supplies were provided through Materials Transfer Agreements. The research was funded by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health (NIH); US Office of National Drug Control Policy; and the National Highway Traffic Safety Administration. In addition, the Institute for Clinical and Translational Science at the University of Iowa is supported by the NIH Clinical and Translational Science Award (CTSA) program, grant U54TR001013. The CTSA program is led by the NIH's National Center for Advancing Translational Sciences (NCATS). This manuscript reflects the opinions of the authors and does not necessarily represent the official positions of funding agencies. NR 47 TC 1 Z9 1 U1 20 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV PY 2016 VL 36 IS 11 BP 1418 EP 1429 DI 10.1002/jat.3295 PG 12 WC Toxicology SC Toxicology GA DY0WW UT WOS:000384817900005 PM 26889769 ER PT J AU Castel, AD Kalmin, MM Hart, RLD Young, HA Hays, H Benator, D Kumar, P Elion, R Parenti, D Ruiz, ME Wood, A D'Angelo, L Rakhmanina, N Rana, S Bryant, M Hebou, A Fernandez, R Abbott, S Peterson, J Wood, K Subramanian, T Binkley, J Happ, LP Kharfen, M Masur, H Greenberg, AE AF Castel, Amanda D. Kalmin, Mariah M. Hart, Rachel L. D. Young, Heather A. Hays, Harlen Benator, Debra Kumar, Princy Elion, Richard Parenti, David Ruiz, Maria Elena Wood, Angela D'Angelo, Lawrence Rakhmanina, Natella Rana, Sohail Bryant, Maya Hebou, Annick Fernandez, Ricardo Abbott, Stephen Peterson, James Wood, Kathy Subramanian, Thilakavathy Binkley, Jeffrey Happ, Lindsey Powers Kharfen, Michael Masur, Henry Greenberg, Alan E. TI Disparities in achieving and sustaining viral suppression among a large cohort of HIV-infected persons in care - Washington, DC SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE Viral suppression; care continuum; HIV; disparities; cohort ID ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; VIROLOGICAL FAILURE; RACIAL DISPARITIES; AFRICAN-AMERICAN; MEDICAL-CARE; RISK-FACTORS; RETENTION; ADHERENCE AB One goal of the HIV care continuum is achieving viral suppression (VS), yet disparities in suppression exist among subpopulations of HIV-infected persons. We sought to identify disparities in both the ability to achieve and sustain VS among an urban cohort of HIV-infected persons in care. Data from HIV-infected persons enrolled at the 13 DC Cohort study clinical sites between January 2011 and June 2014 were analyzed. Univariate and multivariate logistic regression were conducted to identify factors associated with achieving VS (viral load<200 copies/ml) at least once, and Kaplan-Meier (KM) curves and Cox proportional hazards models were used to identify factors associated with sustaining VS and time to virologic failure (VL200 copies/ml after achievement of VS). Among the 4311 participants, 95.4% were either virally suppressed at study enrollment or able to achieve VS during the follow-up period. In multivariate analyses, achieving VS was significantly associated with age (aOR: 1.04; 95%CI: 1.03-1.06 per five-year increase) and having a higher CD4 (aOR: 1.05, 95% CI 1.04-1.06 per 100 cells/mm(3)). Patients infected through perinatal transmission were less likely to achieve VS compared to MSM patients (aOR: 0.63, 95% CI 0.51-0.79). Once achieved, most participants (74.4%) sustained VS during follow-up. Blacks and perinatally infected persons were less likely to have sustained VS in KM survival analysis (log rank chi-square p.001 for both) compared to other races and risk groups. Earlier time to failure was observed among females, Blacks, publically insured, perinatally infected, those with longer standing HIV infection, and those with diagnoses of mental health issues or depression. Among this HIV-infected cohort, most people achieved and maintained VS; however, disparities exist with regard to patient age, race, HIV transmission risk, and co-morbid conditions. Identifying populations with disparate outcomes allows for appropriate targeting of resources to improve outcomes along the care continuum. C1 [Castel, Amanda D.; Kalmin, Mariah M.; Young, Heather A.; Peterson, James; Happ, Lindsey Powers; Greenberg, Alan E.] George Washington Univ, Dept Epidemiol & Biostat, Milken Inst Sch Publ Hlth, 950 New Hampshire Ave NW 5th Floor, Washington, DC 20052 USA. [Hart, Rachel L. D.; Hays, Harlen; Subramanian, Thilakavathy] Cerner Corp, Kansas City, MO USA. [Benator, Debra] Vet Affairs Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. [Kumar, Princy] Georgetown Univ, Div Infect Dis, Washington, DC USA. [Elion, Richard] Whitman Walker Hlth, Washington, DC USA. [Parenti, David] George Washington Med Fac Associates, Div Infect Dis, Washington, DC USA. [Ruiz, Maria Elena] Washington Hosp Ctr, Div Infect Dis, Dept Med, Washington, DC 20010 USA. [Wood, Angela] Family & Med Counseling Serv, Washington, DC USA. [D'Angelo, Lawrence] Childrens Natl Med Ctr, Burgess Adolescent Clin, Washington, DC 20010 USA. [Rakhmanina, Natella] Childrens Natl Med Ctr, Special Immunol Serv, Pediat Clin, Washington, DC 20010 USA. [Rana, Sohail] Howard Univ Hosp, Dept Pediat & Child Hlth, Washington, DC USA. [Bryant, Maya] Howard Univ Hosp, Adult Infect Dis Clin, Washington, DC USA. [Hebou, Annick] MetroHealth, Washington, DC USA. [Fernandez, Ricardo] La Clin Pueblo, Washington, DC USA. [Abbott, Stephen] Unity Hlth Care, Washington, DC USA. [Wood, Kathy] Cerner Corp, Vienna, VA USA. [Binkley, Jeffrey] Cerner Corp, Culver City, CA USA. [Kharfen, Michael] Dist Columbia Dept Hlth, HIV AIDS Hepatitis Sexually Transmitted Dis TB Ad, Washington, DC USA. [Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Castel, AD (reprint author), George Washington Univ, Dept Epidemiol & Biostat, Milken Inst Sch Publ Hlth, 950 New Hampshire Ave NW 5th Floor, Washington, DC 20052 USA. EM acastel@gwu.edu OI Rakhmanina, Natella/0000-0002-2246-4581 FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health [UO1 AI69503-03S2] FX This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [UO1 AI69503-03S2]. NR 53 TC 0 Z9 0 U1 11 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD NOV PY 2016 VL 28 IS 11 BP 1355 EP 1364 DI 10.1080/09540121.2016.1189496 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA DX3ZN UT WOS:000384316700002 PM 27297952 ER PT J AU Vatsveen, TK Borset, M Dikic, A Tian, EM Micci, F Lid, AHB Meza-Zepeda, LA Coward, E Waage, A Sundan, A Kuehl, WM Holien, T AF Vatsveen, Thea Kristin Borset, Magne Dikic, Aida Tian, Erming Micci, Francesca Lid, Ana H. B. Meza-Zepeda, Leonardo A. Coward, Eivind Waage, Anders Sundan, Anders Kuehl, W. Michael Holien, Toril TI VOLIN and KJONTwo novel hyperdiploid myeloma cell lines SO GENES CHROMOSOMES & CANCER LA English DT Article ID PRECEDES MULTIPLE-MYELOMA; C-MYC; MOLECULAR CLASSIFICATION; MONOCLONAL GAMMOPATHY; IN-VITRO; GROWTH; TRANSLOCATIONS; EXPRESSION; INHIBITOR; LEUKEMIA AB Multiple myeloma can be divided into two distinct genetic subgroups: hyperdiploid (HRD) or nonhyperdiploid (NHRD) myeloma. Myeloma cell lines are important tools to study myeloma cell biology and are commonly used for preclinical screening and testing of new drugs. With few exceptions human myeloma cell lines are derived from NHRD patients, even though about half of the patients have HRD myeloma. Thus, there is a need for cell lines of HRD origin to enable more representative preclinical studies. Here, we present two novel myeloma cell lines, VOLIN and KJON. Both of them were derived from patients with HRD disease and shared the same genotype as their corresponding primary tumors. The cell lines' chromosomal content, genetic aberrations, gene expression, immunophenotype as well as some of their growth characteristics are described. Neither of the cell lines was found to harbor immunoglobulin heavy chain translocations. The VOLIN cell line was established from a bone marrow aspirate and KJON from peripheral blood. We propose that these unique cell lines may be used as tools to increase our understanding of myeloma cell biology. (c) 2016 Wiley Periodicals, Inc. C1 [Vatsveen, Thea Kristin; Borset, Magne; Dikic, Aida; Tian, Erming; Waage, Anders; Sundan, Anders; Holien, Toril] NTNU Norwegian Univ Sci & Technol, KG Jebsen Ctr Myeloma Res, Dept Canc Res & Mol Med, Trondheim, Norway. [Vatsveen, Thea Kristin] St Olavs Univ Hosp, Dept Pathol & Med Genet, Trondheim, Norway. [Borset, Magne] St Olavs Univ Hosp, Dept Immunol & Transfus Med, Trondheim, Norway. [Micci, Francesca] Oslo Univ Hosp, Sect Canc Cytogenet, Norwegian Radium Hosp, Oslo, Norway. [Lid, Ana H. B.; Meza-Zepeda, Leonardo A.] Oslo Univ Hosp, Dept Core Facil, Oslo, Norway. [Meza-Zepeda, Leonardo A.] Oslo Univ Hosp, Dept Tumor Biol, Oslo, Norway. [Coward, Eivind] NTNU Norwegian Univ Sci & Technol, Bioinformat Core Facil, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway. [Waage, Anders] St Olavs Univ Hosp, Dept Hematol, Trondheim, Norway. [Sundan, Anders] NTNU Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway. [Kuehl, W. Michael] NCI, Genet Branch, Bethesda, MD 20892 USA. [Vatsveen, Thea Kristin] Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway. [Vatsveen, Thea Kristin] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. RP Holien, T (reprint author), NTNU Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, Prinsesse Kristinas Gt 1, N-7006 Trondheim, Norway. EM toril.holien@ntnu.no OI Holien, Toril/0000-0002-2051-5824 FU Norwegian Cancer Society; Liaison Committee; KG Jebsen Foundation for Medical Research; Intramural research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA FX Supported by: The Norwegian Cancer Society, the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the KG Jebsen Foundation for Medical Research. W.M. Kuehl is supported by the Intramural research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA. The funding sources did not participate in study design, collection, analysis or interpretation of the data, writing of the paper or the decision to submit the paper for publication. NR 42 TC 1 Z9 1 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2016 VL 55 IS 11 BP 890 EP 901 DI 10.1002/gcc.22388 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA DW4AM UT WOS:000383584300007 PM 27311012 ER PT J AU Aguerrebere, C Delbracio, M Bartesaghi, A Sapiro, G AF Aguerrebere, Cecilia Delbracio, Mauricio Bartesaghi, Alberto Sapiro, Guillermo TI Fundamental Limits in Multi-Image Alignment SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE Bayesian Cramer-Rao; Cramer-Rao bound; maximum likelihood estimator; Multi-image alignment; performance bounds; Ziv-Zakai bound ID SIGNAL PARAMETER-ESTIMATION; IMAGE REGISTRATION; NATURAL IMAGES; UNDERSAMPLED IMAGES; PERFORMANCE BOUNDS; SUPERRESOLUTION; LIMITATIONS; STATISTICS; ALGORITHMS; SYSTEMS AB The performance of multiimage alignment, bringing different images into one coordinate system, is critical in many applications with varied signal-to-noise ratio (SNR) conditions. A great amount of effort is being invested into developing methods to solve this problem. Several important questions thus arise, including: Which are the fundamental limits in multiimage alignment performance? Does having access to more images improve the alignment? Theoretical bounds provide a fundamental benchmark to compare methods and can help establish whether improvements can be made. In this work, we tackle the problem of finding the performance limits in image registration when multiple shifted and noisy observations are available. We derive and analyze the Cramer-Rao and Ziv-Zakai lower bounds under different statistical models for the underlying image. We show the existence of different behavior zones depending on the difficulty level of the problem, given by the SNR conditions of the input images. The analysis we present here brings further insight into the fundamental limitations of the multiimage alignment problem. C1 [Aguerrebere, Cecilia; Delbracio, Mauricio; Sapiro, Guillermo] Duke Univ, Dept Elect & Comp Engn, Durham, NC 27708 USA. [Bartesaghi, Alberto] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. RP Aguerrebere, C (reprint author), Duke Univ, Dept Elect & Comp Engn, Durham, NC 27708 USA. EM cecilia.aguerrebere@duke.edu; mauricio.delbracio@duke.edu; bartesaghia@mail.nih.gov; guillermo.sapiro@duke.edu FU ARO; ONR; NGA; AFORS; NSF FX The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Jorge Silva. This work was supported in part the ARO, ONR, NGA, AFORS, and NSF. NR 50 TC 0 Z9 0 U1 3 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X EI 1941-0476 J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD NOV 1 PY 2016 VL 64 IS 21 BP 5707 EP 5722 DI 10.1109/TSP.2016.2600517 PG 16 WC Engineering, Electrical & Electronic SC Engineering GA DX3RQ UT WOS:000384291000020 ER PT J AU Kantor, ED Zhang, XH Wu, KN Signorello, LB Chan, AT Fuchs, CS Giovannucci, EL AF Kantor, Elizabeth D. Zhang, Xuehong Wu, Kana Signorello, Lisa B. Chan, Andrew T. Fuchs, Charles S. Giovannucci, Edward L. TI Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE chemoprevention; chondroitin; colorectal cancer; epidemiology; glucosamine ID DEXTRAN SULFATE SODIUM; C-REACTIVE PROTEIN; KNEE OSTEOARTHRITIS; DIETARY-SUPPLEMENTS; PROSTAGLANDIN E-2; DOWN-REGULATION; NITRIC-OXIDE; INFLAMMATION; ARTHRITIS; CHONDROCYTES AB Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta-analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63-1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59-1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine+chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58-0.999). The association between use of glucosamine+chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow-up (RR: 0.75; 95% CI: 0.58-0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements. C1 [Kantor, Elizabeth D.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,2nd Floor, New York, NY 10017 USA. [Kantor, Elizabeth D.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Zhang, Xuehong; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Wu, Kana; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Signorello, Lisa B.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.] Harvard Med Sch, 181 Longwood Ave,Room 355, Boston, MA 02115 USA. RP Kantor, ED (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,2nd Floor, New York, NY 10017 USA.; Zhang, XH (reprint author), Harvard Med Sch, 181 Longwood Ave,Room 355, Boston, MA 02115 USA.; Zhang, XH (reprint author), Brigham & Womens Hosp, 181 Longwood Ave,Room 355, Boston, MA 02115 USA. EM kantore@mskcc.org; poxue@channing.harvard.edu FU National Cancer Institute of the National Institutes of Health [P50CA127003, UM1CA167552, UM1CA186107, P01CA87969, P01 CA55075] FX Grant sponsor: National Cancer Institute of the National Institutes of Health; Grant numbers: P50CA127003, UM1CA167552, UM1CA186107, P01CA87969, and P01 CA55075 NR 40 TC 0 Z9 0 U1 19 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2016 VL 139 IS 9 BP 1949 EP 1957 DI 10.1002/ijc.30250 PG 9 WC Oncology SC Oncology GA DV9TM UT WOS:000383285100008 PM 27357024 ER PT J AU Bodelon, C Untereiner, ME Machiela, MJ Vinokurova, S Wentzensen, N AF Bodelon, Clara Untereiner, Michael E. Machiela, Mitchell J. Vinokurova, Svetlana Wentzensen, Nicolas TI Genomic characterization of viral integration sites in HPV-related cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HPV; integration ID HUMAN-PAPILLOMAVIRUS GENOMES; CELLULAR FUSION TRANSCRIPTS; LOWER GENITAL-TRACT; CERVICAL-CANCER; INTRAEPITHELIAL NEOPLASIA; ANOGENITAL LESIONS; INVASIVE CANCER; NECK-CANCER; DNA; AMPLIFICATION AB Persistent infection with carcinogenic human papillomaviruses (HPV) causes the majority of anogenital cancers and a subset of head and neck cancers. The HPV genome is frequently found integrated into the host genome of invasive cancers. The mechanisms of how it may promote disease progression are not well understood. Thoroughly characterizing integration events can provide insights into HPV carcinogenesis. Individual studies have reported limited number of integration sites in cell lines and human samples. We performed a systematic review of published integration sites in HPV-related cancers and conducted a pooled analysis to formally test for integration hotspots and genomic features enriched in integration events using data from the Encyclopedia of DNA Elements (ENCODE). Over 1,500 integration sites were reported in the literature, of which 90.8% (N=1,407) were in human tissues. We found 10 cytobands enriched for integration events, three previously reported ones (3q28, 8q24.21 and 13q22.1) and seven additional ones (2q22.3, 3p14.2, 8q24.22, 14q24.1, 17p11.1, 17q23.1 and 17q23.2). Cervical infections with HPV18 were more likely to have breakpoints in 8q24.21 (p=7.68 x 10(-4)) than those with HPV16. Overall, integration sites were more likely to be in gene regions than expected by chance (p=6.93 x 10(-9)). They were also significantly closer to CpG regions, fragile sites, transcriptionally active regions and enhancers. Few integration events occurred within 50 Kb of known cervical cancer driver genes. This suggests that HPV integrates in accessible regions of the genome, preferentially genes and enhancers, which may affect the expression of target genes. C1 [Bodelon, Clara; Untereiner, Michael E.; Machiela, Mitchell J.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Vinokurova, Svetlana] NN Blokhin Russian Canc Res Ctr, Lab Mol Biol Viruses, Moscow, Russia. RP Bodelon, C (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 7E-236, Bethesda, MD 20892 USA.; Wentzensen, N (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 7E-E114, Bethesda, MD 20892 USA. EM clara.bodelon@nih.gov; wentzenn@mail.nih.gov FU Intramural Research Program of the National Cancer Institute FX Grant sponsor: Intramural Research Program of the National Cancer Institute NR 50 TC 1 Z9 1 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2016 VL 139 IS 9 BP 2001 EP 2011 DI 10.1002/ijc.30243 PG 11 WC Oncology SC Oncology GA DV9TM UT WOS:000383285100014 PM 27343048 ER PT J AU Lamers, F Cui, LH Hickie, IB Roca, C Machado-Vieira, R Zarate, CA Merikangas, KR AF Lamers, Femke Cui, Lihong Hickie, Ian B. Roca, Catherine Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. Merikangas, Kathleen R. TI Familial aggregation and heritability of the melancholic and atypical subtypes of depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Familial aggregation; Major depressive disorder; Atypical; Melancholic; Epidemiology ID POPULATION-BASED SAMPLE; MAJOR DEPRESSION; BIPOLAR-II; ENDOGENOUS-DEPRESSION; UNIPOLAR DEPRESSION; CLINICAL-FEATURES; ZURICH COHORT; FEMALE TWINS; DSM-IV; DISORDERS AB Background: The heterogeneity of mood disorders has been a challenge to our understanding of their underlying biologic and genetic pathways. This report examines the specificity of the familial aggregation of atypical and melancholic subtypes of depression and their clinical correlates in a large community based family study of affective spectrum disorders. Methods: The sample includes 457 probands and their directly interviewed adult first degree relatives from the National Institute of Mental Health (NIMH) Family Study of Affective Spectrum Disorder. Depression subtypes were based on best estimate diagnoses using information from semi-structured diagnostic interviews by experienced clinical interviews and multiple family history reports. Results: Atypical depression in probands was significantly associated with the atypical subtype of depression in relatives (OR 1.75 [95%Cl 1.02-3.02], p = 0.04), independent of proband and relative comorbid disorders. Melancholic depression in probands was not associated with melancholic depression in relatives (OR 1.25 [95%CI 0.62-2.55], p=.53). The familial heritability of the atypical subtype was 0.46 (95% CI 0.21-0.71), whereas that of the melancholic subtype was 0.33 (95%Cl 0.21-0.45). Melancholic depression was associated with greater severity in terms of treatment, global functioning, suicide attempts, comorbid disorders, and an earlier age at onset of depression. Limitations: The subsample of interviewed relatives necessary to assess specific subtypes of depression reduced the power to detect the specificity of mood disorder subtypes. Conclusion: The results indicate that the atypical subtype should be incorporated in future treatment, genetic and other etiologic studies of major depression. Findings further suggest that melancholic subtype may be an indicator of clinical severity of depression. Published by Elsevier B.V. C1 [Lamers, Femke; Cui, Lihong; Roca, Catherine; Merikangas, Kathleen R.] NIMH, Gener Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Hickie, Ian B.] Univ Sydney, Brain & Mind Res Inst, Clin Res Unit, Camperdown, NSW, Australia. [Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Lamers, Femke] Vrije Univ Amsterdam Med Ctr, GGZ inGeest, Dept Psychiat, Amsterdam, Netherlands. [Lamers, Femke] Vrije Univ Amsterdam Med Ctr, GGZ inGeest, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. RP Merikangas, KR (reprint author), 35 Convent Dr,MSC 3720 Bldg 35A,Room 2E410, Bethesda, MD 20892 USA. EM Kathleen.merikangas@nih.gov OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Intramural Research Program of the NIMH (Merikangas) [ZIAMH002804, 03-M-0211 (NCT00071786)] FX This research was supported by the Intramural Research Program of the NIMH (Merikangas) (grant number ZIAMH002804) and was conducted under clinical protocol 03-M-0211 (NCT00071786). The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or U.S. Government. The authors wish to thank Dr. Jonathan Stewart for his helpful comments on this paper. NR 52 TC 1 Z9 1 U1 7 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV 1 PY 2016 VL 204 BP 241 EP 246 DI 10.1016/j.jad.2016.06.040 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DW7FT UT WOS:000383817300034 PM 27450632 ER PT J AU Guidi, M Huber, L Lampe, L Gauthier, CJ Moller, HE AF Guidi, Maria Huber, Laurentius Lampe, Leonie Gauthier, Claudine J. Moeller, Harald E. TI Lamina-dependent calibrated BOLD response in human primary motor cortex SO NEUROIMAGE LA English DT Article DE Cortical layers; Calibrated fMRI; SS-SI-VASO; Hypercapnia; Oxygen metabolism; 7 T MRI ID CEREBRAL BLOOD-VOLUME; VASCULAR-SPACE-OCCUPANCY; HIGH-RESOLUTION FMRI; FUNCTIONAL MRI; HUMAN-BRAIN; 7 TESLA; SPIN-ECHO; SOMATOSENSORY STIMULATION; HEMODYNAMIC-RESPONSE; VISUAL-STIMULATION AB Disentangling neural activity at different cortical depths during a functional task has recently generated growing interest, since this would allow to separate feedforward and feedback activity. The majority of layer-dependent studies have, so far, relied on gradient-recalled echo (GRE) blood-oxygenation-level dependent (BOLD) acquisitions, which are weighted towards the large draining veins at the cortical surface. The current study aims to obtain quantitative brain activity responses in the primary motor cortex on a laminar scale without the contamination due to accompanying secondary vascular effects. Evoked oxidative metabolism was evaluated using the Davis model, to investigate its applicability, advantages, and limits in lamina-dependent fMRI. Average values for the calibration parameter, M, and for changes in the cerebral metabolic rate of oxygen consumption (CMRO2) during a unilateral finger-tapping task were (11 +/- 2)% and (30 +/- 7)%, respectively, with distinct variation features across the cortical depth. The results presented here showed an uncoupling between BOLD-based functional magnetic resonance imaging (fMRI) and metabolic changes across cortical depth, while the tight coupling between CMRO2 and CBV was conserved across cortical layers. We conclude that the Davis model can help to obtain estimates of lamina-dependent metabolic changes without contamination from large draining veins, with high consistency and reproducibility across participants. (C) 2016 Elsevier Inc. All rights reserved. C1 [Guidi, Maria; Huber, Laurentius; Lampe, Leonie; Gauthier, Claudine J.; Moeller, Harald E.] Max Planck Inst Human Cognit & Brain Sci, Stephanstr 1A, D-04103 Leipzig, Germany. [Huber, Laurentius] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Room 1D80 10,Ctr Dr MSC 1148, Bethesda, MD 20892 USA. [Gauthier, Claudine J.] Concordia Univ, Richard J Renaud Sci Complex,7141 Sherbrooke W, Montreal, PQ, Canada. RP Guidi, M; Moller, HE (reprint author), Max Planck Inst Human Cognit & Brain Sci, Stephanstr 1A, D-04103 Leipzig, Germany. EM guidi@cbs.mpg.de; moeller@cbs.mpg.de FU Initial Training Network, HiMR - FP7 Marie Curie Actions of the European Commission [FP7-PEOPLE-2012-ITN-316716] FX This study was supported by the Initial Training Network, HiMR, funded by the FP7 Marie Curie Actions of the European Commission (FP7-PEOPLE-2012-ITN-316716). We thank Enrico Reimer for IT support regarding MRI data conversion and developing a 3D MRI data projection viewer for planning slice orientation. We also thank Riccardo Metere for fruitful discussions and Domenica Wilfling and Elisabeth Wladimirow for radiographic assistance. Parts of the this work have been presented at the 23rd Annual Conference of the International Society for Magnetic Resonance in Medicine (ISMRM). NR 79 TC 1 Z9 1 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2016 VL 141 BP 250 EP 261 DI 10.1016/j.neuroimage.2016.06.030 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DX0SF UT WOS:000384074500021 PM 27364473 ER PT J AU Mills, KL Goddings, AL Herting, MM Meuwese, R Blakemore, SJ Crone, EA Dahl, RE Guroglu, B Raznahan, A Sowell, ER Tamnes, CK AF Mills, Kathryn L. Goddings, Anne-Lise Herting, Megan M. Meuwese, Rosa Blakemore, Sarah-Jayne Crone, Eveline A. Dahl, Ronald E. Guroglu, Berna Raznahan, Armin Sowell, Elizabeth R. Tamnes, Christian K. TI Structural brain development between childhood and adulthood: Convergence across four longitudinal samples SO NEUROIMAGE LA English DT Article DE Adolescence; Cerebral cortex; MRI; Replication; Sex differences; White matter ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; CORTICAL THICKNESS; GEOMETRICALLY ACCURATE; INTRACRANIAL VOLUME; HUMAN LIFE; MRI DATA; IN-VIVO; ADOLESCENCE; TRAJECTORIES AB Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8-30 years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Mills, Kathryn L.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. [Mills, Kathryn L.] Univ Oregon, Ctr Translat Neurosci, Eugene, OR 97403 USA. [Goddings, Anne-Lise] UCL, Inst Child Hlth, London, England. [Herting, Megan M.; Sowell, Elizabeth R.] USC Childrens Hosp Los Angeles, Keck Sch Med, Dept Pediat, Los Angeles, CA USA. [Meuwese, Rosa; Crone, Eveline A.; Guroglu, Berna] Leiden Univ, Inst Psychol, Leiden, Netherlands. [Meuwese, Rosa; Crone, Eveline A.; Guroglu, Berna] Leiden Univ, Leiden Inst Brain & Cognit, Leiden, Netherlands. [Blakemore, Sarah-Jayne] UCL, Inst Cognit Neurosci, London, England. [Dahl, Ronald E.] Univ Calif Berkeley, Inst Human Dev, Berkeley, CA 94720 USA. [Raznahan, Armin] NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA. [Tamnes, Christian K.] Univ Oslo, Res Grp Lifespan Changes Brain & Cognit, Dept Psychol, Oslo, Norway. RP Mills, KL (reprint author), 1227 Univ Oregon, Dept Psychol, Lewis Integrat Sci 115, Eugene, OR 97403 USA. EM kathryn.l.mills@gmail.com RI Guroglu, Berna/O-1639-2016; OI Guroglu, Berna/0000-0002-5418-8737; Mills, Kathryn/0000-0002-6463-186X FU NIH Intramural Research Program; NIH Graduate Partnership Program; NIH [R01 DA018910, R01 HD053893, R01 MH087563, F32 HD0708084]; European Research Council [ERC-2010-StG-263234]; Royal Society; Wellcome Trust; Jacobs Foundation; Research Council of Norway; Department of Psychology, University of Oslo FX The authors gratefully acknowledge the continued participation of all families and individuals involved in these longitudinal studies. We thank the Athinoula Martinos Center for Biomedical Imaging for providing software used for the analysis. This study was supported by the NIH Intramural Research Program, NIH Graduate Partnership Program, NIH R01 DA018910 (R.E.D.), R01 HD053893 and R01 MH087563 (E.R.S.), F32 HD0708084 (M.M.H.), the European Research Council starting grant scheme (ERC-2010-StG-263234 to E.A.C.), The Royal Society (S.-J.B.), The Wellcome Trust (S.-J.B.), The Jacobs Foundation (S.-J.B.), and the Research Council of Norway and the Department of Psychology, University of Oslo (C.K.T.). NR 53 TC 6 Z9 6 U1 22 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2016 VL 141 BP 273 EP 281 DI 10.1016/j.neuroimage.2016.07.044 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DX0SF UT WOS:000384074500023 PM 27453157 ER PT J AU Gonzalez-Castillo, J Panwar, P Buchanan, LC Caballero-Gaudes, C Handwerker, DA Jangraw, DC Zachariou, V Inati, S Roopchansingh, V Derbyshire, JA Bandettini, PA AF Gonzalez-Castillo, Javier Panwar, Puja Buchanan, Laura C. Caballero-Gaudes, Cesar Handwerker, Daniel A. Jangraw, David C. Zachariou, Valentinos Inati, Souheil Roopchansingh, Vinai Derbyshire, John A. Bandettini, Peter A. TI Evaluation of multi-echo ICA denoising for task based fMRI studies: Block designs, rapid event-related designs, and cardiac-gated fMRI SO NEUROIMAGE LA English DT Article DE Multi-echo fMRI; ME-ICA; Rapid event related; Block design; Sensitivity ID INDEPENDENT COMPONENT ANALYSIS; BOLD-CONTRAST SENSITIVITY; REMOVING MOTION ARTIFACTS; PHYSIOLOGICAL NOISE; RESPONSE FUNCTION; BRAIN ACTIVITY; TIME-SERIES; 7 T; EPI; REDUCTION AB Multi-echo fMRI, particularly the multi-echo independent component analysis (ME-ICA) algorithm, has previously proven useful for increasing the sensitivity and reducing false positives for functional MRI (fMRI) based resting state connectivity studies. Less is known about its efficacy for task-based fMRI, especially at the single subject level. This work, which focuses exclusively on individual subject results, compares ME-ICA to single-echo fMRI and a voxel-wise T-2*. weighted combination of multi-echo data for task-based fMRI under the following scenarios: cardiac-gated block designs, constant repetition time (TR) block designs, and constant TR rapid event-related designs. Performance is evaluated primarily in terms of sensitivity (i.e., activation extent, activation magnitude, percent detected trials and effect size estimates) using five different tasks expected to evoke neuronal activity in a distributed set of regions. The ME-ICA algorithm significantly outperformed all other evaluated processing alternatives in all scenarios. Largest improvements were observed for the cardiac-gated dataset, where ME-ICA was able to reliably detect and remove non-neural T-1 signal fluctuations caused by non-constant repetition times. Although ME-ICA also outperformed the other options in terms of percent detection of individual trials for rapid event-related experiments, only 46% of all events were detected after ME-ICA; suggesting additional improvements in sensitivity are required to reliably detect individual short event occurrences. We conclude the manuscript with a detailed evaluation of ME-ICA outcomes and a discussion of how the ME-ICA algorithm could be further improved. Overall, our results suggest that ME-ICA constitutes a versatile, powerful approach for advanced denoising of task-based fMRI, not just resting-state data. Published by Elsevier Inc. C1 [Gonzalez-Castillo, Javier; Panwar, Puja; Buchanan, Laura C.; Handwerker, Daniel A.; Jangraw, David C.; Derbyshire, John A.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Caballero-Gaudes, Cesar] Basque Ctr Cognit Brain & Language, San Sebastian, Spain. [Zachariou, Valentinos] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Inati, Souheil; Roopchansingh, Vinai; Bandettini, Peter A.] NIMH, Funct MRI Core, NIH, Bethesda, MD 20892 USA. RP Gonzalez-Castillo, J (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM javier.gonzalez-castillo@nih.gov OI Gonzalez-Castillo, Javier/0000-0002-6520-5125 FU National Institute of Mental Health Intramural Research Program; Spanish Ministry of Economy and Competitiveness through grant PSI Neuroimagen Multimodal and the Severo Ochoa Programme for Centres/Units of Excellence in RD [2013-42343, SEV-2015-490] FX This research was possible thanks to the support of the National Institute of Mental Health Intramural Research Program. Portions of this study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (biowulf.nih.gov). This study is part of NIH clinical protocol number NCT00001360, protocol ID 93-M-0170 and annual report ZIAMH002783-14. Dr. Caballero-Gaudes was supported by the Spanish Ministry of Economy and Competitiveness, through grant PSI 2013-42343 Neuroimagen Multimodal and the Severo Ochoa Programme for Centres/Units of Excellence in R&D (SEV-2015-490). NR 49 TC 1 Z9 1 U1 6 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2016 VL 141 BP 452 EP 468 DI 10.1016/j.neuroimage.2016.07.049 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DX0SF UT WOS:000384074500040 PM 27475290 ER PT J AU Busada, JT Velte, EK Serra, N Cook, K Niedenberger, BA Willis, WD Goulding, EH Eddy, EM Geyer, CB AF Busada, Jonathan T. Velte, Ellen K. Serra, Nicholas Cook, Kenneth Niedenberger, Bryan A. Willis, William D. Goulding, Eugenia H. Eddy, Edward M. Geyer, Christopher B. TI Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice SO REPRODUCTION LA English DT Article ID HOMEOBOX GENE-CLUSTER; NEONATAL MOUSE TESTIS; GERM-CELLS; RETINOIC ACID; SPERMATOGONIAL DIFFERENTIATION; SEXUAL-DIMORPHISM; SPERM PRODUCTION; MALE-FERTILITY; EPIDIDYMIS; SPERMATOZOA AB We previously described a novel germ cell-specific X-linked reproductive homeobox gene (Rhox13) that is upregulated at the level of translation in response to retinoic acid (RA) in differentiating spermatogonia and preleptotene spermatocytes. We hypothesize that RHOX13 plays an essential role in male germ cell differentiation, and have tested this by creating a Rhox13 gene knockout (KO) mouse. Rhox13 KO mice are born in expected Mendelian ratios, and adults have slightly reduced testis weights, yet a full complement of spermatogenic cell types. Young KO mice (at similar to 7-8 weeks of age) have a approximate to 50% reduction in epididymal sperm counts, but numbers increased to WT levels as the mice reach similar to 17 weeks of age. Histological analysis of testes from juvenile KO mice reveals a number of defects during the first wave of spermatogenesis. These include increased apoptosis, delayed appearance of round spermatids and disruption of the precise stage-specific association of germ cells within the seminiferous tubules. Breeding studies reveal that both young and aged KO males produce normal-sized litters. Taken together, our results indicate that RHOX13 is not essential for mouse fertility in a controlled laboratory setting, but that it is required for optimal development of differentiating germ cells and progression of the first wave of spermatogenesis. C1 [Busada, Jonathan T.; Velte, Ellen K.; Serra, Nicholas; Cook, Kenneth; Niedenberger, Bryan A.; Geyer, Christopher B.] East Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27858 USA. [Willis, William D.; Goulding, Eugenia H.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Geyer, Christopher B.] East Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC 27834 USA. [Geyer, Christopher B.] East Carolina Univ, Brody Sch Med, Greenville, NC 27858 USA. RP Geyer, CB (reprint author), East Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27858 USA.; Geyer, CB (reprint author), East Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC 27834 USA.; Geyer, CB (reprint author), East Carolina Univ, Brody Sch Med, Greenville, NC 27858 USA. EM geyerc@ecu.edu FU NIH, National Institute of Child Health and Human Development [HD072552]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01 ES070076] FX This work was supported by a grant from the NIH, National Institute of Child Health and Human Development (HD072552 to C B G) and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES070076 to E M E). NR 44 TC 1 Z9 1 U1 4 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD NOV PY 2016 VL 152 IS 5 BP 379 EP 388 DI 10.1530/REP-16-0268 PG 10 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA DX1PJ UT WOS:000384139100005 PM 27486269 ER PT J AU Guven-Maiorov, E Keskin, O Gursoy, A VanWaes, C Chen, Z Tsai, CJ Nussinov, R AF Guven-Maiorov, Emine Keskin, Ozlem Gursoy, Attila VanWaes, Carter Chen, Zhong Tsai, Chung-Jung Nussinov, Ruth TI TRAF3 signaling: Competitive binding and evolvability of adaptive viral molecular mimicry SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Inflammation; Cancer; Antiviral immunity; Evolvable; Structure; Host-pathogen interactions ID PROTEIN-PROTEIN INTERACTIONS; I INTERFERON-PRODUCTION; KAPPA-B ACTIVATION; SARS-CORONAVIRUS; INTERACTION NETWORK; MULTIPLE-MYELOMA; CROSS-TALK; RECEPTOR; UBIQUITINATION; RECOGNITION AB Background: The tumor necrosis factor receptor (TNFR) associated factor 3 (TRAF3) is a key node in innate and adaptive immune signaling pathways. TRAF3 negatively regulates the activation of the canonical and non canonical NF-kappa B pathways and is one of the key proteins in antiviral immunity. Scope of Review: Here we provide a structural overview of TRAF3 signaling in terms of its competitive binding and consequences to the cellular network. For completion, we also include molecular mimicry of TRAF3 physiological partners by some viral proteins. Major Conclusions: By out-competing host partners, viral proteins aim to subvert TRAF3 antiviral action. Mechanistically, dynamic, competitive binding by the organism's own proteins and same-site adaptive pathogen mimicry follow the same conformational selection principles. General Significance: Our premise is that irrespective of the eliciting event - physiological or acquired pathogenic trait - pathway activation (or suppression) may embrace similar conformational principles. However, even though here we largely focus on competitive binding at a shared site, similar to physiological signaling other pathogen subversion mechanisms can also be at play. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. (C) 2016 Elsevier B.V. All rights reserved. C1 [Guven-Maiorov, Emine; Tsai, Chung-Jung; Nussinov, Ruth] NCI, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. [Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey. [Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey. [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey. [VanWaes, Carter; Chen, Zhong] NIDCD, Clin Genom Unit, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. EM emine.guven-maiorov@nih.gov; okeskin@ku.edu.tr; agursoy@ku.edu.tr; vanwaesc@nidcd.nih.gov; chenz@nidcd.nih.gov; tsaic@mail.nih.gov; nussinor@helix.nih.gov RI Gursoy, Attila/E-9565-2015; OI Gursoy, Attila/0000-0002-2297-2113; Guven Maiorov, Emine/0000-0002-7388-9811 FU Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIDCD [ZIA-DC-000016, 73, 74]; Intramural Research Program of the 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, National Institutes of Health, under contract number HHSN261200800001E, and NIDCD intramural projects ZIA-DC-000016, 73 and 74. 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 research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. O.K. and A.G. acknowledge Science Academy (of Turkey). NR 74 TC 1 Z9 1 U1 13 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 EI 1872-8006 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV PY 2016 VL 1860 IS 11 SI SI BP 2646 EP 2655 DI 10.1016/j.bbagen.2016.05.021 PN B PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DW7IS UT WOS:000383825000005 PM 27208423 ER PT J AU Ma, BY Zhao, J Nussinov, R AF Ma, Buyong Zhao, Jun Nussinov, Ruth TI Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Antibody; Biological drug; Amyloid; Neurodegenerative diseases; Alzheimer's disease; Prion; Antigen ID INTRINSICALLY DISORDERED PROTEINS; ALZHEIMERS-DISEASE; PRION PROTEIN; STRUCTURE REVEALS; BINDING CASCADES; FOLDING FUNNELS; MOLECULAR-BASIS; EMERGING ROLE; TAU PROTEINS; BETA-PEPTIDE AB Background: The dominant feature in neurodegenerative diseases is protein aggregations that lead to neuronal loss. Immunotherapies using antibodies or antibody fragments to target the aggregations are a highly perused approach. The molecular mechanisms underlying the amyloid-based immunotherapy are complex. Deciphering the properties of amyloidogenic proteins responsible for these diseases is essential to obtain insights into antibody recognition of the amyloid antigens. Scope of review: We systematically explore all available crystal structures of antibody-amyloid complexes related to neurodegenerative diseases, including antibodies that recognize the A beta peptide, tau protein, prion protein, alpha-synuclein, huntingtin protein (mHTF), and polyglutamine. Major conclusions: We found that antibodies mostly use the conformational selection mechanism to recognize the highly flexible amyloid antigens. In particular, solanezumab bound to A beta 12-28 tripeptide motif conformation (F19F20A21), which is shared with the A beta 42 fibril. This motif, which is trapped by the antibody, may provide the missing link in amyloid formation. Water molecules often bridge between the antibody and amyloid, contributing to the recognition. General significance: This paper provides the structural basis for antibody recognition of amyloidogenic proteins. The analysis and discussion of known structures are expected to help in the design and optimization of antibodies in neurodegenerative diseases. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. (C) 2016 Elsevier B.V. All rights reserved. C1 [Ma, Buyong; Nussinov, Ruth] NCI, Leidos Biomed Res Inc, Basic Sci Program, Canc & Inflammat Program, Frederick, MD 21702 USA. [Zhao, Jun] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Leidos Biomed Res Inc, Basic Sci Program, Canc & Inflammat Program, Frederick, MD 21702 USA. EM mabuyong@mail.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the 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, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 80 TC 1 Z9 1 U1 25 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 EI 1872-8006 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV PY 2016 VL 1860 IS 11 SI SI BP 2672 EP 2681 DI 10.1016/j.bbagen.2016.05.040 PN B PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DW7IS UT WOS:000383825000008 PM 27266343 ER PT J AU Bornstein, MH Costlow, K Truzzi, A Esposito, G AF Bornstein, M. H. Costlow, K. Truzzi, A. Esposito, G. TI Categorizing the cries of infants with ASD versus typically developing infants: A study of adult accuracy and reaction time SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Cry; Infancy; Autism spectrum disorder; Typical development; Vocalizations; Reaction time ID AUTISM SPECTRUM DISORDER; YOUNG-CHILDREN; VOCAL PRODUCTION; HIGH-RISK; CRY; DISTRESS; PERCEPTION; VOCALIZATIONS; FREQUENCY; SIBLINGS AB Background: The cries of children with Autism Spectrum Disorder (ASD) contain atypical acoustic features. The cries of typically developing infants elicit automatic adult responses, but little is known about how the atypical cries of children with ASD affect the speed with which adults process them. Method. We used a reaction time (RT) categorical task to analyze adults' categorization of typically developing cries, atypical (ASD) cries, mammalian animal cries, and environmental noise control sounds. 40 nonparent women (M age = 27 years) were instructed to categorize acoustic stimuli as human infant cries or non-human sounds as quickly as possible. Results. The RTs for correctly categorizing the cries of children with ASD (M = 831 ms, SEM = 27) were slower than RTs for typically developing child cries (M = 680 ms, SEM = 6) as well as mammalian animal cries (801 ms, SEM = 11) and environmental noise control sounds (M = 692 ms, SEM = 10). Conclusions. This difference may reflect difficulties in adults' perceiving and processing atypical cries of children with ASD, and the findings may have implications for the parent-child relationship and for the quality of care children with ASD receive. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Bornstein, M. H.; Costlow, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD USA. [Truzzi, A.; Esposito, G.] Univ Trento, Dept Psychol & Cognit Sci, Corso Bettini 31, I-38068 Rovereto, TN, Italy. [Esposito, G.] Nanyang Technol Univ, Sch Humanities & Social Sci, Div Psychol, HSS-04-14,14 Nanyang Dr, Singapore 637332, Singapore. RP Esposito, G (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Corso Bettini 31, I-38068 Rovereto, TN, Italy.; Esposito, G (reprint author), Nanyang Technol Univ, Sch Humanities & Social Sci, Div Psychol, HSS-04-14,14 Nanyang Dr, Singapore 637332, Singapore. EM gianluca.esposito@unitn.it FU Intramural Research Program of the NIH, NICHD FX All participants in this study are gratefully acknowledged. The authors thank Andrea Bonassi and Tommaso Giraldi (Unversity of Trento) for their assistance. This research was partially supported by grants from the Intramural Research Program of the NIH, NICHD. NR 44 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD NOV PY 2016 VL 31 BP 66 EP 72 DI 10.1016/j.rasd.2016.08.001 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA DW7HH UT WOS:000383821300006 PM 28138338 ER PT J AU Kalman, LV Datta, V Williams, M Zook, JM Salit, ML Han, JY AF Kalman, Lisa V. Datta, Vivekananda Williams, Mickey Zook, Justin M. Salit, Marc L. Han, Jin-Yeong TI Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships SO ANNALS OF LABORATORY MEDICINE LA English DT Review DE Reference materials; Genetic tests; DNA sequencing; Next generation sequencing; Molecular oncology; Quality control; Assay validation; Genomics; Genome sequencing ID REFERENCE-MATERIAL-PANEL; GENOMIC REFERENCE MATERIALS; DNA REFERENCE MATERIALS; COLLABORATIVE-PROJECT; MOLECULAR-PATHOLOGY; QUALITY; ASSOCIATION; STANDARDS AB Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs. C1 [Kalman, Lisa V.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Datta, Vivekananda; Williams, Mickey] NCI, Frederick Natl Lab Canc Res, Gaithersburg, MD USA. [Zook, Justin M.; Salit, Marc L.] NIST, Gaithersburg, MD 20899 USA. [Han, Jin-Yeong] Dong A Univ, Coll Med, Dept Lab Med, 26 Daesingongwon Ro, Busan 49201, South Korea. RP Han, JY (reprint author), Dong A Univ, Coll Med, Dept Lab Med, 26 Daesingongwon Ro, Busan 49201, South Korea. EM jyhan@dau.ac.kr FU Dong-A University research fund FX This work was supported by the Dong-A University research fund (JY Han). Certain commercial equipment, instruments, or materials are identified in this paper only to specify the experimental procedure adequately. Such identification is not intended to imply recommendation or endorsement by the NIST, nor is it intended to imply that the materials or equipment identified are necessarily the best available for the intended purpose. NR 31 TC 0 Z9 0 U1 8 U2 9 PU KOREAN SOC LABORATORY MEDICINE PI SEOUL PA A505-ASTERIUM SEOUL, 372 HANGANG-DAERO, YONGSAN-GU, SEOUL, 04323, SOUTH KOREA SN 2234-3806 EI 2234-3814 J9 ANN LAB MED JI Ann. Lab. Med. PD NOV PY 2016 VL 36 IS 6 BP 513 EP 520 DI 10.3343/alm.2016.36.6.513 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DV9GP UT WOS:000383248900002 PM 27578503 ER PT J AU McMahen, RL Strynar, MJ McMillan, L DeRose, E Lindstrom, AB AF McMahen, Rebecca L. Strynar, Mark J. McMillan, Larry DeRose, Eugene Lindstrom, Andrew B. TI Comparison of fipronil sources in North Carolina surface water and identification of a novel fipronil transformation product in recycled wastewater SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE Fipronil; Source evaluation; Wastewater; Transformation; High resolution mass spectrometry; Water reuse ID ENVIRONMENTAL FATE; TOXICITY; INSECTICIDE; PESTICIDES; MECHANISMS; CHLORINE; EXPOSURE; STREAMS; INDOOR AB Fipronil is a phenylpyrazole insecticide that is widely used in residential and agricultural settings to control ants, roaches, termites, and other pests. Fipronil and its transformation products have been found in a variety of environmental matrices, but the source[s] which makes the greatest contribution to fipronil in surface water has yet to be determined. A sampling effort designed to prioritize known fipronil inputs (golf courses, residential areas, biosolids application sites and wastewater facilities) was conducted in North Carolina to learn more about the origins of fipronil in surface water. High resolution mass spectrometry (HRMS) analysis indicated that fipronil and its known derivatives were routinely present in all samples, but concentrations were substantially elevated near wastewater treatment plant outfalls (range 10-500 ng/L combined), suggesting that they predominate as environmental sources. Corresponding recycled wastewater samples, which were treated with NaOCl for disinfection, showed disappearance of fipronil and all known degradates. HRMS and nuclear magnetic resonance (NMR) analysis techniques were used to determine that all fipronil-related compounds are oxidized to a previously unidentified fipronil sulfone chloramine species in recycled wastewater. The implications of the presence of a new fipronil-related compound in recycled wastewater need to be considered. Published by Elsevier B.V. C1 [McMahen, Rebecca L.; Strynar, Mark J.; Lindstrom, Andrew B.] US EPA, Natl Exposure Res Lab, 109 TW Alexander Dr, Durham, NC 27705 USA. [McMillan, Larry] US EPA, Natl Caucus & Ctr Black Aged Employee, Natl Exposure Res Lab, 109 TW Alexander Dr, Durham, NC 27705 USA. [DeRose, Eugene] NIEHS, Nucl Magnet Resonance Facil, 111 TW Alexander Dr, Durham, NC 27713 USA. RP Strynar, MJ (reprint author), US EPA, Natl Exposure Res Lab, 109 TW Alexander Dr, Durham, NC 27705 USA. EM strynar.mark@epa.gov NR 26 TC 1 Z9 1 U1 15 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 EI 1879-1026 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD NOV 1 PY 2016 VL 569 BP 880 EP 887 DI 10.1016/j.scitotenv.2016.05.085 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA DU5RM UT WOS:000382269000086 PM 27378152 ER PT J AU Yu, JC Liu, YY Cai, JW Sandler, DP Zhou, HB AF Yu, Jichang Liu, Yanyan Cai, Jianwen Sandler, Dale P. Zhou, Haibo TI Outcome-dependent sampling design and inference for Cox's proportional hazards Model SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Empirical process; Optimal allocation; Outcome-dependent sampling ID CZECH URANIUM MINERS; MAXIMUM-LIKELIHOOD-ESTIMATION; CASE-COHORT DESIGN; LOGISTIC-REGRESSION; MORTALITY; EXPOSURE; EVENTS; RISK AB We propose a cost-effective outcome-dependent sampling design for the failure time data and develop an efficient inference procedure for data collected with this design. To account for the biased sampling scheme, we derive estimators from a weighted partial likelihood estimating equation. The proposed estimators for regression parameters are shown to be consistent and asymptotically normally distributed. A criteria that can be used to optimally implement the ODS design in practice is proposed and studied. The small sample performance of the proposed method is evaluated by simulation studies. The proposed design and inference procedure is shown to be statistically more powerful than existing alternative designs with the same sample sizes. We illustrate the proposed method with an existing real data from the Cancer Incidence and Mortality of Uranium Miners Study. (C) 2016 Elsevier B.V. All rights reserved. C1 [Yu, Jichang] Zhongnan Univ Econ & Law, Sch Math & Stat, Wuhan 430073, Hunan, Peoples R China. [Yu, Jichang; Liu, Yanyan] Wuhan Univ, Sch Math & Stat, Wuhan 430072, Hunan, Peoples R China. [Cai, Jianwen; Zhou, Haibo] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Zhou, HB (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM zhou@bios.unc.edu FU National Science Foundation of China [11501578, 11571263, 11371299]; NIH [R01 ES021900, P01 CA142538] FX The authors are grateful for the valuable comments and suggestions from the associate editor and the referees which drastically improved the article. This work is supported by the National Science Foundation of China grant 11501578 (for Yu), 11571263 and 11371299 (for Liu), and NIH R01 ES021900, P01 CA142538 (for Cai and Zhou). NR 35 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 EI 1873-1171 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV PY 2016 VL 178 BP 24 EP 36 DI 10.1016/j.jspi.2016.05.001 PG 13 WC Statistics & Probability SC Mathematics GA DT9TU UT WOS:000381846000002 PM 28090134 ER PT J AU Villar, RF Patel, J Weaver, GC Kanekiyo, M Wheatley, AK Yassine, HM Costello, CE Chandler, KB McTamney, PM Nabel, GJ McDermott, AB Mascola, JR Carr, SA Lingwood, D AF Villar, Rina F. Patel, Jinal Weaver, Grant C. Kanekiyo, Masaru Wheatley, Adam K. Yassine, Hadi M. Costello, Catherine E. Chandler, Kevin B. McTamney, Patrick. M. Nabel, Gary J. McDermott, Adrian B. Mascola, John R. Carr, Steven A. Lingwood, Daniel TI Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation SO SCIENTIFIC REPORTS LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; ANTIGEN RECEPTOR; NEUTRALIZING EPITOPE; BINDING-PROPERTIES; HUMORAL IMMUNITY; T-CELLS; ANTIBODY; EXPRESSION; RECOGNITION; DIVERSITY AB Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naive B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed. C1 [Villar, Rina F.; Weaver, Grant C.; Lingwood, Daniel] Ragon Inst Massachusetts Gen Hosp Massachusetts I, 400 Technol Sq, Cambridge, MA 02139 USA. [Patel, Jinal; Carr, Steven A.] Broad Inst Massachusetts Inst Technol & Harvard U, 415 Main St, Cambridge, MA 02142 USA. [Kanekiyo, Masaru; McDermott, Adrian B.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20814 USA. [Wheatley, Adam K.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, 792 Elizabeth St, Melbourne, Vic 3000, Australia. [Yassine, Hadi M.] Qatar Univ, Biomed Res Ctr, QU NRC, POB 2713 Doha Qatar, Doha, Qatar. [Costello, Catherine E.; Chandler, Kevin B.] Boston Univ, Sch Med, 670 Albany St, Boston, MA 02118 USA. [McTamney, Patrick. M.] Medimmune LLC, One MedImmune Way, Gaithersburg, MD 20878 USA. [Nabel, Gary J.] Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA. RP Lingwood, D (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, 400 Technol Sq, Cambridge, MA 02139 USA. EM dlingwood@mgh.harvard.edu OI Chandler, Kevin/0000-0001-5514-9652 FU Harvard University CFAR grant [P30 AI060354]; William F. Milton Fund; Gilead Sciences Research Scholars Program in HIV; Broad-Ragon ENDHIV Catalytic Grant; [P41 GM104602]; [S10 OD010724] FX This work was supported by the following awards to D.L.: a Harvard niversity CFAR grant (P30 AI060354); the William F. Milton Fund; the Gilead Sciences Research Scholars Program in HIV; and an Broad-Ragon ENDHIV Catalytic Grant (jointly awarded to D.L. and S.A.C.). C.E.C and K.B.C. were supported by P41 GM104602 and S10 OD010724 grants. NR 64 TC 0 Z9 0 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 31 PY 2016 VL 6 AR 36298 DI 10.1038/srep36298 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EA3MP UT WOS:000386507200001 PM 27796362 ER PT J AU Albracht, CD Guzik-Lendrum, S Rayment, I Gilbert, SP AF Albracht, Clayton D. Guzik-Lendrum, Stephanie Rayment, Ivan Gilbert, Susan P. TI Heterodimerization of Kinesin-2 KIF3AB Modulates Entry into the Processive Run SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATPASE PATHWAY; INTRAFLAGELLAR TRANSPORT; INTRACELLULAR-TRANSPORT; CONVENTIONAL KINESIN; SUPERFAMILY PROTEIN; MICROTUBULE MOTOR; ACCESSORY SUBUNIT; AXONAL-TRANSPORT; COILED-COIL; NECK-LINKER AB Mammalian KIF3AB is an N-terminal processive kinesin-2 that is best known for its roles in intracellular transport. There has been significant interest in KIF3AB to define the key principles that underlie its processivity but also to define the mechanistic basis of its sensitivity to force. In this study, the kinetics for entry into the processive run were quantified. The results show for KIF3AB that the kinetics of microtubule association at 7 mu M-1 s(-1) is less than the rates observed for KIF3AA at 13 mu M-1 s(-1) or KIF3BB at 11.9 mu M-1 s(-1). ADP release after microtubule association for KIF3AB is 33 s(-1) and is significantly slower than ADP release from homodimeric KIF3AA and KIF3BB, which reach 80-90 s(-1). To explore the interhead communication implied by the rate differences at these first steps, we compared the kinetics of KIF3AB microtubule association followed by ADP release with the kinetics for mixtures of KIF3AA plus KIF3BB. Surprisingly, the kinetics of KIF3AB are not equivalent to any of the mixtures of KIF3AA + KIF3BB. In fact, the transients for each of the mixtures overlay the transients for KIF3AA and KIF3BB. These results reveal that intermolecular communication within the KIF3AB heterodimer modulates entry into the processive run, and the results suggest that it is the high rate of microtubule association that drives rebinding to the microtubule after force-dependent motor detachment. C1 [Albracht, Clayton D.; Guzik-Lendrum, Stephanie; Gilbert, Susan P.] Rensselaer Polytech Inst, Dept Biol Sci, Troy, NY 12180 USA. [Albracht, Clayton D.; Guzik-Lendrum, Stephanie; Gilbert, Susan P.] Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA. [Rayment, Ivan] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Albracht, Clayton D.] NIH, Lab Mol Physiol, Bldg 50,Rm 3523, Bethesda, MD 20814 USA. RP Gilbert, SP (reprint author), Rensselaer Polytech Inst, Dept Biol Sci, Troy, NY 12180 USA.; Gilbert, SP (reprint author), Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA. EM sgilbert@rpi.edu FU National Institutes of Health [R37-GM054141] FX This work was supported by National Institutes of Health Grant R37-GM054141 (to S. P. G). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 74 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 2016 VL 291 IS 44 BP 23248 EP 23256 DI 10.1074/jbc.M116.752196 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB2XB UT WOS:000387224800033 PM 27637334 ER PT J AU De La Fuente, S Fernandez-Sanz, C Vail, C Agra, EJ Holmstrom, K Sun, JH Mishra, J Williams, D Finkel, T Murphy, E Joseph, SK Sheu, SS Csordas, G AF De La Fuente, Sergio Fernandez-Sanz, Celia Vail, Caitlin Agra, Elorm J. Holmstrom, Kira Sun, Junhui Mishra, Jyotsna Williams, Dewight Finkel, Toren Murphy, Elizabeth Joseph, Suresh K. Sheu, Shey-Shing Csordas, Gyoergy TI Strategic Positioning and Biased Activity of the Mitochondrial Calcium Uniporter in Cardiac Muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SARCOPLASMIC-RETICULUM; PERMEABILITY TRANSITION; CA2+ UPTAKE; HEART; MICU1; MCU; MYOCYTES; STRESS; COMMUNICATION; HOMEOSTASIS AB Control of myocardial energetics by Ca2+ signal propagation to the mitochondrial matrix includes local Ca2+ delivery from sarcoplasmic reticulum (SR) ryanodine receptors (RyR2) to the inner mitochondrial membrane (IMM) Ca2+ uniporter (mtCU). mtCU activity in cardiac mitochondria is relatively low, whereas the IMM surface is large, due to extensive cristae folding. Hence, stochastically distributed mtCU may not suffice to support local Ca2+ transfer. We hypothesized that mtCU concentrated at mitochondria-SR associations would promote the effective Ca2+ transfer. mtCU distribution was determined by tracking MCU and EMRE, the proteins essential for channel formation. Both proteins were enriched in the IMM-outer mitochondrial membrane (OMM) contact point submitochondrial fraction and, as super-resolution microscopy revealed, located more to the mitochondrial periphery (inner boundary membrane) than inside the cristae, indicating high accessibility to cytosol-derived Ca2+ inputs. Furthermore, MCU immunofluorescence distribution was biased toward the mitochondria-SR interface (RyR2), and this bias was promoted by Ca2+ signaling activity in intact cardiomyocytes. The SR fraction of heart homogenate contains mitochondria with extensive SR associations, and these mitochondria are highly enriched in EMRE. Size exclusion chromatography suggested for EMRE- and MCU-containing complexes a wide size range and also revealed MCU-containing complexes devoid of EMRE (thus disabled) in the mitochondrial but not the SR fraction. Functional measurements suggested more effective mtCU-mediated Ca2+ uptake activity by the mitochondria of the SR than of the mitochondrial fraction. Thus, mtCU "hot spots" can be formed at the cardiac muscle mitochondria-SR associations via localization and assembly bias, serving local Ca2+ signaling and the excitation-energetics coupling. C1 [De La Fuente, Sergio; Vail, Caitlin; Agra, Elorm J.; Joseph, Suresh K.; Csordas, Gyoergy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, MitoCare Ctr Mitochondrial Imaging Res & Diagnost, 527J Jefferson Alumni Hall,1020 Locust St, Philadelphia, PA 19107 USA. [Holmstrom, Kira; Finkel, Toren] NHLBI, Ctr Mol Med, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, Lab Cardiac Physiol, NIH, Bethesda, MD 20892 USA. [Mishra, Jyotsna; Sheu, Shey-Shing] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA. [Williams, Dewight] Univ Penn, Penn EM Resource Lab, Philadelphia, PA 19104 USA. RP Csordas, G (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, MitoCare Ctr Mitochondrial Imaging Res & Diagnost, 527J Jefferson Alumni Hall,1020 Locust St, Philadelphia, PA 19107 USA. EM Gyorgy.Csordas@jefferson.edu FU NHLBI, National Institutes of Health [RO1 HL122124]; American Heart Association Postdoctoral Fellowship [16POST27770032]; National Institutes of Health [RO1 DK103558] FX This work was supported by NHLBI, National Institutes of Health, Grant RO1 HL122124 (to G. C. and S. S. S.), by American Heart Association Postdoctoral Fellowship 16POST27770032 (to S. F.), and National Institutes of Health Grant RO1 DK103558 (to S. K. J.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 47 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 2016 VL 291 IS 44 BP 23343 EP 23362 DI 10.1074/jbc.M116.755496 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB2XB UT WOS:000387224800041 PM 27637331 ER PT J AU Kang, SWS Haydar, G Taniane, C Farrell, G Arias, IM Lippincott-Schwartz, J Fu, D AF Kang, Sun Woo Sophie Haydar, Ghada Taniane, Caitlin Farrell, Geoffrey Arias, Irwin M. Lippincott-Schwartz, Jennifer Fu, Dong TI AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function SO PLOS ONE LA English DT Article ID ACETAMINOPHEN-INDUCED HEPATOTOXICITY; INDUCED LIVER-INJURY; N-TERMINAL KINASE; PROTEIN-KINASE; CELL-DEATH; PERMEABILITY TRANSITION; CULTURED-HEPATOCYTES; ENERGY-EXPENDITURE; DNA FRAGMENTATION; OXIDATIVE STRESS AB Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase ( AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. C1 [Kang, Sun Woo Sophie; Haydar, Ghada; Taniane, Caitlin; Fu, Dong] Univ Sydney, Fac Pharm, Sydney, NSW, Australia. [Farrell, Geoffrey] Australian Natl Univ, Sch Med, Liver Res Grp, Canberra, ACT, Australia. [Arias, Irwin M.] NICHHD, NIH, Bethesda, MD 20892 USA. [Lippincott-Schwartz, Jennifer] Janelia Res Campus, Howard Hughes Med Inst, Ashburn, VA USA. RP Fu, D (reprint author), Univ Sydney, Fac Pharm, Sydney, NSW, Australia. EM dong.fu@sydney.edu.au FU University of Sydney Deputy Vice Chancellor Research (DVCR) compact fund, Innovative Challenge, Faculty of Pharmacy FX The University of Sydney Deputy Vice Chancellor Research (DVCR) compact fund, Innovative Challenge, Faculty of Pharmacy, 2013. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This study was supported by The University of Sydney Deputy Vice-Chancellor Research (DVCR) compact fund, Innovative Challenge, Faculty of Pharmacy. NR 74 TC 0 Z9 0 U1 7 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 28 PY 2016 VL 11 IS 10 AR e0165638 DI 10.1371/journal.pone.0165638 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EE3YA UT WOS:000389537000039 PM 27792760 ER PT J AU Nixon-Abell, J Obara, CJ Weigel, AV Li, D Legant, WR Xu, CS Pasolli, HA Harvey, K Hess, HF Betzig, E Blackstone, C Lippincott-Schwartz, J AF Nixon-Abell, Jonathon Obara, Christopher J. Weigel, Aubrey V. Li, Dong Legant, Wesley R. Xu, C. Shan Pasolli, H. Amalia Harvey, Kirsten Hess, Harald F. Betzig, Eric Blackstone, Craig Lippincott-Schwartz, Jennifer TI Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER SO SCIENCE LA English DT Article ID ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS; PLASMA-MEMBRANE; LIVING CELLS; LIVE CELLS; GENERATION; MICROSCOPY; TRANSFORMATION; MORPHOLOGY; TRACKING AB The endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle that plays crucial roles in numerous cellular functions. We used emerging superresolution imaging technologies to clarify the morphology and dynamics of the peripheral ER, which contacts and modulates most other intracellular organelles. Peripheral components of the ER have classically been described as comprising both tubules and flat sheets. We show that this system consists almost exclusively of tubules at varying densities, including structures that we term ER matrices. Conventional optical imaging technologies had led to misidentification of these structures as sheets because of the dense clustering of tubular junctions and a previously uncharacterized rapid form of ER motion. The existence of ER matrices explains previous confounding evidence that had indicated the occurrence of ER "sheet" proliferation after overexpression of tubular junction-forming proteins. C1 [Nixon-Abell, Jonathon; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Nixon-Abell, Jonathon; Harvey, Kirsten] UCL, UCL Sch Pharm, Dept Pharmacol, London, England. [Obara, Christopher J.; Weigel, Aubrey V.; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Obara, Christopher J.; Weigel, Aubrey V.; Li, Dong; Legant, Wesley R.; Xu, C. Shan; Pasolli, H. Amalia; Hess, Harald F.; Betzig, Eric; Lippincott-Schwartz, Jennifer] HHMI, Janelia Res Campus, Ashburn, VA 20147 USA. [Li, Dong] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China. RP Blackstone, C (reprint author), NINDS, Cell Biol Sect, Neurogenet Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.; Lippincott-Schwartz, J (reprint author), HHMI, Janelia Res Campus, Ashburn, VA 20147 USA. EM blackstc@ninds.nih.gov; lippincottschwartzj@janelia.hhmi.org OI Nixon-Abell, Jonathon/0000-0003-4169-0012 FU NIGMS Postdoctoral Research Associate Program fellowship; AIDS research fellowship from the NIH Office of AIDS Research; NIH Intramural AIDS Targeted Antiviral Program; National Key Research Program of China [2016YFA0500200]; HHMI; Intramural Research Program of NINDS; Intramural Research Program of NICHD; UCL School of Pharmacy PhD studentship FX Supported by a NIGMS Postdoctoral Research Associate Program fellowship (A.V.W.), an intramural AIDS research fellowship from the NIH Office of AIDS Research (C.J.O.), a grant from the NIH Intramural AIDS Targeted Antiviral Program (J.L.-S. and C.J.O.), National Key Research Program of China grant 2016YFA0500200 (D.L.), and HHMI and the Intramural Research Programs of NINDS and NICHD. J.N.-A. is supported by a UCL School of Pharmacy PhD studentship (to K.H.). We thank H. White for assistance with cell culture, L. Shao for assistance with imaging and data processing, P.-P. Zhu for advice on immunocytochemistry, R. Yan for a generous gift of an RTN4A/B antibody, and E. Snapp for provision of an MDCK ER-RFP stable cell line and critical reading of the manuscript. The authors declare that there are no conflicts of interest. All data to support the conclusions are provided either in the manuscript or in the supplementary materials. NR 39 TC 4 Z9 4 U1 14 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 28 PY 2016 VL 354 IS 6311 AR aaf3928 DI 10.1126/science.aaf3928 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EB9AT UT WOS:000387684400032 ER PT J AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, Alexander M. Bezrukov, Sergey M. TI Intermittent free diffusion in the presence of sparse obstacles: mean obstacle encounter time SO JOURNAL OF PHYSICS A-MATHEMATICAL AND THEORETICAL LA English DT Article DE Smoluchowski theory; effective diffusivity; Wiener sausage ID WIENER SAUSAGE; TRAPS; COEFFICIENT; COAGULATION; PARTICLES; KINETICS; VOLUME AB Particle diffusion in the presence of sparse obstacles may be considered as a sequence of relatively long intervals, during which the particle diffuses in regions free of obstacles, separated by relatively short intervals during which the particle suffers multiple collisions with an obstacle. The present paper focuses on the mean duration of the short intervals, called mean encounter time, assuming that the obstacles are identical spheres. Based on scaling arguments, one can deduce that this time is proportional to the ratio of the square of the obstacle radius and the particle diffusivity. We derive an expression for the mean encounter time, which shows that the proportionality coefficient is 1/6. C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Bezrukov, Sergey M.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Mol Transport, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Mol Transport, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); Center for Information Technology; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX AMB is grateful to Yu A Makhnovskii and R A Suris for numerous illuminating and stimulating discussions of different aspects of the theory of diffusion-controlled reactions. This study was supported by the Intramural Research Program of the National Institutes of Health (NIH), the Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 28 TC 0 Z9 0 U1 6 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1751-8113 EI 1751-8121 J9 J PHYS A-MATH THEOR JI J. Phys. A-Math. Theor. PD OCT 28 PY 2016 VL 49 IS 43 AR 434002 DI 10.1088/1751-8113/49/43/434002 PG 10 WC Physics, Multidisciplinary; Physics, Mathematical SC Physics GA DY6YR UT WOS:000385276300005 ER PT J AU Wang, XL Sun, J Li, CC Mao, BY AF Wang, Xiaolei Sun, Jian Li, Chaocui Mao, Bingyu TI EphA7 modulates apical constriction of hindbrain neuroepithelium during neurulation in Xenopus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE EphA7; Xenopus; Neurulation; Apical constriction; Focal adhesion kinase ID FOCAL-ADHESION-KINASE; CELL-ADHESION; NEURAL CREST; EXPRESSION; RECEPTORS; PROTEIN; EMBRYOS; CONTRACTILITY; MORPHOGENESIS; ACTIVATION AB Eph receptor tyrosine kinases (RTKs) and their ephrin ligands play multiple roles in the developing nervous system, including cell segregation, axon guidance and synaptic plasticity. Here we report the expression and function of EphA7 in Xenopus hindbrain development. EphA7 is specifically expressed in the hindbrain throughout neurulation in Xenopus embryos. Knockdown of EphA7 by specific morpholino oligonucleotide (MO) disrupted cranial neural tube closure and disturbed apical constriction of hindbrain neuroepithelial cells, indicating weakened cell surface tension. In neural plate explants, EphA7 knockdown inhibited apical filamentous actin (F-actin) accumulation. We further showed that EphA7 is involved in the phosphorylation and activation of focal adhesion kinase (FAK) in vivo and in vitro, a key regulator of actin assembly. Our findings reveal that EphA7 functions as a critical regulator of apical constriction of hindbrain neuroepithelial cells. (C) 2016 Published by Elsevier Inc. C1 [Wang, Xiaolei; Sun, Jian; Li, Chaocui; Mao, Bingyu] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China. [Wang, Xiaolei] Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650203, Peoples R China. [Sun, Jian] NCI, Lab Cell & Dev Signaling, NIH, Frederick, MD 21702 USA. RP Mao, BY (reprint author), Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China. EM mao@mail.kiz.ac.cn FU National Natural Science Foundation of China [31271566] FX This work was supported by a grant from the National Natural Science Foundation of China (31271566). NR 24 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 2016 VL 479 IS 4 BP 759 EP 765 DI 10.1016/j.bbrc.2016.09.138 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA EB2NY UT WOS:000387200300025 PM 27693790 ER PT J AU Simmonett, AC Pickard, FC Ponder, JW Brooks, BR AF Simmonett, Andrew C. Pickard, Frank C. Ponder, Jay W. Brooks, Bernard R. TI An empirical extrapolation scheme for efficient treatment of induced dipoles SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; POLARIZABLE FORCE-FIELDS; DRUDE OSCILLATOR MODEL; MULTIPOLE WATER MODEL; PARTICLE-MESH EWALD; ELECTRONIC POLARIZATION; SCALABLE EVALUATION; ATOMIC INTERACTION; ENERGY; CHARMM AB Many cutting edge force fields include polarization, to enhance their accuracy and range of applicability. In this work, we develop efficient strategies for the induced dipole polarization method. By fitting various orders of perturbation theory (PT) dipoles to a diverse training set, we arrive at a family of fully analytic methods - whose nth order is referred to OPTn - that span the full spectrum of polarization methods from the fast zeroth-order approach that neglects mutual dipole coupling, approaching the fully variational approach at high order. Our training set contains many difficult cases where the PT series diverges, and we demonstrate that our OPTn methods still deliver excellent results in these cases. Our tests show that the OPTn methods exhibit rapid convergence towards the exact answer with each increasing PT order. The fourth order OPT4 method, whose costs are commensurate with three iterations of the leading conjugate gradient method, is a particularly promising candidate to be used as a drop-in replacement for existing solvers without further parameterization. C1 [Simmonett, Andrew C.; Pickard, Frank C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Ponder, Jay W.] Washington Univ, Dept Chem, St Louis, MO 63130 USA. RP Simmonett, AC (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM andrew.simmonett@nih.gov OI Simmonett, Andrew/0000-0002-5921-9272; Pickard, Frank/0000-0002-9608-3466 FU National Heart, Lung and Blood Institute; AMOEBA force [NIH GM106137, NIH GM114237] FX This work was supported by the intramural research program of the National Heart, Lung and Blood Institute. J.W.P. wishes to acknowledge support for development of the AMOEBA force field from Nos. NIH GM106137 and NIH GM114237. A.C.S. is thankful to Dr. P. K. Eastman for developing the CUDA implementation of OPTn in OpenMM. NR 53 TC 2 Z9 2 U1 3 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 28 PY 2016 VL 145 IS 16 AR 164101 DI 10.1063/1.4964866 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA EB7RA UT WOS:000387586200006 PM 27802661 ER PT J AU Wu, XW Pickard, FC Brooks, BR AF Wu, Xiongwu Pickard, Frank C. Brooks, Bernard R. TI Isotropic periodic sum for multipole interactions and a vector relation for calculation of the Cartesian multipole tensor SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE MESH EWALD; MOLECULAR-DYNAMICS SIMULATIONS; DIELECTRIC-PROPERTIES; INTERACTION ENERGIES; RECURRENCE RELATIONS; COULOMBIC SYSTEMS; FORCE-FIELDS; WATER; ELECTROSTATICS; POTENTIALS AB Isotropic periodic sum (IPS) is a method to calculate long-range interactions based on the homogeneity of simulation systems. By using the isotropic periodic images of a local region to represent remote structures, long-range interactions become a function of the local conformation. This function is called the IPS potential; it folds long-ranged interactions into a short-ranged potential and can be calculated as efficiently as a cutoff method. It has been demonstrated that the IPS method produces consistent simulation results, including free energies, as the particle mesh Ewald (PME) method. By introducing the multipole homogeneous background approximation, this work derives multipole IPS potentials, abbreviated as IPSMm, with m being the maximum order of multipole interactions. To efficiently calculate the multipole interactions in Cartesian space, we propose a vector relation that calculates a multipole tensor as a dot product of a radial potential vector and a directional vector. Using model systems with charges, dipoles, and/or quadrupoles, with and without polarizability, we demonstrate that multipole interactions of order m can be described accurately with the multipole IPS potential of order 2 or m - 1, whichever is higher. Through simulations with the multipole IPS potentials, we examined energetic, structural, and dynamic properties of the model systems and demonstrated that the multipole IPS potentials produce very similar results as PME with a local region radius (cutoff distance) as small as 6 angstrom. C1 [Wu, Xiongwu; Pickard, Frank C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM wuxw@nhlbi.nih.gov FU Intramural Research Programs of National Heart, Lung, and Blood Institute [Z01 HL001027-30] FX This research was supported by the Intramural Research Programs of National Heart, Lung, and Blood Institute (Grant No. Z01 HL001027-30). The authors thank Douglas Joubert, NIH Library Writing Center, for manuscript editing assistance. NR 58 TC 0 Z9 0 U1 3 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 28 PY 2016 VL 145 IS 16 AR 164110 DI 10.1063/1.4966019 PG 18 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA EB7RA UT WOS:000387586200015 PM 27802614 ER PT J AU Amaral, EP Conceicao, EL Costa, DL Rocha, MS Marinho, JM Cordeiro-Santos, M D'Imperio-Lima, MR Barbosa, T Sher, A Andrade, BB AF Amaral, Eduardo P. Conceicao, Elisabete L. Costa, Diego L. Rocha, Michael S. Marinho, Jamocyr M. Cordeiro-Santos, Marcelo D'Imperio-Lima, Maria Regina Barbosa, Theolis Sher, Alan Andrade, Bruno B. TI N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions SO BMC MICROBIOLOGY LA English DT Article DE Tuberculosis; N-acetyl cysteine; Antimicrobial activity; Therapy ID MYCOBACTERIUM-TUBERCULOSIS; ENTEROCOCCUS-FAECALIS; COMBINATION THERAPY; OXIDATIVE STRESS; NADPH OXIDASE; IN-VITRO; ACETYLCYSTEINE; GLUTATHIONE; GROWTH; BIOFILM AB Background: Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Methods: Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. Results: PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. Conclusions: NAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity. C1 [Amaral, Eduardo P.; Costa, Diego L.; Sher, Alan; Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Amaral, Eduardo P.; D'Imperio-Lima, Maria Regina] Univ Sao Paulo, Inst Biomed Sci, Lab Immunol Infect Dis, Dept Immunol, BR-05508900 Sao Paulo, Brazil. [Conceicao, Elisabete L.; Rocha, Michael S.; Barbosa, Theolis; Andrade, Bruno B.] Fundacao Oswaldo Cruz FIOCRUZ, Inst Goncalo Moniz, LIMI, BR-40296710 Salvador, BA, Brazil. [Conceicao, Elisabete L.; Barbosa, Theolis] Univ Fed Bahia, ICS, BR-40110100 Salvador, BA, Brazil. [Marinho, Jamocyr M.] Sch Med & Publ Hlth, Dept Internal Med, BR-41150100 Salvador, BA, Brazil. [Marinho, Jamocyr M.] Hosp Especializado Octavio Mangabeira, Programa Controle TB, BR-40320350 Salvador, BA, Brazil. [Cordeiro-Santos, Marcelo] Fundacao Med Trop Dr Heitor Vieira Dourado, Dept Ensino & Posgrad, Manaus, Amazonas, Brazil. [Cordeiro-Santos, Marcelo] Univ Estado Amazonas, Programa Posgrad Med Trop, Manaus, Amazonas, Brazil. [Andrade, Bruno B.] Fundacao Jose Silveira, Multinatl Org Network Sponsoring Translat & Epide, BR-45204040 Salvador, BA, Brazil. [Andrade, Bruno B.] Fac Tecnol & Ciencias, Curso Med, BR-41741590 Salvador, BA, Brazil. RP Andrade, BB (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Andrade, BB (reprint author), Fundacao Oswaldo Cruz FIOCRUZ, Inst Goncalo Moniz, LIMI, BR-40296710 Salvador, BA, Brazil.; Andrade, BB (reprint author), Fundacao Jose Silveira, Multinatl Org Network Sponsoring Translat & Epide, BR-45204040 Salvador, BA, Brazil.; Andrade, BB (reprint author), Fac Tecnol & Ciencias, Curso Med, BR-41741590 Salvador, BA, Brazil. EM bruno.andrade@bahia.fiocruz.br OI Barbosa, Theolis/0000-0003-1928-0404 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2010/51150-4, 2013/07298-5, 2015/19126-0] FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP grant 2010/51150-4, 2013/07298-5 and 2015/19126-0. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 0 Z9 0 U1 4 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD OCT 28 PY 2016 VL 16 AR 251 DI 10.1186/s12866-016-0872-7 PG 10 WC Microbiology SC Microbiology GA EA1YB UT WOS:000386387000002 PM 27793104 ER EF