FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Funderburg, NT Mehta, NN AF Funderburg, Nicholas T. Mehta, Nehal N. TI Lipid Abnormalities and Inflammation in HIV Inflection SO CURRENT HIV/AIDS REPORTS LA English DT Article DE Antiretroviral therapy; Inflammation; Lipid composition; Oxidized LDL; Statins; HDL cholesterol efflux ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHOLESTEROL EFFLUX CAPACITY; HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; OXIDIZED LDL; STATIN THERAPY AB Infection with the human immunodeficiency virus (HIV), and subsequent treatment with antiretroviral therapy (ART), is often associated with perturbations in lipid profiles. Furthermore, persistent inflammation, in spite of suppression of viral replication by ART, likely contributes to modifications in lipid composition and function, exacerbating risk for development of cardiovascular disease (CVD). Increased levels of several pro-inflammatory lipid species, including oxidized low-density lipoprotein (LDL) and high-density lipoprotein (HDL), have been measured in HIV-infected persons and are associated with markers of immune activation. The mechanisms linked to this bidirectional relationship in which inflammation increases lipid levels and promotes their modification, and these modified lipid species perpetuate inflammatory processes, require further investigation. Treatment with statins and other lifestyle modifications, including improvement in dietary intake and exercise, are critical to reducing CVD risk. Well-designed clinical trials that take into account the complex relationships among lipids and inflammation within persons infected with HIV need to be considered. C1 [Funderburg, Nicholas T.] Ohio State Univ, Sch Hlth & Rehabil Sci, Div Med Lab Sci, 453 W 10th Ave,535A Atwell Hall, Columbus, OH 43210 USA. [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov FU NHLBI FX Nicholas T. Funderburg reports grants from NHLBI and has served as consultant for Gilead Inc. NR 106 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD AUG PY 2016 VL 13 IS 4 BP 218 EP 225 DI 10.1007/s11904-016-0321-0 PG 8 WC Infectious Diseases SC Infectious Diseases GA DU1XF UT WOS:000382003000005 PM 27245605 ER PT J AU Varma, VR Tang, XY Carlson, MC AF Varma, Vijay R. Tang, Xiaoying Carlson, Michelle C. TI Hippocampal Sub-Regional Shape and Physical Activity in Older Adults SO HIPPOCAMPUS LA English DT Article DE aging; surface area; subiculum; accelerometer; exercise ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DENTATE GYRUS; ENVIRONMENTAL ENRICHMENT; RANDOMIZED-TRIAL; VENTRICULAR STRUCTURES; VOLUNTARY EXERCISE; AEROBIC EXERCISE; BRAIN HEALTH; IN-VIVO AB Hippocampal atrophy is a hallmark of Alzheimer's disease pathology, and a target biomarker region for testing intervention efficacy. Over the last few decades, a growing body of evidence from animal and human models suggests that physical activity (PA) is associated with structural benefits to the hippocampus in older adults. Very few human studies, however have explored hippocampal sub-regional specificity of PA; this is significant considering that sub-regions of the hippocampus are associated with distinct cognitive tasks and are differentially affected by disease pathology. This study used objective and self-reported measures of daily walking activity and exercise, and surface-based regional shape analysis using high-field hippocampal sub-regional partitions to explore sub-region specific hippocampal associations in a sample of nondemented, community-dwelling older adults at elevated sociodemographic risk for cognitive decline. Vertex-wise surface areas, which may be more sensitive than global volume measures, were calculated using shape diffeomorphometry, and PA was assessed using step activity monitors and PA questionnaires. We found that daily walking activity in a participant's environment was associated in cross-section mainly with larger surface areas of the subiculum in women. Associations remained significant when controlling for self-reported exercise. Prior studies have found that PA related to exercise and aerobic fitness may be most closely associated with the anterior hippocampus, particu-larly the dentate gyrus of the hippocampus. These novel findings are the first, to our knowledge, in human models to suggest that PA related to navigation that may not reach the level of moderate-intensity exercise may be associated with specific sub-regions of the hippocampus. These findings underscore the importance of better understanding the independent and related biological mechanisms and pathways by which increasing exercise as well as non-exercise, lifestyle PA may influence structural brain health. (C) 2016 Wiley Periodicals, Inc. C1 [Varma, Vijay R.; Carlson, Michelle C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House 8th Floor,624 N Broadway St, Baltimore, MD USA. [Varma, Vijay R.; Carlson, Michelle C.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Tang, Xiaoying] SYSU CMU, Joint Inst Engn, Pittsburgh, PA USA. [Tang, Xiaoying] SYSU CMU, Shunde Int Joint Res Inst, Pittsburgh, PA USA. [Varma, Vijay R.] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. RP Varma, VR (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House 8th Floor,624 N Broadway St, Baltimore, MD USA. EM vvarma1@jhu.edu; mcarlso2@jhu.edu FU National Institute on Aging [P01-AG027735, 3P01AG027735-03S2, 3P01AG027735-02S3, P30-AG021334]; Memory and Aging Training Grant [5T32AG027668]; Epidemiology and Biostatistics of Aging Training Grant [5T32AG000247]; National Natural Science Foundation of China [NSFC 81501546]; SYSU-CMU Shunde International Joint Research Institute Start-up Grant [20150306]; Johns Hopkins OAIC Pepper Center; John D. and Catherine T. MacArthur Foundation; Johns Hopkins Neurobehavioral Research Unit FX Grant sponsor: National Institute on Aging; Grant numbers: P01-AG027735, 3P01AG027735-03S2, 3P01AG027735-02S3, P30-AG021334; Grant sponsor: Memory and Aging Training Grant; Grant number: 5T32AG027668; Grant sponsor: Epidemiology and Biostatistics of Aging Training Grant; Grant number: 5T32AG000247; Grant sponsor: National Natural Science Foundation of China; Grant number: NSFC 81501546; Grant sponsor: the SYSU-CMU Shunde International Joint Research Institute Start-up Grant; Grant number: 20150306; Grant sponsors: Johns Hopkins OAIC Pepper Center; John D. and Catherine T. MacArthur Foundation; Johns Hopkins Neurobehavioral Research Unit. NR 92 TC 0 Z9 0 U1 6 U2 6 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 AUG PY 2016 VL 26 IS 8 BP 1051 EP 1060 DI 10.1002/hipo.22586 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DV9PN UT WOS:000383273400007 PM 27009597 ER PT J AU Batsis, M Dagalakis, U Stratakis, CA Prodanov, T Papadakis, GZ Adams, K Lodish, M Pacak, K AF Batsis, M. Dagalakis, U. Stratakis, C. A. Prodanov, T. Papadakis, G. Z. Adams, K. Lodish, M. Pacak, K. TI Attention Deficit Hyperactivity Disorder in Pediatric Patients with Pheochromocytoma and Paraganglioma SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE catecholamines; neuroendocrine tumor; epinephrine ID DEFICIT/HYPERACTIVITY DISORDER; STIMULANT-DRUGS; SYMPTOMS; CHILDREN; ADOLESCENTS; MANAGEMENT; DIAGNOSIS; UPDATE; ADHD AB The aim of the study is to evaluate if there is an association between attention deficit hyperactivity disorder (ADHD) and the diagnosis of pheochromocytoma/paraganglioma (PHEO/PGL) in pediatric patients. A case series study of 43 patients under the age of 18 with PHEO/PGL tumors who were evaluated at the National Institute of Health between January 2006 and May 2014 is reported. Prior diagnosis of ADHD and treatment course with stimulant medications was recorded. Patient symptoms, catecholamine and metanephrine levels, tumor characteristics, and genetic analyses for syndromes associated with PHEO/PGL were evaluated. A chi-squared test was used to assess the prevalence of ADHD in the PHEO/PGL patients compared to the general population. Nine out of 43 (21%) of patients diagnosed with PHEO/PGL had been diagnosed with ADHD prior to tumor identification. Four of the 9 patients had been treated with amphetamine, dextroamphetamine, and/or methylphenidate, potentially exacerbating an adrenergic crisis. In addition, 4 patients exhibited hypertension at the initial diagnosis of their PHEO/PGL. Three patients had resolution of their ADHD symptoms after successful surgical removal of PHEO/PGL. Our study found a prevalence of ADHD in 21% of our PHEO/PGL patients, significantly higher than 7.2% seen in the general pediatric population. Symptoms of anxiety and difficulty in concentration in these patients may have been related to their underlying PHEO/PGL and were not recognized as part of the constellation of symptoms in a child with PHEO/PGL. In pediatric patients with hypertension and ADHD symptomatology, an evaluation to rule out PHEO/PGL is warranted prior to treatment with stimulant medications. C1 [Batsis, M.; Dagalakis, U.; Stratakis, C. A.; Lodish, M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet Pediat Endocrinol, Interinst Training Program,NIH, Bethesda, MD 20892 USA. [Dagalakis, U.] Albany Med Coll, Albany, NY 12208 USA. [Prodanov, T.; Adams, K.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Papadakis, G. Z.] NIH, Dept Radiol & Imaging Sci, CC, Bldg 10, Bethesda, MD 20892 USA. RP Lodish, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet Pediat Endocrinol, Interinst Training Program,NIH,DEB NICHD, 10 Ctr Dr, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 23 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 AUG PY 2016 VL 48 IS 8 BP 509 EP 513 DI 10.1055/s-0042-106725 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DV8HI UT WOS:000383177700004 PM 27171833 ER PT J AU Mayama, T Marr, AK Kino, T AF Mayama, T. Marr, A. K. Kino, T. TI Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE autoimmune diseases; fasting; glucocorticoids; mammalian target of rapamycin (mTOR); tissue glucocorticoid sensitivity ID CELL-PROLIFERATION; POOR-PROGNOSIS; DECREASED EXPRESSION; BLOOD TRANSCRIPTOME; PROSTATE-CANCER; GENE-EXPRESSION; DOWN-REGULATION; GROWTH ARREST; SARCOIDOSIS; INFLUENZA AB Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA glucocorticoid response element (GRE). To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA GRE. Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy. C1 [Mayama, T.; Kino, T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Nihon Univ, Bethesda, MD USA. [Mayama, T.] Chiba Univ, Dept Integrate Biosci, Grad Sch Med & Pharmaceut Sci, Chiba, Japan. [Marr, A. K.; Kino, T.] Sidra Med & Res Ctr, Div Genet, Doha, Qatar. RP Kino, T (reprint author), Sidra Med & Res Ctr, Div Genet, Out Patient Clin, 5th Floor Rm C5-340 POB 26999,Al Luqta St, Doha, Qatar. EM tkino@sidra.org FU Intramural Research Program of the Sidra Medical and Research Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [Z01 HD008732-05 HNT] FX This study was funded by the Intramural Research Program of the Sidra Medical and Research Center, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Z01 HD008732-05 HNT). We thank Drs. D. Chaussabel, D. Rinchai, N. Marr, and W. Chen for the use of GXB and helpful discussion. NR 55 TC 3 Z9 4 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 AUG PY 2016 VL 48 IS 8 BP 550 EP 557 DI 10.1055/s-0042-106898 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DV8HI UT WOS:000383177700011 PM 27214311 ER PT J AU Shizukuda, Y Tripodi, DJ Rosing, DR AF Shizukuda, Yukitaka Tripodi, Dorothy J. Rosing, Douglas R. TI Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Letter DE Hemochromatosis; Arrhythmia; Oxidative stress; Iron overload; Biomarkers; Electrocardiogram AB Hereditary hemochromatosis (HH) is a genetic disorder which affects the heart due to systemic iron overload and concomitant elevated oxidative stress. Increasing numbers of patients are diagnosed at an asymptomatic stage due to genetic testing. Subclinical abnormal left ventricular diastolic function (LVDF) and increased arrhythmias are noted in this population; however, the mechanism leading to these observances has not been well understood. In this study, we assessed the relationship between arrhythmia activity and biomarkers of oxidative stress and iron overload in order to elucidate the role of oxidative stress in this population since we observed a significant association with LVDF previously. A significant correlation between plasma malondialdehyde, a biomarker of oxidative stress, and supraventricular arrhythmia activity without a significant association with iron overload was identified (n = 22). Our findings further highlight a possible role of oxidative stress in early cardiac manifestations of HH. Further investigation is warranted to assess this role. C1 [Shizukuda, Yukitaka; Tripodi, Dorothy J.; Rosing, Douglas R.] NHLBI, Cardiopulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Shizukuda, Yukitaka] Univ Cincinnati, Div Cardiovasc Hlth & Dis, Dept Internal Med, Cincinnati, OH 45220 USA. [Shizukuda, Yukitaka] Cincinnati VA Med Ctr, Cincinnati, OH 45220 USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiopulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.; Shizukuda, Y (reprint author), Univ Cincinnati, Div Cardiovasc Hlth & Dis, Dept Internal Med, Cincinnati, OH 45220 USA.; Shizukuda, Y (reprint author), Cincinnati VA Med Ctr, Cincinnati, OH 45220 USA. EM shizukya@uc.edu FU Intramural NIH HHS [Z99 HL999999] NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 EI 1937-5395 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD AUG PY 2016 VL 9 IS 4 BP 400 EP 401 DI 10.1007/s12265-016-9704-2 PG 2 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA DU1UN UT WOS:000381995400013 PM 27271161 ER PT J AU Brown, WV Garg, A Gorden, P Shamburek, R AF Brown, William Virgil Garg, Abhimanyu Gorden, Phillip Shamburek, Robert TI JCL roundtable: Diagnosis and clinical management of lipodystrophy SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Editorial Material DE Lipodystrophy; HDL cholesterol; Triglycerides; Obesity; Adipose tissue AB Lipodystrophy comes in several forms, some involving the complete failure to develop adipose tissue and others with a partial absence in various bodily distributions. All appear to have a major genetic basis, and all involve a high frequency of lipoprotein disorders. High triglycerides and low high-density lipoprotein cholesterol are the usual findings that raise interesting questions as to how such abnormalities characteristic of obesity can be caused by genetic variants that produce a paucity of adiposity. We are learning to link some specific genetic variants that seem causal and to manage these disorders in more effective ways. We are joined by 3 experts who have been leaders in the study of the clinical presentation, genetics, abnormal physiology, and the management of lipodystrophy in recent years. They are Drs Abhimanyu Garg from the University of Texas Southwestern, Phillip Gorden of the National Institute of Diabetes, Digestive and Kidney Diseases, and Robert Shamburek of the National Heart, Lung and Blood Institute. (C) 2016 National Lipid Association. All rights reserved. C1 [Brown, William Virgil] Emory Univ, Sch Med, 3208 Habersham Rd, Atlanta, GA 30305 USA. [Garg, Abhimanyu] UT Southwestern Med Ctr, Dallas, TX USA. [Gorden, Phillip; Shamburek, Robert] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Brown, WV (reprint author), Emory Univ, Sch Med, 3208 Habersham Rd, Atlanta, GA 30305 USA. EM wbrow925@bellsouth.net NR 7 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 1933-2874 EI 1876-4789 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD AUG PY 2016 VL 10 IS 4 BP 728 EP 736 DI 10.1016/j.jacl.2016.06.005 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DV7KN UT WOS:000383114900002 PM 27578101 ER PT J AU Etzion, O Novack, V Perl, Y Abel, O Schwartz, D Munteanu, D Abufreha, N Ben-Yaakov, G Maoz, ED Moshaklo, A Dizingf, V Fich, A AF Etzion, Ohad Novack, Victor Perl, Yael Abel, Olga Schwartz, Doron Munteanu, Daniella Abufreha, Naim Ben-Yaakov, Gil Maoz, Eyal D. Moshaklo, Alex Dizingf, Vitaly Fich, Alex TI Sci-B-Vac(TM) Vs ENGERIX-B Vaccines for Hepatitis B Virus in Patients with Inflammatory Bowel Diseases: A Randomised Controlled Trial SO JOURNAL OF CROHNS & COLITIS LA English DT Article DE Hepatitis B virus vaccine; inflammatory bowel disease; immunosuppression ID OPPORTUNISTIC INFECTIONS; CROHNS-DISEASE; COMPARATIVE IMMUNOGENICITY; PRE-S; VACCINATION; INFLIXIMAB; THERAPY; REACTIVATION; RESPONDERS; MANAGEMENT AB Response rate to second-generation hepatitis B virus vaccines is relatively low in patients with inflammatory bowel diseases compared with the general healthy population. We compared the efficacy and safety of a third- vs a second-generation hepatitis B virus vaccine in a group of patients with inflammatory bowel diseases treated with immunosuppressive medications. Prospective, randomised, single-blind, controlled study. Eligible patients were randomly assigned to receive one of two vaccines, ENGERIX-B or Sci-B-Vac. The vaccines were administered in three doses at 0, 1, and 6 months. The primary endpoint was defined as the titre of anti-hepatitis B S [HBs] antibodies following the standard three-dose hepatitis B virus vaccination schedule. A total of 72 patients complied with study protocol [37 and 35 patients in the ENGERIX-B and Sci-B-Vac groups, respectively]. Overall, 75% of the cohort seroconverted. The primary endpoint was met in 81.1% in the ENGERIX-B group and 68.6% in the Sci-B-Vac group [p = 0.22]. Patients in the Sci-B-Vac group showed a statistically significant decreased seroconversion rate compared with the ENGERIX-B group, with use of tumour necrosis factor [TNF] alpha inhibitors [p = 0.03], and higher degree of disease activity [p = 0.03]. Overall seroconversion rate in our cohort was higher than in previous reports in the literature, possibly due to a low disease activity state in the majority of participants. Third-generation hepatitis B virus vaccines showed no apparent advantage over standard of care vaccine in this patient group. C1 [Etzion, Ohad] NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 4-4730, Bethesda, MD 20892 USA. [Etzion, Ohad; Schwartz, Doron; Munteanu, Daniella; Abufreha, Naim; Ben-Yaakov, Gil; Moshaklo, Alex; Dizingf, Vitaly; Fich, Alex] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Dept Gastroenterol & Hepatol, Beer Sheva, Israel. [Novack, Victor; Perl, Yael; Abel, Olga; Maoz, Eyal D.] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Clin Res Ctr, Beer Sheva, Israel. RP Etzion, O (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 4-4730, Bethesda, MD 20892 USA. EM ohad.etzion@nih.gov FU Scigen Ltd. FX This work was supported by Scigen Ltd. The funding source had no role in the study design, collection, analysis, and interpretation of results, writing of the report, or the decision to submit the paper for publication. NR 27 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD AUG PY 2016 VL 10 IS 8 BP 905 EP 912 DI 10.1093/ecco-jcc/jjw046 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DV8RR UT WOS:000383204800006 PM 26928962 ER PT J AU Patel, EU Cox, AL Mehta, SH Boon, D Mullis, CE Astemborski, J Osburn, WO Quinn, J Redd, AD Kirk, GD Thomas, DL Quinn, TC Laeyendecker, O AF Patel, Eshan U. Cox, Andrea L. Mehta, Shruti H. Boon, Denali Mullis, Caroline E. Astemborski, Jacquie Osburn, William O. Quinn, Jeffrey Redd, Andrew D. Kirk, Gregory D. Thomas, David L. Quinn, Thomas C. Laeyendecker, Oliver TI Use of Hepatitis C Virus (HCV) Immunoglobulin G Antibody Avidity as a Biomarker to Estimate the Population-Level Incidence of HCV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HCV; HIV; surveillance; recent infection; antibody response; incidence testing; people who inject drugs ID GENOTYPE 1 INFECTION; INJECT DRUGS; UNITED-STATES; HIV; PEOPLE; EPIDEMIOLOGY; SURVEILLANCE; PREVENTION; ACCESS; HEALTH AB Background. Sensitive methods are needed to estimate the population-level incidence of hepatitis C virus (HCV) infection. Methods. We developed an HCV immunoglobulin G (IgG) antibody avidity assay by modifying the Ortho 3.0 HCV enzyme-linked immunoassay and tested 997 serum or plasma samples from 568 people who inject drugs enrolled in prospective cohort studies. Avidity-based testing algorithms were evaluated by their (1) mean duration of recent infection (MDRI), defined as the average time an individual is identified as having been recently infected, according to a given algorithm; (2) false-recent rate, defined as the proportion of samples collected >2 years after HCV seroconversion that were misclassified as recent; (3) sample sizes needed to estimate incidence; and (4) power to detect a reduction in incidence between serial cross-sectional surveys. Results. A multiassay algorithm (defined as an avidity index of <30%, followed by HCV viremia detection) had an MDRI of 147 days (95% confidence interval [CI], 125-195 days), and the false-recent rates were 0.7% (95% CI,.2%-1.8%) and 7.6% (95% CI, 4.2%-12.3%) among human immunodeficiency virus (HIV)-negative and HIV-positive persons, respectively. In various simulated high-risk populations, this algorithm required <1000 individuals to estimate incidence (relative standard error, 30%) and had >80% power to detect a 50% reduction in incidence. Conclusions. Avidity-based algorithms have the capacity to accurately estimate HCV infection incidence and rapidly assess the impact of public health efforts among high-risk populations. Efforts to optimize this method should be prioritized. C1 [Patel, Eshan U.; Redd, Andrew D.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Lab Immunoregulat, Div Intramural Res,NIAID,NIH, 855 N Wolfe St,Rangos Bldg,Rm 538A, Baltimore, MD 21205 USA. [Cox, Andrea L.; Osburn, William O.; Quinn, Jeffrey; Redd, Andrew D.; Kirk, Gregory D.; Thomas, David L.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, 855 N Wolfe St,Rangos Bldg,Rm 538A, Baltimore, MD 21205 USA. [Patel, Eshan U.; Mehta, Shruti H.; Boon, Denali; Astemborski, Jacquie; Kirk, Gregory D.; Thomas, David L.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Mullis, Caroline E.] New York Med Coll, Dept Med, New York, NY USA. RP Laeyendecker, O (reprint author), Johns Hopkins Univ, 855 N Wolfe St,Rangos Bldg,Rm 538A, Baltimore, MD 21205 USA. EM olaeyen1@jhmi.edu OI Patel, Eshan/0000-0003-2174-5004 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); NIH [T32DA007292, U19 AI088791, R01AI108403, R01AI077757, R01DA12568, R37DA013806, U01DA036297, UM1-AI068613] FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); and by extramural NIH grants (T32DA007292, U19 AI088791, R01AI108403, R01AI077757, R01DA12568, R37DA013806, U01DA036297, and UM1-AI068613). NR 47 TC 1 Z9 1 U1 3 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2016 VL 214 IS 3 BP 344 EP 352 DI 10.1093/infdis/jiw005 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DV9NI UT WOS:000383267100003 PM 26768250 ER PT J AU Buckner, CM Kardava, L Zhang, XZ Gittens, K Justement, JS Kovacs, C McDermott, AB Li, YX Sajadi, MM Chun, TW Fauci, AS Moir, S AF Buckner, Clarisa M. Kardava, Lela Zhang, Xiaozhen Gittens, Kathleen Justement, J. Shawn Kovacs, Colin McDermott, Adrian B. Li, Yuxing Sajadi, Mohammad M. Chun, Tae-Wook Fauci, Anthony S. Moir, Susan TI Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; B cells; elite controllers; humoral immunity; viremia ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-LEVEL VIREMIA; CD8(+) T-CELLS; ANTIRETROVIRAL THERAPY; INFECTED INDIVIDUALS; UNDETECTABLE VIREMIA; IMMUNE ACTIVATION; REPLICATION; SUPPRESSORS; ANTIBODIES AB Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group. However, the initiation of ART in several ECs was associated with reduced frequencies of HIV-specific B cells, suggesting that responses are at least in part sustained by HIV replication. Furthermore, B-cell responses to tetanus toxin but not influenza hemagglutinin in the ART group were lower than those in the EC group. Thus, the superior HIV-specific humoral response in ECs versus ART-treated individuals is likely due to a more intact humoral immune response in ECs and/or distinct responses to residual HIV replication. C1 [Buckner, Clarisa M.; Kardava, Lela; Zhang, Xiaozhen; Justement, J. Shawn; Chun, Tae-Wook; Fauci, Anthony S.; Moir, Susan] NIAID, Immunoregulat Lab, 9000 Rockville Pk,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA. [McDermott, Adrian B.] NIAID, Vaccine Res Ctr, 9000 Rockville Pk,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA. [Gittens, Kathleen] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Li, Yuxing] Inst Biosci & Biotechnol Res, Rockville, MD USA. [Sajadi, Mohammad M.] Univ Maryland, Inst Human Virol, College Pk, MD USA. [Sajadi, Mohammad M.] Baltimore VA Med Ctr, Dept Med, Baltimore, MD USA. [Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON, Canada. [Kovacs, Colin] Maple Leaf Med Clin, Toronto, ON, Canada. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pk,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov FU NIAID, National Institutes of Health FX This work was supported by the Intramural Research Program of the NIAID, National Institutes of Health. NR 50 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2016 VL 214 IS 3 BP 390 EP 398 DI 10.1093/infdis/jiw163 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DV9NI UT WOS:000383267100008 PM 27122593 ER PT J AU Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Similar findings on clinical and neuropsychological measures in asymptomatic mutation versus non-mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Coppola, G.] UCLA, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN USA. [Ghoshal, N.; Graff-Radford, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD USA. [Hsiung, R.; Mackenzie, I.] Univers British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA USA. [Sutherland, M.] NINDS, Bethesda, MD USA. [Toga, A.] USC, LONI, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P118 BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400173 ER PT J AU Rosen, H Boeve, B Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Faroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, GYR Huey, ED Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Rosen, H. Boeve, B. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Faroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, G. -Y. R. Huey, E. D. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on neuropsychiatric measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rosen, H.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.; Toga, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Faroud, T.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.; Vetor, A.] Washington Univ, St Louis, MO USA. [Goldman, J.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, G. -Y. R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Weintraub, S.] Norhtwestern Univ, Chicago, IL 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P119 BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400174 ER PT J AU Kramer, J Weintraub, S Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Faroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Wszolek, Z AF Kramer, J. Weintraub, S. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Faroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Wszolek, Z. TI Differences on neuropsychological measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Kantarci, K.; Kornak, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Weintraub, S.] Northwestern, Chicago, IL USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Faroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] USC, LONI, Los Angeles, CA 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P127 BP 290 EP 291 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400182 ER PT J AU Rankin, K Kramer, J Rosen, H Boeve, B Boxer, A Coppola, G Dickerson, B Dheel, C Fields, J Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Kornak, J Knopman, D Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Rankin, K. Kramer, J. Rosen, H. Boeve, B. Boxer, A. Coppola, G. Dickerson, B. Dheel, C. Fields, J. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Kornak, J. Knopman, D. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on novel measures of social comportment in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rankin, K.; Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Miller, B.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] USC LONI, Los Angeles, CA USA. [Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P150 BP 299 EP 299 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400204 ER PT J AU Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Characteristics and Progress on the Initial 147 Subjects in the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Protocol SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P172 BP 309 EP 309 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400226 ER PT J AU Ferrari, R Grassi, M Graziano, F Palluzzi, F Archetti, S Bonomi, E Bruni, A Maletta, R Bernardi, L Cupidi, C Colao, R Rainero, I Rubino, E Pinessi, L Galimberti, D Scarpini, E Serpente, M Nacmias, B Piaceri, I Bagnoli, S Rossi, G Rossi, G Giaccone, G Tagliavini, F Benussi, L Binetti, G Ghidoni, R Singleton, A Hardy, J Momeni, P Padovani, A Borroni, B AF Ferrari, R. Grassi, M. Graziano, F. Palluzzi, F. Archetti, S. Bonomi, E. Bruni, A. Maletta, R. Bernardi, L. Cupidi, C. Colao, R. Rainero, I. Rubino, E. Pinessi, L. Galimberti, D. Scarpini, E. Serpente, M. Nacmias, B. Piaceri, I. Bagnoli, S. Rossi, G. Rossi, G. Giaccone, G. Tagliavini, F. Benussi, L. Binetti, G. Ghidoni, R. Singleton, A. Hardy, J. Momeni, P. Padovani, A. Borroni, B. TI Effects of multiple genetic loci on age at onset in frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Ferrari, R.; Hardy, J.] UCL, Mol Neurosci, London, England. [Grassi, M.; Graziano, F.; Palluzzi, F.] Univ Pavia, Dept Brain & Behav Sci, Med & Genom Stat Unit, Pavia, Italy. [Archetti, S.] Brescia Hosp, Dept Labs, Lab Anal 3, Brescia, Italy. [Bonomi, E.; Padovani, A.; Borroni, B.] Univ Brescia, Dept Clin & Expt Sci, Neurol Unit, Brescia, Italy. [Bruni, A.; Maletta, R.; Bernardi, L.; Cupidi, C.; Colao, R.] Neurogenet Reg Ctr ASPCZ Lamezia Terme, Lamezia Terme, Italy. [Rainero, I.; Rubino, E.; Pinessi, L.] Univ Turin, Turin, Italy. [Rainero, I.; Rubino, E.; Pinessi, L.] Citta Salute & Sci Torino, Neurol 1, Dept Neurosci, Turin, Italy. [Galimberti, D.; Scarpini, E.; Serpente, M.] Univ Milan, Fdn Ca Granda, IRCCS Osped Policlin, Neurol Unit,Dept Pathophysiol & Transplantat, Milan, Italy. [Nacmias, B.; Piaceri, I.; Bagnoli, S.; Rossi, G.] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy. [Rossi, G.; Rossi, G.; Giaccone, G.; Tagliavini, F.] Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, Milan, Italy. [Benussi, L.; Binetti, G.; Ghidoni, R.] IRCCS Ist Ctr San Giovanni Dio Fatebenefratell, Mol Markers Lab, Brescia, Italy. [Singleton, A.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Momeni, P.] Omixy, London, England. RI Hardy, John/C-2451-2009 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P183 BP 313 EP 314 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400237 ER PT J AU Rosen, H Ljubenkov, P Boeve, B Kramer, J Boxer, A Coppola, G Dheel, C Fields, J Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, GYR Huey, ED Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kukull, W Mackensie, I Miller, B Phelps, C Rademakers, R Shaw, L Sutherland, M Toga, A Weintraub, S Wszolek, Z Faroud, T Faber, K Vetor, A Trojanowski, J Rankin, K AF Rosen, H. Ljubenkov, P. Boeve, B. Kramer, J. Boxer, A. Coppola, G. Dheel, C. Fields, J. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, G. -Y. R. Huey, E. D. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kukull, W. Mackensie, I. Miller, B. Phelps, C. Rademakers, R. Shaw, L. Sutherland, M. Toga, A. Weintraub, S. Wszolek, Z. Faroud, T. Faber, K. Vetor, A. Trojanowski, J. Rankin, K. TI NIH EXAMINER as tool for tracking executive dysfunction in carriers of FTLD-causing mutations within the LEFFTDS Consortium SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rosen, H.; Ljubenkov, P.; Kramer, J.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E. D.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, G. -Y. R.; Mackensie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] Univ Southern Calif, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 USA. [Faroud, T.; Faber, K.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P185 BP 314 EP 314 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400239 ER PT J AU Knopman, D Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Huey, E Hsiung, R Irwin, D Kantarci, K Karydas, A Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Weintraub, S Wszolek, Z Vetor, A AF Knopman, D. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Huey, E. Hsiung, R. Irwin, D. Kantarci, K. Karydas, A. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Weintraub, S. Wszolek, Z. Vetor, A. TI Absence of differences on key measures in mildly (CDR=0.5) versus overtly (CDR >= 1) symptomatic mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Knopman, D.; Boeve, B.; Dheel, C.] Mayo Clin, Neurol, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Fields, J.; Gavrilova, R.; Kantarci, K.] Mayo Clin, Rochester, MN USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P189 BP 316 EP 316 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400243 ER PT J AU Knopman, D Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Knopman, D. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on clinical measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Knopman, D.; Boeve, B.; Dheel, C.; Gavrilova, R.] Mayo Clin, Neurol, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Fields, J.] Mayo Clin, Psychiat, Rochester, MN USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kantarci, K.] Mayo Clin, Radiol, Rochester, MN USA. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P191 BP 317 EP 317 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400245 ER PT J AU Capozzo, R Sassi, C Benahmed-Hammer, M Arcuti, S Zecca, C Barulli, MR Tortelli, R Carnicella, F Dell'Aquila, C Valluzzi, F Panza, F Singleton, A Logroscino, G AF Capozzo, R. Sassi, C. Benahmed-Hammer, M. Arcuti, S. Zecca, C. Barulli, M. R. Tortelli, R. Carnicella, F. Dell'Aquila, C. Valluzzi, F. Panza, F. Singleton, A. Logroscino, G. TI Clinical and genetic analyses of familial and sporadic Frontotemporal Dementia patients in Southern Italy (The Apulia_FTD_Registry) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Capozzo, R.; Arcuti, S.; Zecca, C.; Barulli, M. R.; Tortelli, R.; Panza, F.; Logroscino, G.] Univ Bari, Dept Clin Neurol & Res, Pia Fdn Cardinale G Panico, Tricase Le, Italy. [Sassi, C.; Benahmed-Hammer, M.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Sassi, C.] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England. [Carnicella, F.; Dell'Aquila, C.] Bonomo Hosp, Dept Neurol, Andria, Italy. [Valluzzi, F.] S Giacomo Hosp, Neurol Unit, Monopoli, Italy. [Panza, F.] Univ Study Aldo Moro, Dept Interdisciplinary Med, Geriatr Med Memory Unit, Rare Dis Ctr, Bari, Italy. [Logroscino, G.] Univ Bari, Neurodegenerat Dis Unit, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy. 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P209 BP 324 EP 324 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400263 ER PT J AU Boyd, C Tierney, M Wassermann, E Spina, S Oblak, A Ghetti, B Grafman, J Huey, E AF Boyd, C. Tierney, M. Wassermann, E. Spina, S. Oblak, A. Ghetti, B. Grafman, J. Huey, E. TI Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boyd, C.] Columbia Univ, Neurol, New York, NY USA. [Tierney, M.; Wassermann, E.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Spina, S.; Oblak, A.; Ghetti, B.] Indiana Univ, Pathol, Indianapolis, IN 46204 USA. [Grafman, J.] Rehabil Inst Chicago, Brain Injury Res Program, Chicago, IL 60611 USA. [Huey, E.] Columbia Univ, Psychiat & Neurol, New York, NY 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P308 BP 361 EP 361 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400360 ER PT J AU Floeter, MK Katipally, R Kim, M Schanz, O Stephen, M Danielian, L Wu, T Huey, E Meoded, A AF Floeter, M. K. Katipally, R. Kim, M. Schanz, O. Stephen, M. Danielian, L. Wu, T. Huey, E. Meoded, A. TI Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Floeter, M. K.; Katipally, R.; Kim, M.; Schanz, O.; Stephen, M.; Danielian, L.; Wu, T.; Meoded, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Huey, E.] Columbia Univ, Psychiat & Neurol, New York, NY 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P307 BP 361 EP 361 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400359 ER PT J AU Boxer, A Rosen, H Boeve, B Heuer, H Laxineta, S Grossman, M Coppola, G Dickerson, B Bordelon, Y Conwit, R Dheel, C Faber, K Feldman, H Ferguson, J Fields, J Fong, J Foroud, T Galpern, W Ghoshal, N Graff-Radford, N Hsiung, R Huey, E Irwin, D Kantarci, K Kaufer, D Karydas, A Klein, A Knopman, D Kornak, J Kramer, J Kukull, W Litvan, I Mackenzie, I Mendez, M Miller, B Miller, M Onyike, C Pantelyat, A Rademakers, R Roberson, E Sutherland, M Tartaglia, MC Tatton, N Toga, A Vetor, A Weintraub, S Wszolek, Z AF Boxer, A. Rosen, H. Boeve, B. Heuer, H. Laxineta, S. Grossman, M. Coppola, G. Dickerson, B. Bordelon, Y. Conwit, R. Dheel, C. Faber, K. Feldman, H. Ferguson, J. Fields, J. Fong, J. Foroud, T. Galpern, W. Ghoshal, N. Graff-Radford, N. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Kaufer, D. Karydas, A. Klein, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Litvan, I. Mackenzie, I. Mendez, M. Miller, B. Miller, M. Onyike, C. Pantelyat, A. Rademakers, R. Roberson, E. Sutherland, M. Tartaglia, M. C. Tatton, N. Toga, A. Vetor, A. Weintraub, S. Wszolek, Z. TI Characteristics and progress on the Initial 256 participants in the advancing research and treatment in frontotemporal lobar degeneration (ARTFL) North American Rare disease clinical research consortium SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boxer, A.; Rosen, H.; Heuer, H.; Laxineta, S.; Fong, J.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Kantarci, K.; Knopman, D.; Miller, M.] Mayo Clin, Rochester, MN USA. [Grossman, M.; Irwin, D.] Univ Penn, Philadelphia, PA 19104 USA. [Coppola, G.; Bordelon, Y.; Mendez, M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Cambridge, MA USA. [Conwit, R.; Ferguson, J.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Faber, K.; Foroud, T.; Vetor, A.] NCRAD, Indianapolis, IN USA. [Feldman, H.; Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Galpern, W.] Janssen Pharmaceut, Washington, DC USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Graff-Radford, N.; Rademakers, R.; Roberson, E.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Huey, E.] Columbia Univ, New York, NY USA. [Kaufer, D.] Univ N Carolina, Chapel Hill, NC USA. [Klein, A.] CurePSP, New York, NY USA. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Litvan, I.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mendez, M.; Onyike, C.; Pantelyat, A.] Johns Hopkins Univ, Baltimore, MD USA. [Roberson, E.] Univ Alabama Birmingham, Birmingham, AL USA. [Tartaglia, M. C.] Univ Toronto, Toronto, ON, Canada. [Tatton, N.] AFTD, Radnor, PA USA. [Toga, A.] Univ Southern Calif, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P352 BP 379 EP 379 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400403 ER PT J AU Moore, AZ Hernandez, DG Tanaka, T Pilling, LC Nalls, MA Bandinelli, S Singleton, AB Ferrucci, L AF Moore, Ann Zenobia Hernandez, Dena G. Tanaka, Toshiko Pilling, Luke C. Nalls, Mike A. Bandinelli, Stefania Singleton, Andrew B. Ferrucci, Luigi TI Change in Epigenome-Wide DNA Methylation Over 9 Years and Subsequent Mortality: Results From the InCHIANTI Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Epigenome-wide DNA methylation; Chronological age; Survival ID NF-KAPPA-B; HUMAN-DISEASE; EPIGENETICS; AGE AB Patterns of DNA methylation (DNAm) that track with aging have been identified. However, the relevance of these patterns for aging outcomes remains unclear. Longitudinal epigenome-wide DNAm information was obtained from the InCHIANTI study, a large representative European population. DNAm was evaluated using the Illumina HumanMethylation450 array on blood samples collected at baseline and 9-year follow-up: observations from 499 participants with paired longitudinal blood sample and information on differential blood count were included in analyses. A total of 56,579 markers were significantly associated with age in cross-sectional analysis of DNAm at year 9, 31,252 markers were changed significantly over the 9-year follow-up, and 16,987 markers were both cross-sectionally associated with age and significantly changed over time. Rates of change at 76 markers and year 9 level of DNAm at 88 markers were identified as strongly associated with mortality in Cox proportional hazard models adjusted for age and relevant covariates (mean follow-up time 4.4 years). Less than 0.05% of markers associated with age or that changed over time were also associated with mortality after adjusting for chronological age. Although the influence of DNAm on health and longevity remains unclear, these findings confirm that aging is associated cross-sectionally and longitudinally with robust and consistent patterns of methylation change. C1 [Moore, Ann Zenobia; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Hernandez, Dena G.; Nalls, Mike A.; Singleton, Andrew B.] NIA, Lab Neurogenet, Bethesda, MD 20892 USA. [Pilling, Luke C.] Univ Exeter, Sch Med, Epidemiol & Publ Hlth, Exeter EX4 4QJ, Devon, England. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. RP Moore, AZ (reprint author), Biomed Res Ctr, 251 Bayview Blvd,Rm 10B121, Baltimore, MD 21224 USA. EM mooreaz@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Aging; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002); supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. NR 25 TC 4 Z9 4 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2016 VL 71 IS 8 BP 1029 EP 1035 DI 10.1093/gerona/glv118 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DV9BX UT WOS:000383235400006 PM 26355017 ER PT J AU Schrack, JA Cooper, R Koster, A Shiroma, EJ Murabito, JM Rejeski, WJ Ferrucci, L Harris, TB AF Schrack, Jennifer A. Cooper, Rachel Koster, Annemarie Shiroma, Eric J. Murabito, Joanne M. Rejeski, W. Jack Ferrucci, Luigi Harris, Tamara B. TI Assessing Daily Physical Activity in Older Adults: Unraveling the Complexity of Monitors, Measures, and Methods SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Review DE Physical activity; Exercise; Physical performance; Functional performance; Physical function ID RANDOMIZED CONTROLLED-TRIAL; ACTIVITY ENERGY-EXPENDITURE; SEDENTARY BEHAVIOR; ACCELEROMETER MEASUREMENTS; CARDIOVASCULAR HEALTH; PRIMARY PREVENTION; ACTIVITY PATTERNS; NATIONAL-SURVEY; WOMENS HEALTH; UNITED-STATES AB At the 67th Gerontological Society of America Annual Meeting, a preconference workshop was convened to discuss the challenges of accurately assessing physical activity in older populations. The advent of wearable technology (eg, accelerometers) to monitor physical activity has created unprecedented opportunities to observe, quantify, and define physical activity in the real-world setting. These devices enable researchers to better understand the associations of physical activity with aging, and subsequent health outcomes. However, a consensus on proper methodological use of these devices in older populations has not been established. To date, much of the validation research regarding device type, placement, and data interpretation has been performed in younger, healthier populations, and translation of these methods to older populations remains problematic. A better understanding of these devices, their measurement properties, and the data generated is imperative to furthering our understanding of daily physical activity, its effects on the aging process, and vice versa. The purpose of this article is to provide an overview of the highlights of the preconference workshop, including properties of the different types of accelerometers, the methodological challenges of employing accelerometers in older study populations, a brief summary of ongoing aging-related research projects that utilize different types of accelerometers, and recommendations for future research directions. C1 [Schrack, Jennifer A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 North Wolfe St,E7144, Baltimore, MD 21205 USA. [Cooper, Rachel] UCL, MRC Unit Lifelong Hlth & Ageing, London, England. [Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, NL-6200 MD Maastricht, Netherlands. [Shiroma, Eric J.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Shiroma, Eric J.] Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Sect Gen Internal Med, Dept Med, Boston, MA 02215 USA. [Murabito, Joanne M.] NHLBI, Framingham Heart Study, Boston, MA USA. [Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Schrack, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 North Wolfe St,E7144, Baltimore, MD 21205 USA. EM jschrac1@jhu.edu RI Koster, Annemarie/E-7438-2010 FU UK Medical Research Council [MC_UU_12019/4, MC_UU_12019/1]; National Heart, Lung and Blood Institute [N01-HC-25195, HHSN268201500001l]; Intramural Research Program of the National Institute on Aging; National Institutes of Health [CA154647]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; NIA [N01-AG-1-2100]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Science Foundation Graduate Research Fellowship [DGE-0940903]; National Institutes of Health Intramural Research Program [Z01 DK071013, Z01 DK071014]; [R01AG047645]; [K01AG048765]; [HHSN311210300177P] FX The MRC National Survey of Health and Development is funded by the UK Medical Research Council. The authors wish to acknowledge the NSHD participants and scientific and data collection teams (led by Professor Diana Kuh and including members of the MRC Unit for Lifelong Health and Ageing at UCL and the MRC Epidemiology Unit, University of Cambridge). Dr. Cooper is funded by the UK Medical Research Council (program codes: MC_UU_12019/4 and MC_UU_12019/1).; The Framingham Heart Study is supported by contract N01-HC-25195 and HHSN268201500001l of the National Heart, Lung and Blood Institute. The accelerometry study was supported by R01AG047645. The authors wish to acknowledge FHS participants and staff for participation in the Actical study.; The Baltimore Longitudinal Study of Aging is supported by the Intramural Research Program of the National Institute on Aging. The authors wish to acknowledge BLSA participants and staff for participation in the study. Dr. Schrack is supported by K01AG048765 and HHSN311210300177P.; The WHS accelerometry ancillary study was supported by research grants CA154647 from the National Institutes of Health. Dr. Shiroma was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.; The Age, Gene/Environment Susceptibility-Reykjavik Study has been funded by NIA contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). This work was also supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-0940903 and by the National Institutes of Health Intramural Research Program, study numbers: Z01 DK071013 and Z01 DK071014 to R.J.B. and K.Y.C. The researchers are indebted to the participants for their willingness to participate in the study. NR 71 TC 2 Z9 2 U1 13 U2 14 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 AUG PY 2016 VL 71 IS 8 BP 1039 EP 1048 DI 10.1093/gerona/glw026 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DV9BX UT WOS:000383235400007 PM 26957472 ER PT J AU Koob, GF Volkow, ND AF Koob, George F. Volkow, Nora D. TI Neurobiology of addiction: a neurocircuitry analysis SO LANCET PSYCHIATRY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; VENTROMEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; INDUCED DOPAMINE RELEASE; KAPPA-OPIOID RECEPTORS; VENTRAL TEGMENTAL AREA; HEAVY ALCOHOL-USE; NUCLEUS-ACCUMBENS; COCAINE-SEEKING; DRUG-ADDICTION AB Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction. C1 [Koob, George F.] NIAAA, 5635 Fishers Lane,Room 2001,Suite 2000, Rockville, MD 20852 USA. [Volkow, Nora D.] NIDA, NIH, Rockville, MD USA. RP Koob, GF (reprint author), NIAAA, 5635 Fishers Lane,Room 2001,Suite 2000, Rockville, MD 20852 USA. EM gkoob@scripps.edu RI koob, george/P-8791-2016 NR 186 TC 13 Z9 13 U1 59 U2 67 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD AUG PY 2016 VL 3 IS 8 BP 760 EP 773 PG 14 WC Psychiatry SC Psychiatry GA DU5TU UT WOS:000382276500025 PM 27475769 ER PT J AU Deeks, SG Lewin, SR Ross, AL Ananworanich, J Benkirane, M Cannon, P Chomont, N Douek, D Lifson, JD Lo, YR Kuritzkes, D Margolis, D Mellors, J Persaud, D Tucker, JD Barre-Sinoussi, F Alter, G Auerbach, J Autran, B Barouch, DH Behrens, G Cavazzana, M Chen, ZW Cohen, EA Corbelli, GM Eholie, S Eyal, N Fidler, S Garcia, L Grossman, C Henderson, G Henrich, TJ Jefferys, R Kiem, HP McCune, J Moodley, K Newman, PA Nijhuis, M Nsubuga, MS Ott, M Palmer, S Richman, D Saez-Cirion, A Sharp, M Siliciano, J Silvestri, G Singh, J Spire, B Taylor, J Tolstrup, M Valente, S van Lunzen, J Walensky, R Wilson, I Zack, J AF Deeks, Steven G. Lewin, Sharon R. Ross, Anna Laura Ananworanich, Jintanat Benkirane, Monsef Cannon, Paula Chomont, Nicolas Douek, Daniel Lifson, Jeffrey D. Lo, Ying-Ru Kuritzkes, Daniel Margolis, David Mellors, John Persaud, Deborah Tucker, Joseph D. Barre-Sinoussi, Francoise Alter, Galit Auerbach, Judith Autran, Brigitte Barouch, Dan H. Behrens, Georg Cavazzana, Marina Chen, Zhiwei Cohen, Eric A. Corbelli, Giulio Maria Eholie, Serge Eyal, Nir Fidler, Sarah Garcia, Laurindo Grossman, Cynthia Henderson, Gail Henrich, Timothy J. Jefferys, Richard Kiem, Hans-Peter McCune, Joseph Moodley, Keymanthri Newman, Peter A. Nijhuis, Monique Nsubuga, Moses Supercharger Ott, Melanie Palmer, Sarah Richman, Douglas Saez-Cirion, Asier Sharp, Matthew Siliciano, Janet Silvestri, Guido Singh, Jerome Spire, Bruno Taylor, Jeffrey Tolstrup, Martin Valente, Susana van Lunzen, Jan Walensky, Rochelle Wilson, Ira Zack, Jerome CA Int AIDS Soc Cure Working Grp TI International AIDS Society global scientific strategy: towards an HIV cure 2016 SO NATURE MEDICINE LA English DT Article ID CD4(+) T-CELLS; SUPPRESSIVE ANTIRETROVIRAL THERAPY; BROADLY NEUTRALIZING ANTIBODIES; HISTONE DEACETYLASE INHIBITOR; HIGHLY PATHOGENIC SIV; LATENT HIV-1; VIRAL RESERVOIR; IN-VIVO; TREATMENT INTERRUPTION; RALTEGRAVIR INTENSIFICATION AB Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy. C1 [Deeks, Steven G.; Auerbach, Judith; Henrich, Timothy J.; McCune, Joseph] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lewin, Sharon R.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia. [Lewin, Sharon R.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Lewin, Sharon R.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Lewin, Sharon R.] Monash Univ, Melbourne, Vic, Australia. [Ross, Anna Laura] ANRS, Int & Sci Relat Off, Paris, France. [Ananworanich, Jintanat] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Ananworanich, Jintanat] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA. [Benkirane, Monsef] Univ Montpellier, CNRS UPR 1142, Inst Human Genet, Mol Virol Lab, Montpellier, France. [Cannon, Paula] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Chomont, Nicolas] Univ Montreal, Fac Med, CRCHUM, Montreal, PQ, Canada. [Chomont, Nicolas] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Douek, Daniel] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA. [Lo, Ying-Ru] World Hlth Org Reg Off Western Pacific, Manila, Philippines. [Kuritzkes, Daniel; Henrich, Timothy J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Margolis, David; Henderson, Gail] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Mellors, John] Univ Pittsburgh, Dept Med, Div Infect Dis, 930 Scaife Hall, Pittsburgh, PA 15260 USA. [Persaud, Deborah] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Persaud, Deborah] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Tucker, Joseph D.] Univ North Carolina Project China, Guangzhou, Guangdong, Peoples R China. [Barre-Sinoussi, Francoise] Inst Pasteur, Paris, France. [Alter, Galit; Barouch, Dan H.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Autran, Brigitte] Univ Paris 06, Sorbonne Univ, CIMI, Paris, France. [Autran, Brigitte] CIMI Paris, INSERM, U1135, Paris, France. [Autran, Brigitte] Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris, France. [Barouch, Dan H.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Behrens, Georg] Hannover Med Sch, Clin Immunol & Rhematol, Hannover, Germany. [Cavazzana, Marina] Hop Necker Enfants Malad, Ctr Invest Clin Biotherapie, Paris, France. [Chen, Zhiwei] Univ Hong Kong, AIDS Inst, Pok Fu Lam, Hong Kong, Peoples R China. [Cohen, Eric A.] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada. [Corbelli, Giulio Maria] European AIDS Treatment Grp, Rome, Italy. [Eholie, Serge] Ctr Hosp Univ Treichville, Programme PAC CI, Abidjan, Cote Ivoire. [Eyal, Nir] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Fidler, Sarah] Imperial Coll London, Dept Med, London, England. [Garcia, Laurindo] B Change Grp, Manila, Philippines. [Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA. [Jefferys, Richard] Treatment Act Grp, New York, NY 10016 USA. [Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Moodley, Keymanthri] Univ Stellenbosch, Dept Med, Ctr Med Eth & Law, Western Cape, South Africa. [Newman, Peter A.] Univ Toronto, Factor Inwentash Fac Social Work, Toronto, ON, Canada. [Nijhuis, Monique] Univ Med Ctr Utrecht, Dept Med Microbiol, Virol, Utrecht, Netherlands. [Nsubuga, Moses Supercharger] Joint Clin Res Ctr, Kampala, Uganda. [Ott, Melanie] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. [Palmer, Sarah] Univ Sydney, Westmead Millennium Inst Med Res, Sydney, NSW, Australia. [Richman, Douglas] Virginia San Diego Healthcare Syst, San Diego, CA 92161 USA. [Richman, Douglas] Univ Calif San Diego, San Diego, CA 92103 USA. [Saez-Cirion, Asier] Inst Pasteur, Paris, France. [Sharp, Matthew] Independent HIV Educ & Advocacy Consultant, San Francisco, CA USA. [Siliciano, Janet] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Singh, Jerome] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa. [Spire, Bruno] INSERM, UMR S912, Marseille, France. [Taylor, Jeffrey] CARE Collaboratory Community Advisory Board, Palm Springs, CA USA. [Tolstrup, Martin] Aarhus Univ, Inst Clin Med, Aarhus, Denmark. [Valente, Susana] Scripps Res Inst, Dept Immunol & Microbial Sci, Jupiter, FL 33458 USA. [van Lunzen, Jan] ViiV Healthcare, London, England. [Walensky, Rochelle] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wilson, Ira] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Zack, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Deeks, SG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM steven.deeks@ucsf.edu RI Behrens, Georg/Q-4486-2016; Spire, Bruno/F-5546-2013; OI Spire, Bruno/0000-0002-3546-8020; Deeks, Steven/0000-0001-6371-747X; Saez-Cirion, Asier/0000-0003-2406-7536; Lewin, Sharon Ruth/0000-0002-0330-8241 FU federal funds from the NCI/NIH [HHSN261200800001E] FX J.L. is supported in part by federal funds from the NCI/NIH under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. government. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense or the US National Institutes of Health. Y.-R.L. is a World Health Organization (WHO) staff member. The opinions herein are those of the authors and should not be construed as official or representing the views of the WHO. The authors acknowledge T. Rasmussen, T. Mota and M. Crane for assistance with preparation of figures. NR 125 TC 12 Z9 12 U1 16 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 839 EP 850 DI 10.1038/nm.4108 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200009 PM 27400264 ER PT J AU Kabanova, A Marcandalli, J Zhou, TQ Bianchi, S Baxa, U Tsybovsky, Y Lilleri, D Silacci-Fregni, C Foglierini, M Fernandez-Rodriguez, BM Druz, A Zhang, BS Geiger, R Pagani, M Sallusto, F Kwong, PD Corti, D Lanzavecchia, A Perez, L AF Kabanova, Anna Marcandalli, Jessica Zhou, Tongqing Bianchi, Siro Baxa, Ulrich Tsybovsky, Yaroslav Lilleri, Daniele Silacci-Fregni, Chiara Foglierini, Mathilde Fernandez-Rodriguez, Blanca Maria Druz, Aliaksandr Zhang, Baoshan Geiger, Roger Pagani, Massimiliano Sallusto, Federica Kwong, Peter D. Corti, Davide Lanzavecchia, Antonio Perez, Laurent TI Platelet-derived growth factor-alpha receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer SO NATURE MICROBIOLOGY LA English DT Article ID DISINTEGRIN-LIKE DOMAIN; ENDOTHELIAL-CELLS; ELECTRON-MICROSCOPY; EPITHELIAL-CELLS; ENTRY; TROPISM; COMPLEX; FUSION; GENES; VISUALIZATION AB Human cytomegalovirus encodes at least 25 membrane glycoproteins that are found in the viral envelope(1). While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, and the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells(2-5). Two reports suggested that gB binds to ErbB1 and PDGFRa (refs 6,7); however, these results do not explain the tropism of the virus and were recently challenged(8,9). Here, we provide a 19 angstrom reconstruction for the gHgLgO trimer and show that it binds with high affinity through the gO subunit to PDGFRa, which is expressed on fibroblasts but not on epithelial cells. We also provide evidence that the trimer is essential for viral entry in both fibroblasts and epithelial cells. Furthermore, we identify the pentamer, which is essential for infection of epithelial cells, as a trigger for the ErbB pathway. These findings help explain the broad tropism of human cytomegalovirus and indicate that PDGFRa and the viral gO subunit could be targeted by novel anti-viral therapies. C1 [Kabanova, Anna; Marcandalli, Jessica; Silacci-Fregni, Chiara; Foglierini, Mathilde; Fernandez-Rodriguez, Blanca Maria; Geiger, Roger; Sallusto, Federica; Lanzavecchia, Antonio; Perez, Laurent] Univ Italian Switzerland, Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. [Zhou, Tongqing; Druz, Aliaksandr; Zhang, Baoshan; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Bianchi, Siro; Corti, Davide] Humabs BioMed SA, Via Mirasole 1, CH-6500 Bellinzona, Switzerland. [Baxa, Ulrich; Tsybovsky, Yaroslav] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res, Frederick, MD 21702 USA. [Lilleri, Daniele] Fdn IRCCS Policlin San Matteo, Lab Sperimentali Ricerca Area Trapiantol, I-27100 Pavia, Italy. [Geiger, Roger; Lanzavecchia, Antonio] Swiss Fed Inst Technol, Inst Microbiol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland. [Pagani, Massimiliano] Ist Nazl Genet Mol Romeo & Enrica Invernizzi, I-20122 Milan, Italy. [Kabanova, Anna] Univ Siena, Dept Life Sci, Via Aldo Moro 2, I-53100 Siena, Italy. RP Lanzavecchia, A; Perez, L (reprint author), Univ Italian Switzerland, Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.; Lanzavecchia, A (reprint author), Swiss Fed Inst Technol, Inst Microbiol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland. EM lanzavecchia@irb.usi.ch; laurent.perez@irb.usi.ch FU Helmut Horten Foundation; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Leidos Biomedical Research FX The authors thank A. von Heyl for graphical representation, the Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, for the HCMV clinical isolate and deficient virus, Horizon Genomics GmbH for the HAP-1 parental line and CRISPR/Cas9 KO cells and Oxford University, Central Proteomics Facility, Oxford, UK, for mass spectrometry analysis. The Institute for Research in Biomedicine is supported by the Helmut Horten Foundation. This project has been funded in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract no. HHSN261200800001E, and by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Leidos Biomedical Research provided support in the form of a salary for author Y.T. NR 39 TC 4 Z9 4 U1 5 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND EI 2058-5276 J9 NAT MICROBIOL JI NAT. MICROBIOL PD AUG PY 2016 VL 1 IS 8 AR 16082 DI 10.1038/NMICROBIOL.2016.82 PG 8 WC Microbiology SC Microbiology GA DW4IH UT WOS:000383605900018 PM 27573107 ER PT J AU Pisklakova, A McKenzie, B Zemp, F Lun, XQ Kenchappa, RS Etame, AB Rahman, MM Reilly, K Pilon-Thomas, S McFadden, G Kurz, E Forsyth, PA AF Pisklakova, Alexandra McKenzie, Brienne Zemp, Franz Lun, Xueqing Kenchappa, Rajappa S. Etame, Arnold B. Rahman, Masmudur M. Reilly, Karlyne Pilon-Thomas, Shari McFadden, Grant Kurz, Ebba Forsyth, Peter A. TI M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE apoptosis; brain tumor-initiating cells; glioma; oncolytic virus ID STEM-CELLS; PREVENTS APOPTOSIS; MICE; M11L; CANCER; BCL-2; PROLIFERATION; MITOCHONDRIA; INHIBITOR; ANTITUMOR AB Myxoma virus (MYXV) is a promising oncolytic agent and is highly effective against immortalized glioma cells but less effective against brain tumor initiating cells (BTICs), which are believed to mediate glioma development/recurrence. MYXV encodes various proteins to attenuate host cell apoptosis, including an antiapoptotic Bcl-2 homologue known as M011L. Such proteins may limit the ability of MYXV to kill BTICs, which have heightened resistance to apoptosis. We hypothesized that infecting BTICs with an M011L-deficient MYXV construct would overcome BTIC resistance to MYXV. We used patient-derived BTICs to evaluate the efficacy of M011L knockout virus (vMyx-M011L-KO) versus wild-type MYXV (vMyx-WT) and characterized the mechanism of virus-induced cell death in vitro. To extend our findings in a novel immunocompetent animal model, we derived, cultured, and characterized a C57Bl/6J murine BTIC (mBTIC0309) from a spontaneous murine glioma and evaluated vMyx-M011L-KO efficacy with and without temozolomide (TMZ) in mBTIC0309-bearing mice. We demonstrated that vMyx-M011L-KO induces apoptosis in BTICs, dramatically increasing sensitivity to the virus. vMyx-WT failed to induce apoptosis as M011L protein prevented Bax activation and cytochrome c release. In vivo, intracranial implantation of mBTIC0309 generated tumors that closely recapitulated the pathological and molecular profile of human gliomas. Treatment of tumor-bearing mice with vMyx-M011L-KO significantly prolonged survival in immunocompetent-but not immunodeficient-mouse models, an effect that is significantly enhanced in combination with TMZ. Our data suggest that vMyx-M011L-KO is an effective, well-tolerated, proapoptotic oncolytic virus and a strong candidate for clinical translation. C1 [Pisklakova, Alexandra; Kenchappa, Rajappa S.; Etame, Arnold B.; Forsyth, Peter A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Neurooncol & Tumor Biol, Tampa, FL USA. [McKenzie, Brienne; Zemp, Franz; Lun, Xueqing; Kurz, Ebba; Forsyth, Peter A.] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB, Canada. [Rahman, Masmudur M.; McFadden, Grant] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Reilly, Karlyne] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Pilon-Thomas, Shari] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL USA. [McKenzie, Brienne] Univ Alberta, Dept Med Microbiol & Immunol, Heritage Med Res Ctr 6 11, Edmonton, AB T6G 2R3, Canada. RP Forsyth, PA (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Neurooncol, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM peter.forsyth@moffitt.org FU V Foundation; Moffitt Cancer Center Foundation; Terry Fox Foundation; Florida Center for Brain Tumor Research and Accelerate Brain Cancer Cure; Canadian Institutes for Health Research (CIHR); Alberta Innovates-Health Solutions; CIHR; Izaak Walton Killam scholarship; NIH [R01 AI080607, R01 CA138541]; National Cancer Institute, USA FX This work was supported by the V Foundation (P.A.F.), Moffitt Cancer Center Foundation (P.A.F.), and Terry Fox Foundation (P.A.F.). Funding (P.A.F.) was also provided by a research grant from the Florida Center for Brain Tumor Research and Accelerate Brain Cancer Cure (ABC). B.A.M. was funded the Canadian Institutes for Health Research (CIHR). F.J.Z. was funded by Alberta Innovates-Health Solutions, a Vanier scholarship (CIHR), and the Izaak Walton Killam scholarship. G.M.'s lab was funded by NIH grants R01 AI080607 and R01 CA138541. K.M.R. is supported by the Intramural Research Program of the National Cancer Institute, USA. NR 39 TC 0 Z9 0 U1 5 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2016 VL 18 IS 8 BP 1088 EP 1098 DI 10.1093/neuonc/now006 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DV9TT UT WOS:000383285800007 ER PT J AU Weaver, KR Fourie, NH Abey, SK Sherwin, LB Henderson, WA AF Weaver, K. R. Fourie, N. H. Abey, S. K. Sherwin, L. B. Henderson, W. A. TI Microbial translocation in IBS; relevance of sex, stress, and IBS subtype SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Weaver, K. R.; Fourie, N. H.; Abey, S. K.; Sherwin, L. B.; Henderson, W. A.] NINR, NIH, Bethesda, MD 20892 USA. [Weaver, K. R.] NYU, Coll Nursing, New York, NY USA. [Sherwin, L. B.] Univ Missouri, Sch Nursing, Columbia, MO 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 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD AUG PY 2016 VL 28 SU 1 SI SI MA 92 BP 33 EP 33 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DV9VS UT WOS:000383290900092 ER PT J AU Sherwin, LB Henderson, WA Leary, E AF Sherwin, L. B. Henderson, W. A. Leary, E. TI The influence of catastrophizing on psychosocial and functional outcomes in irritable bowel syndrome SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Sherwin, L. B.; Leary, E.] Univ Missouri, Columbia, MO USA. [Sherwin, L. B.; Henderson, W. A.] 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 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD AUG PY 2016 VL 28 SU 1 SI SI MA 202 BP 62 EP 62 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DV9VS UT WOS:000383290900198 ER PT J AU Fourie, NH Wang, D Abey, SK Creekmore, AL Hong, S Wiley, JW Henderson, WA AF Fourie, N. H. Wang, D. Abey, S. K. Creekmore, A. L. Hong, S. Wiley, J. W. Henderson, W. A. TI Structural and functional alterations in the colonic microbiome in a chronic stress rat model of irritable bowel syndrome SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Fourie, N. H.; Wang, D.; Abey, S. K.; Henderson, W. A.] DHHS, Div Intramural Res, Digest Disorders Unit, NIH, Bethesda, MD USA. [Creekmore, A. L.; Hong, S.; Wiley, J. W.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 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 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD AUG PY 2016 VL 28 SU 1 SI SI MA 323 BP 95 EP 95 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DV9VS UT WOS:000383290900317 ER PT J AU Mellem, MS Jasmin, KM Peng, C Martin, A AF Mellem, Monika S. Jasmin, Kyle M. Peng, Cynthia Martin, Alex TI Sentence processing in anterior superior temporal cortex shows a social-emotional bias SO NEUROPSYCHOLOGIA LA English DT Article DE Affective; Emotion; fMRI; Language; Social brain ID FUNCTIONAL CONNECTIVITY; PHYSIOLOGICAL NOISE; SEMANTIC MEMORY; 1.5 T; LOBES; BRAIN; COGNITION; REPRESENTATION; MODULATION; KNOWLEDGE AB The anterior region of the left superior temporal gyms/superior temporal sulcus (aSTG/STS) has been implicated in two very different cognitive functions: sentence processing and social-emotional processing. However, the vast majority of the sentence stimuli in previous reports have been of a social or social-emotional nature suggesting that sentence processing may be confounded with semantic content. To evaluate this possibility we had subjects read word lists that differed in phrase/constituent size (single words, 3-word phrases, 6-word sentences) and semantic content (social-emotional, social, and inanimate objects) while scanned in a 7 T environment. This allowed us to investigate if the aSTG/STS responded to increasing constituent structure (with increased activity as a function of constituent size) with or without regard to a specific domain of concepts, i.e., social and/or social-emotional content. Activity in the left aSTG/STS was found to increase with constituent size. This region was also modulated by content, however, such that social-emotional concepts were preferred over social and object stimuli. Reading also induced content type effects in domain-specific semantic regions. Those preferring social-emotional content included aSTG/STS, inferior frontal gyrus, posterior STS, lateral fusiform, ventromedial prefrontal cortex, and amygdala, regions included in the "social brain", while those preferring object content included parahippocampal gyrus, retrosplenial cortex, and caudate, regions involved in object processing. These results suggest that semantic content affects higher-level linguistic processing and should be taken into account in future studies. (C) 2016 Published by Elsevier Ltd. C1 [Mellem, Monika S.; Jasmin, Kyle M.; Peng, Cynthia; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Jasmin, Kyle M.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. RP Mellem, MS (reprint author), Bldg 10,Room 4C-104 MSC 1366, Bethesda, MD 20892 USA. EM monika.mellem@nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health FX We thank Sophie Wohltjen for help with data analysis and Steve Gotts for helpful discussions. This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, and it was conducted under NIH Clinical Study Protocol 93-M-0170 (ZIAMH002588); NCT00001360. NR 53 TC 0 Z9 0 U1 6 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD AUG PY 2016 VL 89 BP 217 EP 224 DI 10.1016/j.neuropsychologia.2016.06.019 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DV5XD UT WOS:000383003100020 PM 27329686 ER PT J AU Kang, L Liu, AY Tian, LL AF Kang, Le Liu, Aiyi Tian, Lili TI Linear combination methods to improve diagnostic/prognostic accuracy on future observations SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article DE Multiple biomarkers; receiver operating characteristic curve; area under the receiver operating characteristic curve; linear combination; diagnostic; prognostic accuracy ID OPERATING CHARACTERISTIC CURVE; LOGISTIC-REGRESSION; DISCRIMINANT-ANALYSIS; BIOMARKERS; CLASSIFICATION; PROBABILITY; EFFICIENCY; INFERENCE; SUBJECT; MARKERS AB Multiple diagnostic tests or biomarkers can be combined to improve diagnostic accuracy. The problem of finding the optimal linear combinations of biomarkers to maximise the area under the receiver operating characteristic curve has been extensively addressed in the literature. The purpose of this article is threefold: (1) to provide an extensive review of the existing methods for biomarker combination; (2) to propose a new combination method, namely, the nonparametric stepwise approach; (3) to use leave-one-pair-out cross-validation method, instead of re-substitution method, which is overoptimistic and hence might lead to wrong conclusion, to empirically evaluate and compare the performance of different linear combination methods in yielding the largest area under receiver operating characteristic curve. A data set of Duchenne muscular dystrophy was analysed to illustrate the applications of the discussed combination methods. C1 [Kang, Le] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD USA. [Tian, Lili] SUNY Buffalo, Dept Biostat, 706 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. RP Tian, LL (reprint author), SUNY Buffalo, Dept Biostat, 706 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. EM ltian@buffalo.edu OI Liu, Aiyi/0000-0002-6618-5082 FU US Department of Energy; US Food and Drug Administration; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX Le Kang was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. Aiyi Liu was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. The opinions expressed are solely those of the authors and not necessarily those of the Editors. The authors thank the referees for helpful discussion and comments. A supplementary R code to implement the methods described in this article is in the Appendix. NR 32 TC 4 Z9 4 U1 8 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD AUG PY 2016 VL 25 IS 4 SI SI BP 1359 EP 1380 DI 10.1177/0962280213481053 PG 22 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA DV4CA UT WOS:000382871200018 PM 23592714 ER PT J AU Cervenakoya, L Saa, P Yakoyleva, O Vasilyeva, I de Castro, J Brown, P Dodd, R AF Cervenakoya, Larisa Saa, Paula Yakoyleva, Oksana Vasilyeva, Irina de Castro, Jorge Brown, Paul Dodd, Roger TI Are prions transported by plasma exosomes? SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Review DE Prion protein; Blood; Plasma; Extracellular vesicles; Prion infectivity ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; MISFOLDING CYCLIC AMPLIFICATION; CHRONIC WASTING DISEASE; INFECTIOUS PRIONS; EXTRACELLULAR VESICLES; BLOOD INFECTIVITY; PROTEIN; VARIANT; SCRAPIE AB Blood has been shown to contain disease-associated misfolded prion protein (PrPTsE) in animals naturally and experimentally infected with various transmissible spongiform encephalopathy (TSE) agents, and in humans infected with variant Creutzfeldt-Jakob disease (vCJD). Recently, we have demonstrated PrPTsE in extracellular vesicle preparations (EVs) containing exosomes from plasma of mice infected with mouse-adapted vCJD by Protein Misfolding Cyclic Amplification (PMCA). Here we report the detection of PrPTsE by PMCA in EVs from plasma of mice infected with Fukuoka-1 (FU), an isolate from a Gerstmann-Straussler-Scheinker disease patient. We used Tga20 transgenic mice that over-express mouse cellular prion protein, to assay by intracranial injections the level of infectivity in a FU infected brain homogenate from wild-type mice (FU-BH), and in blood cellular components (BCC), consisting of red blood cells, white blood cells and platelets, plasma EVs, and plasma EVs subjected to multiple rounds of PMCA. Only FU-BH and plasma EVs from FU-infected mice subjected to PMCA that contained PrPTsE transmitted disease to Tga20 mice. Plasma EVs not subjected to PMCA and BCC from FU-infected mice failed to transmit disease. These findings confirm the high sensitivity of PMCA for PrPTsE detection in plasma EVs and the efficiency of this in vitro method to produce highly infectious prions. The results of our study encourage further research to define the role of EVs and, more specifically exosomes, as blood-borne carriers of PrPTsE. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Cervenakoya, Larisa; Saa, Paula; Yakoyleva, Oksana; Vasilyeva, Irina; de Castro, Jorge; Dodd, Roger] Amer Natl Red Cross, Sci Affairs, Rockville, MD USA. [Yakoyleva, Oksana] US FDA, Lab Bacterial & Transmissible Spongiforrn Encepha, DETTD, OBRR,CBER, Silver Spring, MD USA. [de Castro, Jorge] Meso Scale Diagnost LLC, Rockville, MD USA. [Brown, Paul] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Cervenakoya, L (reprint author), Amer Natl Red Cross, Sci Affairs, JH Holland Lab, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM larisa.cervenakova@redcross.org FU Fondation pour la Recherche Medicale/Foundation Alliance BioSecure, France; American National Red Cross FX We are grateful to Professor Charles Weissmann for permission to use Tga20 mice and Prnp0/0 mice, Dr. Ragy Ragheb (Malvern Instruments) for NTA analysis of mouse plasma EV samples, Mr. Carroll McKenzie and Mr. Anton Cervenak for excellent technical assistance, and Mr. Craig Mayer and Mr. Ward B. Cunningham for daily animal care. This study was funded by the Fondation pour la Recherche Medicale/Foundation Alliance BioSecure, France and by the American National Red Cross. NR 87 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD AUG PY 2016 VL 55 IS 1 BP 70 EP 83 DI 10.1016/j.transci.2016.07.013 PG 14 WC Hematology SC Hematology GA DV5YW UT WOS:000383007600010 PM 27499183 ER PT J AU Christophersen, IE Yin, XY Larson, MG Lubitz, SA Magnani, JW McManus, DD Ellinor, PT Benjamin, EJ AF Christophersen, Ingrid E. Yin, Xiaoyan Larson, Martin G. Lubitz, Steven A. Magnani, Jared W. McManus, David D. Ellinor, Patrick T. Benjamin, Emelia J. TI A comparison of the CHARGE-AF and the CHA(2)DS(2)-VASc risk scores for prediction of atrial fibrillation in the Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID PROPORTIONAL HAZARDS MODEL; AFRICAN-AMERICANS; SURVIVAL ANALYSIS; COMPETING RISKS; ISCHEMIC-STROKE; CHADS(2); COHORT; VALIDATION; OUTCOMES; SUBDISTRIBUTION AB Background Atrial fibrillation (AF) affects more than 33 million individuals worldwide and increases risks of stroke, heart failure, and death. The CHARGE-AF risk score was developed to predict incident AF in three American cohorts and it was validated in two European cohorts. The CHA(2)DS(2)-VASc risk score was derived to predict risk of stroke, peripheral embolism, and pulmonary embolism in individuals with AF, but it has been increasingly used for AF risk prediction. We compared CHARGE-AF risk score versus CHA(2)DS(2)-VASc risk score for incident AF risk in a community-based cohort. Methods and Results We studied Framingham Heart Study participants aged 46 to 94 years without prevalent AF and with complete covariates. We predicted AF risk using Fine-Gray proportional sub-distribution hazards regression. We used the Wald chi(2) statistic for model fit, C-statistic for discrimination, and Hosmer-Lemeshow (HL) chi(2) statistic for calibration. We included 9722 observations (mean age 63.9 +/- 10.6 years, 56% women) from 4548 unique individuals: 752 (16.5%) developed incident AF and 793 (17.4%) died. The mean CHARGE-AF score was 12.0 +/- 1.2 and the sub-distribution hazard ratio (sHR) for AF per unit increment was 2.15 (95% CI, 99-131%; P <.0001). The mean CHA(2)DS(2)-VASc score was 2.0 +/- 1.5 and the sHR for AF per unit increment was 1.43 (95% CI, 37%-51%; P<.0001). The CHARGE-AF model had better fit than CHA(2)DS(2)-VASc (Wald chi(2) = 403 vs 209, both with 1 df), improved discrimination (C-statistic = 0.75, 95% CI, 0.73-0.76 vs C-statistic = 0.71, 95% CI, 0.69-0.73), and better calibration (HL chi(2) = 5.6, P =.69 vs HL chi(2) = 28.5, P <.0001). Conclusion The CHARGE-AF risk score performed better than the CHA(2)DS(2)-VASc risk score at predicting AF in a community-based cohort. C1 [Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Christophersen, Ingrid E.] Vestre Viken Hosp Trust, Brum Hosp, Dept Med Res, Drammen, Norway. [Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02215 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Cardiovasc Med Div, Worcester, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.; Benjamin, EJ (reprint author), Boston Univ, Sch Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu FU Bayer HealthCare FX Dr Ellinor is a principal investigator on a grant from Bayer HealthCare to the Broad Institute. NR 52 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD AUG PY 2016 VL 178 BP 45 EP 54 DI 10.1016/j.ahj.2016.05.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT6JK UT WOS:000381590300006 PM 27502851 ER PT J AU Inaguma, S Wang, ZF Lasota, J Sarlomo-Rikala, M McCue, PA Ikeda, H Miettinen, M AF Inaguma, Shingo Wang, Zengfeng Lasota, Jerzy Sarlomo-Rikala, Maarit McCue, Peter A. Ikeda, Hiroshi Miettinen, Markku TI Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1) Analysis in 5536 Cases Revealed Consistent Expression in Trophoblastic Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE programmed cell death ligand 1 (PD-L1); immunohistochemistry; choriocarcinoma; classical Hodgkin lymphoma; anaplastic large cell lymphoma (ALCL); schwannoma; mismatch-repair deficiency; Epstein-Barr virus ID EPSTEIN-BARR-VIRUS; B7-H1 EXPRESSION; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; HODGKIN LYMPHOMA; B7 FAMILY; NIVOLUMAB; MEMBER; IMMUNOSUPPRESSION AB Programmed cell death 1/programmed cell death ligand (PD-1/PD-Ls) axis is crucial for the modulation of immune responses and self-tolerance. Also, aberrant PD-L1 expression on the tumor cells or tumor-associated inflammatory cells accelerates immune evasion of tumor cells. In the past decade, PD-1/PD-L immune checkpoint inhibitors were introduced to cancer treatment trials and, in some cases, showed significant anticancer effects. PD-L1 immunohistochemical staining is considered a potential predictor of clinical response to PD-1/PD-L immune checkpoint inhibitor treatment. However, immunohistochemical data on PD-L1 expression in different types of cancer especially rare entities remain incomplete. In this study, PD-L1 expression was immunohistochemically analyzed in 5536 tumors including germ cell, epithelial, mesenchymal, melanocytic/neuroectodermal, and lymphohematopoietic tumors, as well as in a set of human normal tissues including a fetus. Immunohistochemical analysis was performed with E1L3N rabbit monoclonal antibody and Leica Bond Max automation using multitumor blocks containing up to 70 tumor samples. PD-L1 was constitutively and strongly expressed in placental trophoblasts as well as choriocarcinomas and trophoblastic components of germ cell tumors. Also, the neoplastic cells of classical Hodgkin lymphoma, anaplastic large cell lymphoma, schwannoma, thymoma, and squamous cell carcinoma of various sites frequently expressed PD-L1. In gastrointestinal adenocarcinomas, PD-L1-expression was associated with EBER positivity and mismatch-repair deficiency. In addition, PD-L1 was variably expressed in non-neoplastic macrophages and dendritic cells. PD-L1 immunohistochemistry may have some role in the immunophenotypic differential diagnosis of tumors and pinpointing potential candidates for anti-PD-1/PD-L immune checkpoint therapy. C1 [Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy; Miettinen, Markku] NCI, Pathol Lab, Bldg 10,Room B1B47,Ctr Dr 10, Bethesda, MD 20892 USA. [McCue, Peter A.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Cell Biol & Anat, Philadelphia, PA 19107 USA. [McCue, Peter A.] Univ Hosp, Philadelphia, PA USA. [Inaguma, Shingo; Ikeda, Hiroshi] Aichi Med Univ, Sch Med, Dept Pathol, Nagakute, Aichi, Japan. [Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, Dept Pathol, Haartman Inst, Helsinki, Finland. [Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, HusLab, Helsinki, Finland. RP Inaguma, S (reprint author), NCI, Pathol Lab, Bldg 10,Room B1B47,Ctr Dr 10, Bethesda, MD 20892 USA. EM inaguma@aichi-med-u.ac.jp FU National Cancer Institute's intramural research program FX Supported as a part of National Cancer Institute's intramural research program. The authors have disclosed that they have no relationships with, or financial interest in, any commercial companies pertaining to this article. NR 39 TC 6 Z9 6 U1 9 U2 9 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 AUG PY 2016 VL 40 IS 8 BP 1133 EP 1142 DI 10.1097/PAS.0000000000000653 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA DT4CT UT WOS:000381428400016 PM 27158757 ER PT J AU Rice, TA Brenner, TA Percopo, CM Ma, M Keicher, JD Domachowske, JB Rosenberg, HF AF Rice, Tyler A. Brenner, Todd A. Percopo, Caroline M. Ma, Michelle Keicher, Jesse D. Domachowske, Joseph B. Rosenberg, Helene F. TI Signaling via pattern recognition receptors NOD2 and TLR2 contributes to immunomodulatory control of lethal pneumovirus infection SO ANTIVIRAL RESEARCH LA English DT Article DE Inflammation; Cytokines; Pattern recognition receptors; Pneumovirus; Probiotic ID RESPIRATORY SYNCYTIAL VIRUS; TOLL-LIKE RECEPTORS; MOUSE LUNG-TISSUE; MICE PVM MODEL; TRAINED IMMUNITY; VIRAL BRONCHIOLITIS; TRACT INFECTIONS; PNEUMONIA VIRUS; INNATE IMMUNITY; RESPONSES AB Pattern recognition receptors (PRRs) engage microbial components in the lung, although their role in providing primary host defense against respiratory virus infection is not fully understood. We have previously shown that Gram-positive Lactobacillus plantarum (Lp) administered to the respiratory tract promotes full and sustained protection in response to an otherwise lethal mouse pneumovirus (PVM) infection, a robust example of heterologous immunity. While Lp engages PRRs TLR2 and NOD2 in ex vivo signaling assays, we found that Lp-mediated protection was unimpaired in single gene-deleted TLR2(-/-) and NOD2(-/-) mice. Here we demonstrate substantial loss of Lp-mediated protection in a double gene deleted NOD2(-/-)TLR2(-/-) strain. Furthermore, we demonstrate protection against PVM infection by administration of the bi-functional NOD2 TLR2 agonist, CL-429. The bi-functional NOD2-TLR2 ligand CL 429 not only suppresses virus-induced inflammation, it is significantly more effective at preventing lethal infection than equivalent amounts of mono-molecular TLR2 and NOD2 agonists. Interestingly, and in contrast to biochemical NOD2 and/or TLR2 agonists, Lp remained capable of eliciting primary proinflammatory responses from NOD2(-/-)TLR2(-/-) mice in vivo and from alveolar macrophages challenged ex vivo. Taken together, we conclude that coordinate engagement of NOD2 and TLR2 constitutes a key step in the genesis of Lp-mediated protection from a lethal respiratory virus infection, and represents a critical target for modulation of virus-induced inflammatory pathology. Published by Elsevier B.V. C1 [Rice, Tyler A.; Brenner, Todd A.; Percopo, Caroline M.; Ma, Michelle; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Keicher, Jesse D.] GlaxoSmithKline, Drug Discovery Infect Dis, Res Triangle Pk, NC 27709 USA. [Domachowske, Joseph B.] SUNY Upstate Med Ctr, Div Infect Dis, Dept Pediat, Syracuse, NY 13210 USA. [Rice, Tyler A.] Yale Univ, Grad Dept Immunobiol, New Haven, CT USA. [Keicher, Jesse D.] Symmune Therapeut, Durham, NC 27701 USA. RP Rosenberg, HF (reprint author), NIAID, NIH, Bldg 10,Room 11C215 MSC 1883,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU NIAID Division of Intramural Research [AI000943] FX This manuscript is dedicated to Dr. Kimberly D. Dyer and include our wishes for her speedy recovery. The work herein was supported by funds from NIAID Division of Intramural Research (AI000943) to HFR. NR 64 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD AUG PY 2016 VL 132 BP 131 EP 140 DI 10.1016/j.antiviral.2016.06.002 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA DU6SO UT WOS:000382345100018 PM 27312104 ER PT J AU Robinson, LM Waran, NK Leach, MC Morton, FB Paukner, A Lonsdorf, E Handel, I Wilson, VAD Brosnan, SF Weiss, A AF Robinson, Lauren M. Waran, Natalie K. Leach, Matthew C. Morton, F. Blake Paukner, Annika Lonsdorf, Elizabeth Handel, Ian Wilson, Vanessa A. D. Brosnan, Sarah F. Weiss, Alexander TI Happiness is positive welfare in brown capuchins (Sapajus apella) SO APPLIED ANIMAL BEHAVIOUR SCIENCE LA English DT Article DE Capuchin; Personality; Primate; Stereotypy; Subjective well-being; Welfare ID MACAQUES MACACA-MULATTA; QUALITY-OF-LIFE; ANIMAL-WELFARE; RHESUS MACAQUES; CEBUS-APELLA; PERSONALITY; BEHAVIOR; RATINGS; MONKEYS; HEALTH AB Questionnaires that allow people who are familiar with individual animals to rate the welfare of these animals are an underutilised tool. We designed a 12-item welfare questionnaire and tested its reliability and associations with subjective well-being (SWB), locomotor stereotypy, and personality traits. The welfare questionnaire included questions relating to physical health, stress and coping, satisfaction with social relationships, psychological stimulation, and the display of positive and negative welfare indicators. We collected ratings of 66 brown capuchins (Sapajus apella) living in three facilities. Each capuchin was rated on the welfare questionnaire by an average of 2.8 raters. The interrater reliability of the welfare questionnaire items ranged from ICC(3,k) 0.51 to 0.86. A principal components analysis indicated that the 12 welfare items loaded onto one component. We repeated this process with the welfare and four items used to measure subjective well-being and found all the items were defined by a single component (welfareSWB). We then conducted three sets of analyses, one predicting the welfare component, one predicting the SWB component, and predicting the welfareSWB component. The independent variables were frequency of locomotor stereotypy, personality, age, and sex; facility was included as a random effect. In models including stereotypy, age, and sex we found frequency of stereotypy to be significantly associated with all three predicted components (ps < 0.01). After controlling for stereotypy (b = -0.25, p = 0.17), age (b = -0.54, p = 0.01), and sex (b = -0.32, p = 0.07), the personality traits of Sociability (b = 1.02, p < 0.001), Assertiveness, (b = 0.63, p < 0.001), and Attentiveness (b = 0.54, p = 0.01) were associated with higher scores on the joint welfareSWB component; Neuroticism was negatively associated with welfare SWB (b = -0.60, p = 0.01). Our results suggest that welfare questionnaires is a useful, reliable, and valid tool for primate welfare assessment. (C) 2016 Elsevier B.V. All rights reserved. C1 [Robinson, Lauren M.; Wilson, Vanessa A. D.; Weiss, Alexander] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. [Robinson, Lauren M.; Waran, Natalie K.] Univ Edinburgh, Royal Dick Sch Vet Studies, Jeanne Marchig Int Ctr Anim Welf Educ, Easter Bush Vet Ctr, Roslin EH25 9RG, Midlothian, Scotland. [Robinson, Lauren M.; Morton, F. Blake; Wilson, Vanessa A. D.; Weiss, Alexander] Scottish Primate Res Grp, Edinburgh, Midlothian, Scotland. [Leach, Matthew C.] Newcastle Univ, Food & Rural Dev, Sch Agr, Agr Bldg, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Morton, F. Blake; Lonsdorf, Elizabeth] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17603 USA. [Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Dickerson, MD 20842 USA. [Handel, Ian] Univ Edinburgh, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland. [Handel, Ian] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9RG, Midlothian, Scotland. [Brosnan, Sarah F.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RP Robinson, LM (reprint author), Univ Edinburgh, Sch Philosophy Psychol & Language Sci, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. EM l.robinson@ed.ac.uk NR 61 TC 0 Z9 0 U1 7 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1591 EI 1872-9045 J9 APPL ANIM BEHAV SCI JI Appl. Anim. Behav. Sci. PD AUG PY 2016 VL 181 BP 145 EP 151 DI 10.1016/j.applanim.2016.05.029 PG 7 WC Agriculture, Dairy & Animal Science; Behavioral Sciences; Veterinary Sciences SC Agriculture; Behavioral Sciences; Veterinary Sciences GA DT0KB UT WOS:000381171300019 ER PT J AU Dorans, KS Wilker, EH Li, WY Rice, MB Ljungman, PL Schwartz, J Coull, BA Kloog, I Koutrakis, P D'Agostino, RB Massaro, JM Hoffmann, U O'Donnell, CJ Mittleman, MA AF Dorans, Kirsten S. Wilker, Elissa H. Li, Wenyuan Rice, Mary B. Ljungman, Petter L. Schwartz, Joel Coull, Brent A. Kloog, Itai Koutrakis, Petros D'Agostino, Ralph B., Sr. Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. Mittleman, Murray A. TI Residential Proximity to Major Roads, Exposure to Fine Particulate Matter, and Coronary Artery Calcium: The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE air pollution; atherosclerosis; coronary artery calcium; epidemiology; multidetector computed tomography ID LONG-TERM EXPOSURE; INTIMA-MEDIA THICKNESS; ACUTE MYOCARDIAL-INFARCTION; AIR-POLLUTION; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT; ATHEROSCLEROSIS; ASSOCIATION; METAANALYSIS; MORTALITY AB Objective Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study. Approach and Results We measured CAC 2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with log(e)(CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable. Conclusions Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter. C1 [Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Schwartz, Joel; Mittleman, Murray A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wilker, Elissa H.; Schwartz, Joel; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Rice, Mary B.; Ljungman, Petter L.; Mittleman, Murray A.] Harvard Med Sch, Cardiovasc Epidemiol Res Unit, Dept Cardiol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rice, Mary B.] Harvard Med Sch, Div Pulm Crit Care & Sleep Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hoffmann, Udo] Harvard Med Sch, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Med Sch, Cardiovasc Med, Brigham & Womens Hosp, Boston, MA USA. [Ljungman, Petter L.] Karolinska Inst, Inst Environm Med, Environm Epidemiol Unit, Stockholm, Sweden. [Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, Beer Sheva, Israel. [D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, Christopher J.] Boston Vet Adm Hlth Syst, Cardiol Sect, Dept Med, Boston, MA USA. RP Mittleman, MA (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave,Suite 505, Boston, MA 02215 USA. EM mmittlem@hsph.harvard.edu OI Dorans, Kirsten/0000-0002-3182-5633 FU National Institutes of Health (NIH) [NHLBI T32 HL007575, NIEHS R00 ES022243, K23ES026204]; US Environmental Protection Agency [RD-83479801, RD-83587201]; NHLBI's Framingham Heart Study [HHSN268201500001I] FX This work was supported by the National Institutes of Health (NIH; NHLBI T32 HL007575; NIEHS R00 ES022243, K23ES026204). This publication was made possible by US Environmental Protection Agency grants RD-83479801 and RD-83587201. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US Environmental Protection Agency. Further, US Environmental Protection Agency does not endorse the purchase of any commercial products or services mentioned in the publication. From the Framingham Heart Study of the NHLBI of the NIH and Boston University School of Medicine; this work was supported by the NHLBI's Framingham Heart Study (Contract No. HHSN268201500001I). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI, the NIH, or the US Department of Health and Human Services. NR 34 TC 3 Z9 3 U1 2 U2 2 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 AUG PY 2016 VL 36 IS 8 BP 1679 EP 1685 DI 10.1161/ATVBAHA.116.307141 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DT4TM UT WOS:000381474000025 PM 27312220 ER PT J AU Yamada, Y Schneider, JP AF Yamada, Yuji Schneider, Joel P. TI Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules SO BIOMACROMOLECULES LA English DT Article ID DOXORUBICIN CONJUGATE; DELIVERY; NANOPARTICLES; DEXTRAN; PHARMACOKINETICS; THERAPEUTICS; CARRIER AB Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOXPDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (similar to 10 kPa) and adherent (adhesive stress similar to 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death. C1 [Yamada, Yuji; Schneider, Joel P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA. RP Schneider, JP (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA. EM joel.schneider@nih.gov FU JSPS Fellowship for Japanese Biomedical and Behavioral Researcher at NIH (KAITOKU-NIH); Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This research was supported by a JSPS Fellowship for Japanese Biomedical and Behavioral Researcher at NIH (KAITOKU-NIH) and the Intramural Research Program of the National Cancer Institute, National Institutes of Health. We thank Dr. Michael Giano for collecting the fibrin glue maximal adhesive stress data. NR 20 TC 0 Z9 0 U1 18 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 EI 1526-4602 J9 BIOMACROMOLECULES JI Biomacromolecules PD AUG PY 2016 VL 17 IS 8 BP 2634 EP 2641 DI 10.1021/acs.biomac.6b00701 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA DT1HF UT WOS:000381231600014 PM 27388026 ER PT J AU Fink, BC Steele, VR Maurer, MJ Fede, SJ Calhoun, VD Kiehl, KA AF Fink, Brandi C. Steele, Vaughn R. Maurer, Michael J. Fede, Samantha J. Calhoun, Vince D. Kiehl, Kent A. TI Brain potentials predict substance abuse treatment completion in a prison sample SO BRAIN AND BEHAVIOR LA English DT Article DE Event-related potentials; pattern classifier; principal component analysis; prison inmate; substance abuse treatment; support vector machine ID FOLLOW-UP OUTCOMES; WORKING-MEMORY; DRUG-ABUSE; DEPENDENT INDIVIDUALS; PATTERN-RECOGNITION; P300 DECREMENTS; TASK; COMPONENT; COCAINE; RESPONSES AB IntroductionNational estimates suggest that up to 80% of prison inmates meet diagnostic criteria for a substance use disorder. Because more substance abuse treatment while incarcerated is associated with better post-release outcomes, including a reduced risk of accidental overdose death, the stakes are high in developing novel predictors of substance abuse treatment completion in inmate populations. MethodsUsing electroencephalography (EEG), this study investigated stimulus-locked ERP components elicited by distractor stimuli in three tasks (VO-Distinct, VO-Repeated, Go/NoGo) as a predictor of treatment discontinuation in a sample of male and female prison inmates. We predicted that those who discontinued treatment early would exhibit a less positive P3a amplitude elicited by distractor stimuli. ResultsOur predictions regarding ERP components were partially supported. Those who discontinued treatment early exhibited a less positive P3a amplitude and a less positive PC4 in the VO-D task. In the VO-R task, however, those who discontinued treatment early exhibited a more negative N200 amplitude rather than the hypothesized less positive P3a amplitude. The discontinuation group also displayed less positive PC4 amplitude. Surprisingly, there were no time-domain or principle component differences among the groups in the Go/NoGo task. Support Vector Machine (SVM) models of the three tasks accurately classified individuals who discontinued treatment with the best model accurately classifying 75% of inmates. PCA techniques were more sensitive in differentiating groups than the classic time-domain windowed approach. ConclusionsOur pattern of findings are consistent with the context-updating theory of P300 and may help identify subtypes of ultrahigh-risk substance abusers who need specialized treatment programs. C1 [Fink, Brandi C.] Univ New Mexico, Clin & Translat Sci Ctr, Dept Psychiat & Behav Sci, Albuquerque, NM 87131 USA. [Steele, Vaughn R.] NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD USA. [Steele, Vaughn R.; Maurer, Michael J.; Fede, Samantha J.; Calhoun, Vince D.; Kiehl, Kent A.] Mind Res Network & Lovelace Biomed & Environm Res, Albuquerque, NM USA. [Steele, Vaughn R.; Maurer, Michael J.; Fede, Samantha J.; Kiehl, Kent A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Fink, BC (reprint author), Univ New Mexico, Dept Psychiat & Behav Sci, MSC 09 5030, Albuquerque, NM 87131 USA. EM bcfink@unm.edu FU National Institute on Alcohol Abuse and Alcoholism [R21 AA022367]; National Center for Advancing Translational Sciences [KL2 TR001448, UL1 TR001449]; Intramural Research Program of the National Institute on Drug Abuse, National Institute on Drug Abuse [R01 DA020870-01] FX National Institute on Alcohol Abuse and Alcoholism (Grant/Award Number: R21 AA022367), National Center for Advancing Translational Sciences (Grant/Award Number: KL2 TR001448, UL1 TR001449), Intramural Research Program of the National Institute on Drug Abuse, National Institute on Drug Abuse (Grant/Award Number: R01 DA020870-01). NR 52 TC 0 Z9 0 U1 3 U2 3 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 AUG PY 2016 VL 6 IS 8 AR e00501 DI 10.1002/brb3.501 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DV1JK UT WOS:000382676900013 PM 27547503 ER PT J AU Sheng, Y Filichia, E Shick, E Preston, KL Phillips, KA Cooperman, L Lin, ZC Tesar, P Hoffer, B Luo, Y AF Sheng, Yang Filichia, Emily Shick, Elizabeth Preston, Kenzie L. Phillips, Karran A. Cooperman, Leslie Lin, Zhicheng Tesar, Paul Hoffer, Barry Luo, Yu TI Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics SO BRAIN AND BEHAVIOR LA English DT Article DE 3 VNTR; hDAT gene; iPSCs; opioid dependent ID PLURIPOTENT STEM-CELLS; VENTRAL TEGMENTAL AREA; TRANSPORTER GENE DAT1; VALPROIC ACID; PARKINSONS-DISEASE; MAINTENANCE TREATMENT; RECEPTOR EXPRESSION; HUNTINGTONS-DISEASE; SUBSTANTIA-NIGRA; CLINICAL-TRIAL AB IntroductionThe dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. MethodsIn this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3 VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. ResultsWe present the first evidence suggesting that the 3 VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. ConclusionsOur data suggest that human iPSC-derived DA neurons may be useful in invitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development. C1 [Sheng, Yang; Filichia, Emily; Hoffer, Barry; Luo, Yu] Case Western Reserve Univ, Dept Neurol Surg, Cleveland, OH 44106 USA. [Shick, Elizabeth; Cooperman, Leslie; Tesar, Paul] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Preston, Kenzie L.; Phillips, Karran A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Lin, Zhicheng] Harvard Univ, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. RP Luo, Y (reprint author), Case Western Reserve Univ, Dept Neurol Surg, Cleveland, OH 44106 USA. EM yxl710@case.edu FU NIH, NIDA [R21DA032962, R01DA021409]; National Institute on Drug Abuse, National Institutes of Health FX This study was supported by NIH, NIDA (R21DA032962, R01DA021409) and by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 61 TC 0 Z9 0 U1 3 U2 3 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 AUG PY 2016 VL 6 IS 8 AR e00491 DI 10.1002/brb3.491 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DV1JK UT WOS:000382676900006 PM 27547496 ER PT J AU Parekh, PR Choudhuri, R Weyemi, U Martin, OA Bonner, WM Redon, CE AF Parekh, Palak R. Choudhuri, Rohini Weyemi, Urbain Martin, Olga A. Bonner, William M. Redon, Christophe E. TI Evaluation of surrogate tissues as indicators of drug activity in a melanoma skin model SO CANCER MEDICINE LA English DT Article DE Apoptosis; drug response; melanoma tissue model; surrogate tissue; H2 AX ID PHASE-II TRIAL; ONCOLOGY CLINICAL-TRIALS; HUMAN PROSTATE TISSUE; DOUBLE-STRAND BREAKS; DNA-DAMAGE; INHIBITOR SELUMETINIB; H2AX PHOSPHORYLATION; COMBINATION THERAPY; GAMMA-H2AX ASSAY; RANDOMIZED-TRIAL AB The development of novel cancer treatments is a challenging task, partly because results from model systems often fail to predict drug efficacy in humans, and also tumors are often inaccessible for biochemical analysis, preventing effective monitoring of drug activity in vivo. Utilizing a model system, we evaluated the use of drug-induced DNA damage in surrogate tissues as indicators of drug efficacy. Samples of a commercially available melanoma skin model (Mattek MLNM-FT-A375) containing keratinocyte and fibroblast layers with melanoma nodules were subjected to various chemotherapeutic regimens for one, four, or eight days. At these times they were analyzed for DNA double-stranded breaks (H2AX foci) and apoptosis (TUNEL). A wide range of drug responses in both tumor and normal tissues were observed and cataloged. For the melanoma, the most common drug response was apoptosis. The basal keratinocyte layer, which was the most reliable indicator of drug response in the melanoma skin model, responded with H2AX foci formation that was abrupt and transient. The relationships between tumor and surrogate tissue drug responses are complex, indicating that while surrogate tissue drug responses may be useful clinical tools, careful control of variables such as the timing of sampling may be important in interpreting the results. C1 [Parekh, Palak R.] Univ Maryland, Sch Med, Dept Radiat Oncol, Greenbaum Canc Ctr, 655 W Baltimore St,Bressler Res Bldg,Rm 10-010, Baltimore, MD 21201 USA. [Parekh, Palak R.; Choudhuri, Rohini; Weyemi, Urbain; Martin, Olga A.; Bonner, William M.; Redon, Christophe E.] NCI, Genom Integr Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Choudhuri, Rohini] Univ Maryland, College Pk, MD 20742 USA. [Martin, Olga A.] Univ Melbourne, Div Radiat Oncol, Melbourne, Vic, Australia. [Martin, Olga A.] Univ Melbourne, Peter MacCallum Canc Ctr, Canc Imaging & Mol Radiat Biol Lab, Melbourne, Vic, Australia. [Martin, Olga A.] Univ Melbourne, Dept Oncol, Melbourne, Vic, Australia. RP Parekh, PR (reprint author), Univ Maryland, Sch Med, Dept Radiat Oncol, Greenbaum Canc Ctr, 655 W Baltimore St,Bressler Res Bldg,Rm 10-010, Baltimore, MD 21201 USA. EM pparekh@som.umaryland.edu FU Intramural Research Program of the National Cancer Institute; Center for Cancer Research; National Institutes of Health FX This work was funded by the Intramural Research Program of the National Cancer Institute, the Center for Cancer Research, the National Institutes of Health. NR 42 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 5 IS 8 BP 1731 EP 1741 DI 10.1002/cam4.726 PG 11 WC Oncology SC Oncology GA DS6XM UT WOS:000380926600002 PM 27339860 ER PT J AU Shea, A Harish, V Afzal, Z Chijioke, J Kedir, H Dusmatova, S Roy, A Ramalinga, M Harris, B Blancato, J Verma, M Kumar, D AF Shea, Amanda Harish, Varsha Afzal, Zainab Chijioke, Juliet Kedir, Habib Dusmatova, Shahnoza Roy, Arpita Ramalinga, Malathi Harris, Brent Blancato, Jan Verma, Mukesh Kumar, Deepak TI MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics SO CANCER MEDICINE LA English DT Review DE cancer therapy; microRNA; glioblastoma multiforme ID GLIOMA STEM-CELLS; GROWTH-FACTOR RECEPTOR; OLIGONUCLEOTIDE ENHANCES CHEMOSENSITIVITY; EPITHELIAL-MESENCHYMAL TRANSITION; PROMOTES TUMOR-GROWTH; BLOOD-BRAIN-BARRIER; HIGH-GRADE GLIOMA; DOWN-REGULATION; IN-VITRO; UP-REGULATION AB Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment. C1 [Shea, Amanda; Afzal, Zainab; Chijioke, Juliet; Kedir, Habib; Dusmatova, Shahnoza; Roy, Arpita; Ramalinga, Malathi; Kumar, Deepak] Univ Dist Columbia, Canc Res Lab, Div Sci & Math, 4200 Connecticut Ave NW, Washington, DC 20008 USA. [Harish, Varsha] Groton Sch, Groton, MA 01450 USA. [Harris, Brent] Georgetown Univ, Dept Neurol & Pathol, Washington, DC 20057 USA. [Blancato, Jan; Kumar, Deepak] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Verma, Mukesh] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA. RP Kumar, D (reprint author), Univ Dist Columbia, Canc Res Lab, Div Sci & Math, 4200 Connecticut Ave NW, Washington, DC 20008 USA. EM dkumar@udc.edu FU National Cancer Institute [CA141935, CA162264, CA194730] FX This work was supported by National Cancer Institute CA141935, CA162264, CA194730. NR 334 TC 4 Z9 5 U1 8 U2 8 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 AUG PY 2016 VL 5 IS 8 BP 1917 EP 1946 DI 10.1002/cam4.775 PG 30 WC Oncology SC Oncology GA DS6XM UT WOS:000380926600022 PM 27282910 ER PT J AU Mafolasire, A Yao, XP Nawaf, C Suarez-Sarmiento, A Chow, WH Zhao, W Corley, D Hofmann, JN Purdue, M Adeniran, AJ Shuch, B AF Mafolasire, Abiodun Yao, Xiaopan Nawaf, Cayce Suarez-Sarmiento, Alfredo Chow, Wong-Ho Zhao, Wei Corley, Douglas Hofmann, Jonathan N. Purdue, Mark Adeniran, Adebowale J. Shuch, Brian TI Racial disparities in renal cell carcinoma: a single-payer healthcare experience SO CANCER MEDICINE LA English DT Article DE Health disparity; kidney cancer; outcome; RCC; survival ID AFRICAN-AMERICANS; KIDNEY CANCER; SOCIOECONOMIC-STATUS; HISTOLOGIC SUBTYPE; WHITE PATIENTS; RISK-FACTORS; SURVIVAL; HYPERTENSION; RACE; NEPHRECTOMY AB Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single-payer healthcare system. As part of a case-control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66years, P<0.001), were more likely to have papillary RCC (15% vs. 5.2%, P<0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P=0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology. C1 [Mafolasire, Abiodun; Nawaf, Cayce; Suarez-Sarmiento, Alfredo; Shuch, Brian] Yale Sch Med, Dept Urol, POB 208058, New Haven, CT 06520 USA. [Yao, Xiaopan] Yale Sch Med, Yale Ctr Analyt Sci, New Haven, CT USA. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zhao, Wei; Corley, Douglas] Kaiser Permanente San Francisco Med Ctr, Kaiser Permanente Div Res, San Francisco, CA USA. [Hofmann, Jonathan N.; Purdue, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Adeniran, Adebowale J.] Yale Univ, Yale Sch Med, Dept Pathol, New Heaven, CT USA. RP Shuch, B (reprint author), Yale Sch Med, Dept Urol, POB 208058, New Haven, CT 06520 USA. EM Brian.shuch@yale.edu FU National Institutes of Health; NCI CTSA [KL2 TR000140]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics FX This research was supported by the National Institutes of Health, NCI CTSA Grant KL2 TR000140 (BS). This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics (MPP, JNH). NR 29 TC 1 Z9 1 U1 0 U2 0 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 AUG PY 2016 VL 5 IS 8 BP 2101 EP 2108 DI 10.1002/cam4.755 PG 8 WC Oncology SC Oncology GA DS6XM UT WOS:000380926600039 PM 27228559 ER PT J AU Ardeljan, D Taylor, MS Burns, KH Boeke, JD Espey, MG Woodhouse, EC Howcroft, TK AF Ardeljan, Daniel Taylor, Martin S. Burns, Kathleen H. Boeke, Jef D. Espey, Michael Graham Woodhouse, Elisa C. Howcroft, Thomas Kevin TI Meeting Report: The Role of the Mobilome in Cancer SO CANCER RESEARCH LA English DT Editorial Material ID SOMATIC L1 RETROTRANSPOSITION; TRANSPOSABLE ELEMENTS; HUMAN BRAIN; EXPRESSION; MUTAGENESIS; DROSOPHILA; MOSAICISM; EVOLUTION; CARCINOMA; GENOMES AB Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. (C) 2016 AACR. C1 [Ardeljan, Daniel; Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Ardeljan, Daniel] Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD USA. [Taylor, Martin S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Boeke, Jef D.] NYU, Langone Med Ctr, Inst Syst Genet, New York, NY USA. [Espey, Michael Graham; Woodhouse, Elisa C.; Howcroft, Thomas Kevin] NCI, Div Canc Biol, NIH, Rockville, MD USA. RP Woodhouse, EC (reprint author), NCI, Tumor Biol & Metastasis Branch, 9609 Med Ctr Dr,Room 6W416, Bethesda, MD 20892 USA. EM woodhousee@mail.nih.gov OI Taylor, Martin/0000-0001-5824-142X FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA163705]; NIGMS NIH HHS [T32 GM007309, P50 GM107632] NR 29 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2016 VL 76 IS 15 BP 4316 EP 4319 DI 10.1158/0008-5472.CAN-15-3421 PG 4 WC Oncology SC Oncology GA DU6AO UT WOS:000382295300004 PM 27527733 ER PT J AU Richmond, J Robbins, A Evans, K Beck, D Kurmasheva, RT Billups, CA Carol, H Heatley, S Sutton, R Marshall, GM White, D Pimanda, J Houghton, PJ Smith, MA Lock, RB AF Richmond, Jennifer Robbins, Alissa Evans, Kathryn Beck, Dominik Kurmasheva, Raushan T. Billups, Catherine A. Carol, Hernan Heatley, Sue Sutton, Rosemary Marshall, Glenn M. White, Deborah Pimanda, John Houghton, Peter J. Smith, Malcolm A. Lock, Richard B. TI Acute Sensitivity of Ph-like Acute Lymphoblastic Leukemia to the SMAC-Mimetic Birinapant SO CANCER RESEARCH LA English DT Article ID PRECLINICAL TESTING PROGRAM; ALPHA-DEPENDENT APOPTOSIS; IN-VIVO EFFICACY; T-CELL; XENOGRAFT MODELS; IAP PROTEINS; CANCER-CELLS; SOLID TUMORS; CHILDHOOD; EXPRESSION AB Ph-like acute lymphoblastic leukemia (ALL) is a genetically defined high-risk ALL subtype with a generally poor prognosis. In this study, we evaluated the efficacy of birinapant, a small-molecule mimetic of the apoptotic regulator SMAC, against a diverse set of ALL subtypes. Birinapant exhibited potent and selective cytotoxicity against B-cell precursor ALL (BCP-ALL) cells that were cultured ex vivo or in vivo as patient-derived tumor xenografts (PDX). Cytotoxicity was consistently most acute in Ph-like BCP-ALL. Unbiased gene expression analysis of BCP-ALL PDX specimens identified a 68-gene signature associated with birinapant sensitivity, including an enrichment for genes involved in inflammatory response, hematopoiesis, and cell death pathways. All Ph-like PDXs analyzed clustered within this 68-gene classifier. Mechanistically, birinapant sensitivity was associated with expression of TNF receptor TNFR1 and was abrogated by interfering with the TNF alpha/TNFR1 interaction. In combination therapy, birinapant enhanced the in vivo efficacy of an induction-type regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering a preclinical rationale to further evaluate this SMAC mimetic for BCP-ALL treatment. (C) 2016 AACR. C1 [Richmond, Jennifer; Robbins, Alissa; Evans, Kathryn; Carol, Hernan; Sutton, Rosemary; Lock, Richard B.] Univ New South Wales Australia, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia. [Beck, Dominik; Pimanda, John] Univ New South Wales Australia, Lowy Canc Res Ctr, Sydney, NSW, Australia. [Kurmasheva, Raushan T.; Houghton, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Billups, Catherine A.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Heatley, Sue; White, Deborah] South Australia Hlth & Med Res Inst, Adelaide, SA, Australia. [Marshall, Glenn M.] Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW, Australia. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Lock, RB (reprint author), Childrens Canc Inst, POB 81, Sydney, NSW 2031, Australia. EM RLock@ccia.org.au RI Lock, Richard/G-4253-2013; OI White, Deborah/0000-0003-4844-333X FU NCI NIH HHS [N01CM42216] NR 52 TC 1 Z9 1 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2016 VL 76 IS 15 BP 4579 EP 4591 DI 10.1158/0008-5472.CAN-16-0523 PG 13 WC Oncology SC Oncology GA DU6AO UT WOS:000382295300027 PM 27302164 ER PT J AU Altan-Bonnet, N AF Altan-Bonnet, Nihal TI Extracellular vesicles are the Trojan horses of viral infection SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID HEPATITIS-C VIRUS; UNCONVENTIONAL SECRETION; CELLS; AUTOPHAGY; TRANSMISSION; EXOSOMES; PROTEIN; MEMBRANES; RNA AB Extracellular vesicles have recently emerged as a novel mode of viral propagation exploited by both enveloped and non enveloped viruses. In particular non-enveloped viruses utilize the hosts' production of extracellular vesicles to exit from cells non-lytically and to hide and manipulate the immune system. Moreover, challenging the long held idea that viruses behave as independent genetic units, extracellular vesicles enable multiple viral particles and genomes to collectively traffic in and out of cells, which can promote genetic cooperativity among viral quasispecies and enhance the fitness of the overall viral population. C1 [Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Altan-Bonnet, N (reprint author), NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nihal.altan-bonnet@nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 41 TC 2 Z9 2 U1 5 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD AUG PY 2016 VL 32 BP 77 EP 81 DI 10.1016/j.mib.2016.05.004 PG 5 WC Microbiology SC Microbiology GA DU6SK UT WOS:000382344700016 PM 27232382 ER PT J AU Long, CA Zavala, F AF Long, Carole A. Zavala, Fidel TI Malaria vaccines and human immune responses SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM MALARIA; EFFECTOR MECHANISMS; PROTECTIVE EFFICACY; ACQUIRED-IMMUNITY; VIVAX MALARIA; IMMUNIZATION; TRANSMISSION; SPOROZOITES; ANTIGENS; ANTIBODIES AB Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. C1 [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. [Zavala, Fidel] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Malaria Res Inst, 615 N Wolfe St, Baltimore, MD 21205 USA. RP Long, CA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM clong@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This review was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health to CAL, and F.Z. thanks the Bloomberg Family Foundation and PATH-MVI for continued support. NR 49 TC 2 Z9 2 U1 17 U2 20 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD AUG PY 2016 VL 32 BP 96 EP 102 DI 10.1016/j.mib.2016.04.006 PG 7 WC Microbiology SC Microbiology GA DU6SK UT WOS:000382344700019 PM 27262417 ER PT J AU De Buck, M Gouwy, M Wang, JM Van Snick, J Proost, P Struyf, S Van Damme, J AF De Buck, Mieke Gouwy, Mieke Wang, Ji Ming Van Snick, Jacques Proost, Paul Struyf, Sofie Van Damme, Jo TI The cytokine-serum amyloid A-chemokine network SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE SAA; FPR2; Chemotaxis; Cytokines; TLR2 ID NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; NF-KAPPA-B; ACUTE-PHASE RESPONSE; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; ENDOTHELIAL-CELL INTERACTIONS; SIGNAL-TRANSDUCTION PATHWAY; INTESTINAL EPITHELIAL-CELLS; MESSENGER-RNA EXPRESSION; HIGH-DENSITY-LIPOPROTEIN AB Levels of serum amyloid A (SAA), a major acute phase protein in humans, are increased up to 1000-fold upon infection, trauma, cancer or other inflammatory events. However, the exact role of SAA in host defense is yet not fully understood. Several pro- and anti-inflammatory properties have been ascribed to SAA. Here, the regulated production of SAA by cytokines and glucocorticoids is discussed first. Secondly, the cytokine and chemokine inducing capacity of SAA and its receptor usage are reviewed. Thirdly, the direct (via FPR2) and indirect (via TLR2) chemotactic effects of SAA and its synergy with chemokines are unraveled. Altogether, a complex cytokine-SAA-chemokine network is established, in which SAA plays a key role in regulating "the inflammatory response. (C) 2015 Elsevier Ltd. All rights reserved. C1 [De Buck, Mieke; Gouwy, Mieke; Proost, Paul; Struyf, Sofie; Van Damme, Jo] Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Rega Inst Med Res,Lab Mol Immunol, Minderbroedersstr 10, B-3000 Leuven, Belgium. [Wang, Ji Ming] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Van Snick, Jacques] Brussels Branch, Ludwig Canc Res, Brussels, Belgium. [Van Snick, Jacques] Catholic Univ Louvain, de Duve Inst, Brussels, Belgium. RP Van Damme, J (reprint author), Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Rega Inst Med Res,Lab Mol Immunol, Minderbroedersstr 10, B-3000 Leuven, Belgium. EM mieke.debuck@rega.kuleuven.be; mieke.gouwy@rega.kuleuven.be; wangji@mail.nih.gov; jacques.vansnick@bru.licr.org; paul.proost@rega.kuleuven.be; sofie.struyf@rega.kuleuven.be; jo.vandamme@rega.kuleuven.be OI Struyf, Sofie/0000-0003-4558-0769 FU Fund for Scientific Research of Flanders (F.W.O.-Vlaanderen); Interuniversity Attraction Poles Program; Belgian Science Policy Office (I.A.P. project) [P7/40]; Concerted Research Actions (G.O.A.) of the Regional Government of Flanders [2013/015] FX The authors would like to thank the Fund for Scientific Research of Flanders (F.W.O.-Vlaanderen), the Interuniversity Attraction Poles Program initiated by the Belgian Science Policy Office (I.A.P. project P7/40) and the Concerted Research Actions (G.O.A., 2013/015) of the Regional Government of Flanders for financial support. The stimulatory discussions with Prof. G. Opdenakker and Prof. P. Matthys are much appreciated. NR 142 TC 3 Z9 3 U1 6 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 EI 1879-0305 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD AUG PY 2016 VL 30 SI SI BP 55 EP 69 DI 10.1016/j.cytogfr.2015.12.010 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DU7QL UT WOS:000382409600006 PM 26794452 ER PT J AU Welsh, KJ Kirkman, MS Sacks, DB AF Welsh, Kerry J. Kirkman, M. Sue Sacks, David B. TI Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions SO DIABETES CARE LA English DT Article ID SERUM FRUCTOSAMINE CONCENTRATION; HEMOGLOBIN A(1C) MEASUREMENT; BLOOD-GLUCOSE CONTROL; ET-AL. SRAGE; END-PRODUCTS; CARDIOVASCULAR-DISEASE; MICROVASCULAR COMPLICATIONS; SKIN AUTOFLUORESCENCE; CLINICAL-USEFULNESS; FOLLOW-UP C1 [Welsh, Kerry J.; Sacks, David B.] NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. [Kirkman, M. Sue] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov FU National Institutes of Health Clinical Center Intramural Program FX Work in the laboratory of D.B.S. is supported by the National Institutes of Health Clinical Center Intramural Program. NR 96 TC 7 Z9 7 U1 9 U2 11 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 AUG PY 2016 VL 39 IS 8 BP 1299 EP 1306 DI 10.2337/dc15-2727 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT4CN UT WOS:000381427800020 PM 27457632 ER PT J AU Wing, RR Espeland, MA Clark, JM Hazuda, HP Knowler, WC Pownall, HJ Unick, J Wadden, T Wagenknecht, L AF Wing, Rena R. Espeland, Mark A. Clark, Jeanne M. Hazuda, Helen P. Knowler, William C. Pownall, Henry J. Unick, Jessica Wadden, Thomas Wagenknecht, Lynne CA Action Hlth Diabet Look AHEAD TI Association of Weight Loss Maintenance and Weight Regain on 4-Year Changes in CVD Risk Factors: the Action for Health in Diabetes (Look AHEAD) Clinical Trial SO DIABETES CARE LA English DT Article ID LIFE-STYLE INTERVENTION; BODY-WEIGHT; CARDIOVASCULAR-DISEASE; MORTALITY; MEN; INDIVIDUALS; FLUCTUATION; POPULATION; OVERWEIGHT; PREVENTION AB OBJECTIVEShort-term weight loss improves cardiovascular disease (CVD) risk factors. We sought to determine the longer-term effects of maintaining weight loss or, conversely, regaining weight.RESEARCH DESIGN AND METHODSWe used data from Action for Health in Diabetes (Look AHEAD), a randomized trial of intensive lifestyle intervention (ILI) compared to a control condition in overweight/obese individuals with type 2 diabetes. ILI participants were grouped according to weight change patterns, as follows: 1) no weight loss (3% at years 1 and 4); 2) moderate weight loss (3-8% at years 1 and 4); 3) large weight loss (8-20% at years 1 and 4); 4) moderate loss/full regain (3-8% at year 1/3% at year 4); 5) large loss/full regain (8-20% at year 1/+/- 3% year 4); and 6) large loss/partial regain (8-20% at year 1/3-8% at year 4) and changes in CVD risk factors were compared.RESULTSAdjusting for baseline differences and medication use, larger weight losses produced greater improvements in HbA(1c), systolic blood pressure, HDL cholesterol, and triglycerides at years 1 and 4 (all P 0.02). Despite maintenance of weight loss, HbA(1c) levels worsened between years 1 and 4, and remained below baseline only in those with large weight losses. We found no negative associations of losing and regaining weight relative to not having lost weight. Moreover, those who had large initial weight loss but full regain of weight had greater improvements in HbA(1c) levels at year 4 than those with smaller or no initial weight loss.CONCLUSIONSLarger initial weight loss should be encouraged in individuals with type 2 diabetes, despite the possibility of regain. C1 [Wing, Rena R.; Unick, Jessica] Miriam Hosp, Providence, RI 02906 USA. [Espeland, Mark A.; Wagenknecht, Lynne] Wake Forest Sch Med, Winston Salem, NC USA. [Clark, Jeanne M.] Johns Hopkins Univ, Baltimore, MD USA. [Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Pownall, Henry J.] Methodist Hosp, Res Inst, 6535 Fannin, Houston, TX 77030 USA. [Wadden, Thomas] Univ Penn, Philadelphia, PA 19104 USA. RP Wing, RR (reprint author), Miriam Hosp, Providence, RI 02906 USA. EM rwing@lifespan.org FU Department of Health and Human Services through the following cooperative agreements with the National Institutes of Health [DK-57136, DK-57149, DK-56990, DK-57177, DK-57171, DK-57151, DK-57182, DK-57131, DK-57002, DK-57078, DK-57154, DK-57178, DK-57219, DK-57008, DK-57135, DK-56992]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Department of Veterans Affairs; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01-RR-02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center [M01-RR-01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01-RR-00051]; Clinical Nutrition Research Unit [P30-DK-48520]; University of Tennessee at Memphis General Clinical Research Center [M01-RR-0021140]; University of Pittsburgh General Clinical Research Center [M01-RR-000056]; Clinical and Translational Science Award [UL1 RR 024153]; National Institutes of Health [DK-046204]; Frederic C. Bartter General Clinical Research Center [M01-RR-01346] FX This study is supported by the Department of Health and Human Services through the following cooperative agreements with the National Institutes of Health: DK-57136, DK-57149, DK-56990, DK-57177, DK-57171, DK-57151, DK-57182, DK-57131, DK-57002, DK-57078, DK-57154, DK-57178, DK-57219, DK-57008, DK-57135, and DK-56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; the Centers for Disease Control and Prevention; and the Department of Veterans Affairs. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service provided personnel, medical oversight, and use of facilities. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (grant M01-RR-02719), the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (grant M01-RR-01066), the University of Colorado Health Sciences Center General Clinical Research Center (grant M01-RR-00051) and Clinical Nutrition Research Unit (P30-DK-48520), the University of Tennessee at Memphis General Clinical Research Center (M01-RR-0021140), the University of Pittsburgh General Clinical Research Center (M01-RR-000056), the Clinical Translational Research Center funded by a Clinical and Translational Science Award (UL1 RR 024153), a National Institutes of Health grant (DK-046204), and a Frederic C. Bartter General Clinical Research Center grant (M01-RR-01346). The following organizations have committed to make major contributions to the Look AHEAD Study: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST of Nestle HealthCare Nutrition, Inc.; Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast Brand of Unilever North America. NR 29 TC 1 Z9 1 U1 6 U2 8 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 AUG PY 2016 VL 39 IS 8 BP 1345 EP 1355 DI 10.2337/dc16-0509 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT4CN UT WOS:000381427800027 ER PT J AU Robinson, C Cochran, E Gorden, P Brown, RJ AF Robinson, Cemre Cochran, Elaine Gorden, Phillip Brown, Rebecca J. TI Management of Diabetic Ketoacidosis in Severe Insulin Resistance SO DIABETES CARE LA English DT Letter C1 [Robinson, Cemre] Natl Inst Dent & Craniofacial Res, Sect Skeletal Dis & Mineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Robinson, Cemre] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Cochran, Elaine; Gorden, Phillip; Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Brown, RJ (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM brownrebecca@niddk.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 2016 VL 39 IS 8 BP E116 EP E118 DI 10.2337/dc16-0635 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT4CN UT WOS:000381427800006 PM 27271188 ER PT J AU Lee-Winn, AE Reinblatt, SP Mojtabai, R Mendelson, T AF Lee-Winn, Angela E. Reinblatt, Shauna P. Mojtabai, Ramin Mendelson, Tamar TI Gender and racial/ethnic differences in binge eating symptoms in a nationally representative sample of adolescents in the United States SO EATING BEHAVIORS LA English DT Article DE Binge eating disorder; National Comorbidity Survey Adolescent Supplement (NCS-A); Gender differences; Racial/ethnic differences; Adolescents; Psychiatric epidemiology ID COMORBIDITY-SURVEY-REPLICATION; SUPPLEMENT NCS-A; DISORDER SYMPTOMS; BODY-IMAGE; ETHNIC-DIFFERENCES; PROTECTIVE FACTORS; AFRICAN-AMERICAN; YOUNG-ADULTS; RISK-FACTORS; PREVALENCE AB Objective: Binge eating disorder (BED) is the most prevalent eating disorder in the U.S. adolescent population. Both BED and subthreshold binge eating disorder (SBED) are associated with physical and mental health problems. Gender and racial/ethnic differences in prevalence of binge eating in a nationally representative sample of adolescents have been reported but have not yet been assessed in relation to individual symptoms of binge eating. We examined gender and racial/ethnic differences in endorsement of eight binge eating symptoms in a nationally representative sample of U.S. adolescents. Methods: We used data from the National Comorbidity Survey-Adolescent Supplement (NCS-A; 2001-2004), a nationally representative cross-sectional study of adolescents aged 13 to 18 years (n = 9336). We compared binge eating symptoms across gender and racial/ethnic groups using multivariable regression models. Results: Females endorsed more binge eating symptoms than males associated with loss of control ('eat when not hungry') (adjusted prevalence ratio [aPR] = 1.18, 95% confidence interval [CI] = 1.02, 1.37, p = 0.024) and distress (e.g., 'afraid of weight gain while binge eating' [aPR] = 3.29, CI = 2.43, 4.47, p < 0.001). Racial/ethnic minorities displayed different patterns of binge eating symptoms than non-Hispanic Whites. Hispanics reported being more 'afraid of weight gain while binge eating' (aPR = 2.05, CI = 1.25, 3.37, p = 0.006) than non-Hispanic Blacks. Discussion: Our findings suggest significant gender and racial/ethnic differences in binge eating symptom presentation. Future work should explore reasons for these gender and racial/ethnic differences and consider these differences when determining how best to prevent and treat binge eating in adolescents. Published by Elsevier Ltd. C1 [Lee-Winn, Angela E.; Mojtabai, Ramin; Mendelson, Tamar] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 North Broadway, Baltimore, MD 21205 USA. [Reinblatt, Shauna P.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, 550 North Broadway, Baltimore, MD 21205 USA. RP Lee-Winn, AE (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd 7B13, Rockville, MD 20892 USA. EM aleewin1@jhu.edu; sreinbl1@jhmi.edu; rmojtab1@jhu.edu; tmendel1@jhu.edu FU U.S. National Institutes of Health, National Institute of Mental Health (NIMH) [K23MH083000] FX S. Reinblatt received research support from the U.S. National Institutes of Health, National Institute of Mental Health (NIMH) for manuscript preparation (K23MH083000). The NIMH had no role in the study design, collection, analysis or interpretation of the data and the decision to submit the paper for publication. NR 56 TC 1 Z9 1 U1 13 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD AUG PY 2016 VL 22 BP 27 EP 33 DI 10.1016/j.eatbeh.2016.03.021 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DT1PN UT WOS:000381254700006 PM 27085166 ER PT J AU Lee-Winn, AE Townsend, L Reinblatt, SP Mendelson, T AF Lee-Winn, Angela E. Townsend, Lisa Reinblatt, Shauna P. Mendelson, Tamar TI Associations of neuroticism-impulsivity and coping with binge eating in a nationally representative sample of adolescents in the United States SO EATING BEHAVIORS LA English DT Article DE Binge eating disorder; National Comorbidity Survey: Adolescent Supplement (NCS-A); Personality; Coping; Adolescents; Psychiatric epidemiology ID COMORBIDITY-SURVEY-REPLICATION; SUPPLEMENT NCS-A; NEGATIVE URGENCY; BIG 5; COMMUNITY SAMPLE; BULIMIA-NERVOSA; COLLEGE-WOMEN; DAILY STRESS; DISORDERS; PERSONALITY AB Objective: Binge eating behavior is a public health concern due to its negative physical and mental health consequences. Little is known about the interplay of personality traits, coping styles, and binge eating in the general adolescent population. We examined the associations among the combination of neuroticism and impulsivity (NI), maladaptive coping styles (poor problem solving, distraction, and escape-avoidance), and lifetime prevalence of binge eating in a nationally representative sample of U.S. adolescents. We also explored coping as a moderator of the NI-lifetime binge eating association and gender as a moderator of the NI-coping associations and coping-lifetime binge eating associations. Methods: We used data from the National Comorbidity Survey: Adolescent Supplement (NCS-A: 2001-2004), a cross-sectional nationally representative study of adolescents aged 13 to 18 years (n = 10,028). We studied the associations of NI and coping with lifetime binge eating using multivariate regression models. Results: High NI was significantly associated with all three coping styles, especially escape-avoidance (beta = 3.96, confidence interval [CI] = 3.62, 4.29, p < 0.001). Gender was a significant moderator of the NI - distraction coping association (beta = -0.68, CI = -1.33,-0.03, p = 0.041), indicating a stronger association inmales (beta = 1.20, CI = 0.81, 1.58, p < 0.001) than females (beta = 0.53, CI = 0.02, 1.03, p = 0.042). Lifetime prevalence of binge eating was 1.13 times higher with increased escape-avoidance coping (CI = 1.10, 1.18, p < 0.001). Discussion: Our findings indicate significant associations among high NI, increased escape-avoidance coping, and higher lifetime prevalence of binge eating in adolescents. Findings of our study have potential to inform development of interventions that target modification of maladaptive personality traits and coping styles to reduce problematic eating. Published by Elsevier Ltd. C1 [Lee-Winn, Angela E.; Townsend, Lisa; Mendelson, Tamar] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 North Broadway Hampton House, Baltimore, MD 21205 USA. [Reinblatt, Shauna P.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, 550 North Broadway,Room 206D, Baltimore, MD 21205 USA. RP Lee-Winn, AE (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd 7B13, Rockville, MD 20892 USA. EM aleewin1@jhu.edu; ltownse8@jhu.edu; sreinbl1@jhmi.edu; tmendel1@jhu.edu FU U.S. National Institutes of Health, National Institute of Mental Health (NIMH) [K23MH083000] FX S. Reinblatt received research support from the U.S. National Institutes of Health, National Institute of Mental Health (NIMH) for manuscript preparation (K23MH083000). The NIMH had no role in the study design, collection, analysis or interpretation of the data and the decision to submit the paper for publication. NR 97 TC 0 Z9 0 U1 13 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD AUG PY 2016 VL 22 BP 133 EP 140 DI 10.1016/j.eatbeh.2016.06.009 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DT1PN UT WOS:000381254700025 PM 27289518 ER PT J AU Kelly, NR Shomaker, LB Radin, RM Thompson, KA Cassidy, OL Brady, S Mehari, R Courville, AB Chen, KY Galescu, OA Tanofsky-Kraff, M Yanovski, JA AF Kelly, Nichole R. Shomaker, Lauren B. Radin, Rachel M. Thompson, Katherine A. Cassidy, Omni L. Brady, Sheila Mehari, Rim Courville, Amber B. Chen, Kong Y. Galescu, Ovidiu A. Tanofsky-Kraff, Marian Yanovski, Jack A. TI Associations of sleep duration and quality with disinhibited eating behaviors in adolescent girls at-risk for type 2 diabetes SO EATING BEHAVIORS LA English DT Article DE Binge eating; Eating in the absence of hunger; Obesity; Sleep; Sleepiness ID EXCESSIVE DAYTIME SLEEPINESS; POSITIVE ENERGY-BALANCE; OBESE CHILDREN; YOUNG-ADULTS; POOR SLEEP; DEPRESSIVE SYMPTOMS; AFFECTIVE-DISORDERS; INSULIN-RESISTANCE; EMOTION REGULATION; SCHOOL-CHILDREN AB Objectives: Short sleep duration and daytime sleepiness have been associated with an increased risk for the onset of type 2 diabetes in adults. There has been far less attention to the characterization of sleep in adolescents at-risk for diabetes or to the possible behavioral mechanisms, such as disinhibited eating, through which sleep may affect metabolic functioning. Methods: We evaluated the associations of sleep duration and daytime sleepiness with a multi- modal assessment of disinhibited eating in 119 adolescent girls at-risk for type 2 diabetes based upon being overweight/obese and having a family history of diabetes. Girls also endorsed mild-to-moderate depressive symptoms. Adolescents reported sleep duration and daytime sleepiness with the Sleep Habits Survey and Children's Sleep Habits Questionnaire. They were administered a series of successive test meals to measure total energy intake and eating in the absence of hunger (EAH). Adolescent binge eating was assessed with the Eating Disorder Examination interview. Results: Accounting for age, race, puberty, body composition, depressive symptoms, and perceived stress, reported sleep duration was positively related to test meal total energy intake (p = 0.04), but not to EAH. Adjusting for the same covariates, daytime sleepiness was associated with a greater odds of objective binge eating in the previous month (p = 0.009). Conclusions: In adolescent girls at-risk for type 2 diabetes, reported sleep characteristics are associated with disinhibited eating behaviors that have been linked to excessive weight and adverse metabolic outcomes. Future studies are called for to evaluate these links using objective measures of sleep. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Kelly, Nichole R.; Shomaker, Lauren B.; Radin, Rachel M.; Thompson, Katherine A.; Cassidy, Omni L.; Brady, Sheila; Mehari, Rim; Galescu, Ovidiu A.; Tanofsky-Kraff, Marian; Yanovski, Jack A.] Natl Inst Child Hlth & Human Dev NICHD, Sect Growth & Obes, NIH, DHHS, 10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. [Kelly, Nichole R.; Radin, Rachel M.; Cassidy, Omni L.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Def, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. [Shomaker, Lauren B.] Colorado State Univ, Dept Human Dev & Family Studies, 410 Pitkin St,Campus Delivery 1570, Ft Collins, CO 80523 USA. [Courville, Amber B.] NIH Clin Ctr, Dept Nutr, DHHS, 10 Ctr Dr,MSC 1078, Bethesda, MD 20892 USA. [Chen, Kong Y.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, DHHS, 10 Ctr Dr, Bethesda, MD 20814 USA. RP Shomaker, LB (reprint author), Colorado State Univ, Dept Human Dev & Family Studies, 410 Pitkin St,Campus Delivery 1570, Ft Collins, CO 80523 USA. EM Lauren.Shomaker@colostate.edu OI Chen, Kong/0000-0002-0306-1904 FU NICHD, NIH Intramural Research Program Grant from NICHD [K99/R00HD069516, 1ZIAHD000641]; NIH Bench to Bedside Program; Office of Disease Prevention, NIH; Office of Behavioral and Social Sciences Research FX Supported by K99/R00HD069516 (PI: Shomaker) from NICHD, NIH Intramural Research Program Grant 1ZIAHD000641 (PI: Yanovski) from NICHD with supplemental funding from the NIH Bench to Bedside Program (PIs: Yanovski, Tanofsky-Kraff, Shomaker), the Office of Disease Prevention, NIH (PI: Yanovski), and the Office of Behavioral and Social Sciences Research (PI: Yanovski). NR 78 TC 0 Z9 0 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD AUG PY 2016 VL 22 BP 149 EP 155 DI 10.1016/j.eatbeh.2016.06.019 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DT1PN UT WOS:000381254700028 PM 27289521 ER PT J AU Poirier, MC AF Poirier, Miriam C. TI Linking DNA adduct formation and human cancer risk in chemical carcinogenesis SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE chemical carcinogen; DNA adduct; molecular dosimetry; molecular cancer epidemiology ID WHITE BLOOD-CELLS; HEPATOCELLULAR-CARCINOMA PATIENTS; PERIPHERAL MONONUCLEAR-CELLS; PARAFFIN-EMBEDDED TISSUES; ARISTOLOCHIC ACID; MASS-SPECTROMETRY; LUNG-CANCER; ENVIRONMENTAL-POLLUTANTS; XERODERMA-PIGMENTOSUM; UROTHELIAL CANCER AB Over two centuries ago, Sir Percival Pott, a London surgeon, published a pioneering treatise showing that soot exposure was the cause of high incidences of scrotal cancers occurring in young men who worked as chimney sweeps. Practicing at a time when cellular pathology was not yet recognized, Sir Percival nonetheless observed that the high incidence and short latency of the chimney sweep cancers, was fundamentally different from the rare scrotal cancers typically found in elderly men. Furthermore, his diagnosis that the etiology of these cancers was related to chimney soot exposure, was absolutely accurate, conceptually novel, and initiated the field of occupational cancer epidemiology. After many intervening years of research focused on mechanisms of chemical carcinogenesis, briefly described here, it is clear that DNA damage, or DNA adduct formation, is necessary but not sufficient for tumor induction, and that many additional factors contribute to carcinogenesis. This review includes a synopsis of carcinogen-induced DNA adduct formation in experimental models and in the human population, with particular attention paid to molecular dosimetry and molecular cancer epidemiology. Environ. Mol. Mutagen. 57:499-507, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov NR 82 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2016 VL 57 IS 7 BP 499 EP 507 DI 10.1002/em.22030 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DV0DC UT WOS:000382587200001 PM 27346877 ER PT J AU Liu, YM Park, ES Gibbons, AT Shide, ED Divi, RL Woodward, RA Poirier, MC AF Liu, Yongmin Park, Eunwoo Shim Gibbons, Alexander T. Shide, Eric D. Divi, Rao L. Woodward, Ruth A. Poirier, Miriam C. TI Mitochondrial compromise in 3-year old patas monkeys exposed in utero to human-equivalent antiretroviral therapies SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE zidovudine; lamivudine; abacavir; nevirapine; mitochondrial DNA; Seahorse analyzer ID REVERSE-TRANSCRIPTASE INHIBITORS; HIV-UNINFECTED CHILDREN; GENOTOXICITY; TOXICITY; CARCINOGENICITY; DYSFUNCTION; ZIDOVUDINE; MOTHERS; DRUGS; NRTIS AB Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10weeks (50%) of gestation. Infants kept for 1 and 3years also received drug for the first 6weeks of life. In offpsring at birth, 1 and 3years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P<0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3-year-old patas offspring was approximate to 50% reduced in AZT/3TC/ABC-exposed patas (P<0.01), but not in AZT/3TC/NVP-exposed patas. Overall the data show that 3-year-old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526-534, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Liu, Yongmin; Park, Eunwoo Shim; Gibbons, Alexander T.; Shide, Eric D.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet, CCR,NIH, Madison, WI USA. [Divi, Rao L.] NCI, Methods & Technol Branch, DCCPS, NIH, Madison, WI USA. [Woodward, Ruth A.] NIH, Shared Anim Facil, Anim Ctr, Madison, WI USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM poir-ierm@exchange.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH [ZIA-BC 010770] FX The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. We wish to thank Alexandra Michalowski for statistical help. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, under project number ZIA-BC 010770. NR 33 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2016 VL 57 IS 7 BP 526 EP 534 DI 10.1002/em.22033 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DV0DC UT WOS:000382587200004 PM 27452341 ER PT J AU Ma, YS Persuitte, GM Andrews, C Hovey, KM LaMonte, MJ Culver, AL Manson, JE Phillips, LS Liu, SM Eaton, C Martin, LW Howard, BV Balasubramanian, R Bird, CE Ockene, IS Sturgeon, SR Ockene, JK Tinker, L Nassir, R Rossouw, J AF Ma, Yunsheng Persuitte, Gioia M. Andrews, Christopher Hovey, Kathleen M. LaMonte, Michael J. Culver, Annie L. Manson, JoAnn E. Phillips, Lawrence S. Liu, Simin Eaton, Charles Martin, Lisa W. Howard, Barbara V. Balasubramanian, Raji Bird, Chloe E. Ockene, Ira S. Sturgeon, Susan R. Ockene, Judith K. Tinker, Lesley Nassir, Rami Rossouw, Jacques TI Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Epidemiology; Diabetes; Drug-related problem; Cardiovascular disease ID HEALTHY EATING INDEX; 27 RANDOMIZED-TRIALS; PRIMARY PREVENTION; METABOLIC SYNDROME; INDIVIDUAL DATA; DIET QUALITY; SELF-REPORTS; METAANALYSIS; THERAPY; RISK AB To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women's Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28-1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12-1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins. C1 [Ma, Yunsheng; Culver, Annie L.; Ockene, Judith K.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, 55 Lake Ave North, Worcester, MA 01655 USA. [Persuitte, Gioia M.] Corrona LLC, 352 Boston Turnpike, Southborough, MA 01772 USA. [Andrews, Christopher] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Hovey, Kathleen M.; LaMonte, Michael J.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA. [Manson, JoAnn E.] Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Phillips, Lawrence S.] Emory Univ, Div Endocrinol, Atlanta, GA 30322 USA. [Liu, Simin] Brown Univ, Sch Publ Hlth, Providence, RI 02903 USA. [Eaton, Charles] Brown Univ, Sch Med, Dept Family Med, Providence, RI 02912 USA. [Martin, Lisa W.] George Washington Univ, Sch Med & Hlth Sci, Div Cardiol, Washington, DC 20037 USA. [Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD 20782 USA. [Balasubramanian, Raji; Sturgeon, Susan R.] Univ Massachusetts Amherst, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Bird, Chloe E.] RAND Corp, Santa Monica, CA 90407 USA. [Ockene, Ira S.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA. [Tinker, Lesley] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Nassir, Rami] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Rossouw, Jacques] NHLBI, Womens Hlth Initiat Branch, Bldg 10, Bethesda, MD 20892 USA. RP Ma, YS (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, 55 Lake Ave North, Worcester, MA 01655 USA. EM Yunsheng.Ma@umassmed.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; [5R01HL122241-02] FX Y.M. and G.M.P wrote the manuscript and researched data. A.L.C., J.E.M., L.S.P., S.L., C.E., M.L., L.W.M, B.V.H, R.B., C.E.B., I.S.O., S.R.S., J.K.O., L.T, R.N., and J.R. contributed to the discussion and reviewed and edited the manuscript. C.A. and K.H performed data analyses and reviewed and edited the manuscript. The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. Our investigation also was supported in part by 5R01HL122241-02. A list of WHI investigators is available in Supplementary Data online. The authors thank the principal investigators of all WHI clinical centers and the data coordinating center for their contribution to the study. They are also indebted to the dedicated and committed participants of the WHI. NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD AUG PY 2016 VL 31 IS 8 BP 747 EP 761 DI 10.1007/s10654-016-0153-7 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DV1QE UT WOS:000382695100004 PM 27188186 ER PT J AU Silverman, DT Attfield, MD Blair, AE Lubin, JH Stewart, PA Vermeulen, R AF Silverman, Debra T. Attfield, Michael D. Blair, Aaron E. Lubin, Jay H. Stewart, Patricia A. Vermeulen, Roel TI Re: "The hidden impact of a healthy-worker effect on the results of the Diesel Exhaust in Miners Study" SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID LUNG-CANCER; MORTALITY; COHORT C1 [Silverman, Debra T.; Blair, Aaron E.; Stewart, Patricia A.; Vermeulen, Roel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rm 6E142,9609 Med Ctr Dr, Bethesda, MD 20892 USA. [Attfield, Michael D.] NIOSH, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV USA. [Lubin, Jay H.] NCI, Biostat Branch, Div Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. RP Silverman, DT (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rm 6E142,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM silvermd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 6 TC 1 Z9 2 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD AUG PY 2016 VL 31 IS 8 BP 805 EP 806 DI 10.1007/s10654-016-0188-9 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DV1QE UT WOS:000382695100010 PM 27518301 ER PT J AU Nussinov, R Tsai, CJ Jang, H AF Nussinov, Ruth Tsai, Chung-Jung Jang, Hyunbum TI Independent and core pathways in oncogenic KRAS signaling SO EXPERT REVIEW OF PROTEOMICS LA English DT Editorial Material DE KRAS; K-Ras4B; lung cancer; pancreatic cancer; Ras pathways; cell cycle; Ras effectors; PI3K; Raf; Ras isoforms ID ENGINEERED MOUSE MODELS; BETA-CATENIN ACTIVATION; REGULATES C-MYC; CELL-CYCLE; PANCREATIC-CANCER; LUNG-CANCER; K-RAS; HYPERVARIABLE REGION; TARGETED THERAPIES; TUMOR INITIATION C1 [Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum] NCI, Basic Sci Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res,Canc & Inflammat Prog, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Sci Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res,Canc & Inflammat Prog, Frederick, MD 21701 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, Tel Aviv, Israel. EM NussinoR@helix.nih.gov FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E] NR 86 TC 1 Z9 1 U1 4 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1478-9450 EI 1744-8387 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD AUG PY 2016 VL 13 IS 8 BP 711 EP 716 DI 10.1080/14789450.2016.1209417 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DU6ZS UT WOS:000382363700002 PM 27389825 ER PT J AU Hernandez, L Kim, MK Lyle, LT Bunch, KP House, CD Ning, F Noonan, AM Annunziata, CM AF Hernandez, Lidia Kim, Marianne K. Lyle, L. Tiffany Bunch, Kristen P. House, Carrie D. Ning, Franklin Noonan, Anne M. Annunziata, Christina M. TI Characterization of ovarian cancer cell lines as in vivo models for preclinical studies SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Xenografts; Cell lines; Mouse model ID CARCINOMA; GENE; METASTASIS; EXPRESSION; RESISTANCE; VITRO; MICE AB Objective. The value of cell lines for pre-clinical work lies in choosing those with similar characteristics. Selection of cell lines is typically based on patient history, histological subtype at diagnosis, mutation patterns, or signaling pathways. Although recent studies established consensus regarding molecular characteristics of ovarian cancer cell lines, data on in vivo tumorigenicity remains only sporadically available, impeding translation of in vitro work to xenograft models. Methods. We introduced 18 ovarian cancer cell lines into athymic nude mice through subcutaneous, intraperitoneal, and ovary intrabursal routes, and observed tumor development over 6 weeks. We also profiled cell line gene expression and identified differentially expressed gene sets based on their ability to form tumors in the subcutaneous or intraperitoneal locations. Representative cell lines were further subjected to proteomic analyses. Results. Ovarian cancer cell lines showed variable ability to grow in mice when implanted subcutaneous, intraperitoneal, or intrabursal. While some cell lines grew well in both SC and IP locations, others showed a strong propensity to grow in one location only. Gene expression profiles suggested that cell lines showing preference for IP growth had gene expression patterns more similar to primary tumors. Conclusions. We report the tumorigenicity of 17 human ovarian cancer cell lines and one mouse cell line in three distinct anatomical locations, and associated gene networks. Growth patterns and histopathology, linked to molecular characteristics, provide a valuable resource to the research community, and better guide the choice of cell lines for in vitro studies to translate efficiently into xenograft testing. Published by Elsevier Inc. C1 [Hernandez, Lidia; Kim, Marianne K.; Lyle, L. Tiffany; Bunch, Kristen P.; House, Carrie D.; Ning, Franklin; Noonan, Anne M.; Annunziata, Christina M.] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bunch, Kristen P.] Walter Reed Natl Mil Med Ctr, Dept Gynecol Oncol, Bethesda, MD USA. [Noonan, Anne M.] Ohio State Univ, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA. RP Annunziata, CM (reprint author), 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU National Cancer Institute Intramural Research Program [ZIA BC 011054] FX We thank Elena Kuznetsova and Geneti Gaga for the excellent surgical expertise during intrabursal injections. This work was funded by the National Cancer Institute Intramural Research Program (CMA, #ZIA BC 011054).The authors declare no conflict of interest. NR 40 TC 0 Z9 0 U1 4 U2 4 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 AUG PY 2016 VL 142 IS 2 BP 332 EP 340 DI 10.1016/j.ygyno.2016.05.028 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DS4EH UT WOS:000380733700022 PM 27235858 ER PT J AU Laurent, C Fabiani, B Do, C Tchernonog, E Cartron, G Gravelle, P Amara, N Malot, S Palisoc, MM Copie-Bergman, C Glehen, AT Copin, MC Brousset, P Pittaluga, S Jaffe, ES Coppo, P AF Laurent, Camille Fabiani, Bettina Do, Catherine Tchernonog, Emmanuelle Cartron, Guillaume Gravelle, Pauline Amara, Nadia Malot, Sandrine Palisoc, Maryknoll Mawanay Copie-Bergman, Christiane Glehen, Alexandra Traverse Copin, Marie-Christine Brousset, Pierre Pittaluga, Stefania Jaffe, Elaine S. Coppo, Paul TI Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients SO HAEMATOLOGICA LA English DT Article ID B-CELL LYMPHOMA; DEATH-LIGAND 1; INDOLEAMINE 2,3-DIOXYGENASE; FOLLICULAR LYMPHOMA; HODGKINS LYMPHOMA; EBV INFECTION; ORAL-CAVITY; BLOCKADE; DISORDERS; RITUXIMAB AB Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency virus infection. Therefore, its immune escape strategy may involve the upregulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better 2-year event-free survival than Epstein-Barr virus negative cases (P=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60%-72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease. C1 [Laurent, Camille; Gravelle, Pauline; Amara, Nadia; Brousset, Pierre] Inst Univ Canc Oncopole, Dept Pathol, Toulouse, France. [Laurent, Camille; Gravelle, Pauline; Brousset, Pierre] Ctr Rech Cancerol Toulouse Purpan, INSERM, U1037, Toulouse, France. [Fabiani, Bettina] Hop St Antoine, AP HP, Dept Pathol, Paris, France. [Do, Catherine] Columbia Univ, Inst Canc Genet, New York, NY USA. [Tchernonog, Emmanuelle; Cartron, Guillaume] Hop Gui Chauliac St Eloi, Serv Hematol, Montpellier, France. [Malot, Sandrine; Coppo, Paul] Hop St Antoine, AP HP, Serv Hematol, Paris, France. [Malot, Sandrine; Coppo, Paul] AP HP, Ctr Reference Microangiopathies Thrombot, Paris, France. [Palisoc, Maryknoll Mawanay; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Copie-Bergman, Christiane] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Pathol, Creteil, France. [Glehen, Alexandra Traverse] Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France. [Copin, Marie-Christine] Ctr Hosp Lille, Dept Pathol, Lille, France. [Coppo, Paul] Univ Paris 06, F-75252 Paris 05, France. [Coppo, Paul] Inst Gustave Roussy, INSERM, U1170, Villejuif, France. RP Laurent, C (reprint author), Inst Univ Canc Oncopole, Dept Pathol, Toulouse, France.; Laurent, C (reprint author), Ctr Rech Cancerol Toulouse Purpan, INSERM, U1037, Toulouse, France. EM laurent.c@chu-toulouse.fr RI GRAVELLE, PAULINE/D-1405-2015 OI GRAVELLE, PAULINE/0000-0002-0462-5652 NR 50 TC 5 Z9 5 U1 4 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD AUG PY 2016 VL 101 IS 8 BP 976 EP 984 DI 10.3324/haematol.2016.141978 PG 9 WC Hematology SC Hematology GA DU1BT UT WOS:000381941900021 PM 27175027 ER PT J AU Teerlink, CC Leongamornlert, D Dadaev, T Thomas, A Farnham, J Stephenson, RA Riska, S McDonnell, SK Schaid, DJ Catalona, WJ Zheng, SL Cooney, KA Ray, AM Zuhlke, KA Lange, EM Giles, GG Southey, MC Fitzgerald, LM Rinckleb, A Luedeke, M Maier, C Stanford, JL Ostrander, EA Kaikkonen, EM Sipeky, C Tammela, T Schleutker, J Wiley, KE Isaacs, SD Walsh, PC Isaacs, WB Xu, JF Cancel-Tassin, G Cussenot, O Mandal, D Laurie, C Laurie, C Thibodeau, SN Eeles, RA Kote-Jarai, Z Cannon-Albright, L AF Teerlink, Craig C. Leongamornlert, Daniel Dadaev, Tokhir Thomas, Alun Farnham, James Stephenson, Robert A. Riska, Shaun McDonnell, Shannon K. Schaid, Daniel J. Catalona, William J. Zheng, S. Lilly Cooney, Kathleen A. Ray, Anna M. Zuhlke, Kimberly A. Lange, Ethan M. Giles, Graham G. Southey, Melissa C. Fitzgerald, Liesel M. Rinckleb, Antje Luedeke, Manuel Maier, Christiane Stanford, Janet L. Ostrander, Elaine A. Kaikkonen, Elina M. Sipeky, Csilla Tammela, Teuvo Schleutker, Johanna Wiley, Kathleen E. Isaacs, Sarah D. Walsh, Patrick C. Isaacs, William B. Xu, Jianfeng Cancel-Tassin, Geraldine Cussenot, Olivier Mandal, Diptasri Laurie, Cecelia Laurie, Cathy Thibodeau, Stephen N. Eeles, Rosalind A. Kote-Jarai, Zsofia Cannon-Albright, Lisa CA PRACTICAL Consortium Int TI Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21 SO HUMAN GENETICS LA English DT Article ID RISK-ASSOCIATED LOCI; SUSCEPTIBILITY LOCI; GERMLINE MUTATIONS; GENETIC-VARIATION; SEQUENCING DATA; MULTIPLE LOCI; VARIANTS; METAANALYSIS; DISEASE; AGGRESSIVENESS AB Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies < 1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus. C1 [Teerlink, Craig C.; Thomas, Alun; Farnham, James; Cannon-Albright, Lisa] Univ Utah, Dept Internal Med, Sch Med, Salt Lake City, UT 84108 USA. [Leongamornlert, Daniel; Dadaev, Tokhir; Eeles, Rosalind A.; Kote-Jarai, Zsofia] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Stephenson, Robert A.] Univ Utah, Dept Urol, Sch Med, Salt Lake City, UT 84132 USA. [Stephenson, Robert A.] Univ Utah, Dept Surg, Sch Med, Salt Lake City, UT 84132 USA. [Stephenson, Robert A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Riska, Shaun; McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Catalona, William J.; Zheng, S. Lilly] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.] Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA. [Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.] Univ Michigan, Dept Urol, Sch Med, Ann Arbor, MI 48109 USA. [Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Giles, Graham G.; Fitzgerald, Liesel M.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Rinckleb, Antje; Luedeke, Manuel] Univ Hosp Ulm, Dept Urol, D-53179 Ulm, Germany. [Maier, Christiane] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Kaikkonen, Elina M.; Sipeky, Csilla] Univ Turku, Dept Med Biochem & Genet, FIN-20520 Turku, Finland. [Tammela, Teuvo] Univ Tampere, Dept Urol, Tampere 33520, Finland. [Tammela, Teuvo] Tampere Univ Hosp, Tampere 33520, Finland. [Schleutker, Johanna] Turku Univ Hosp, Dept Med Genet, Tyks Microbiol & Genet, Turku 20520, Finland. [Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.] Johns Hopkins Univ, Brady Urol Inst, Baltimore, MD 21287 USA. [Xu, Jianfeng] NorthShore Univ Hlth Syst, Program Personalized Canc Care, Evanston, IL 60201 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier] Hop Tenon, AP HP, CeRePP, F-75020 Paris, France. [Mandal, Diptasri] Louisiana State Univ, Dept Genet, Hlth Sci Ctr, New Orleans, LA 70112 USA. [Laurie, Cecelia; Laurie, Cathy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Cannon-Albright, Lisa] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA. RP Teerlink, CC (reprint author), Univ Utah, Dept Internal Med, Sch Med, Salt Lake City, UT 84108 USA. EM craig.teerlink@utah.edu OI Teerlink, Craig/0000-0002-1992-2326; Farnham, James/0000-0002-8213-949X; Leongamornlert, Daniel/0000-0002-3486-3168; albright, lisa/0000-0003-2602-3668; Giles, Graham/0000-0003-4946-9099; Thomas, Alun/0000-0001-5650-7044; Ostrander, Elaine/0000-0001-6075-9738; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU National Cancer Institute [U01 CA 89600]; Center for Inherited Disease Research [HHSN268201200008I]; NIH [R01 CA080122, R01 CA056678, R01 CA092579]; Fred Hutchinson Cancer Research Center; Prostate Cancer Foundation; European Community [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112-the GAME-ON initiative]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR); Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Institute of Health Research; Royal Marsden NHS Foundation Trust; Prostate Cancer UK FX This research was supported by the National Cancer Institute Grant U01 CA 89600 (Support for the ICPCG), and a grant from the Center for Inherited Disease Research supported the genotyping aspect of the study (contract no. HHSN268201200008I; PI Cannon-Albright). The Geneva Coordinating Center at the University of Washington conducted quality control aspects of the study and submitted public facing data to the database of Genotypes and Phenotypes (dbGaP) at the National Center for Biotechnology Information. The authors acknowledge the Keith and Susan Warshaw Fund, the Maurice Warshaw Fund, the C. Scott Watkins Fund, and the Tennity Family Fund. The FHCRC portion of the study was supported by NIH grants R01 CA080122, R01 CA056678, and R01 CA092579, Fred Hutchinson Cancer Research Center and the Prostate Cancer Foundation. Funding for the iCOGS infrastructure (PRACTICAL data) came from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112-the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The Biomedical Research Centre at the Institute of Cancer Research (UK) acknowledges the support of the National Institute of Health Research, the Royal Marsden NHS Foundation Trust, and Prostate Cancer UK. NR 51 TC 0 Z9 0 U1 2 U2 3 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 AUG PY 2016 VL 135 IS 8 BP 923 EP 938 DI 10.1007/s00439-016-1690-6 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA DR7DR UT WOS:000380060700009 PM 27262462 ER PT J AU Del Gobbo, LC Imamura, F Aslibekyan, S Marklund, M Virtanen, JK Wennberg, M Yakoob, MY Chiuve, SE dela Cruz, L Frazier-Wood, AC Fretts, AM Guallar, E Matsumoto, C Prem, K Tanaka, T Wu, JHY Zhou, X Helmer, C Ingelsson, E Yuan, JM Barberger-Gateau, P Campos, H Chaves, PHM Djousse, L Giles, GG Gomez-Aracena, J Hodge, AM Hu, FB Jansson, JH Johansson, I Khaw, KT Koh, WP Lemaitre, RN Lind, L Luben, RN Rimm, EB Riserus, U Samieri, C Franks, PW Siscovick, DS Stampfer, M Steffen, LM Steffen, BT Tsai, MY van Dam, RM Voutilainen, S Willett, WC Woodward, M Mozaffarian, D AF Del Gobbo, Liana C. Imamura, Fumiaki Aslibekyan, Stella Marklund, Matti Virtanen, Jyrki K. Wennberg, Maria Yakoob, Mohammad Y. Chiuve, Stephanie E. dela Cruz, Luicito Frazier-Wood, Alexis C. Fretts, Amanda M. Guallar, Eliseo Matsumoto, Chisa Prem, Kiesha Tanaka, Tosh Wu, Jason H. Y. Zhou, Xia Helmer, Catherine Ingelsson, Erik Yuan, Jian-Min Barberger-Gateau, Pascale Campos, Hannia Chaves, Paulo H. M. Djousse, Luc Giles, Graham G. Gomez-Aracena, Jose Hodge, Allison M. Hu, Frank B. Jansson, Jan-Hakan Johansson, Ingegerd Khaw, Kay-Tee Koh, Woon-Puay Lemaitre, Rozenn N. Lind, Lars Luben, Robert N. Rimm, Eric B. Riserus, Ulf Samieri, Cecilia Franks, Paul W. Siscovick, David S. Stampfer, Meir Steffen, Lyn M. Steffen, Brian T. Tsai, Michael Y. van Dam, Rob M. Voutilainen, Sari Willett, Walter C. Woodward, Mark Mozaffarian, Dariush CA Cohorts Heart Aging Res Genomic Ep Fatty Acids Outcomes Res Consortiu TI omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies SO JAMA INTERNAL MEDICINE LA English DT Article ID ALPHA-LINOLENIC ACID; LONG-CHAIN N-3; CARDIOVASCULAR-DISEASE; CONTROLLED-TRIALS; FISH CONSUMPTION; ADIPOSE-TISSUE; BREAST-CANCER; DOSE-RESPONSE; RISK-FACTORS; DIETARY AB IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD. C1 [Del Gobbo, Liana C.; Yakoob, Mohammad Y.; Ingelsson, Erik] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Imamura, Fumiaki] Univ Cambridge, Sch Clin Med, Epidemiol Unit, Med Res Council,Inst Metab Sci, Cambridge, England. [Aslibekyan, Stella] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. [Marklund, Matti; Riserus, Ulf] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Virtanen, Jyrki K.; Voutilainen, Sari] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland. [Wennberg, Maria; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Chiuve, Stephanie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chiuve, Stephanie E.; Rimm, Eric B.; Stampfer, Meir; Willett, Walter C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [dela Cruz, Luicito; Hodge, Allison M.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Frazier-Wood, Alexis C.] ARS, USDA, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX USA. [Fretts, Amanda M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Guallar, Eliseo; Woodward, Mark] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Matsumoto, Chisa] Tokyo Med Univ, Div Cardiol, Tokyo, Japan. [Matsumoto, Chisa; Djousse, Luc] Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Matsumoto, Chisa; Djousse, Luc; Hu, Frank B.; Rimm, Eric B.; Stampfer, Meir; Willett, Walter C.] Harvard Med Sch, Boston, MA USA. [Prem, Kiesha; Koh, Woon-Puay; van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. [Tanaka, Tosh] NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA. [Wu, Jason H. Y.; Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney Med Sch, Sydney, NSW, Australia. [Zhou, Xia; Steffen, Lyn M.; Steffen, Brian T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Helmer, Catherine; Barberger-Gateau, Pascale; Samieri, Cecilia] Inst Sante Publ Epidemiol & Dev, Inst Natl Sante & Rech Med, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France. [Helmer, Catherine; Barberger-Gateau, Pascale; Samieri, Cecilia] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France. [Ingelsson, Erik; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Yuan, Jian-Min] Univ Pittsburgh, Div Canc Control & Populat Sci, Inst Canc, Pittsburgh, PA USA. [Yuan, Jian-Min] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Campos, Hannia; Hu, Frank B.; Rimm, Eric B.; Stampfer, Meir; van Dam, Rob M.; Willett, Walter C.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Chaves, Paulo H. M.] Florida Int Univ, Benjamin Leon Ctr Geriatr Res & Educ, Miami, FL 33199 USA. [Gomez-Aracena, Jose] Univ Malaga, Dept Prevent Med, Malaga, Spain. [Hu, Frank B.; Rimm, Eric B.; Stampfer, Meir; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Khaw, Kay-Tee; Luben, Robert N.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Koh, Woon-Puay] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Lemaitre, Rozenn N.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Lund, Sweden. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [van Dam, Rob M.] Natl Univ Singapore, Dept Med, Yong Loo Lin Sch Med, Singapore, Singapore. [van Dam, Rob M.] Natl Univ Hlth Syst, Singapore, Singapore. [Woodward, Mark] Univ Oxford, George Inst Global Hlth, Nuffield Dept Publ Hlth, Oxford, England. [Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. RP Del Gobbo, LC (reprint author), Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. EM delgobbo@stanford.edu RI HELMER, Catherine/I-6581-2015; Samieri, Cecilia/E-3334-2014; Djousse, Luc/F-5033-2017 OI HELMER, Catherine/0000-0002-5169-7421; Samieri, Cecilia/0000-0001-9809-7506; Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, R01HL081549, UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712, P30 DK46200, UM1 CA186107, R01 CA49449, R01 HL034594, P01CA87969, R01HL034594, R01HL088521, UM1 CA182876, R01CA 144034, UL1RR025005]; National Institute on Aging [R01AG023629]; Dutch Ministry of Health; Cancer Research Switzerland [AKT76]; Swiss National Science Foundation [32-9257-87]; Medical Research Council; Medical Research Council Epidemiology Unit [MC_UU_12015/5]; Intramural Research Program of the National Institutes of Health [N01-AG-916413, N01-AG821336, 263 MD 9164 13, 263 MD 821336]; Academy of Finland, Helsinki, Finland [1041086, 41471]; VicHealth; Australia's National Health and Medical Research Council [209057, 251553, 504711]; Swedish Cancer Society; Swedish Research Council; National Cancer Institute [R21 HL088081, CA-34944, CA-40360, CA-097193]; Fondation pour la Recherche Medicale; Caisse Nationale Maladie des Travailleurs Salaries; Direction Generale de la Sante; Institut de la Longevite; Conseils Regionaux d'Aquitaine et Bourgogne; Fondation de France; Ministry of Research-Institut National de la Sante et de la Recherche Medicale Programme Cohortes et collections de donnees biologiques; grant COGINUT from the Agence Nationale de la Recherche [ANR-06-PNRA-005]; grant FCS from the Fondation Plan Alzheimer; Caisse Nationale pour la Solidarite et l'Autonomie; Scottish Health Department Chief Scientist Organization; British Heart Foundation; FP Fleming Trust; Singapore National Medical Research Council [NMRC 1270/2010]; Swedish Research Council for Health, Working Life and Welfare; Uppsala City Council; National Institutes of Health Roadmap for Medical Research; National Institute of Neurological Disorders and Stroke; Commission of the European Communities; Cancer Research UK; Italian Ministry of Health [ICS 110.1\RS97.71]; Cancer Council Victoria; MGEN; Fondation Plan Alzheimer; [N01HC85082]; [N01HC85083]; [N01HC85086]; [U01HL080295]; [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]; [UL1-TR-001079]; [UL1-TR000040]; [N02-HL-64278]; [HL-34595]; [HL-26490]; [N01HC85081] FX The Atherosclerosis Risk in Communities study was performed as a collaborative study supported by contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, and R01HL086694 from the National Heart, Lung, and Blood Institute; contract U01HG004402 from the National Human Genome Research Institute; and contract HHSN268200625226C from the National Institutes of Health. We thank the staff and participants of the Atherosclerosis Risk in Communities study for their important contributions. Infrastructure was partly supported by grant UL1RR025005, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research. The Cardiovascular Health Study (CHS) was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant U01HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by grant R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI. org. The Costa Rican adult study was supported by grant R01HL081549 from the National Institutes of Health. The European Study on Antioxidants, Myocardial Infarction and Cancer was supported by the Commission of the European Communities, as a Concerted Action within Directorate General-XII, with additional support from Directorate General-V Europe against Cancer. The national studies were financed by the Dutch Ministry of Health. Ulster Cancer Foundation and Milk Intervention Board, grant AKT76 from Cancer Research Switzerland, grant 32-9257-87 from the Swiss National Science Foundation, The Spanish Fondo de Investigaciones Sanitarias and Ministry of Science and Education, and German Federal Health Office. EPIC-Norfolk was funded by grants from Medical Research Council and Cancer Research UK. Dr Imamura received support from grant MC_UU_12015/5 from the Medical Research Council Epidemiology Unit. The Health Professionals Follow-up Study (HPFS) was supported by grants UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712, and P30 DK46200 from the National Institutes of Health. The InChianti study was supported by grant ICS 110.1\RS97.71 as a targeted project by the Italian Ministry of Health and in part by contracts N01-AG-916413, N01-AG821336, 263 MD 9164 13, and 263 MD 821336 from the Intramural Research Program of the National Institutes of Health. The Kuopio Ischaemic Heart Disease Risk Factor Study was supported by grants 41471 and 1041086 from the Academy of Finland, Helsinki, Finland. The Melbourne Collaborative Cohort Study recruitment was funded by VicHealth and Cancer Council Victoria and was further supported by grants 209057, 251553, and 504711 from Australia's National Health and Medical Research Council and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with MESA investigators.; Support for MESA is provided by 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, N01-HC-95169, UL1-TR-001079, and UL1-TR000040 from the National Heart, Lung, and Blood Institute. Funding for SHARe genotyping was provided by contract N02-HL-64278 from the National Heart, Lung, and Blood Institute. Genotyping was performed at Affymetrix and the Broad Institute of Harvard and MIT using the Affymetrix Genome-Wide Human SNP Array 6.0. The Northern Sweden Health and Disease Studies I and II were supported by the Swedish Cancer Society and the Swedish Research Council. The Nurses Health Study was supported by research grants UM1 CA186107, R01 CA49449, R01 HL034594, P01CA87969, R01HL034594, and R01HL088521 from the National Institutes of Health. The Physician's Health Study was supported by grants R21 HL088081, CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute. The Three-City study was conducted under a partnership agreement between the Institut National de la Sante et de la Recherche Medicale, the University Bordeaux 2 Victor Segalen, and Sanofi. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The Three-City study was also supported by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux d'Aquitaine et Bourgogne, Fondation de France, Ministry of Research-Institut National de la Sante et de la Recherche Medicale Programme Cohortes et collections de donnees biologiques, grant COGINUT ANR-06-PNRA-005 from the Agence Nationale de la Recherche, grant FCS 2009-2012 from the Fondation Plan Alzheimer, and the Caisse Nationale pour la Solidarite et l'Autonomie. Dr Samieri was sponsored by a grant from the Fondation Plan Alzheimer. The Scottish Heart Health Extended Cohort study was funded by the Scottish Health Department Chief Scientist Organization, British Heart Foundation, and FP Fleming Trust. The Singapore Chinese Health Study was supported by grant NMRC 1270/2010 from the Singapore National Medical Research Council and grants R01CA 144034 and UM1 CA182876 from the National Institutes of Health. The Uppsala Longitudinal Studies of Adult Men 50 and 70 were funded by the Swedish Research Council for Health, Working Life and Welfare, Uppsala City Council, and Swedish Research Council. NR 58 TC 9 Z9 9 U1 11 U2 16 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 AUG PY 2016 VL 176 IS 8 BP 1155 EP 1166 DI 10.1001/jamainternmed.2016.2925 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000027 PM 27357102 ER PT J AU Chen, SC Pearson, SD AF Chen, Stephanie C. Pearson, Steven D. TI Policy Framework for Covering Preventive Services Without Cost Sharing Saving Lives and Saving Money? SO JAMA INTERNAL MEDICINE LA English DT Review ID VALUE-BASED INSURANCE; TASK-FORCE AB The US Affordable Care Act mandates that private insurers cover a list of preventive services without cost sharing. The list is determined by 4 expert committees that evaluate the overall health effect of preventive services. We analyzed the process by which the expert committees develop their recommendations. Each committee uses different criteria to evaluate preventive services and none of the committees consider cost systematically. We propose that the existing committees adopt consistent evidence review methodologies and expand the scope of preventive services reviewed and that a separate advisory committee be established to integrate economic considerations into the final selection of free preventive services. The comprehensive framework and associated criteria are intended to help policy makers in the future develop a more evidence-based, consistent, and ethically sound approach. C1 [Chen, Stephanie C.; Pearson, Steven D.] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Pearson, Steven D.] Inst Clin & Econ Review, Boston, MA USA. RP Pearson, SD (reprint author), Dept Bioeth, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov FU Intramural Research Program at the National Institutes of Health (NIH) FX This research is supported by the Intramural Research Program at the National Institutes of Health (NIH). NR 20 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2016 VL 176 IS 8 BP 1185 EP 1189 DI 10.1001/jamainternmed.2016.3052 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000031 PM 27366833 ER PT J AU Griffith, LM Cowan, MJ Notarangelo, LD Kohn, DB Puck, JM Shearer, WT Burroughs, LM Torgerson, TR Decaluwe, H Haddad, E AF Griffith, Linda M. Cowan, Morton J. Notarangelo, Luigi D. Kohn, Donald B. Puck, Jennifer M. Shearer, William T. Burroughs, Lauri M. Torgerson, Troy R. Decaluwe, Helene Haddad, Elie TI Primary Immune Deficiency Treatment Consortium (PIDTC) update SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allogeneic hematopoietic cell transplantation; gene therapy; primary immunodeficiency; clinical trial ID SEVERE COMBINED IMMUNODEFICIENCY; STEM-CELL TRANSPLANTATION; WISKOTT-ALDRICH-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; CLASS-SWITCH RECOMBINATION; GENE-THERAPY; HEMATOLOGIC MALIGNANCIES; NEUROCOGNITIVE FUNCTION; SEVERE INFECTIONS; T-CELLS AB The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PIDs), including severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PIDs in multicenter longitudinal retrospective, prospective, and cross-sectional studies. Since 2009, participating centers have enrolled more than 800 subjects on PIDTC protocols for SCID, and enrollment in the studies on WAS and CGD is underway. Four pilot projects have been funded, and 12 junior investigators have received fellowship awards. Important publications of the consortium describe the outcomes of hematopoietic cell transplantation for SCID during 2000-2009, diagnostic criteria for SCID, and the pilot project of newborn screening for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups, and international colleagues. Funded by the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, the PIDTC has recently received renewal for another 5 years. Here we review accomplishments of the group, projects underway, highlights of recent workshops, and challenges for the future. C1 [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, 5601 Fishers Ln,Rm 7D49, Bethesda, MD 20892 USA. [Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, Div Allergy Immunol & Blood & Marrow Transplantat, Dept Pediat, San Francisco, CA 94143 USA. [Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, UCSF Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Notarangelo, Luigi D.] Harvard Med Sch, Childrens Hosp, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Med Sch, Harvard Stem Cell Inst, Boston, MA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90024 USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Immunol & Mol Genet, Los Angeles, CA 90024 USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Pediat Allergy & Immunol, Houston, TX 77030 USA. [Burroughs, Lauri M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Pediat Hematol Oncol, Seattle, WA 98195 USA. [Torgerson, Troy R.] Univ Washington, Sch Med, Seattle Childrens Res Inst, Pediat Rheumatol, Seattle, WA USA. [Decaluwe, Helene; Haddad, Elie] Univ Montreal, Mother & Child Ste Justine Hosp, Pediat Immunol & Pediat, Montreal, PQ H3C 3J7, Canada. RP Griffith, LM (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 5601 Fishers Ln,Rm 7D49, Bethesda, MD 20892 USA. EM LGriffith@niaid.nih.gov OI Decaluwe, Helene/0000-0001-6617-0633 FU Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); Intramural Research Program of the NIAID; Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Md [U54-AI082973, U54-NS064808, U01-TR001263, R13-AI094943]; Immune Deficiency Foundation, Towson, Md; Jeffrey Modell Foundation, New York, NY; David Center, Texas Children's Hospital, Houston, Tex; John P. McGovern Foundation, Houston, Tex; Seattle Cancer Care Alliance, Seattle, Wash; Seattle Children's Research Institute and Seattle Children's Hospital, Seattle, Wash; AbbVie, St-Laurent, Quebec, Canada; ADMA Biologics, Ramsey, NJ; Baxalta, Deerfield, Ill; Bristol-Myers Squibb Canada, St-Laurent, Quebec, Canada; CSL Behring, King of Prussia, Pa; CSL Behring, Ottawa, Ontario, Canada; GRI-FOLS Canada, Mississauga, Ontario, Canada; Horizon Pharma USA, Deerfield, Ill; Miltenyi Biotec, Auburn, Calif; Octapharma Canada, Toronto, Ontario, Canada; Otsuka Canada Pharmaceutical, St-Laurent, Quebec, Canada; Sigma-Tau Pharmaceuticals, Gaithersburg, Md; ORDR, NCATS; Division of Allergy Immunology and Transplantation (DAIT), NIAID FX Supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); the Intramural Research Program of the NIAID; and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Md: U54-AI082973 (PI: M. J. Cowan), U54-NS064808 and U01-TR001263 (PI: J. P. Krischer), and R13-AI094943 (PIs: M. J. Cowan, L. D. Notarangelo). The workshops were also supported in part by the Immune Deficiency Foundation, Towson, Md; the Jeffrey Modell Foundation, New York, NY; the David Center, Texas Children's Hospital, Houston, Tex; the John P. McGovern Foundation, Houston, Tex; Seattle Cancer Care Alliance, Seattle, Wash; Seattle Children's Research Institute and Seattle Children's Hospital, Seattle, Wash; AbbVie, St-Laurent, Quebec, Canada; ADMA Biologics, Ramsey, NJ; Baxalta, Deerfield, Ill; Bristol-Myers Squibb Canada, St-Laurent, Quebec, Canada; CSL Behring, King of Prussia, Pa; CSL Behring, Ottawa, Ontario, Canada; GRI-FOLS Canada, Mississauga, Ontario, Canada; Horizon Pharma USA, Deerfield, Ill; Miltenyi Biotec, Auburn, Calif; Octapharma Canada, Toronto, Ontario, Canada; Otsuka Canada Pharmaceutical, St-Laurent, Quebec, Canada; and Sigma-Tau Pharmaceuticals, Gaithersburg, Md. The Primary Immune Deficiency Treatment Consortium (PIDTC) is a part of the Rare Diseases Clinical Research Network (RDCRN) of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is sponsored by the ORDR, NCATS, and the Division of Allergy Immunology and Transplantation (DAIT), NIAID. The opinions expressed are those of the authors and do not represent the position of the NIAID, the ORDR, the NCATS, the NIH, or the US Government. NR 57 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2016 VL 138 IS 2 BP 375 EP 385 DI 10.1016/j.jaci.2016.01.051 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA DS5PY UT WOS:000380835800006 PM 27262745 ER PT J AU Mendola, P Wallace, M Hwang, BS Liu, DP Robledo, C Mannisto, T Sundaram, R Sherman, S Ying, Q Grantz, KL AF Mendola, Pauline Wallace, Maeve Hwang, Beom Seuk Liu, Danping Robledo, Candace Mannisto, Tuija Sundaram, Rajeshwari Sherman, Seth Ying, Qi Grantz, Katherine L. TI Preterm birth and air pollution: Critical windows of exposure for women with asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; pregnancy; preterm birth; air pollution ID TIME-SERIES-ANALYSIS; PREGNANCY OUTCOMES; PARTICULATE MATTER; CHILDREN BORN; COHORT; PARTICLES; RISK; PRECONCEPTION; PENNSYLVANIA; METAANALYSIS AB Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied. Objective: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk. Methods: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O-3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated. Results: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O-3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma. Conclusions: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy. C1 [Mendola, Pauline; Wallace, Maeve; Hwang, Beom Seuk; Liu, Danping; Sundaram, Rajeshwari; Grantz, Katherine L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Rm 7B03F, Rockville, MD 20852 USA. [Robledo, Candace] Univ North Texas, Hlth Sci Ctr, Dept Behav & Community Hlth, Ft Worth, TX USA. [Mannisto, Tuija] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Oulu, Finland. [Mannisto, Tuija] Northern Finland Lab Ctr Nordlab, Oulu, Finland. [Mannisto, Tuija] Univ Oulu, Dept Clin Chem, Oulu, Finland. [Sherman, Seth] Emmes Corp, Rockville, MD USA. [Ying, Qi] Texas A&M Univ, Zachary Dept Civil Engn, College Stn, TX USA. RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Rm 7B03F, Rockville, MD 20852 USA. EM pauline.mendola@nih.gov OI Mannisto, Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844; Sundaram, Rajeshwari/0000-0002-6918-5002; Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Air Quality and Reproductive Health Study [HHSN275200800002I, HHSN27500008]; [HHSN267200603425C] 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 (NICHD), including funding for the Consortium on Safe Labor (Contract No. HHSN267200603425C) and the Air Quality and Reproductive Health Study (Contract No. HHSN275200800002I, Task Order No. HHSN27500008). This article has been cleared for publication by the NICHD, but the funding source had no role in the design, analysis, interpretation, or writing of the manuscript. Disclosure of potential conflict of interest: T. Mannisto has received grants from Laboratoriolaaketieteen edistamissaatio and Paulo Foundation. NR 42 TC 1 Z9 1 U1 8 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2016 VL 138 IS 2 BP 432 EP + DI 10.1016/j.jaci.2015.12.1309 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA DS5PY UT WOS:000380835800013 PM 26944405 ER PT J AU Hsu, AP West, RR Calvo, KR Cuellar-Rodriguez, J Parta, M Kelly, SJ Ganson, NJ Hershfield, MS Holland, SM Hickstein, DD AF Hsu, Amy P. West, Robert R. Calvo, Katherine R. Cuellar-Rodriguez, Jennifer Parta, Mark Kelly, Susan J. Ganson, Nancy J. Hershfield, Michael S. Holland, Steven M. Hickstein, Dennis D. TI Adenosine deaminase type 2 deficiency masquerading as GATA2 deficiency: Successful hematopoietic stem cell transplantation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID EOSINOPHILIC ESOPHAGITIS; ELIMINATION DIET; MONOMAC SYNDROME; ADA2; MUTATIONS; IDENTIFICATION; VASCULOPATHY; CHILDREN; FOODS C1 [Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [West, Robert R.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Cuellar-Rodriguez, Jennifer] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infect Dis, Mexico City, DF, Mexico. [Parta, Mark] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. [Kelly, Susan J.; Ganson, Nancy J.; Hershfield, Michael S.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Hershfield, Michael S.] Duke Univ, Sch Med, Dept Biochem, Durham, NC USA. RP Hickstein, DD (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. EM hicksted@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 AI999999]; NCI NIH HHS [HHSN261200800001E] NR 12 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2016 VL 138 IS 2 BP 628 EP 630 DI 10.1016/j.jaci.2016.03.016 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA DS5PY UT WOS:000380835800047 PM 27130863 ER PT J AU Olfson, M King, M Schoenbaum, M AF Olfson, Mark King, Marissa Schoenbaum, Michael TI Stimulant Treatment of Young People in the United States SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; MENTAL-HEALTH-CARE; IMMEDIATE-RELEASE METHYLPHENIDATE; COMMUNITY SAMPLE; ADHD SYMPTOMS; US CHILDREN; SERVICE USE; TRENDS; PRESCHOOLERS AB Objective: To describe national stimulant treatment patterns among young people focusing on patient age and prescribing specialty. Methods: Stimulant prescriptions to patients aged 3-24 were analyzed from the 2008 IMS LifeLink LRx Longitudinal Prescription database (n = 3,147,352), which includes 60% of all U.S. retail pharmacies. A subset of young people from 2009 with service claims (n = 197,654) were also analyzed. Denominators were adjusted to generalize estimates to the U.S. population. Population percentages filling >= 1 stimulant prescription during the study year by sex and age group (younger children, 3-5 years; older children, 6-12 years; adolescents, 13-18 years; and young adults, 19-24 years) were determined. Percentages prescribed stimulants by psychiatrists, child and adolescent psychiatrists, pediatricians, and other physicians were also determined along with percentages that were treated for a long or short duration; coprescribed other psychotropic medications; used psychosocial services; and received clinical psychiatric diagnoses. Results: Population percentages with any stimulant use varied across younger children (0.4%), older children (4.5%), adolescents (4.0%), and young adults (1.7%). Among children and adolescents, males were over twice as likely as females to receive stimulants. Percentages of stimulant-treated young people with >= 1 stimulant prescription from a child and adolescent psychiatrist varied from younger children (19.1%), older children (17.1%), and adolescents (18.2%) to young adults (10.1%), and these percentages increased among those who were also prescribed other psychotropic medications: young children (31.0%), older children (37.9%), adolescents (35.1%), and young adults (15.8%). Antipsychotics were the most commonly coprescribed class to stimulant-treated younger (15.0%) and older children (11.8%), while antidepressants were most commonly coprescribed to adolescents (17.5%) and young adults (23.9%). Conclusions: Stimulant treatment peaks during middle childhood, especially for boys. For young people treated with stimulants, including younger children, low rates of treatment by child and adolescent psychiatrists highlight difficulties with access to specialty mental health services. C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [King, Marissa] Yale Sch Management, New Haven, CT USA. [Schoenbaum, Michael] NIMH, Off Sci Policy Planning & Commun, NIH, Bethesda, MD 20892 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 National Institutes of Health; New York State Psychiatric Institute FX This research was funded by contracts from the National Institutes of Health to Yale University (M.K.) and Columbia University (M.O.). M.O. is also supported by the New York State Psychiatric Institute. NR 41 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2016 VL 26 IS 6 BP 520 EP 526 DI 10.1089/cap.2015.0228 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA DU6FA UT WOS:000382308300005 PM 26982632 ER PT J AU Hotchkiss, L Donkervoort, S Leach, ME Mohassel, P Bharucha-Goebel, DX Bradley, N Nguyen, D Hu, Y Gurgel-Giannetti, J Bonnemann, CG AF Hotchkiss, Leslie Donkervoort, Sandra Leach, Meganne E. Mohassel, Payam Bharucha-Goebel, Diana X. Bradley, Nathaniel Nguyen, David Hu, Ying Gurgel-Giannetti, Juliana Bonnemann, Carsten G. TI Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE hereditary spastic paraplegia; neuromuscular disorders; KIF1A; genetics ID MOTOR DOMAIN; PARAPARESIS; NEUROPATHY; KINESIN AB Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A. C1 [Hotchkiss, Leslie; Donkervoort, Sandra; Leach, Meganne E.; Mohassel, Payam; Bharucha-Goebel, Diana X.; Bradley, Nathaniel; Nguyen, David; Hu, Ying; Bonnemann, Carsten G.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hotchkiss, Leslie] Weill Cornell Med Coll, New York, NY USA. [Leach, Meganne E.; Bharucha-Goebel, Diana X.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gurgel-Giannetti, Juliana] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, Bldg 35 Porter NRC,Room 2A-116, Bethesda, MD 20892 USA. EM carsten.bonnemann@nih.gov FU NIH FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: All funding was provided by NIH. NR 12 TC 1 Z9 1 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2016 VL 31 IS 9 BP 1114 EP 1119 DI 10.1177/0883073816639718 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA DS7DN UT WOS:000380943100003 PM 27034427 ER PT J AU Cherkassky, L Morello, A Villena-Vargas, J Feng, Y Dimitrov, DS Jones, DR Sadelain, M Adusumilli, PS AF Cherkassky, Leonid Morello, Aurore Villena-Vargas, Jonathan Feng, Yang Dimitrov, Dimiter S. Jones, David R. Sadelain, Michel Adusumilli, Prasad S. TI Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANTIBODY-LIKE IMMUNORECEPTORS; ANTITUMOR-ACTIVITY; MESOTHELIN OVEREXPRESSION; ANTI-PD-1 ANTIBODY; PANCREATIC-CANCER; ADVANCED MELANOMA; HIGH-AFFINITY; CHIMERIC TCR; SOLID TUMORS; LUNG-CANCER AB Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB-based second-generation CAR T cells achieved tumor eradication. CAR-mediated CD28 and 4-1BB costimulation resulted in similar levels of T cell persistence in animals treated with low T cell doses; however, PD-1 upregulation within the tumor microenvironment inhibited T cell function. At lower doses, 4-1BB CAR T cells retained their cytotoxic and cytokine secretion functions longer than CD28 CAR T cells. The prolonged function of 4-1BB CAR T cells correlated with improved survival. PD-1/PD-1 ligand [PD-L1] pathway interference, through PD-1 antibody checkpoint blockade, cell-intrinsic PD-1 shRNA blockade, or a PD-1 dominant negative receptor, restored the effector function of CD28 CAR T cells. These findings provide mechanistic insights into human CAR T cell exhaustion in solid tumors and suggest that PD-1/PD-L1 blockade may be an effective strategy for improving the potency of CAR T cell therapies. C1 [Cherkassky, Leonid; Morello, Aurore; Villena-Vargas, Jonathan; Sadelain, Michel; Adusumilli, Prasad S.] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10021 USA. [Cherkassky, Leonid; Morello, Aurore; Villena-Vargas, Jonathan; Jones, David R.; Adusumilli, Prasad S.] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, New York, NY 10021 USA. [Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21701 USA. RP Adusumilli, PS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, Ctr Cell Engn, 1275 York Ave, New York, NY 10065 USA. EM adusumip@mskcc.org FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH); NIH [P30 CA008748, P50 CA086438-13]; US Department of Defense [PR101053, LC110202, BC132124]; Commonwealth Foundation for Cancer Research; Experimental Therapeutics Center; Stand Up To Cancer - Cancer Research Institute Cancer Immunology Translational Cancer research grant [SU2C-AACR-DT1012]; DallePezze Foundation; Derfner Foundation; American College of Surgeons resident research scholarship; ETC Edythe Griffinger Fellowship Program FX The authors' laboratory work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), grants from the NIH (P30 CA008748 and P50 CA086438-13), the US Department of Defense (PR101053, LC110202, and BC132124), Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center, a Stand Up To Cancer - Cancer Research Institute Cancer Immunology Translational Cancer research grant (SU2C-AACR-DT1012), the DallePezze Foundation, the Derfner Foundation, the American College of Surgeons resident research scholarship, and the ETC Edythe Griffinger Fellowship Program. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. We thank David Sewell and Alex Torres of the Memorial Sloan Kettering Cancer Center (MSK) Thoracic Surgery Service for their editorial assistance. We also thank Nina Lampen and Laurent Schmitt for the electron microscopy image. NR 71 TC 14 Z9 14 U1 9 U2 13 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 AUG 1 PY 2016 VL 126 IS 8 BP 3130 EP 3144 DI 10.1172/JCI83092 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DU1BZ UT WOS:000381943000032 PM 27454297 ER PT J AU Liangpunsakul, S Gao, B AF Liangpunsakul, Suthat Gao, Bin TI Alcohol and fat promote steatohepatitis: a critical role for fat-specific protein 27/CIDEC SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE Liver Diseases; Alcoholic; Fatty Liver ID ADIPOSE TRIGLYCERIDE LIPASE; ADIPOCYTE-SPECIFIC GENE; HEPATIC STEATOSIS; INSULIN SENSITIVITY; LIPID-METABOLISM; CIDE PROTEINS; LIVER-DISEASE; PATHOGENESIS; EXPRESSION; FSP27 AB Alcoholic liver disease (ALD) is a major public health problem worldwide and is the leading cause of end-stage liver disease. While the ultimate control of ALD will require the prevention of alcohol abuse, better understanding of the mechanisms of alcohol-induced liver injury may lead to treatments of fatty liver, alcoholic hepatitis, and prevention or delay of occurrence of cirrhosis. The elucidation and the discovery of several new concepts in ALD pathogenesis have raised our understanding on the complex mechanisms and the potential in developing the new strategies for therapeutic benefits. In this review, we provide the most up-to-date information on the basic molecular mechanisms focusing on the role of fat-specific protein 27/CIDEC in the pathogenesis of ALD. C1 [Liangpunsakul, Suthat] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Dept Med, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA. [Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD 20852 USA. RP Liangpunsakul, S (reprint author), Div Gastroenterol & Hepatol, 550 N Univ Blvd,UH 4100, Indianapolis, IN 46202 USA. EM sliangpu@iupui.edu FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health; VA Merit Award [1I01CX000361]; NIH [U01AA021840]; US DOD [W81XWH-12-1-0497] FX This work was supported by the intramural program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (to BG), VA Merit Award 1I01CX000361, NIH U01AA021840, US DOD W81XWH-12-1-0497 (to SL). NR 34 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD AUG PY 2016 VL 64 IS 6 BP 1078 EP 1081 DI 10.1136/jim-2016-000204 PG 4 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA DV0BJ UT WOS:000382582300002 PM 27342423 ER PT J AU Henderson, BW Gentry, EG Rush, T Troncoso, JC Thambisetty, M Montine, TJ Herskowitz, JH AF Henderson, Benjamin W. Gentry, Erik G. Rush, Travis Troncoso, Juan C. Thambisetty, Madhav Montine, Thomas J. Herskowitz, Jeremy H. TI Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer's disease and ROCK1 depletion reduces amyloid- levels in brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid-; mild cognitive impairment; Rho kinase; ROCK1; ROCK2 ID BETA PRODUCTION; GROWTH CONE; PHOSPHORYLATION; DEGENERATION; INHIBITION; MECHANISM; SYNAPSE; MICE AB Alzheimer's disease (AD) is the leading cause of dementia and mitigating amyloid- (A) levels may serve as a rational therapeutic avenue to slow AD progression. Pharmacologic inhibition of the Rho-associated protein kinases (ROCK1 and ROCK2) is proposed to curb A levels, and mechanisms that underlie ROCK2s effects on A production are defined. How ROCK1 affects A generation remains a critical barrier. Here, we report that ROCK1 protein levels were elevated in mild cognitive impairment due to AD (MCI) and AD brains compared to controls. A42 oligomers marginally increased ROCK1 and ROCK2 protein levels in neurons but strongly induced phosphorylation of Lim kinase 1 (LIMK1), suggesting that A42 activates ROCKs. RNAi depletion of ROCK1 or ROCK2 suppressed endogenous A40 production in neurons, and A40 levels were reduced in brains of ROCK1 heterozygous knock-out mice compared to wild-type littermate controls. ROCK1 knockdown decreased amyloid precursor protein (APP), and treatment with bafilomycin accumulated APP levels in neurons depleted of ROCK1. These observations suggest that reduction of ROCK1 diminishes A levels by enhancing APP protein degradation. Collectively, these findings support the hypothesis that both ROCK1 and ROCK2 are therapeutic targets to combat A production in AD. C1 [Henderson, Benjamin W.; Gentry, Erik G.; Rush, Travis; Herskowitz, Jeremy H.] Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL USA. [Henderson, Benjamin W.; Gentry, Erik G.; Rush, Travis; Herskowitz, Jeremy H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Thambisetty, Madhav] NIA, Unit Clin & Translat Neurosci, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Montine, Thomas J.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Herskowitz, Jeremy H.] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL USA. RP Herskowitz, JH (reprint author), Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, 1825 Univ Blvd, Birmingham, AL 35294 USA.; Herskowitz, JH (reprint author), Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Dept Neurobiol, 1825 Univ Blvd, Birmingham, AL 35294 USA. EM jhersko@uab.edu FU National Institutes of Health through NIA [AG043552-05]; New Investigator Research Grant from the Alzheimer's Association [2015-NIRG-339422]; Viral Vector Core of the Emory Neuroscience NINDS Core Facilities grant [P30NS055077]; Johns Hopkins University Alzheimer's Disease Research Center NIH [AG05146, AG05136]; Intramural Research Program of the NIH, National Institute on Aging FX This work was supported by the National Institutes of Health through NIA AG043552-05 to J.H.H. This work was also supported by a New Investigator Research Grant 2015-NIRG-339422 from the Alzheimer's Association to J.H.H. This research project was supported in part by the Viral Vector Core of the Emory Neuroscience NINDS Core Facilities grant, P30NS055077, the Johns Hopkins University Alzheimer's Disease Research Center NIH AG05146 to Dr Juan Troncoso, and AG05136 to T.J.M. We are grateful to participants in the Baltimore Longitudinal Study of Aging for their invaluable contribution. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. We thank Drs James Lah, Allan Levey, and Erik Roberson for helpful discussions and Dr Jeremy Day's lab for technical assistance. The authors have no conflict of interest to declare. NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 IS 4 BP 525 EP 531 DI 10.1111/jnc.13688 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU8ZZ UT WOS:000382507300004 PM 27246255 ER PT J AU Hediger, ML Fuchs, KM Grantz, KL Grewal, J Kim, S Gore-Langton, RE Louis, GMB D'Alton, ME Albert, PS AF Hediger, Mary L. Fuchs, Karin M. Grantz, Katherine L. Grewal, Jagteshwar Kim, Sungduk Gore-Langton, Robert E. Louis, Germaine M. Buck D'Alton, Mary E. Albert, Paul S. TI Ultrasound Quality Assurance for Singletons in the National Institute of Child Health and Human Development Fetal Growth SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE obstetrics; obstetric ultrasound; quality assurance; quality control; reliability; ultrasound ID REPRODUCIBILITY; RELIABILITY; BIOMETRY AB Objectives-To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability. Methods-After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. Results-The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (> 0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. Conclusions-Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth. C1 [Hediger, Mary L.; Grantz, Katherine L.; Grewal, Jagteshwar; Kim, Sungduk; Louis, Germaine M. Buck; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA. [Fuchs, Karin M.; D'Alton, Mary E.] Columbia Univ, Dept Obstet & Gynecol, Med Ctr, New York, NY USA. [Gore-Langton, Robert E.] Emmes Corp, Rockville, MD USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, 6710B Rockledge Dr,MSC 7004, Rockville, MD 20817 USA. EM louisg@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural program [HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C]; American Recovery and Reinvestment Act FX We thank the principal investigators at the clinical sites for their support and the site sonographers for their good and careful work. The principal investigators were: Anthony Sciscione, DO (Christiana Care Health System, Newark, DE); Deborah A. Wing, MD, MBA (University of California, Irvine, Long Beach Memorial Medical Center, Long Beach, CA; and Fountain Valley Regional Hospital and Medical Center, Fountain Valley, CA); William A. Grobman, MD, MBA (Northwestern University Feinberg School of Medicine, Chicago, IL); Roger B. Newman, MD (Medical University of South Carolina, Charleston, SC); Ronald Wapner, MD (Columbia University Medical Center, New York, NY); Daniel Skupski, MD (New York Hospital Queens, Flushing, NY); Angela C. Ranzini, MD (St Peter's University Hospital, New Brunswick, NJ); John Owen, MD, MSPH (University of Alabama at Birmingham, Birmingham, AL); Edward K. Chien, MD (Women and Infants Hospital of Rhode Island, Providence, RI); and Sabrina Craigo, MD (Tufts Medical Center, Boston, MA). We also thank Patricia Morgan, RDMS, who served as the primary expert sonographer, and George Bega, MD, who served as a backup expert for quality assurance (QA), for their contributions. Matthew Beyers (The Emmes Corporation) was instrumental in setting up the image management system to conduct the QA, and Scott McCrimmon (The Emmes Corporation) contributed his invaluable technical expertise in image management. This research was supported by funding through the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural program (contracts HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, and HHSN275201000009C) and included funding through the American Recovery and Reinvestment Act of 2009. NR 20 TC 0 Z9 0 U1 2 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD AUG 1 PY 2016 VL 35 IS 8 BP 1725 EP 1733 DI 10.7863/ultra.15.09087 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA DU9HJ UT WOS:000382527000013 PM 27353072 ER PT J AU Lee, JH Gamarel, KE Bryant, KJ Zaller, ND Operario, D AF Lee, Ji Hyun Gamarel, Kristi E. Bryant, Kendall J. Zaller, Nickolas D. Operario, Don TI Discrimination, Mental Health, and Substance Use Disorders Among Sexual Minority Populations SO LGBT HEALTH LA English DT Article DE discrimination; gender; mental health; sexual minorities; substance use ID UNITED-STATES; GENDER-DIFFERENCES; BISEXUAL ADULTS; PERCEIVED DISCRIMINATION; STRUCTURAL STIGMA; ALCOHOL-USE; STRESS; GAY; PREVALENCE; ABUSE AB Purpose: Sexual minority (lesbian, gay, bisexual) populations have a higher prevalence of mental health and substance use disorders compared to their heterosexual counterparts. Such disparities have been attributed, in part, to minority stressors, including distal stressors such as discrimination. However, few studies have examined associations between discrimination, mental health, and substance use disorders by gender among sexual minority populations. Methods: We analyzed data from 577 adult men and women who self-identified as lesbian, gay, or bisexual and participated in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Six questions assessed discrimination due to sexual orientation. Weighted multivariable logistic regression examined associations between experiences of sexual orientation discrimination and both mental health and substance use disorders. Analyses were conducted separately for sexual minority men and women, adjusting for sociodemographic covariates. Results: Sexual minority men who ever experienced discrimination (57.4%) reported higher odds of any lifetime drug use disorder and cannabis use disorder compared to sexual minority men who never experienced discrimination. Sexual minority women who ever experienced discrimination (42.9%) reported higher odds of any lifetime mood disorder and any lifetime anxiety disorder compared to sexual minority women who never experienced discrimination. Conclusion: The findings suggest that discrimination is differentially associated with internalizing (mental health) and externalizing (substance use) disorders for sexual minority men and women. These findings indicate a need to consider how homophobia and heteronormative discrimination may contribute to distinct health outcomes for lesbian and bisexual women compared with gay and bisexual men. C1 [Lee, Ji Hyun; Operario, Don] Brown Univ, Sch Publ Hlth, 121 South Main St, Providence, RI 02906 USA. [Gamarel, Kristi E.] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02912 USA. [Bryant, Kendall J.] NIAAA, Rockville, MD 20852 USA. [Zaller, Nickolas D.] Univ Arkansas, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72204 USA. RP Operario, D (reprint author), Brown Univ, Sch Publ Hlth, 121 South Main St, Providence, RI 02906 USA. EM don_operario@brown.edu FU National Institute on Alcohol Abuse and Alcoholism [U24-AA022000, P01-AA019072]; National Institute of Mental Health [T32-MH07878] FX Funding was provided by the National Institute on Alcohol Abuse and Alcoholism (grants U24-AA022000 and P01-AA019072) and National Institute of Mental Health (grant T32-MH07878). NR 41 TC 0 Z9 0 U1 6 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD AUG PY 2016 VL 3 IS 4 BP 258 EP 265 DI 10.1089/lgbt.2015.0135 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DT4XM UT WOS:000381484700004 PM 27383512 ER PT J AU Avtanski, DB Nagalingam, A Tomaszewski, JE Risbood, P Difillippantonio, MJ Saxena, NK Malhotra, SV Sharma, D AF Avtanski, Dimiter B. Nagalingam, Arumugam Tomaszewski, Joseph E. Risbood, Prabhakar Difillippantonio, Michael J. Saxena, Neeraj K. Malhotra, Sanjay V. Sharma, Dipali TI Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis SO MOLECULAR ONCOLOGY LA English DT Article DE p53; miR34a; Indolo-pyrido-isoquinolin based alkaloid; Breast cancer; EMT; Invasion ID EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; IN-VIVO; P53 FUNCTION; STEM-CELLS; MUTANT P53; MDM2; RESTORATION; PROMOTES; METASTASIS AB The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-methoxy-2,3,4,13-tetrahydro-1H-indolo [2',3':3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. P18 treatment results in downregulation of mesenchymal markers and concurrent upregulation of epithelial markers as well as inhibition of migration and invasion. Experimental epithelial mesenchymal-transition (EMT) induced by exposure to TGF beta/TNF alpha is also completely reversed by P18. Importantly, P18 also inhibits mammosphere-formation along with a reduction in the expression of sternness factors, Oct4, Nanog and Sox2. We show that P18 induces expression, phosphorylation and accumulation of p53 in cancer cells. P18-mediated induction of p53 leads to increased nuclear localization and elevated expression of p53 target genes. Using isogenic cancer cells differing only in p53 status, we show that p53 plays an important role in P18 mediated alteration of mesenchymal and epithelial genes, inhibition of migration and invasion of cancer cells. Furthermore, P18 increases miR-34a expression in p53-dependent manner and miR-34a is integral for P18-mediated inhibition of growth, invasion and mammosphere-formation. miR-34a mimics potentiate P18 efficacy while miR-34a antagomirs antagonize P18. Collectively, these data provide evidence that P18 may represent a promising therapeutic strategy for the inhibition of growth and progression of breast cancer and p53-miR-34a axis is important for P18 function. (C) 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Avtanski, Dimiter B.; Nagalingam, Arumugam; Sharma, Dipali] Johns Hopkins Univ, Sch Med, Dept Oncol, 1650 Orleans St,CRB 1,Rm 145, Baltimore, MD 21231 USA. [Avtanski, Dimiter B.; Nagalingam, Arumugam; Sharma, Dipali] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Tomaszewski, Joseph E.; Risbood, Prabhakar; Difillippantonio, Michael J.] NCI, Div Canc Treatment & Diag, NIH, Rockville, MD 20852 USA. [Sharma, Dipali] Johns Hopkins, Grad Program Cellular & Mol Med, Baltimore, MD 21231 USA. [Saxena, Neeraj K.] Univ Maryland, Sch Med, Dept Med, 660 W Redwood St,Howard Hall,Rm 301, Baltimore, MD 21201 USA. [Malhotra, Sanjay V.] Stanford Univ, Dept Radiat Oncol, Palo Alto, CA 94304 USA. [Malhotra, Sanjay V.] Stanford Univ, Stanford Canc Inst, Palo Alto, CA 94304 USA. RP Sharma, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, 1650 Orleans St,CRB 1,Rm 145, Baltimore, MD 21231 USA.; Saxena, NK (reprint author), Univ Maryland, Sch Med, Dept Med, 660 W Redwood St,Howard Hall,Rm 301, Baltimore, MD 21201 USA.; Sharma, D (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,CRB 1,Rm 145, Baltimore, MD 21231 USA.; Malhotra, SV (reprint author), Stanford Univ, Div Radiat & Canc Biol, Radiat Oncol, Palo Alto, CA USA. EM nsaxena@medicine.umaryland.edu; smalhotra@stanford.edu; dsharma7@jhmi.edu FU NIDDK NIH [K01DK077137, R03DK089130]; NCI NIH [R21CA185943, R01CA131294, R21CA155686]; Avon Foundation; NCI; NIH [HHSN261200800001E]; Breast Cancer Research Foundation (BCRF) [90047965] FX This work was supported by NIDDK NIH, K01DK077137, R03DK089130 and NCI NIH R21CA185943 (to NKS); NCI NIH R01CA131294, NCI NIH R21CA155686, Avon Foundation, NCI, NIH contract no. HHSN261200800001E (to SVM), Breast Cancer Research Foundation (BCRF) 90047965 (to DS). NR 52 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 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD AUG PY 2016 VL 10 IS 7 BP 1118 EP 1132 DI 10.1016/j.molonc.2016.04.003 PG 15 WC Oncology SC Oncology GA DU1FC UT WOS:000381952600013 PM 27259808 ER PT J AU Arthur, KC Calvo, A Price, TR Geiger, JT Chio, A Traynor, BJ AF Arthur, Karissa C. Calvo, Andrea Price, T. Ryan Geiger, Joshua T. Chio, Adriano Traynor, Bryan J. TI Projected increase in amyotrophic lateral sclerosis from 2015 to 2040 SO NATURE COMMUNICATIONS LA English DT Article ID MOTOR-NEURON DISEASE; EPIDEMIOLOGY; ALS; PREVALENCE AB Although amyotrophic lateral sclerosis (ALS) is relatively rare, the socioeconomic significance of the disease is extensive. It is therefore vital to project the epidemiologic trend of ALS. To date, there have been few published studies attempting to estimate the number and distribution of ALS cases in the upcoming years. Here we show that the number of ALS cases across the globe will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. This increase is predominantly due to ageing of the population, particularly among developing nations. This projection is likely an underestimate due to improving healthcare and economic conditions. The results should be used to inform healthcare policy to more efficiently allocate healthcare resources. C1 [Arthur, Karissa C.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Arthur, Karissa C.] Commonwealth Med Coll, Scranton, PA 18509 USA. [Calvo, Andrea; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, I-10124 Turin, Italy. [Calvo, Andrea; Chio, Adriano] Neurosci Inst Torino, I-10124 Turin, Italy. [Price, T. Ryan] NIA, Stat Genet Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Geiger, Joshua T.] NINDS, Neurodegenerat Dis Res Unit, Neurogenet Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21205 USA. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.; Traynor, BJ (reprint author), Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21205 USA. EM traynorb@mail.nih.gov FU Intramural Research Program of the US National Institutes of Health (NIH), National Institute on Aging [Z01-AG000949-02]; National Institute of Neurological Disorders and Stroke; NIH; European Community's Health Seventh Framework Programme [259867]; Joint Programme-Neurodegenerative Disease Research (Italian Ministry of Education and University) (Strength Project) FX This work was supported in part by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute on Aging (Z01-AG000949-02) and National Institute of Neurological Disorders and Stroke. 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 the Doris Duke Charitable 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. This work was supported in part by the European Community's Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867), the Joint Programme-Neurodegenerative Disease Research (Italian Ministry of Education and University) (Strength Project) and the Vialli and Mauro Foundation for ALS (grant no. 4). NR 37 TC 0 Z9 0 U1 12 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2016 VL 7 AR 12408 DI 10.1038/ncomms12408 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT5MA UT WOS:000381526100001 PM 27510634 ER PT J AU Lamprecht, DA Finin, PM Rahman, MA Cumming, BM Russell, SL Jonnala, SR Adamson, JH Steyn, AJC AF Lamprecht, Dirk A. Finin, Peter M. Rahman, Md Aejazur Cumming, Bridgette M. Russell, Shannon L. Jonnala, Surendranadha R. Adamson, John H. Steyn, Adrie J. C. TI Turning the respiratory flexibility of Mycobacterium tuberculosis against itself SO NATURE COMMUNICATIONS LA English DT Article ID MULTIDRUG-RESISTANT TUBERCULOSIS; ESCHERICHIA-COLI; CORYNEBACTERIUM-GLUTAMICUM; CYTOCHROME BD; CLINICAL CANDIDATE; ENERGY-METABOLISM; N-ACETYLCYSTEINE; GLYCOLYTIC FLUX; ATP HOMEOSTASIS; CLOFAZIMINE AB The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of the ETC as a drug target, by measuring Mtb's respiration using extracellular flux technology. We find that Mtb's ETC rapidly reroutes around inhibition by these drugs and increases total respiration to maintain ATP levels. Rerouting is possible because Mtb rapidly switches between terminal oxidases, and, unlike eukaryotes, is not susceptible to back pressure. Increased ETC activity potentiates clofazimine's production of reactive oxygen species, causing rapid killing in vitro and in a macrophage model. Our results indicate that combination therapy targeting the ETC can be exploited to enhance killing of Mtb. C1 [Lamprecht, Dirk A.; Finin, Peter M.; Rahman, Md Aejazur; Cumming, Bridgette M.; Russell, Shannon L.; Adamson, John H.; Steyn, Adrie J. C.] KwaZulu Natal Res Inst TB & HIV K RITH, K RITH Tower Bldg,Level 3,719 Umbilo Rd, ZA-4001 Durban, South Africa. [Finin, Peter M.] Univ Pittsburgh, Dept Internal Med, 1218 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. [Jonnala, Surendranadha R.] NIAID, TB Res Sect, NIH, 6610 Rockledge Dr, Bethesda, MD 20817 USA. [Steyn, Adrie J. C.] Univ Alabama Birmingham, Dept Microbiol, 1720 2nd Ave South, Birmingham, AL 35294 USA. [Steyn, Adrie J. C.] Univ Alabama Birmingham, Ctr AIDS Res, 1720 2nd Ave South, Birmingham, AL 35294 USA. [Steyn, Adrie J. C.] Univ Alabama Birmingham, Ctr Free Rad Biol, 1720 2nd Ave South, Birmingham, AL 35294 USA. RP Steyn, AJC (reprint author), KwaZulu Natal Res Inst TB & HIV K RITH, K RITH Tower Bldg,Level 3,719 Umbilo Rd, ZA-4001 Durban, South Africa.; Steyn, AJC (reprint author), Univ Alabama Birmingham, Dept Microbiol, 1720 2nd Ave South, Birmingham, AL 35294 USA.; Steyn, AJC (reprint author), Univ Alabama Birmingham, Ctr AIDS Res, 1720 2nd Ave South, Birmingham, AL 35294 USA.; Steyn, AJC (reprint author), Univ Alabama Birmingham, Ctr Free Rad Biol, 1720 2nd Ave South, Birmingham, AL 35294 USA. EM asteyn@uab.edu FU Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council; South African Department of Science and Technology; National Institutes of Health Grant [R01AI058131]; Department of Defence Award [W81XWH-13-1-0149]; UAB Centres for AIDS Research and Free Radical Biology; UKZN CHS; K-RITH; Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation; University of KwaZulu-Natal FX We thank Dr William Jacobs for Mtb mc26230, Dr Helena Boshoff for the Mtb cydKO mutant (generated in the lab of Dr Valerie Mizrahi) and qcrB SNP strains, and Dr Digby Warner for BDQ. Research reported in this publication was supported by the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council with funds received from the South African Department of Science and Technology. Part of this work is supported by the National Institutes of Health Grant R01AI058131, Department of Defence Award W81XWH-13-1-0149 and the UAB Centres for AIDS Research and Free Radical Biology to AJCS. AJCS is a Burroughs Welcome Investigator in the Pathogenesis of Infectious Diseases. DAL received support from the UKZN CHS and K-RITH. PMF was a Howard Hughes Medical Institute Medical Research Fellow. Open access publication of this article has been made possible through support from the Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation and the University of KwaZulu-Natal. NR 61 TC 1 Z9 1 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2016 VL 7 AR 12393 DI 10.1038/ncomms12393 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT5LY UT WOS:000381525900001 PM 27506290 ER PT J AU Benveniste, O Rider, LG AF Benveniste, Olivier Rider, Lisa G. CA ENMC Myositis Outcomes Study Grp TI 213th ENMC International Workshop: Outcome measures and clinical trial readiness in idiopathic inflammatory myopathies, Heemskerk, The Netherlands, 18-20 September 2015 SO NEUROMUSCULAR DISORDERS LA English DT Article ID QUALITY-OF-LIFE; INCLUSION-BODY MYOSITIS; CUTANEOUS ASSESSMENT-TOOL; TERM-FOLLOW-UP; DERMATOMYOSITIS DISEASE AREA; INTERSTITIAL LUNG-DISEASE; FUNCTIONAL RATING-SCALE; ADULT MUSCLE DISEASE; JUVENILE DERMATOMYOSITIS; PULMONARY-FIBROSIS C1 [Benveniste, Olivier] Hop La Pitie Salpetriere, AP HP, Dept Med Interne & Immunol Clin, DHU I2B, Paris, France. [Benveniste, Olivier] Univ Paris 04, UPMC, INSERM, U974, Paris, France. [Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Clin Res Branch, NIH, Bldg 10,Rm 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, Clin Res Branch, NIH, Bldg 10,Rm 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.; Benveniste, O (reprint author), Hop La Pitie Salpetriere, Dept Med Interne & Immunol Clin, 47 Blvd Hop, F-75013 Paris, France. EM olivier.benveniste@aphp.fr; riderl@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458 FU European Neuromuscular Centre (ENMC); Association Francaise contre les Myopathies (France); Deutsche Gesellschaft fur Muskelkranke (Germany); Muscular Dystrophy Campaign (UK); Muskelsvindfonden (Denmark); Prinses Beatrix Fonds (The Netherlands); Schweizerische Stiftung fur die Erforschung der Muskelkrankheiten (Switzerland); Telethon Foundation (Italy); Spierziekten Nederland (The Netherlands); Finnish Neuromuscular Association (Finland); Myositis UK; Myositis Association; AstraZeneca; aTyr Pharmaceuticals; LFB Group; MedImmune; intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences FX This workshop was made possible with the financial support of the European Neuromuscular Centre (ENMC) and its main sponsors: Association Francaise contre les Myopathies (France), Deutsche Gesellschaft fur Muskelkranke (Germany), Muscular Dystrophy Campaign (UK), Muskelsvindfonden (Denmark), Prinses Beatrix Fonds (The Netherlands), Schweizerische Stiftung fur die Erforschung der Muskelkrankheiten (Switzerland), Telethon Foundation (Italy), Spierziekten Nederland (The Netherlands) and Associated members, and the Finnish Neuromuscular Association (Finland). The workshop received supplementary funding from Myositis UK, The Myositis Association, AstraZeneca, aTyr Pharmaceuticals, LFB Group, and MedImmune. This work was supported in part by the intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences. The views expressed are those of the authors and not necessarily those of the US government, the (UK) National Health Service (NHS), the NIHR, or the (UK) Department of Health. We thank Drs. James Katz and Lisa Christopher-Stine for critical reading of the manuscript. NR 103 TC 1 Z9 1 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD AUG PY 2016 VL 26 IS 8 BP 523 EP 534 DI 10.1016/j.nmd.2016.05.014 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DT5TK UT WOS:000381545300009 PM 27312023 ER PT J AU Melani, C Roschewski, M AF Melani, Christopher Roschewski, Mark TI Molecular Monitoring of Cell-Free Circulating Tumor DNA in Non-Hodgkin Lymphoma SO ONCOLOGY-NEW YORK LA English DT Review ID RESIDUAL DISEASE DETECTION; CANCER-PATIENTS; FOLLICULAR LYMPHOMA; NUCLEIC-ACIDS; THERAPY; REMISSION; RITUXIMAB; BLOOD; PET; ERA AB The ability to precisely monitor the effectiveness of therapy for non-Hodgkin lymphoma has important clinical implications. In patients with curable lymphomas, such as diffuse large B-cell lymphoma, the eradication of all disease is necessary for cure. In patients with incurable lymphomas, such as follicular lymphoma and mantle cell lymphoma, deep and durable remissions are associated with improvements in survival. Radiographic imaging modalities such as computed tomography and positron emission tomography are the current gold standard for monitoring therapy, but they are fundamentally limited by radiation risks, costs, lack of tumor specificity, and inability to detect disease at the molecular level. Novel sequencing-based methods can detect circulating tumor DNA (ctDNA) in the peripheral blood with great sensitivity, which opens new opportunities for molecular monitoring before, during, and after therapy. Beyond monitoring, ctDNA can also be used as a "liquid biopsy" to assess for molecular changes after therapy that may identify treatment-resistant clones. ctDNA is an emerging tool that may transform our ability to offer precision therapy in non-Hodgkin lymphoma. C1 [Melani, Christopher] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Roschewski, Mark] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. RP Roschewski, M (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. EM mark.roschewski@nih.gov FU intramural research program of the National Institutes of Health FX The authors acknowledge support from the intramural research program of the National Institutes of Health, especially Wyndham Wilson, Kieron Dunleavy, and the rest of the research team. NR 40 TC 1 Z9 1 U1 5 U2 5 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 2016 VL 30 IS 8 BP 731 EP 738 PG 8 WC Oncology SC Oncology GA DT4LN UT WOS:000381452700008 ER PT J AU Hoyme, HE Kalberg, WO Elliott, AJ Blankenship, J Buckley, D Marais, AS Manning, MA Robinson, LK Adam, MP Abdul-Rahman, O Jewett, T Coles, CD Chambers, C Jones, KL Adnams, CM Shah, PE Riley, EP Charness, ME Warren, KR May, PA AF Hoyme, H. Eugene Kalberg, Wendy O. Elliott, Amy J. Blankenship, Jason Buckley, David Marais, Anna-Susan Manning, Melanie A. Robinson, Luther K. Adam, Margaret P. Abdul-Rahman, Omar Jewett, Tamison Coles, Claire D. Chambers, Christina Jones, Kenneth L. Adnams, Colleen M. Shah, Prachi E. Riley, Edward P. Charness, Michael E. Warren, Kenneth R. May, Philip A. TI Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders SO PEDIATRICS LA English DT Article ID MATERNAL RISK-FACTORS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PALPEBRAL FISSURE LENGTH; PREGNANCY RECOGNITION; HEAD CIRCUMFERENCE; BIRTH-DEFECTS; NEUROBEHAVIORAL PROFILE; FULL SPECTRUM; BRAIN VOLUME; SOUTH-AFRICA AB The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol. C1 [Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Sanford Res, Sioux Falls, SD USA. [Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Univ South Dakota, Dept Pediat, Sanford Sch Med, Sioux Falls, SD USA. [Hoyme, H. Eugene] Univ Arizona, Coll Med, Ctr Appl Genet & Genom, Tucson, AZ USA. [Hoyme, H. Eugene] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA. [Kalberg, Wendy O.; Blankenship, Jason; Buckley, David; May, Philip A.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. [Marais, Anna-Susan] Univ Stellenbosch, Fac Med & Hlth Sci, Stellenbosch, South Africa. [Manning, Melanie A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Manning, Melanie A.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Robinson, Luther K.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14260 USA. [Adam, Margaret P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Abdul-Rahman, Omar] Univ Mississippi, Sch Med, Dept Pediat, Jackson, MS 39216 USA. [Jewett, Tamison] Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27109 USA. [Coles, Claire D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Chambers, Christina; Jones, Kenneth L.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Adnams, Colleen M.] Univ Cape Town, Fac Hlth Sci, Dept Psychiat & Mental Hlth, Cape Town, South Africa. [Shah, Prachi E.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA. [Riley, Edward P.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Charness, Michael E.] Harvard Med Sch, Dept Neurol, VA Boston Healthcare Syst, Boston, MA USA. [Charness, Michael E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Warren, Kenneth R.] NIAAA, Bethesda, MD USA. [May, Philip A.] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Inst Nutr Res, Chapel Hill, NC USA. RP Hoyme, HE (reprint author), Sanford Hlth, Genet & Genom Med, POB 5039, Sioux Falls, SD 57117 USA. EM gene.hoyme@sanfordhealth.org FU National Institutes of Health (NIH): National Institute on Alcohol Abuse and Alcoholism [R01 AA11685, R01/U01 AA01115134, U01 AA019879-01/NIH-NIAAA]; Oxnard Foundation, Newport Beach, CA; National Institutes of Health (NIH) FX This project was funded by the National Institutes of Health (NIH): National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685, R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence); and by the Oxnard Foundation, Newport Beach, CA. Funded by the National Institutes of Health (NIH). NR 112 TC 4 Z9 4 U1 19 U2 20 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 AUG PY 2016 VL 138 IS 2 AR e20154256 DI 10.1542/peds.2015-4256 PG 18 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500017 ER PT J AU McKinney, CO Hahn-Holbrook, J Chase-Lansdale, PL Ramey, SL Krohn, J Reed-Vance, M Raju, TNK Shalowitz, MU AF McKinney, Chelsea O. Hahn-Holbrook, Jennifer Chase-Lansdale, P. Lindsay Ramey, Sharon L. Krohn, Julie Reed-Vance, Maxine Raju, Tonse N. K. Shalowitz, Madeleine U. CA Community Child Hlth Res Network TI Racial and Ethnic Differences in Breastfeeding SO PEDIATRICS LA English DT Article ID UNITED-STATES; DURATION; INITIATION; ACCULTURATION; DISPARITIES; DEPRESSION; HOSPITALS; COUNTRIES; CHILDREN; PROGRESS AB OBJECTIVES: Breastfeeding rates differ among racial/ethnic groups in the United States. Our aim was to test whether racial/ethnic disparities in demographic characteristics, hospital use of infant formula, and family history of breastfeeding mediated racial/ethnic gaps in breastfeeding outcomes. METHODS: We analyzed data from the Community and Child Health Network study (N = 1636). Breastfeeding initiation, postnatal intent to breastfeed, and breastfeeding duration were assessed postpartum. Hierarchical linear modeling was used to estimate relative odds of breastfeeding initiation, postnatal intent, and duration among racial/ethnic groups and to test the candidate mediators of maternal age, income, household composition, employment, marital status, postpartum depression, preterm birth, smoking, belief that "breast is best," family history of breastfeeding, in-hospital formula introduction, and WIC participation. RESULTS: Spanish-speaking Hispanic mothers were most likely to initiate (91%), intend (92%), and maintain (mean duration, 17.1 weeks) breastfeeding, followed by English-speaking Hispanic mothers (initiation 90%, intent 88%; mean duration, 10.4 weeks) and white mothers (initiation 78%, intent 77%; mean duration, 16.5 weeks); black mothers were least likely to initiate (61%), intend (57%), and maintain breastfeeding (mean duration, 6.4 weeks). Demographic variables fully mediated disparities between black and white mothers in intent and initiation, whereas demographic characteristics and in-hospital formula feeding fully mediated breastfeeding duration. Family breastfeeding history and demographic characteristics helped explain the higher breastfeeding rates of Hispanic mothers relative to white and black mothers. CONCLUSIONS: Hospitals and policy makers should limit in-hospital formula feeding and consider family history of breastfeeding and demographic characteristics to reduce racial/ethnic breastfeeding disparities. C1 [McKinney, Chelsea O.; Shalowitz, Madeleine U.] NorthShore Univ HealthSyst, Dept Pediat, 1001 Univ Pl,Suite 348, Evanston, IL 60201 USA. [McKinney, Chelsea O.; Shalowitz, Madeleine U.] Res Inst, 1001 Univ Pl,Suite 348, Evanston, IL 60201 USA. [Hahn-Holbrook, Jennifer] Chapman Univ, Crean Coll Hlth & Behav Sci, Orange, CA USA. [Chase-Lansdale, P. Lindsay] Northwestern Univ, Inst Policy Res, Evanston, IL USA. [Ramey, Sharon L.] Virginia Tech, Caril Res Inst, Roanoke, VA USA. [Krohn, Julie] Lake Cty Hlth Dept, Waukegan, IL USA. [Krohn, Julie] Ctr Community Hlth, Waukegan, IL USA. [Reed-Vance, Maxine] Baltimore Hlth Start Inc, Baltimore, MD USA. [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Rockville, MD USA. [Shalowitz, Madeleine U.] Univ Chicago, Pritzker Sch Med, Dept Pediat, Chicago, IL USA. RP McKinney, CO (reprint author), NorthShore Univ HealthSyst, Dept Pediat, 1001 Univ Pl,Suite 348, Evanston, IL 60201 USA.; McKinney, CO (reprint author), Res Inst, 1001 Univ Pl,Suite 348, Evanston, IL 60201 USA. EM chelseaomckinney@gmail.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [UHD44207, U HD44219, UHD44226, U HD44245, U HD44253, U HD54791, U HD54019, UHD44226-05S1, U HD44245-06S1, R03 HD59584]; National Institute for Nursing Research [U NR008929]; National Institutes of Health (NIH) FX All phases of this study were supported by grants to the Community and Child Health Network through cooperative agreements with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UHD44207, U HD44219, UHD44226, U HD44245, U HD44253, U HD54791, U HD54019, UHD44226-05S1, U HD44245-06S1, and R03 HD59584) and the National Institute for Nursing Research (U NR008929). Funded by the National Institutes of Health (NIH). NR 36 TC 1 Z9 1 U1 6 U2 10 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 AUG PY 2016 VL 138 IS 2 AR e20152388 DI 10.1542/peds.2015-2388 PG 11 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500004 ER PT J AU Freund, J May, RM Yang, EJ Li, HC McCullen, M Zhang, B Lenvik, T Cichocki, F Anderson, SK Kambayashi, T AF Freund, Jacquelyn May, Rebecca M. Yang, Enjun Li, Hongchuan McCullen, Matthew Zhang, Bin Lenvik, Todd Cichocki, Frank Anderson, Stephen K. Kambayashi, Taku TI Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells SO PLOS BIOLOGY LA English DT Article ID NK CELLS; ADAPTER PROTEIN; DENDRITIC CELLS; LY49 RECEPTORS; MISSING-SELF; BONE-MARROW; IN-VIVO; MHC; EXPRESSION; REPERTOIRE AB It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respond, expand, and differentiate into memory-like cells in a ligand-specific manner. MHC I-binding inhibitory receptors, including those belonging to the Ly49 and KIR families, are expressed in a variegated manner, which creates ligand-specific diversity within the NK cell pool. However, how NK cells determine which inhibitory receptors to express on their cell surface during a narrow window of development is largely unknown. In this manuscript, we demonstrate that signals from activating receptors are critical for induction of Ly49 and KIR receptors during NK cell development; activating receptor-derived signals increased the probability of the Ly49 bidirectional Pro1 promoter to transcribe in the forward versus the reverse direction, leading to stable expression of Ly49 receptors in mature NK cells. Our data support a model where the balance of activating and inhibitory receptor signaling in NK cells selects for the induction of appropriate inhibitory receptors during development, which NK cells use to create a diverse pool of ligand-specific NK cells. C1 [Freund, Jacquelyn; May, Rebecca M.; Yang, Enjun; Kambayashi, Taku] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Li, Hongchuan; Anderson, Stephen K.] Leidos Biomed Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD USA. [McCullen, Matthew; Anderson, Stephen K.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Zhang, Bin; Lenvik, Todd; Cichocki, Frank] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Box 736 UMHC, Minneapolis, MN 55455 USA. RP Kambayashi, T (reprint author), Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM taku.kambayashi@uphs.upenn.edu OI McCullen, Matthew/0000-0001-9138-1483 FU National Cancer Institute (NCI), National Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research Program of the NIH, NCI, Center for Cancer Research; NIH [R01HL111501, R01HL107589, T32-AI055428] FX This project has been funded in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under contract HHSN261200800001E, the Intramural Research Program of the NIH, NCI, Center for Cancer Research and by NIH grants R01HL111501 (TK), R01HL107589 (TK), T32-AI055428 (JF) http://www.nhlbi.nih.gov/. The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 1 Z9 1 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD AUG PY 2016 VL 14 IS 8 AR e1002526 DI 10.1371/journal.pbio.1002526 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA DU7LM UT WOS:000382395700002 PM 27500644 ER PT J AU Hartford, SA Chittela, R Ding, X Vyas, A Martin, B Burkett, S Haines, DC Southon, E Tessarollo, L Sharan, SK AF Hartford, Suzanne A. Chittela, Rajanikant Ding, Xia Vyas, Aradhana Martin, Betty Burkett, Sandra Haines, Diana C. Southon, Eileen Tessarollo, Lino Sharan, Shyam K. TI Interaction with PALB2 Is Essential for Maintenance of Genomic Integrity by BRCA2 SO PLOS GENETICS LA English DT Article ID BREAST-CANCER; HOMOLOGOUS RECOMBINATION; HETEROZYGOUS MUTATIONS; NUCLEAR-ORGANIZATION; EMBRYONIC LETHALITY; GERMLINE MUTATION; DNA-REPLICATION; MOUSE MODEL; MICE; SUSCEPTIBILITY AB Human breast cancer susceptibility gene, BRCA2, encodes a 3418-amino acid protein that is essential for maintaining genomic integrity. Among the proteins that physically interact with BRCA2, Partner and Localizer of BRCA2 (PALB2), which binds to the N-terminal region of BRCA2, is vital for its function by facilitating its subnuclear localization. A functional redundancy has been reported between this N-terminal PALB2-binding domain and the C-terminal DNA-binding domain of BRCA2, which undermines the relevance of the interaction between these two proteins. Here, we describe a genetic approach to examine the functional significance of the interaction between BRCA2 and PALB2 by generating a knock-in mouse model of Brca2 carrying a single amino acid change (Gly25Arg, Brca2G25R) that disrupts this interaction. In addition, we have combined Brca2G25R homozygosity as well as hemizygosity with Palb2 and Trp53 heterozygosity to generate an array of genotypically and phenotypically distinct mouse models. Our findings reveal defects in body size, fertility, meiotic progression, and genome stability, as well as increased tumor susceptibility in these mice. The severity of the phenotype increased with a decrease in the interaction between BRCA2 and PALB2, highlighting the significance of this interaction. In addition, our findings also demonstrate that hypomorphic mutations such as Brca2G25R have the potential to be more detrimental than the functionally null alleles by increasing genomic instability to a level that induces tumorigenesis, rather than apoptosis. C1 [Hartford, Suzanne A.; Chittela, Rajanikant; Ding, Xia; Vyas, Aradhana; Burkett, Sandra; Southon, Eileen; Tessarollo, Lino; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Martin, Betty; Haines, Diana C.; Southon, Eileen] NCI, Leidos Biomed Inc, Frederick, MD 21701 USA. [Chittela, Rajanikant] Bhabha Atom Res Ctr, Bombay, Maharashtra, India. RP Sharan, SK (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. EM sharans@mail.nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health [HHSN261200800001E] FX This research was sponsored by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health under Contract No. HHSN261200800001E. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 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 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006236 DI 10.1371/journal.pgen.1006236 PG 27 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500033 PM 27490902 ER PT J AU Lavender, CA Cannady, KR Hoffman, JA Trotter, KW Gilchrist, DA Bennett, BD Burkholder, AB Burd, CJ Fargo, DC Archer, TK AF Lavender, Christopher A. Cannady, Kimberly R. Hoffman, Jackson A. Trotter, Kevin W. Gilchrist, Daniel A. Bennett, Brian D. Burkholder, Adam B. Burd, Craig J. Fargo, David C. Archer, Trevor K. TI Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters SO PLOS GENETICS LA English DT Article ID FACTOR-BINDING; RNA EXOSOME; ELEMENTS; GENE; SEQUENCES; EXPRESSION; VERTEBRATE; DROSOPHILA; INITIATION; RESOLUTION AB Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment. C1 [Lavender, Christopher A.; Cannady, Kimberly R.; Hoffman, Jackson A.; Trotter, Kevin W.; Gilchrist, Daniel A.; Archer, Trevor K.] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Lavender, Christopher A.; Bennett, Brian D.; Burkholder, Adam B.; Fargo, David C.] NIEHS, Integrat Bioinformat, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Burd, Craig J.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Burd, Craig J.] Ohio State Univ, Wexner Med Ctr, Columbus, OH USA. [Gilchrist, Daniel A.] NHGRI, Bethesda, MD 20892 USA. RP Archer, TK (reprint author), NIEHS, Epigenet & Stem Cell Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Fargo, DC (reprint author), NIEHS, Integrat Bioinformat, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM fargod@niehs.nih.gov; archer1@niehs.nih.gov RI Burd, Craig/D-9500-2017; OI Burd, Craig/0000-0002-6899-6751 FU Intramural Research Program of the NIH - National Institute of Environmental Health Sciences [Z01 ES071006-15] FX This research was supported by the Intramural Research Program of the NIH - National Institute of Environmental Health Sciences [Z01 ES071006-15; nih.gov]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 2 Z9 2 U1 3 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006224 DI 10.1371/journal.pgen.1006224 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500026 ER PT J AU Lo, CL Lossie, AC Liang, TB Liu, YL Xuei, XL Lumeng, L Zhou, FC Muir, WM AF Lo, Chiao-Ling Lossie, Amy C. Liang, Tiebing Liu, Yunlong Xuei, Xiaoling Lumeng, Lawrence Zhou, Feng C. Muir, William M. TI High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model SO PLOS GENETICS LA English DT Article ID QUANTITATIVE TRAIT LOCI; CORTICOTROPIN-RELEASING-FACTOR; ESTIMATING F-STATISTICS; FALSE DISCOVERY RATE; WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; POPULATION-STRUCTURE; NATURAL-SELECTION; PROTEIN FUNCTION; DRUG-ADDICTION AB Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved similar to 46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits. C1 [Lo, Chiao-Ling; Lossie, Amy C.; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C.; Muir, William M.] Indiana Univ Sch Med, Indiana Alcohol Res Ctr, Indianapolis, IN 46202 USA. [Lo, Chiao-Ling; Zhou, Feng C.] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Lossie, Amy C.; Muir, William M.] Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA. [Liang, Tiebing; Lumeng, Lawrence; Muir, William M.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Liu, Yunlong] Indiana Univ Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. [Xuei, Xiaoling] Indiana Univ Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. [Zhou, Feng C.] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA. [Lossie, Amy C.] NIDA, Genet Epigenet & Dev Neurosci Branch, Div Neurosci & Behav, NIH, Bethesda, MD 20892 USA. RP Zhou, FC; Muir, WM (reprint author), Indiana Univ Sch Med, Indiana Alcohol Res Ctr, Indianapolis, IN 46202 USA.; Zhou, FC (reprint author), Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA.; Muir, WM (reprint author), Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA.; Muir, WM (reprint author), Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.; Zhou, FC (reprint author), Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA. EM imce100@iu.edu; bmuir@purdue.edu FU National Institute of Health [P60 AA07611, AA016698] FX This work was supported by the National Institute of Health P60 AA07611 and AA016698. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006178 DI 10.1371/journal.pgen.1006178 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500011 PM 27490364 ER PT J AU Rijal, K Maraia, RJ AF Rijal, Keshab Maraia, Richard J. TI Active Center Control of Termination by RNA Polymerase III and tRNA Gene Transcription Levels In Vivo SO PLOS GENETICS LA English DT Article ID TRIGGER LOOP FUNCTIONS; SACCHAROMYCES-CEREVISIAE; ELONGATION COMPLEX; FISSION YEAST; DNA HYBRID; DEPENDENT TRANSCRIPTION; SUBSTRATE-SPECIFICITY; MUTATIONAL ANALYSIS; CLEAVAGE ACTIVITY; STRUCTURAL BASIS AB The ability of RNA polymerase (RNAP) III to efficiently recycle from termination to reinitiation is critical for abundant tRNA production during cellular proliferation, development and cancer. Yet understanding of the unique termination mechanisms used by RNAP III is incomplete, as is its link to high transcription output. We used two tRNA-mediated suppression systems to screen for Rpc1 mutants with gain-and loss-of termination phenotypes in S. pombe. 122 point mutation mutants were mapped to a recently solved 3.9 angstrom structure of yeast RNAP III elongation complex (EC); they cluster in the active center bridge helix and trigger loop, as well as the pore and funnel, the latter of which indicate involvement of the RNA cleavage domain of the C11 subunit in termination. Purified RNAP III from a readthrough (RT) mutant exhibits increased elongation rate. The data strongly support a kinetic coupling model in which elongation rate is inversely related to termination efficiency. The mutants exhibit good correlations of terminator RT in vitro and in vivo, and surprisingly, amounts of transcription in vivo. Because assessing in vivo transcription can be confounded by various parameters, we used a tRNA reporter with a processing defect and a strong terminator. By ruling out differences in RNA decay rates, the data indicate that mutants with the RT phenotype synthesize more RNA than wild type cells, and than can be accounted for by their increased elongation rate. Finally, increased activity by the mutants appears unrelated to the RNAP III repressor, Maf1. The results show that the mobile elements of the RNAP III active center, including C11, are key determinants of termination, and that some of the mutations activate RNAP III for overall transcription. Similar mutations in spontaneous cancer suggest this as an unforeseen mechanism of RNAP III activation in disease. C1 [Rijal, Keshab; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [HD000412-28] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. The Grant number is HD000412-28. The URL of the funders website is http://data.nidb.nih.gov/reports/viewreports.taf?ipid=90327&ts=144061033 6. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 1 Z9 1 U1 4 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006253 DI 10.1371/journal.pgen.1006253 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500047 ER PT J AU Shen, H Yu, XB Yang, FM Zhang, ZH Shen, JX Sun, J Choksi, S Jitkaew, S Shu, YQ AF Shen, Hua Yu, Xiaobo Yang, Fengming Zhang, Zhihua Shen, Jianxin Sun, Jin Choksi, Swati Jitkaew, Siriporn Shu, Yongqian TI Reprogramming of Normal Fibroblasts into Cancer-Associated Fibroblasts by miRNAs-Mediated CCL2/VEGFA Signaling SO PLOS GENETICS LA English DT Article ID TUMOR-GROWTH; BREAST-CANCER; STROMAL FIBROBLASTS; OVARIAN-CANCER; STEM-CELLS; MICRORNAS; ANGIOGENESIS; PROGRESSION; EXPRESSION; CARCINOMA AB Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa. When the miRNA-reprogrammed NFs and CAFs were co-cultured with lung cancer cells (LCCs), a similar pattern of cytokine expression profiling were observed between two groups. Using a combination of cytokine expression profiling and miRNAs algorithms, we identified VEGFA/CCL2 and FOXO3a as direct targets of miR-1, miR-206 and miR-31, respectively. Importantly, systemic delivery of anti-VEGFA/CCL2 or pre-miR-1, pre-miR-206 and anti-miR-31 significantly inhibited tumor angiogenesis, TAMs accumulation, tumor growth and lung metastasis. Our results show that miRNAs-mediated FOXO3a/VEGF/CCL2 signaling plays a prominent role in LCCs-mediated NFs into CAFs, which may have clinical implications for providing novel biomarker(s) and potential therapeutic target(s) of lung cancer in the future. C1 [Shen, Hua; Yang, Fengming; Shu, Yongqian] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Jiangsu, Peoples R China. [Shen, Hua; Yang, Fengming; Shu, Yongqian] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Jiangsu, Peoples R China. [Yu, Xiaobo] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Thorac Surg, Shanghai, Peoples R China. [Zhang, Zhihua] Hebei North Univ, Affiliated Hosp 1, Dept Respirat, Zhangjiakou, Hebei Province, Peoples R China. [Shen, Jianxin] Hebei North Univ, Affiliated Hosp 1, Dept Clin Lab, Zhangjiakou, Hebei Province, Peoples R China. [Sun, Jin] Nanjing Med Univ, Affiliated Hosp 1, Dept Nucl Med, Nanjing, Jiangsu, Peoples R China. [Choksi, Swati] NIH, Bldg 10, Bethesda, MD 20892 USA. [Jitkaew, Siriporn] Chulalongkorn Univ, Fac Allied Hlth Sci, Dept Clin Chem, Bangkok, Thailand. RP Shu, YQ (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Jiangsu, Peoples R China.; Shu, YQ (reprint author), Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Jiangsu, Peoples R China. EM shuyongqian1999@126.com FU National Natural Science Foundation of China [81202032, 81172140, 81272532]; Jiangsu 233 Province Clinical Science and Technology Projects (Clinical Research Center) [BL2012008]; Priority Academic Program Development of Jiangsu Higher Education Institutions [JX10231801] FX This work was supported in part by National Natural Science Foundation of China (81202032, 81172140, 81272532); by the Jiangsu 233 Province Clinical Science and Technology Projects (Clinical Research Center, BL2012008), the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 2 Z9 2 U1 6 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006244 DI 10.1371/journal.pgen.1006244 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500040 PM 27541266 ER PT J AU Martin, A AF Martin, Alex TI GRAPES-Grounding representations in action, perception, and emotion systems: How object properties and categories are represented in the human brain SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Review DE Concepts and categories; Cognitive neuroscience of memory; Embodied cognition; Neuroimaging and memory ID AUTISM SPECTRUM DISORDERS; ANTERIOR TEMPORAL-LOBES; VENTRAL OCCIPITOTEMPORAL CORTEX; FUNCTIONAL CONNECTIVITY; MANIPULATABLE OBJECTS; COLOR KNOWLEDGE; CONCEPTUAL KNOWLEDGE; MULTIPLE SEMANTICS; SOCIAL COGNITION; NEURAL FRAMEWORK AB In this article, I discuss some of the latest functional neuroimaging findings on the organization of object concepts in the human brain. I argue that these data provide strong support for viewing concepts as the products of highly interactive neural circuits grounded in the action, perception, and emotion systems. The nodes of these circuits are defined by regions representing specific object properties (e.g., form, color, and motion) and thus are property-specific, rather than strictly modality-specific. How these circuits are modified by external and internal environmental demands, the distinction between representational content and format, and the grounding of abstract social concepts are also discussed. C1 [Martin, Alex] NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM alexmartin@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health, Division of Intramural Research [1 ZIA MH 002588-25, NCT01031407] FX I thank Chris Baker, Alfonso Caramazza, Anjan Chatterjee, Dwight Kravitiz, Brad Mahon, and the members of my laboratory for their critical comments on earlier versions of this manuscript. This work was supported by the National Institute of Mental Health, National Institutes of Health, Division of Intramural Research (1 ZIA MH 002588-25; NCT01031407). The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the United States Government. NR 126 TC 5 Z9 5 U1 7 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 EI 1531-5320 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD AUG PY 2016 VL 23 IS 4 BP 979 EP 990 DI 10.3758/s13423-015-0842-3 PG 12 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA DT0MK UT WOS:000381177500003 PM 25968087 ER PT J AU Gotts, SJ AF Gotts, Stephen J. TI Incremental learning of perceptual and conceptual representations and the puzzle of neural repetition suppression SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Review DE Priming; Predictive coding; Plasticity; Sharpening; Synchrony; Semantic memory ID INFERIOR TEMPORAL CORTEX; MONKEY INFEROTEMPORAL CORTEX; PRIMATE PREFRONTAL CORTEX; OBJECT-SELECTIVE CORTEX; TERM IMPLICIT MEMORY; VISUAL-CORTEX; CATEGORY-SELECTIVITY; STIMULUS REPETITION; CORTICAL ACTIVITY; NEURONAL SYNCHRONIZATION AB Incremental learning models of long-term perceptual and conceptual knowledge hold that neural representations are gradually acquired over many individual experiences via Hebbian-like activity-dependent synaptic plasticity across cortical connections of the brain. In such models, variation in task relevance of information, anatomic constraints, and the statistics of sensory inputs and motor outputs lead to qualitative alterations in the nature of representations that are acquired. Here, the proposal that behavioral repetition priming and neural repetition suppression effects are empirical markers of incremental learning in the cortex is discussed, and research results that both support and challenge this position are reviewed. Discussion is focused on a recent fMRI-adaptation study from our laboratory that shows decoupling of experience-dependent changes in neural tuning, priming, and repetition suppression, with representational changes that appear to work counter to the explicit task demands. Finally, critical experiments that may help to clarify and resolve current challenges are outlined. C1 [Gotts, Stephen J.] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-104, Bethesda, MD 20892 USA. RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-104, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov FU National Institute of Mental Health, NIH, Division of Intramural Research FX The author would like to thank Alex Martin, Jay McClelland, David Plaut, Carson Chow, Gary Dell, Gary Oppenheim, and Sharon Thompson-Schill for helpful discussions, and Brad Mahon, Ken Norman, and an anonymous reviewer for insightful comments on the manuscript. The writing of this paper was supported by the National Institute of Mental Health, NIH, Division of Intramural Research. NR 196 TC 2 Z9 2 U1 15 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 EI 1531-5320 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD AUG PY 2016 VL 23 IS 4 BP 1055 EP 1071 DI 10.3758/s13423-015-0855-y PG 17 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA DT0MK UT WOS:000381177500010 PM 27294423 ER PT J AU Satyamitra, MM DiCarlo, AL Taliaferro, L AF Satyamitra, Merriline M. DiCarlo, Andrea L. Taliaferro, Lanyn TI Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015 SO RADIATION RESEARCH LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; THROMBIN FRAGMENT TP508; DISSEMINATED INTRAVASCULAR COAGULATION; CIRCULATING ENDOTHELIAL-CELLS; ATOMIC-BOMB SURVIVORS; IN-VIVO; PROGENITOR CELLS; SENESCENT CELLS; IONIZING-RADIATION; INDUCED APOPTOSIS AB After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. (C) 2016 by Radiation Research Society C1 [Satyamitra, Merriline M.; DiCarlo, Andrea L.; Taliaferro, Lanyn] NIAID, Div Allergy Immunol & Transplantat, NIH, Rockville, MD 20852 USA. RP Satyamitra, MM (reprint author), NIAID, RNCP, DAIT, NIH, 5601 Fishers Lane,Room 7A67, Rockville, MD 20852 USA. EM merriline.satyamitra@nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 109 TC 1 Z9 1 U1 1 U2 1 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 AUG PY 2016 VL 186 IS 2 BP 99 EP 111 DI 10.1667/RR14436.1 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DU6DW UT WOS:000382305100001 PM 27387859 ER PT J AU Mizrachi, A Cotrim, AP Katabi, N Mitchell, JB Verheij, M Haimovitz-Friedman, A AF Mizrachi, Aviram Cotrim, Ana P. Katabi, Nora Mitchell, James B. Verheij, Marcel Haimovitz-Friedman, Adriana TI Radiation-Induced Microvascular Injury as a Mechanism of Salivary Gland Hypofunction and Potential Target for Radioprotectors SO RADIATION RESEARCH LA English DT Article ID REDOX SIGNALING PLATFORMS; ENDOTHELIAL APOPTOSIS; IONIZING-RADIATION; NECK IRRADIATION; INDUCED DAMAGE; MOUSE MODEL; CANCER; TEMPOL; PROTECTION; CERAMIDE AB Radiation therapy is commonly used to treat patients with head and neck squamous cell carcinoma (HNSCC). One of the major side effects of radiotherapy is injury to the salivary glands (SG), which is thought to be mediated by microvascular dysfunction leading to permanent xerostomia. The goal of this study was to elucidate the mechanism of radiation-induced microvasculature damage and its impact on SG function. We measured bovine aortic endothelial cell (BAEC) apoptosis and ceramide production in response to 5 Gy irradiation, either alone or with reactive oxygen species (ROS) scavengers. We then investigated the effect of a single 15 Gy radiation dose on murine SG function. BAECs exposed to 5 Gy underwent apoptosis with increased ceramide production, both prevented by ROS scavengers. Among the 15 Gy irradiated mice, there was considerable weight loss, alopecia and SG hypofunction manifested by reduced saliva production and lower lysozyme levels. All of these effects, except for the lysozyme levels, were prevented by pretreatment with ROS scavengers. Microvessel density was significantly lower in the SG of irradiated mice compared to the control group, and this effect was significantly attenuated by pretreatment with Tempol. This study demonstrates that radiation-induced SG hypofunction is to a large extent mediated by microvascular dysfunction involving ceramide and ROS generation. These findings strongly suggest that ROS scavengers may serve as potential radioprotectors of SG function in patients undergoing radiotherapy for HNSCC. (C) 2016 by Radiation Research Society C1 [Mizrachi, Aviram] Mem Sloan Kettering Canc Ctr, Dept Surg Head & Neck Serv, 1275 York Ave, New York, NY 10021 USA. [Katabi, Nora] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Haimovitz-Friedman, Adriana] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. [Cotrim, Ana P.; Mitchell, James B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Verheij, Marcel] Netherlands Canc Inst, Dept Radiat Oncol, Amsterdam, Netherlands. RP Haimovitz-Friedman, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM a-haimovitz-friedman@ski.mskcc.org FU NIH/NCI Cancer Center Support Core Grant [P30 CA008748]; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center FX We thank Karen Reede for assistance in preparation of the manuscript and Evan Darling from the Molecular Cytology Facility for his help with the IF apoptotic staining. This study was supported in part through the NIH/NCI Cancer Center Support Core Grant (no. P30 CA008748), and by the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center. NR 29 TC 0 Z9 0 U1 4 U2 4 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 AUG PY 2016 VL 186 IS 2 BP 189 EP 195 DI 10.1667/RR14431.1 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DU6DW UT WOS:000382305100008 PM 27459704 ER PT J AU Kaplan, G Lee, F Onda, M Kolyvas, E Bhardwaj, G Baker, D Pastan, I AF Kaplan, Gilad Lee, Fred Onda, Masanori Kolyvas, Emily Bhardwaj, Gaurav Baker, David Pastan, Ira TI K Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A SO TOXINS LA English DT Article DE recombinant immunotoxin; mesothelin; Pseudomonas exotoxin A; disulfide bond ID CELL-SURFACE; RECOMBINANT IMMUNOTOXIN; TUMOR MICROENVIRONMENT; PROPROTEIN CONVERTASE; LOW IMMUNOGENICITY; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; TARGETING CD22; CANCER; MESOTHELIN AB Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connected to domain III (PE24) by a furin cleavage site (FCS), thereby removing unneeded sequences of domain II. However, the PE24 containing RITs do not contain the naturally occurring disulfide bond around the furin cleavage sequence, because it was removed when domain II was deleted. This could potentially allow PE24 containing immunotoxins to be cleaved and inactivated before internalization by cell surface furin or other proteases in the blood stream or tumor microenvironment. Here, we describe five new RITs in which a disulfide bond is engineered to protect the FCS. The most active of these, SS1-Fab-DS3-PE24, shows a longer serum half-life than an RIT without the disulfide bond and has the same anti-tumor activity, despite being less cytotoxic in vitro. These results have significance for the production of de-immunized, low toxicity, PE24-based immunotoxins with a longer serum half-life. C1 [Kaplan, Gilad; Lee, Fred; Onda, Masanori; Kolyvas, Emily; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. [Bhardwaj, Gaurav; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Bhardwaj, Gaurav; Baker, David] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA. [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM gilad.kaplan@nih.gov; fred.lee@nih.gov; OndaM@mail.nih.gov; emily.kolyvas@nih.gov; Gauravb@uw.edu; dabaker@uw.edu; pastani@mail.nih.gov FU Intramural Research Program of the NIH, NCI, Center for Cancer Research; Howard Hughes Medical Institute FX This work was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research and in part by Howard Hughes Medical Institute. NR 35 TC 0 Z9 0 U1 1 U2 1 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD AUG PY 2016 VL 8 IS 8 AR 217 DI 10.3390/toxins8080217 PG 14 WC Toxicology SC Toxicology GA DU5RK UT WOS:000382268800001 ER PT J AU Spencer, BR Johnson, B Wright, DJ Kleinman, S Glynn, SA Cable, RG AF Spencer, Bryan R. Johnson, Bryce Wright, David J. Kleinman, Steven Glynn, Simone A. Cable, Ritchard G. CA REDS-II Rise Anal Grp TI Potential impact on blood availability and donor iron status of changes to donor hemoglobin cutoff and interdonation intervals SO TRANSFUSION LA English DT Article ID STATUS EVALUATION RISE; DEFICIENCY AB BACKGROUNDA minimum male hemoglobin (Hb) level of 13.0 g/dL becomes a Food and Drug Administration requirement effective May 2016. In addition, extending whole blood (WB) interdonation intervals (IDIs) beyond 8 weeks has been considered to reduce iron depletion in repeat blood donors. This study estimates the impact these changes might have on blood availability and donor iron status. STUDY DESIGN AND METHODSSix blood centers participating in Retrovirus Epidemiology Donor Study-II (REDS-II) collected information on all donation visits from 2006 to 2009. Simulations were developed from these data using a multistage approach that first sought to adequately reproduce the patterns of donor return, Hb and ferritin levels, and outcomes of a donor's visit (successful single- or double-red blood cell donation, deferral for low Hb) observed in REDS-II data sets. Modified simulations were used to predict the potential impact on the blood supply and donor iron status under different Hb cutoff and IDI qualification criteria. RESULTSMore than 10% of WB donations might require replacement under many simulated scenarios. Longer IDIs would reduce the proportion of donors with iron depletion, but 80% of these donors may remain iron-depleted if minimal IDIs increased to 12 or 16 weeks. CONCLUSIONHigher Hb cutoffs and longer IDIs are predicted to have a potentially large impact on collections but only a modest impact on donor iron depletion. Efforts to address iron depletion should be targeted to at-risk donors, such as iron supplementation programs for frequent donors, and policy makers should try to avoid broadly restrictive donation requirements that could substantially reduce blood availability. C1 [Spencer, Bryan R.] Amer Red Cross Blood Serv, Massachusetts Reg, Dedham, MA USA. [Johnson, Bryce; Wright, David J.] Westat Corp, Rockville, MD USA. [Kleinman, Steven] Univ British Columbia, Vancouver, BC, Canada. [Glynn, Simone A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Cable, Ritchard G.] Amer Red Cross Blood Serv, Connecticut Reg, Farmington, CT USA. RP Spencer, BR (reprint author), Amer Red Cross, Massachusetts Reg, 180 Rustcraft Rd,Suite 115, Dedham, MA 02026 USA. EM bryan.spencer@redcross.org FU National Heart, Lung, and Blood Institute [N01HB47168, N01HB47169, N01HB47170, N01HB47171, N01HB47172, N01HB 47174, N01HB47175, N01HB57181] FX This study was supported by contracts N01HB47168, N01HB47169, N01HB47170, N01HB47171, N01HB47172, N01HB 47174, N01HB47175, and N01HB57181 from the National Heart, Lung, and Blood Institute. NR 14 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 2016 VL 56 IS 8 BP 1994 EP 2004 DI 10.1111/trf.13663 PG 11 WC Hematology SC Hematology GA DU8ZP UT WOS:000382506100013 PM 27237451 ER PT J AU Cable, RG Brambilla, D Glynn, SA Kleinman, S Mast, AE Spencer, BR Stone, M Kiss, JE AF Cable, Ritchard G. Brambilla, Donald Glynn, Simone A. Kleinman, Steven Mast, Alan E. Spencer, Bryan R. Stone, Mars Kiss, Joseph E. CA Natl Heart Lung Blood Inst TI Effect of iron supplementation on iron stores and total body iron after whole blood donation SO TRANSFUSION LA English DT Article ID STATUS EVALUATION RISE; TRANSFERRIN RECEPTOR; NATIONAL-HEALTH; DONORS; DEFICIENCY; TRIAL AB BACKGROUNDUnderstanding the effect of blood donation and iron supplementation on iron balance will inform strategies to manage donor iron status. STUDY DESIGN AND METHODSA total of 215 donors were randomized to receive ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation. Iron stores were assessed using ferritin and soluble transferrin receptor. Hemoglobin (Hb) iron was calculated from total body Hb. Total body iron (TBI) was estimated by summing iron stores and Hb iron. RESULTSAt 24 weeks, TBI in donors taking iron increased by 281.0 mg (95% confidence interval [CI], 223.4-338.6 mg) compared to before donation, while TBI in donors not on iron decreased by 74.1 mg (95% CI, -112.3 to -35.9; p<0.0001, iron vs. no iron). TBI increased rapidly after blood donation with iron supplementation, especially in iron-depleted donors. Supplementation increased TBI compared to controls during the first 8 weeks after donation: 367.8 mg (95% CI, 293.5-442.1) versus -24.1 mg (95% CI, -82.5 to 34.3) for donors with a baseline ferritin level of not more than 26 ng/mL and 167.8 mg (95% CI, 116.5-219.2) versus -68.1 mg (95% CI, -136.7 to 0.5) for donors with a baseline ferritin level of more than 26 ng/mL. A total of 88% of the benefit of iron supplementation occurred during the first 8 weeks after blood donation. CONCLUSIONDonors on iron supplementation replaced donated iron while donors not on iron did not. Eight weeks of iron supplementation provided nearly all of the measured improvement in TBI. Daily iron supplementation after blood donation allows blood donors to recover the iron loss from blood donation and prevents sustained iron deficiency. C1 [Cable, Ritchard G.] Amer Red Cross, 209 Farmington Ave, Farmington, CT 06032 USA. [Brambilla, Donald] RTI, Rockville, MD USA. [Glynn, Simone A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Kleinman, Steven] Univ British Columbia, Victoria, BC, Canada. [Mast, Alan E.] BloodCtr Wisconsin, Milwaukee, WI USA. [Spencer, Bryan R.] Amer Red Cross, Dedham, MA USA. [Stone, Mars] Blood Syst Res Inst, San Francisco, CA USA. [Kiss, Joseph E.] Inst Transfus Med, Pittsburgh, PA USA. RP Cable, RG (reprint author), Amer Red Cross, 209 Farmington Ave, Farmington, CT 06032 USA. EM Ritchard.Cable@redcross.org FU NHLBI [HHSN2682011 00001I, HHSN268201100002I, HHSN268201100003I, HHSN268 201100004I, HHSN268201100005I, HHSN268201100006I] FX This work was supported by NHLBI contracts HHSN2682011 00001I, HHSN268201100002I, HHSN268201100003I, HHSN268 201100004I, HHSN268201100005I, and HHSN268201100006I. NR 16 TC 2 Z9 2 U1 2 U2 2 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 AUG PY 2016 VL 56 IS 8 BP 2005 EP 2012 DI 10.1111/trf.13659 PG 8 WC Hematology SC Hematology GA DU8ZP UT WOS:000382506100014 PM 27232535 ER PT J AU Vahidnia, F Stramer, SL Kessler, D Goncalez, TT Shaz, BH Leparc, G Krysztof, DE Dodd, RY Glynn, SA Custer, B AF Vahidnia, Farnaz Stramer, Susan L. Kessler, Debra Goncalez, Thelma T. Shaz, Beth H. Leparc, German Krysztof, David E. Dodd, Roger Y. Glynn, Simone A. Custer, Brian CA NHLBI Retrovirus Epidemiology TI Motivations for donating and attitudes toward screening policies in US blood donors with viral infection SO TRANSFUSION LA English DT Article ID TRANSFUSION-TRANSMISSIBLE INFECTIONS; IMMUNODEFICIENCY-VIRUS TYPE-1; RISK-FACTORS; SAO-PAULO; TEST-SEEKING; HAD SEX; MEN; BRAZIL; BEHAVIORS; QUESTIONNAIRE AB BACKGROUNDDifferences in motivating factors that contribute to the decision to donate blood between infected and uninfected donors may help to identify areas for improving donor education. STUDY DESIGN AND METHODSAs part of a risk factor study, confirmed-positive donors (cases) based on serology-only (human T-lymphotropic virus [HTLV]) or serology and nucleic acid testing (NAT) or NAT-only (human immunodeficiency virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV]), and serology-unconfirmed, NAT-negative false-positive donors (controls) were asked about motivations and opinions toward blood donation. Test seeking was inferred if a donor answered yes to I wanted to get my test results and one of the following: blood center testing is confidential, free, more accurate than other test centers, or tests will identify problems with my blood. Cases were compared to controls using descriptive and multivariable analyses. RESULTSWhether a case or control, the most common donation reason was to help someone in need (>90% in each group). After adjusting for demographic characteristics, test seeking was not significantly associated with infection status. Test seeking was more common in first-time, younger males and nonwhite, non-Hispanic donors. Of donors with HIV, 13% considered selection policies to be unfair, compared with 1, 2, 0.5, and 6% of donors with HBV, HCV, and HTLV and controls, respectively (adjusted odds ratio for HIV cases vs. controls, 3.9; 95% confidence interval, 2.3-6.7). CONCLUSIONSMost donors give to help those in need, including HIV-positive donors. Our results establish a baseline from which additional studies can be compared focused on alternate ways to reduce noncompliance and improved messaging to ensure that high-risk potential donors understand the reasons for blood donor screening policies. C1 [Vahidnia, Farnaz; Goncalez, Thelma T.; Custer, Brian] Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. [Stramer, Susan L.; Krysztof, David E.] Amer Red Cross, Gaithersburg, MD USA. [Kessler, Debra; Shaz, Beth H.] New York Blood Ctr, New York, NY 10021 USA. [Leparc, German] OneBlood, Tampa, FL USA. [Dodd, Roger Y.] Amer Red Cross, Holland Lab, Rockville, MD USA. [Glynn, Simone A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Custer, Brian] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Vahidnia, F (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM Fvahidnia@bloodsystems.org OI Vahidnia, Farnaz/0000-0003-1130-4643 FU Retrovirus Epidemiology Donor Study-II (REDS-II) - National Heart, Lung, and Blood Institute, National Institutes of Health [HHSN26820041717] FX This study was funded by Research Contract HHSN26820041717 from the Retrovirus Epidemiology Donor Study-II (REDS-II) sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 40 TC 1 Z9 1 U1 9 U2 9 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 AUG PY 2016 VL 56 IS 8 BP 2013 EP 2020 DI 10.1111/trf.13678 PG 8 WC Hematology SC Hematology GA DU8ZP UT WOS:000382506100015 PM 27351292 ER PT J AU Bingham, CR Simons-Morton, BG Pradhan, AK Li, KG Almani, F Falk, EB Shope, JT Buckley, L Ouimet, MC Albert, PS AF Bingham, C. Raymond Simons-Morton, Bruce G. Pradhan, Anuj K. Li, Kaigang Almani, Farideh Falk, Emily B. Shope, Jean T. Buckley, Lisa Ouimet, Marie Claude Albert, Paul S. TI Peer passenger norms and pressure: Experimental effects on simulated driving among teenage males SO TRANSPORTATION RESEARCH PART F-TRAFFIC PSYCHOLOGY AND BEHAVIOUR LA English DT Article DE Teen driver; Risky driving behavior; Simulated driving; Hazard perception; Social influences; Injunctive norms ID UNITED-STATES; DEVELOPMENTAL PERSPECTIVE; ADOLESCENT DRIVERS; SOCIAL-INFLUENCE; RISK PERCEPTION; CRASHES; BEHAVIOR; NOVICE; SAFETY; INVOLVEMENT AB Objective: Serious crashes are more likely when teenage drivers have teenage passengers. One likely source of this increased risk is social influences on driving performance. This driving simulator study experimentally tested the effects of peer influence (i.e., risk-accepting compared to risk-averse peer norms reinforced by pressure) on the driving risk behavior (i.e., risky driving behavior and inattention to hazards) of male teenagers. It was hypothesized that peer presence would result in greater driving risk behavior (i.e., increased driving risk and reduced latent hazard anticipation), and that the effect would be greater when the peer was risk-accepting. Methods: Fifty-three 16- and 17-year-old male participants holding a provisional U.S., State of Michigan driver license were randomized to either a risk-accepting or risk-averse condition. Each participant operated a driving simulator while alone and separately with a confederate peer passenger. The simulator world included scenarios designed to elicit variation in driving risk behavior with a teen passenger present in the vehicle. Results: Significant interactions of passenger presence (passenger present vs. alone) by risk condition (risk-accepting vs. risk-averse) were observed for variables measuring: failure to stop at yellow light intersections (Incident Rate Ratio (IRR) = 2.16; 95% confidence interval [950]= 1.06, 4.43); higher probability of overtaking (IRR = 10.17; 95CI = 1.43, 73.35); shorter left turn latency (IRR = 0.43; 95CI = 0.31, 0.60); and, failure to stop at an intersection with an occluded stop sign (IRR = 7.90; 95CI = 2.06, 30.35). In all cases, greater risky driving by participants was more likely with a risk-accepting passenger versus a risk-averse passenger present and a risk-accepting passenger present versus driving alone. Conclusions: Exposure of male teenagers to a risk-accepting confederate peer passenger who applied peer influence increased simulated risky driving behavior compared with exposure to a risk-averse confederate peer passenger or driving alone. These results are consistent with the contention that variability in teenage risky driving is in part explained by social influences. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Bingham, C. Raymond; Pradhan, Anuj K.; Almani, Farideh; Shope, Jean T.; Buckley, Lisa] Univ Michigan, Transportat Res Inst, 2091 Baxter Rd, Ann Arbor, MI 48109 USA. [Simons-Morton, Bruce G.; Li, Kaigang; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd Room 7B13M,MSC 7510, Bethesda, MD 20892 USA. [Falk, Emily B.] Univ Penn, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA. [Ouimet, Marie Claude] Univ Sherbrooke, Dept Sci Sante Communautaire, 2500 Boul Univ, Sherbrooke, PQ J1K 2R1, Canada. RP Bingham, CR (reprint author), Univ Michigan, Transportat Res Inst, 2091 Baxter Rd, Ann Arbor, MI 48109 USA. EM rbingham@umich.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute on Child Health and Human Development [HHSN275201000007C] FX This research was funded through contract HHSN275201000007C by the Eunice Kennedy Shriver National Institute on Child Health and Human Development. The authors have no conflicts of interest to disclose relating to this research. NR 58 TC 0 Z9 0 U1 6 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1369-8478 EI 1873-5517 J9 TRANSPORT RES F-TRAF JI Transp. Res. Pt. F-Traffic Psychol. Behav. PD AUG PY 2016 VL 41 BP 124 EP 137 DI 10.1016/j.trf.2016.06.007 PN A PG 14 WC Psychology, Applied; Transportation SC Psychology; Transportation GA DU6RZ UT WOS:000382343600014 PM 27818610 ER PT J AU Hickman, HD Pierson, TC AF Hickman, Heather D. Pierson, Theodore C. TI Zika in the Brain: New Models Shed Light on Viral Infection SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material AB The current Zika virus (ZIKV) outbreak is associated with high numbers of human congenital birth defects, yet it has been unclear how ZIKV infection during pregnancy causes these abnormalities. Three new mouse models now show that ZIKV crosses the placenta and replicates in the brains of fetal mice. C1 [Hickman, Heather D.; Pierson, Theodore C.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pierson, TC (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 10 TC 0 Z9 0 U1 48 U2 57 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD AUG PY 2016 VL 22 IS 8 BP 639 EP 641 DI 10.1016/j.molmed.2016.06.004 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DT5NR UT WOS:000381530400005 PM 27345865 ER PT J AU Barfield, WL Plank-Bazinet, JL Clayton, JA AF Barfield, Whitney L. Plank-Bazinet, Jennifer L. Clayton, Janine Austin TI Advancement of Women in the Biomedical Workforce: Insights for Success SO ACADEMIC MEDICINE LA English DT Editorial Material AB Women continue to face unique barriers in the biomedical workforce that affect their advancement and retention in this field. The National Institutes of Health (NIH) formed the Working Group on Women in Biomedical Careers to address these issues. Through the efforts of the working group, the NIH funded 14 research grants to identify barriers or to develop and/or test interventions to support women in the biomedical workforce. The grantees that were funded through this endeavor later established the grassroots Research Partnership on Women in Biomedical Careers, and they continue to conduct research and disseminate information on the state of women in academic medicine. This Commentary explores the themes introduced in a collection of articles organized by the research partnership and published in this issue of Academic Medicine. The authors highlight the role that government plays in the advancement of women in academic medicine and highlight the findings put forward in this collection. C1 [Barfield, Whitney L.] NIH, Amer Assoc Adv Sci, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. [Plank-Bazinet, Jennifer L.; Clayton, Janine Austin] NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. [Clayton, Janine Austin] NIH, Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. RP Plank-Bazinet, JL (reprint author), 6707 Democracy Blvd,Suite 400, Bethesda, MD 20817 USA. EM jennifer.bazinet@nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 17 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 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2016 VL 91 IS 8 BP 1047 EP 1049 DI 10.1097/ACM.0000000000001274 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000012 PM 27306970 ER PT J AU Plank-Bazinet, JL Whittington, KB Cassidy, SKB Filart, R Cornelison, TL Begg, L Clayton, JA AF Plank-Bazinet, Jennifer L. Whittington, Kjersten Bunker Cassidy, Sara K. B. Filart, Rosemarie Cornelison, Terri L. Begg, Lisa Clayton, Janine Austin TI Programmatic Efforts at the National Institutes of Health to Promote and Support the Careers of Women in Biomedical Science SO ACADEMIC MEDICINE LA English DT Article ID INTERDISCIPLINARY RESEARCH CAREERS AB Although women have reached parity at the training level in the biological sciences and medicine, they are still significantly underrepresented in the professoriate and in mid-and senior-level life science positions. Considerable effort has been devoted by individuals and organizations across science sectors to understanding this disparity and to developing interventions in support of women's career development. The National Institutes of Health (NIH) formed the Office of Research on Women's Health (ORWH) in 1990 with the goals of supporting initiatives to improve women's health and providing opportunities and support for the recruitment, retention, reentry, and sustained advancement of women in biomedical careers. Here, the authors review several accomplishments and flagship activities initiated by the NIH and ORWH in support of women's career development during this time. These include programming to support researchers returning to the workforce after a period away (Research Supplements to Promote Reentry into Biomedical and Behavioral Research Careers), career development awards made through the Building Interdisciplinary Research Careers in Women's Health program, and trans-NIH involvement and activities stemming from the NIH Working Group on Women in Biomedical Careers. These innovative programs have contributed to advancement of women by supporting the professional and personal needs of women in science. The authors discuss the unique opportunities that accompany NIH partnerships with the scientific community, and conclude with a summary of the impact of these programs on women in science. C1 [Plank-Bazinet, Jennifer L.; Begg, Lisa; Clayton, Janine Austin] NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. [Whittington, Kjersten Bunker] NIH, Amer Assoc Adv Sci, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. [Whittington, Kjersten Bunker] Reed Coll, Dept Sociol, Portland, OR 97202 USA. [Cassidy, Sara K. B.] NHGRI, NIH, Bethesda, MD 20892 USA. [Filart, Rosemarie] Penn State Univ, Milton S Hershey Med Ctr, Inpatient Consultat, Hummelstown, PA USA. [Filart, Rosemarie] Penn State Univ, Milton S Hershey Med Ctr, Res, Hummelstown, PA USA. [Filart, Rosemarie] Penn State Univ, Milton S Hershey Med Ctr, Dept Phys Med & Rehabil, Hummelstown, PA USA. [Cornelison, Terri L.] NIH, Off Res Womens Hlth, Clin Res, Bldg 10, Bethesda, MD 20892 USA. [Clayton, Janine Austin] NIH, Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. RP Plank-Bazinet, JL (reprint author), 6707 Democracy Blvd,Suite 400, Bethesda, MD 20817 USA. EM jennifer.plank@nih.gov FU National Institutes of Health Office of Research on Women's Health FX National Institutes of Health Office of Research on Women's Health. NR 30 TC 6 Z9 6 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2016 VL 91 IS 8 BP 1057 EP 1064 DI 10.1097/ACM.0000000000001239 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000015 PM 27191836 ER PT J AU Ginther, DK Kahn, S Schaffer, WT AF Ginther, Donna K. Kahn, Shulamit Schaffer, Walter T. TI Gender, Race/Ethnicity, and National Institutes of Health R01 Research Awards: Is There Evidence of a Double Bind for Women of Color? SO ACADEMIC MEDICINE LA English DT Article ID ETHNICITY; RACE; INVESTIGATORS; GAP; SEX AB Purpose To analyze the relationship between gender, race/ethnicity, and the probability of being awarded an R01 grant from the National Institutes of Health (NIH). Method The authors used data from the NIH Information for Management, Planning, Analysis, and Coordination grants management database for the years 2000-2006 to examine gender differences and race/ethnicity-specific gender differences in the probability of receiving an R01 Type 1 award. The authors used descriptive statistics and probit models to determine the relationship between gender, race/ethnicity, degree, investigator experience, and R01 award probability, controlling for a large set of observable characteristics. Results White women PhDs and MDs were as likely as white men to receive an R01 award. Compared with white women, Asian and black women PhDs and black women MDs were significantly less likely to receive funding. Women submitted fewer grant applications, and blacks and women who were new investigators were more likely to submit only one application between 2000 and 2006. Conclusions Differences by race/ethnicity explain the NIH funding gap for women of color, as white women have a slight advantage over men in receiving Type 1 awards. Findings of a lower submission rate for women and an increased likelihood that they will submit only one proposal are consistent with research showing that women avoid competition. Policies designed to address the racial and ethnic diversity of the biomedical workforce have the potential to improve funding outcomes for women of color. C1 [Ginther, Donna K.] Univ Kansas, Dept Econ, 1460 Jayhawk Blvd, Lawrence, KS 66045 USA. [Ginther, Donna K.] Univ Kansas, Ctr Sci Technol & Econ Policy, Lawrence, KS 66045 USA. [Ginther, Donna K.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Kahn, Shulamit] Boston Univ, Questrom Sch Business, Dept Markets Publ Policy & Law, Boston, MA 02215 USA. [Schaffer, Walter T.] NIH, Div Biomed Workforce, Off Extramural Res, Bldg 10, Bethesda, MD 20892 USA. RP Ginther, DK (reprint author), Univ Kansas, Dept Econ, 1460 Jayhawk Blvd, Lawrence, KS 66045 USA. EM dginther@ku.edu RI Ginther, Donna/F-7317-2016 OI Ginther, Donna/0000-0002-0881-7969 FU National Institutes of Health (NIH) [1R01AG36820-01]; NIH [07-6008 OD OER] FX Ginther and Kahn acknowledge financial support from a National Institutes of Health (NIH) grant (1R01AG36820-01). Schaffer was an employee of NIH, and, as a result, NIH supported this work through an NIH Evaluation Set-Aside Award (07-6008 OD OER). NR 17 TC 7 Z9 7 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2016 VL 91 IS 8 BP 1098 EP 1107 DI 10.1097/ACM.0000000000001278 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000023 PM 27306969 ER PT J AU Girod, S Fassiotto, M Grewal, D Ku, MC Sriram, N Nosek, BA Valantine, H AF Girod, Sabine Fassiotto, Magali Grewal, Daisy Ku, Manwai Candy Sriram, Natarajan Nosek, Brian A. Valantine, Hannah TI Reducing Implicit Gender Leadership Bias in Academic Medicine With an Educational Intervention SO ACADEMIC MEDICINE LA English DT Article ID ASSOCIATION TEST; SEX-DIFFERENCES; WOMEN LEADERS; RACE BIAS; FACULTY; PREJUDICE; SCIENCE; MALLEABILITY; STEREOTYPES; FEMALE AB Purpose One challenge academic health centers face is to advance female faculty to leadership positions and retain them there in numbers equal to men, especially given the equal representation of women and men among graduates of medicine and biological sciences over the last 10 years. The purpose of this study is to investigate the explicit and implicit biases favoring men as leaders, among both men and women faculty, and to assess whether these attitudes change following an educational intervention. Method The authors used a standardized, 20-minute educational intervention to educate faculty about implicit biases and strategies for overcoming them. Next, they assessed the effect of this intervention. From March 2012 through April 2013, 281 faculty members participated in the intervention across 13 of 18 clinical departments. Results The study assessed faculty members' perceptions of bias as well as their explicit and implicit attitudes toward gender and leadership. Results indicated that the intervention significantly changed all faculty members' perceptions of bias (P < .05 across all eight measures). Although, as expected, explicit biases did not change following the intervention, the intervention did have a small but significant positive effect on the implicit biases surrounding women and leadership of all participants regardless of age or gender (P = .008). Conclusions These results suggest that providing education on bias and strategies for reducing it can serve as an important step toward reducing gender bias in academic medicine and, ultimately, promoting institutional change, specifically the promoting of women to higher ranks. C1 [Girod, Sabine] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Girod, Sabine] Stanford Univ, Dept Otolaryngol, Sch Med, Stanford, CA 94305 USA. [Fassiotto, Magali] Stanford Univ, Sch Med, Programs & Res, Off Fac Dev & Divers, Stanford, CA 94305 USA. [Grewal, Daisy] Stanford Univ, Off Vice Provost Undergrad Educ, Stanford, CA 94305 USA. [Ku, Manwai Candy] Apple Inc, Cupertino, CA USA. [Sriram, Natarajan] Implisci, Charlottesville, VA USA. [Nosek, Brian A.] Univ Virginia, Dept Psychol, Gilmer Hall, Charlottesville, VA 22903 USA. [Nosek, Brian A.] Ctr Open Sci, Charlottesville, VA USA. [Valantine, Hannah] NIH, Sci Workforce Divers, Bldg 10, Bethesda, MD 20892 USA. [Valantine, Hannah] Stanford Univ, Stanford, CA 94305 USA. RP Valantine, H (reprint author), NIH, Off Director, 300 Rockville Pike, Rockville, MD 20850 USA. EM Hannah.valantine@nih.gov OI Nosek, Brian/0000-0001-6797-5476 FU National Institutes of Health [1UL1 RR025744-01, 1DP4GM096849-01] FX This work was supported by National Institutes of Health Clinical and Translational Science Award 1UL1 RR025744-01 and the National Institutes of Health Director's Pathfinder Award (1DP4GM096849-01). NR 49 TC 6 Z9 6 U1 17 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2016 VL 91 IS 8 BP 1143 EP 1150 DI 10.1097/ACM.0000000000001099 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000028 PM 26826068 ER PT J AU Heggeness, ML Evans, L Pohlhaus, JR Mills, SL AF Heggeness, Misty L. Evans, Lisa Pohlhaus, Jennifer Reineke Mills, Sherry L. TI Measuring Diversity of the National Institutes of Health-Funded Workforce SO ACADEMIC MEDICINE LA English DT Article ID REPRESENTATION; ETHNICITY; RACE AB Purpose To measure diversity within the National Institutes of Health (NIH)-funded workforce. The authors use a relevant labor market perspective to more directly understand what the NIH can influence in terms of enhancing diversity through NIH policies. Method Using the relevant labor market (defined as persons with advanced degrees working as biomedical scientists in the United States) as the conceptual framework, and informed by accepted economic principles, the authors used the American Community Survey and NIH administrative data to calculate representation ratios of the NIH-funded biomedical workforce from 2008 to 2012 by race, ethnicity, sex, and citizenship status, and compared this against the pool of characteristic individuals in the potential labor market. Results In general, the U.S. population during this time period was an inaccurate comparison group for measuring diversity of the NIH-funded scientific workforce. Measuring accurately, we found the representation of women and traditionally underrepresented groups in NIH-supported postdoc fellowships and traineeships and mentored career development programs was greater than their representation in the relevant labor market. The same analysis found these demographic groups are less represented in the NIH-funded independent investigator pool. Conclusions Although these findings provided a picture of the current NIH-funded workforce and a foundation for understanding the federal role in developing, maintaining, and renewing diverse scientific human resources, further study is needed to identify whether junior-and early-stage investigators who are part of more diverse cohorts will naturally transition into independent NIH-funded investigators, or whether they will leave the workforce before achieving independent researcher status. C1 [Heggeness, Misty L.] US Bur Census, Longitudinal Res Evaluat & Outreach Branch, Social Econ & Housing Stat Div, Suitland, MD 20746 USA. [Heggeness, Misty L.; Evans, Lisa] NIH, Div Biomed Res Workforce, Off Director, Bldg 10, Bethesda, MD 20892 USA. [Pohlhaus, Jennifer Reineke] Ripple Effect Commun Inc, Rockville, MD USA. [Mills, Sherry L.] NIH, Off Extramural Programs, Off Director, Bldg 10, Bethesda, MD 20892 USA. RP Heggeness, ML (reprint author), US Bur Census, 4600 Silver Hill Rd,Room 6H065, Suitland, MD 20746 USA. EM misty.l.heggeness@census.gov OI Heggeness, Misty/0000-0003-4113-7698 FU NIH FX All authors are employees or contractors of the NIH; in this way, this work was supported by the NIH. NR 23 TC 4 Z9 4 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2016 VL 91 IS 8 BP 1164 EP 1172 DI 10.1097/ACM.0000000000001209 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000031 PM 27224301 ER PT J AU Appiah, D Schreiner, PJ Durant, RW Kiefe, CI Loria, C Lewis, CE Williams, OD Person, SD Sidney, S AF Appiah, Duke Schreiner, Pamela J. Durant, Raegan W. Kiefe, Catarina I. Loria, Catherine Lewis, Cora E. Williams, O. Dale Person, Sharina D. Sidney, Stephen TI Relation of longitudinal changes in body mass index with atherosclerotic cardiovascular disease risk scores in middle-aged black and white adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Obesity; Cardiovascular disease; Risk prediction ID HEART-DISEASE; UNITED-STATES; CEREBROVASCULAR DISEASES; OBESITY; HYPERTENSION; PREVALENCE; MORTALITY; HEALTH; TRENDS; IMPACT AB Purpose: We assessed whether longitudinal changes in body mass index (BMI) are positively associated with changes in 10-year American College of Cardiology/American Heart Association atherosclerotic cardiovascular disease (ASCVD) risk scores in middle-aged blacks compared to whites. Methods: Data were from 1691 participants enrolled in the Coronary Artery Risk Development in Young Adults Study aged 40 years or more in 2000-2001, who had follow-up examinations 5 and 10 years later. Results: The prevalence of obesity increased from 32.3% in 2000-2001 (mean age: 42.8 years) to 41.7% in 2010-2011, higher in blacks than whites. The corresponding change in 10-year ASCVD risk was significantly higher for blacks (men: 4.5%-9.6%, women: 1.7%-5.0%) than whites (men: 2.4%-5.2%, women: 0.7%-1.6%). In 2010-2011, 57.5% of black men had ASCVD risk scores of 7.5% or more compared to white men (14.7%), black women (17.4%), and white women (1.6%). Although BMI trends were positively associated with 10-year change in ASCVD risk scores (0.07% per 1 kg/m(2) increase), it explained very little variance in risk score trends in all race sex groups. Conclusions: In middle-aged adults, longitudinal changes in BMI had little independent influence on changes in 10 -year ASCVD risk scores as its effect may be largely mediated through ASCVD risk factors already accounted for in the risk score. (C) 2016 Elsevier Inc. All rights reserved. C1 [Appiah, Duke; Schreiner, Pamela J.] Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. [Durant, Raegan W.; Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Kiefe, Catarina I.; Person, Sharina D.] Univ Massachusetts, Quantitat Hlth Sci, Worcester, MA 01605 USA. [Loria, Catherine] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [Williams, O. Dale] Florida Int Univ, Dept Biostat, Miami, FL 33199 USA. [Sidney, Stephen] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. RP Appiah, D (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM dappiah@umn.edu FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA [AG0005]; NHLBI [AG0005, T32HL007779] FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), an intra-agency agreement between NIA and NHLBI (AG0005). Dr. Appiah was supported by NHLBI training grant T32HL007779. NR 40 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 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2016 VL 26 IS 8 BP 521 EP 526 DI 10.1016/j.annepidem.2016.06.008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DU3HU UT WOS:000382102200001 PM 27402259 ER PT J AU Withrow, DR Racey, CS Jamal, S AF Withrow, Diana R. Racey, C. Sarai Jamal, Sehar TI A critical review of methods for assessing cancer survival disparities in indigenous population SO ANNALS OF EPIDEMIOLOGY LA English DT Review DE Neoplasms; Survival analysis; Indians; North American; Oceanic Ancestry Group; Health status disparities; Health care disparities ID SQUAMOUS-CELL CARCINOMA; HISPANIC WHITE WOMEN; NEW-ZEALAND; AMERICAN-INDIANS; BREAST-CANCER; CERVICAL-CANCER; NEW-MEXICO; PROSTATE-CANCER; UNITED-STATES; LUNG-CANCER AB Purpose: An increasing cancer burden among indigenous populations has led to a growing literature about survival disparities between indigenous and nonindigenous persons. We aim to describe and appraise methods used to measure cancer survival in indigenous persons in the United States, Canada, Australia, and New Zealand. Methods: We searched Medline, Web of Science, and EMBASE for articles published between 1990 and 2015 that estimated survival in populations indigenous to one of these four countries. We gathered information about data sources, analytical methods, and the extent to which threats to validity were discussed. Results: The search retrieved 83 articles. The most common approach to survival analysis was cause specific survival (n = 49). Thirty-eight articles measured all-cause survival and 11 measured excess mortality attributable to cancer (relative survival). Three sources of information bias common to all studies (ethnic misclassification, incomplete case ascertainment, and incomplete death ascertainment) were acknowledged in a minority of articles. Conclusions: The methodological considerations we present here are shared with studies of cancer survival across other subpopulations. We urge future researchers on this and related topics to clearly describe their data sources, to justify analytic choices, and to fully discuss the potential impact of those choices on the results and interpretation. Published by Elsevier Inc. C1 [Withrow, Diana R.; Jamal, Sehar] Canc Care Ontario, Aboriginal Canc Control Unit, Prevent & Canc Control, Toronto, ON, Canada. [Withrow, Diana R.; Racey, C. Sarai] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Epidemiol, Toronto, ON, Canada. RP Withrow, DR (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 7E590, Rockville, MD 20850 USA. EM diana.withrow@nih.gov FU Canadian Institutes of Health Research Doctoral Award FX The authors acknowledge insightful comments on drafts of this article from Wendy Lou, Loraine Marrett, Diane Nishri, and Jason Pole. Caroline Cawley contributed valuable editorial expertise. D.R.W. was supported by a Canadian Institutes of Health Research Doctoral Award. The funder had no role in the preparation of this article. NR 124 TC 2 Z9 2 U1 6 U2 9 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 AUG PY 2016 VL 26 IS 8 BP 579 EP 591 DI 10.1016/j.annepidem.2016.06.007 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DU3HU UT WOS:000382102200009 PM 27431064 ER PT J AU Barnett, CF Alvarez, P Park, MH AF Barnett, Christopher F. Alvarez, Paulino Park, Myung H. TI Pulmonary Arterial Hypertension: Diagnosis and Treatment SO CARDIOLOGY CLINICS LA English DT Article DE Pulmonary arterial hypertension; Echocardiography; Right heart catheterization; Prostacyclin; Phosphodiesterase inhibitor; Endothelin antagonist ID ENDOTHELIN RECEPTOR ANTAGONIST; RANDOMIZED CONTROLLED-TRIAL; 5 INHIBITOR THERAPY; ORAL TREPROSTINIL; HEART-FAILURE; DOUBLE-BLIND; ECHOCARDIOGRAPHY; PROSTACYCLIN; MULTICENTER; MANAGEMENT AB Pulmonary arterial hypertension (PAH) is a specific, rare disease characterized by a well-described pattern of pulmonary vascular remodeling. The elevated pulmonary artery pressure in PAH results in increased right ventricular afterload, which, if untreated, leads rapidly to right ventricular failure and death. Recent marked expansion in knowledge about PAH has resulted in the development of effective therapies that improve quality of life and survival. However, delays in diagnosis and suboptimal treatment remain significant barriers to achieving optimal patient outcomes. Continued success in raising PAH awareness, earlier diagnosis, and the availability of new therapies mean a promising future for PAH patients. C1 [Barnett, Christopher F.] Medstar Heart & Vasc Inst, 110 Irving St Northwest, Washington, DC 20010 USA. [Barnett, Christopher F.] NIH, Dept Crit Care Med, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. [Alvarez, Paulino] Houston Methodist Hosp, Dept Cardiol, Methodist DeBakey Heart & Vasc Ctr, 6550 Fannin St,Smith Tower,Suite 1901, Houston, TX 77030 USA. [Park, Myung H.] Houston Methodist Hosp, Div Heart Failure & Transplant, Dept Cardiol, Methodist DeBakey Heart & Vasc Ctr, 6550 Fannin St,Smith Tower,Suite 1901, Houston, TX 77030 USA. RP Park, MH (reprint author), Houston Methodist Hosp, Div Heart Failure & Transplant, Dept Cardiol, Methodist DeBakey Heart & Vasc Ctr, 6550 Fannin St,Smith Tower,Suite 1901, Houston, TX 77030 USA. EM mhpark@houstonmethodist.org NR 40 TC 2 Z9 2 U1 6 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD AUG PY 2016 VL 34 IS 3 BP 375 EP + DI 10.1016/j.ccl.2016.04.006 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT2SU UT WOS:000381331500004 PM 27443135 ER PT J AU Cragg, G AF Cragg, Gordon TI Tribute to the late Emeritus Professor Lester A Mitscher SO JOURNAL OF ANTIBIOTICS LA English DT Biographical-Item C1 [Cragg, Gordon] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cragg, G (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM gmcragg2@gmail.com NR 1 TC 0 Z9 0 U1 1 U2 1 PU JAPAN ANTIBIOTICS RESEARCH ASSOC PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD AUG PY 2016 VL 69 IS 8 SI SI BP 580 EP 580 DI 10.1038/ja.2016.83 PG 1 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA DU3GS UT WOS:000382099400002 PM 27569907 ER PT J AU Newman, D AF Newman, David TI A tribute to the late Emeritus Professor Lester A Mitscher SO JOURNAL OF ANTIBIOTICS LA English DT Biographical-Item C1 [Newman, David] NCI, Nat Prod Branch, Frederick Natl Lab, Frederick, MD 21701 USA. RP Newman, D (reprint author), NCI, Nat Prod Branch, Frederick Natl Lab, Frederick, MD 21701 USA. EM djnewman664@verizon.net NR 1 TC 0 Z9 0 U1 0 U2 0 PU JAPAN ANTIBIOTICS RESEARCH ASSOC PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD AUG PY 2016 VL 69 IS 8 SI SI BP 581 EP 581 DI 10.1038/ja.2016.85 PG 1 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA DU3GS UT WOS:000382099400003 PM 27569908 ER PT J AU Bailey, AL Lauck, M Ghai, RR Nelson, CW Heimbruch, K Hughes, AL Goldberg, TL Kuhn, JH Jasinska, AJ Freimer, NB Apetrei, C O'Connor, DH AF Bailey, Adam L. Lauck, Michael Ghai, Ria R. Nelson, Chase W. Heimbruch, Katelyn Hughes, Austin L. Goldberg, Tony L. Kuhn, Jens H. Jasinska, Anna J. Freimer, Nelson B. Apetrei, Cristian O'Connor, David H. CA Int Vervet Res Consortium TI Arteriviruses, Pegiviruses, and Lentiviruses Are Common among Wild African Monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN HEMORRHAGIC-FEVER; GB-VIRUS-C; RESPIRATORY SYNDROME VIRUS; NEUTRALIZATION EPITOPE; GP5 ECTODOMAIN; PRIMATE; INFECTION; HOST; TRANSMISSION; PHYLOGENY AB Nonhuman primates (NHPs) are a historically important source of zoonotic viruses and are a gold-standard model for research on many human pathogens. However, with the exception of simian immunodeficiency virus (SIV) (family Retroviridae), the blood-borne viruses harbored by these animals in the wild remain incompletely characterized. Here, we report the discovery and characterization of two novel simian pegiviruses (family Flaviviridae) and two novel simian arteriviruses (family Arteriviridae) in wild African green monkeys from Zambia (malbroucks [Chlorocebus cynosuros]) and South Africa (vervet monkeys [Chlorocebus pygerythrus]). We examine several aspects of infection, including viral load, genetic diversity, evolution, and geographic distribution, as well as host factors such as age, sex, and plasma cytokines. In combination with previous efforts to characterize blood-borne RNA viruses in wild primates across sub-Saharan Africa, these discoveries demonstrate that in addition to SIV, simian pegiviruses and simian arteriviruses are widespread and prevalent among many African cercopithecoid (i.e., Old World) monkeys. IMPORTANCE Primates are an important source of viruses that infect humans and serve as an important laboratory model of human virus infection. Here, we discover two new viruses in African green monkeys from Zambia and South Africa. In combination with previous virus discovery efforts, this finding suggests that these virus types are widespread among African monkeys. Our analysis suggests that one of these virus types, the simian arteriviruses, may have the potential to jump between different primate species and cause disease. In contrast, the other virus type, the pegiviruses, are thought to reduce the disease caused by human immunodeficiency virus (HIV) in humans. However, we did not observe a similar protective effect in SIV-infected African monkeys coinfected with pegiviruses, possibly because SIV causes little to no disease in these hosts. C1 [Bailey, Adam L.; Lauck, Michael; Heimbruch, Katelyn; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. [Bailey, Adam L.; Lauck, Michael; Heimbruch, Katelyn; Goldberg, Tony L.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Ghai, Ria R.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Nelson, Chase W.; Hughes, Austin L.] Univ South Carolina, Dept Biol Sci, Columbia, SC 29208 USA. [Goldberg, Tony L.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Jasinska, Anna J.; Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Apetrei, Cristian] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. [Apetrei, Cristian] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.; O'Connor, DH (reprint author), Wisconsin Natl Primate Res Ctr, Madison, WI USA. EM doconnor@primate.wisc.edu OI Ghai, Ria/0000-0001-9775-4826; Kuhn, Jens H./0000-0002-7800-6045 FU National Institutes of Health (NIH) [R01AI077376-01, R01AI084787, R01RR025781, P01AI088564, R01AI116382-01]; National Science Foundation (NSF) [NSF1029302, NSF1029323, NSF1029451, DGE0929297]; NIH-NSF Ecology of Infectious Diseases program [TW009237]; United Kingdom Economic and Social Research Council [TW009237]; Wisconsin Partnership Program through the Wisconsin Center for Infectious Diseases; National Institutes of Health National Center for Research Resources [P51RR000167, R01OD010980]; Office of Research Infrastructure Programs (ORIP) [OD011104]; Research Facilities Improvement Program [RR15459-01, RR020141-01]; University of Wisconsin Medical Scientist Training Program (MSTP) [T32 GM008692]; National Research Service Award (NRSA) through the Microbes in Health and Disease (MHD) training program at the University of Wisconsin [T32 AI55397]; NSF [DGE-0929297]; University of South Carolina (USC); USC Department of Biological Sciences Kathryn Hinnant-Johnson, M.D., Memorial Fellowship; Battelle Memorial Institute's prime contract; U.S. National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I] FX This work was funded by the National Institutes of Health (NIH) (grants R01AI077376-01, R01AI084787, R01RR025781, P01AI088564, and R01AI116382-01), the National Science Foundation (NSF) (grants NSF1029302, NSF1029323, NSF1029451, and DGE0929297), the joint NIH-NSF Ecology of Infectious Diseases program and the United Kingdom Economic and Social Research Council (grant TW009237), and the Wisconsin Partnership Program through the Wisconsin Center for Infectious Diseases. This publication was made possible in part by grants from the National Institutes of Health National Center for Research Resources (grant P51RR000167 to the WNPRC, University of Wisconsin-Madison, and grant R01OD010980, formerly R01RR016300, to the University of California, Los Angeles) and grant OD011104 to the Tulane National Primate Research Center from the Office of Research Infrastructure Programs (ORIP). This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01. A.L.B. performed this work with support from the University of Wisconsin Medical Scientist Training Program (MSTP) (grant T32 GM008692) and a National Research Service Award (NRSA) through the Microbes in Health and Disease (MHD) training program at the University of Wisconsin (grant T32 AI55397). C.W.N. performed this work with support from NSF Graduate Research Fellowship DGE-0929297, the University of South Carolina (USC) Presidential Fellowship, and the USC Department of Biological Sciences Kathryn Hinnant-Johnson, M.D., Memorial Fellowship. This work was also funded in part through Battelle Memorial Institute's prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under contract no. HHSN272200700016I. A subcontractor to Battelle Memorial Institute who performed this work is J.H.K., an employee of Tunnell Government Services, Inc. NR 67 TC 1 Z9 2 U1 1 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 AUG PY 2016 VL 90 IS 15 BP 6724 EP 6737 DI 10.1128/JVI.00573-16 PG 14 WC Virology SC Virology GA DU6EF UT WOS:000382306100009 PM 27170760 ER PT J AU Hogg, JR AF Hogg, J. Robert TI Viral Evasion and Manipulation of Host RNA Quality Control Pathways SO JOURNAL OF VIROLOGY LA English DT Review ID SARCOMA-ASSOCIATED HERPESVIRUS; PRE-MESSENGER-RNA; POLYADENYLATED NUCLEAR-RNA; EXON JUNCTION COMPLEX; CIS-ACTING ELEMENTS; REV GENE-PRODUCT; NONSENSE CODONS; TRIPLE-HELIX; NUCLEOCYTOPLASMIC EXPORT; ENDONUCLEOLYTIC CLEAVAGE AB Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance. C1 [Hogg, J. Robert] NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Hogg, JR (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM j.hogg@nih.gov OI Hogg, J. Robert/0000-0001-5729-5135 FU HHS \ NIH \ National Heart, Lung, and Blood Institute (NHLBI); HHS \ NIH \ National Heart, Lung, and Blood Institute (NHLBI) \ Intramural Research Program FX This work, including the efforts of J. Robert Hogg, was funded by HHS vertical bar NIH vertical bar National Heart, Lung, and Blood Institute (NHLBI).; This work was supported by HHS vertical bar NIH vertical bar National Heart, Lung, and Blood Institute (NHLBI) vertical bar Intramural Research Program. NR 122 TC 2 Z9 2 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 AUG PY 2016 VL 90 IS 16 BP 7010 EP 7018 DI 10.1128/JVI.00607-16 PG 9 WC Virology SC Virology GA DU6EJ UT WOS:000382306500001 PM 27226372 ER PT J AU Nelson, EV Schmidt, KM Deflube, LR Doganay, S Banadyga, L Olejnik, J Hume, AJ Ryabchikova, E Ebihara, H Kedersha, N Ha, T Muhlberger, E AF Nelson, Emily V. Schmidt, Kristina M. Deflube, Laure R. Doganay, Sultan Banadyga, Logan Olejnik, Judith Hume, Adam J. Ryabchikova, Elena Ebihara, Hideki Kedersha, Nancy Ha, Taekjip Muehlberger, Elke TI Ebola Virus Does Not Induce Stress Granule Formation during Infection and Sequesters Stress Granule Proteins within Viral Inclusions SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; MARBURG-VIRUS; KINASE PKR; INTERFERON ANTAGONISM; PROCESSING BODIES; VP35 PROTEIN; P-BODIES; REPLICATION; CELLS; NUCLEOPROTEIN AB A hallmark of Ebola virus (EBOV) infection is the formation of viral inclusions in the cytoplasm of infected cells. These viral inclusions contain the EBOV nucleocapsids and are sites of viral replication and nucleocapsid maturation. Although there is growing evidence that viral inclusions create a protected environment that fosters EBOV replication, little is known about their role in the host response to infection. The cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation and translational arrest mediated by the phosphorylation of a translation initiation factor, the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha). Here, we show that selected SG proteins are sequestered within EBOV inclusions, where they form distinct granules that colocalize with viral RNA. These inclusion-bound (IB) granules are functionally and structurally different from canonical SGs. Formation of IB granules does not indicate translational arrest in the infected cells. We further show that EBOV does not induce formation of canonical SGs or eIF2 alpha phosphorylation at any time postinfection but is unable to fully inhibit SG formation induced by different exogenous stressors, including sodium arsenite, heat, and hippuristanol. Despite the sequestration of SG marker proteins into IB granules, canonical SGs are unable to form within inclusions, which we propose might be mediated by a novel function of VP35, which disrupts SG formation. This function is independent of VP35's RNA binding activity. Further studies aim to reveal the mechanism for SG protein sequestration and precise function within inclusions. IMPORTANCE Although progress has been made developing antiviral therapeutics and vaccines against the highly pathogenic Ebola virus (EBOV), the cellular mechanisms involved in EBOV infection are still largely unknown. To better understand these intracellular events, we investigated the cellular stress response, an antiviral pathway manipulated by many viruses. We show that EBOV does not induce formation of stress granules (SGs) in infected cells and is therefore unrestricted by their concomitant translational arrest. We identified SG proteins sequestered within viral inclusions, which did not impair protein translation. We further show that EBOV is unable to block SG formation triggered by exogenous stress early in infection. These findings provide insight into potential targets of therapeutic intervention. Additionally, we identified a novel function of the interferon antagonist VP35, which is able to disrupt SG formation. C1 [Nelson, Emily V.; Schmidt, Kristina M.; Deflube, Laure R.; Olejnik, Judith; Hume, Adam J.; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Nelson, Emily V.; Schmidt, Kristina M.; Deflube, Laure R.; Olejnik, Judith; Hume, Adam J.; Muehlberger, Elke] Boston Univ, Natl Emerging Infect Dis Labs, Boston, MA 02215 USA. [Doganay, Sultan; Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL USA. [Banadyga, Logan; Ebihara, Hideki] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA. [Ryabchikova, Elena] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. [Kedersha, Nancy] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. [Schmidt, Kristina M.] Inst Novel & Emerging Infect Dis, Fed Res Inst Anim Hlth, Friedrich Loeffler Inst, Greifswald, Germany. RP Muhlberger, E (reprint author), Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.; Muhlberger, E (reprint author), Boston Univ, Natl Emerging Infect Dis Labs, Boston, MA 02215 USA. EM muehlber@bu.edu RI Ryabchikova, Elena /G-3089-2013 OI Ryabchikova, Elena /0000-0003-4714-1524 FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [U01-AI082954, R03-AI114293, UC6AI058618, AI0655858, CA168872, U19-AI083025]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID) FX This work, including the efforts of Elke Muhlberger, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (U01-AI082954). This work, including the efforts of Elke Muhlberger, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R03-AI114293). This work, including the efforts of Elke Muhlberger, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (UC6AI058618). This work, including the efforts of Nancy Kedersha, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (AI0655858). This work, including the efforts of Nancy Kedersha, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (CA168872). This work, including the efforts of Taekjip Ha, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (U19-AI083025). This work, including the efforts of Hideki Ebihara, was funded by Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID). NR 83 TC 0 Z9 0 U1 2 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 AUG PY 2016 VL 90 IS 16 BP 7268 EP 7284 DI 10.1128/JVI.00459-16 PG 17 WC Virology SC Virology GA DU6EJ UT WOS:000382306500021 PM 27252530 ER PT J AU Rostad, CA Stobart, CC Gilbert, BE Pickles, RJ Hotard, AL Meng, J Blanco, JCG Moin, SM Graham, BS Piedra, PA Moore, ML AF Rostad, Christina A. Stobart, Christopher C. Gilbert, Brian E. Pickles, Ray J. Hotard, Anne L. Meng, Jia Blanco, Jorge C. G. Moin, Syed M. Graham, Barney S. Piedra, Pedro A. Moore, Martin L. TI A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats SO JOURNAL OF VIROLOGY LA English DT Article ID ENHANCED PULMONARY PATHOLOGY; NEUTRALIZING ANTIBODY; IN-VITRO; SH GENE; INFECTION; DISEASE; GLYCOPROTEIN; DEOPTIMIZATION; IMMUNIZATION; PATHOGENESIS AB Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (Delta SH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-Delta SH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log(10) total PFU and 2.7 log(10) PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. C1 [Rostad, Christina A.; Stobart, Christopher C.; Hotard, Anne L.; Meng, Jia; Moore, Martin L.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Rostad, Christina A.; Stobart, Christopher C.; Hotard, Anne L.; Meng, Jia; Moore, Martin L.] Childrens Healthcare Atlanta, Atlanta, GA 30342 USA. [Gilbert, Brian E.; Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Pickles, Ray J.] Univ North Carolina Chapel Hill, Marsico Lung Inst, Chapel Hill, NC USA. [Pickles, Ray J.] Univ North Carolina Chapel Hill, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Blanco, Jorge C. G.] Sigmovir Biosyst Inc, Rockville, MD USA. [Moin, Syed M.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Moore, ML (reprint author), Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.; Moore, ML (reprint author), Childrens Healthcare Atlanta, Atlanta, GA 30342 USA. EM martin.moore@emory.edu FU HHS\ NIH\ National Institute of Allergy and Infectious Diseases (NIAID) [1R01AI087798, 1U19AI095227, T32AI074492, HHSN272201000004I]; HHS \ NIH \ National Institute of Child Health and Human Development (NICHD) [5K12HD072245] FX This work, including the efforts of Martin L. Moore, Christina Rostad, Christopher C. Stobart, Anne L. Hotard, and Jia Meng, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (1R01AI087798 and 1U19AI095227). This work, including the efforts of Christopher C. Stobart, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (T32AI074492). This work, including the efforts of Brian Edward Gilbert and Pedro A. Piedra, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (HHSN272201000004I). This work, including the efforts of Christina Rostad, was funded by HHS vertical bar NIH vertical bar National Institute of Child Health and Human Development (NICHD) (5K12HD072245). NR 35 TC 3 Z9 3 U1 5 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 AUG PY 2016 VL 90 IS 16 BP 7508 EP 7518 DI 10.1128/JVI.00012-16 PG 11 WC Virology SC Virology GA DU6EJ UT WOS:000382306500038 PM 27279612 ER PT J AU Calascibetta, F Micci, L Carnathan, D Lawson, B Vanderford, TH Bosinger, SE Easley, K Chahroudi, A Mackel, J Keele, BF Long, S Lifson, J Paiardini, M Silvestri, G AF Calascibetta, Francesca Micci, Luca Carnathan, Diane Lawson, Benton Vanderford, Thomas H. Bosinger, Steven E. Easley, Kirk Chahroudi, Ann Mackel, Joseph Keele, Brandon F. Long, Samuel Lifson, Jeffrey Paiardini, Mirko Silvestri, Guido TI Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; CHRONIC HIV-INFECTION; SIV INFECTION; RHESUS MACAQUES; HOMEOSTATIC PROLIFERATION; LENTIVIRAL INFECTIONS; IMMUNE ACTIVATION; VIRAL RESERVOIR; SUPPRESSION; DEPLETION AB Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4(+) central memory (T-CM) and stem cell memory (T-SCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4(+) transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4(+) TCM cells, (ii) increased levels of CD4(+) T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8(+) T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4(+) TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV-infected sooty mangabeys, a natural host for the infection, with a potent antiretroviral therapy (ART) regimen for periods ranging from 2 to 12 months and monitored in detail how suppression of virus replication affected the main virological and immunological features of this nonpathogenic infection. The observed findings provide novel information on both the pathogenesis of residual immunological disease under ART during pathogenic infection and the mechanisms involved in virus persistence during primate lentiviral infections. C1 [Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Chahroudi, Ann; Mackel, Joseph; Paiardini, Mirko; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Chahroudi, Ann; Mackel, Joseph; Paiardini, Mirko; Silvestri, Guido] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Calascibetta, Francesca] Univ Milan, L Sacco Dept Biomed & Clin Sci, Milan, Italy. [Easley, Kirk] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Chahroudi, Ann] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Silvestri, Guido] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Silvestri, G (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.; Silvestri, G (reprint author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.; Silvestri, G (reprint author), Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. EM gsilves@emory.edu RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU HHS \ NIH \ National Cancer Institute (NCI) [HHSN261200800001E]; HHS \ National Institutes of Health (NIH) [R37 AI66998]; R33 NIH grant [AI104278]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [P51 OD011132]; Merck FX This work, including the efforts of Jeffrey Lifson, was funded by HHS vertical bar NIH vertical bar National Cancer Institute (NCI) (HHSN261200800001E). This work, including the efforts of Guido Silvestri, was funded by HHS vertical bar National Institutes of Health (NIH) (R37 AI66998).; This work was supported by an R33 NIH grant (AI104278) with principal investigators Guido Silvestri and Mirko Paiardini. Research reported in this publication was also supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number P51 OD011132 (to the YNPRC) and also in part by Merck. NR 45 TC 1 Z9 1 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 AUG PY 2016 VL 90 IS 16 BP 7541 EP 7551 DI 10.1128/JVI.00598-16 PG 11 WC Virology SC Virology GA DU6EJ UT WOS:000382306500041 PM 27279614 ER PT J AU Feigin, VL Roth, GA Naghavi, M Parmar, P Krishnamurthi, R Chugh, S Mensah, GA Norrving, B Shiue, I Ng, M Estep, K Cercy, K Murray, CJL Forouzanfar, MH AF Feigin, Valery L. Roth, Gregory A. Naghavi, Mohsen Parmar, Priya Krishnamurthi, Rita Chugh, Sumeet Mensah, George A. Norrving, Bo Shiue, Ivy Ng, Marie Estep, Kara Cercy, Kelly Murray, Christopher J. L. Forouzanfar, Mohammad H. CA Global Burden Dis Injuries Risk Factors Study Stroke Experts TI Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 SO LANCET NEUROLOGY LA English DT Article ID CAUSE-SPECIFIC MORTALITY; HEMORRHAGIC STROKE; CARDIOVASCULAR-DISEASE; PREVALENCE; DISABILITY; COHORT; METAANALYSIS; PREVENTION; CALIFORNIA; INJURIES AB Background The contribution of modifiable risk factors to the increasing global and regional burden of stroke is unclear, but knowledge about this contribution is crucial for informing stroke prevention strategies. We used data from the Global Burden of Disease Study 2013 (GBD 2013) to estimate the population-attributable fraction (PAF) of stroke-related disability-adjusted life-years (DALYs) associated with potentially modifiable environmental, occupational, behavioural, physiological, and metabolic risk factors in different age and sex groups worldwide and in high-income countries and low-income and middle-income countries, from 1990 to 2013. Methods We used data on stroke-related DALYs, risk factors, and PAF from the GBD 2013 Study to estimate the burden of stroke by age and sex (with corresponding 95% uncertainty intervals [UI]) in 188 countries, as measured with stroke related DALYs in 1990 and 2013. We evaluated attributable DALYs for 17 risk factors (air pollution and environmental, dietary, physical activity, tobacco smoke, and physiological) and six clusters of risk factors by use of three inputs: risk factor exposure, relative risks, and the theoretical minimum risk exposure level. For most risk factors, we synthesised data for exposure with a Bayesian meta-regression method (DisMod-MR) or spatial-temporal Gaussian process regression. We based relative risks on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks, such as high body-mass index (BMI), through other risks, such as high systolic blood pressure (SBP) and high total cholesterol. Findings Globally, 90.5% (95% UI 88.5-92.2) of the stroke burden (as measured in DALYs) was attributable to the modifiable risk factors analysed, including 74.2% (95% UI 70.7-76.7) due to behavioural factors (smoking, poor diet, and low physical activity). Clusters of metabolic factors (high SBP, high BMI, high fasting plasma glucose, high total cholesterol, and low glomerular filtration rate; 72.4%, 95% UI 70.2-73.5) and environmental factors (air pollution and lead exposure; 33.4%, 95% UI 32.4-34.3) were the second and third largest contributors to DALYs. Globally, 29.2% (95% UI 28.2-29.6) of the burden of stroke was attributed to air pollution. Although globally there were no significant differences between sexes in the proportion of stroke burden due to behavioural, environmental, and metabolic risk clusters, in the low-income and middle-income countries, the PAF of behavioural risk clusters in males was greater than in females. The PAF of all risk factors increased from 1990 to 2013 (except for second-hand smoking and household air pollution from solid fuels) and varied significantly between countries. Interpretation Our results suggest that more than 90% of the stroke burden is attributable to modifiable risk factors, and achieving control of behavioural and metabolic risk factors could avert more than three-quarters of the global stroke burden. Air pollution has emerged as a significant contributor to global stroke burden, especially in low-income and middle-income countries, and therefore reducing exposure to air pollution should be one of the main priorities to reduce stroke burden in these countries. C1 [Feigin, Valery L.; Parmar, Priya; Krishnamurthi, Rita] Auckland Univ Technol, Fac Hlth & Environm Studies, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand. [Roth, Gregory A.; Naghavi, Mohsen; Chugh, Sumeet; Ng, Marie; Estep, Kara; Cercy, Kelly; Murray, Christopher J. L.; Forouzanfar, Mohammad H.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Mensah, George A.] NHLBI, CTRIS, NIH, Bldg 10, Bethesda, MD 20892 USA. [Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden. [Shiue, Ivy] Northumbria Univ, Fac Hlth & Life Sci, Newcastle Upon Tyne, Tyne & Wear, England. [Shiue, Ivy] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. RP Feigin, VL (reprint author), Auckland Univ Technol, Fac Hlth & Environm Studies, Sch Publ Hlth & Psychosocial Studies, Natl Inst Stroke & Appl Neurosci, North Shore Campus, Auckland 0627, New Zealand. EM valery.feigin@aut.ac.nz FU Bill & Melinda Gates Foundation; American Heart Association Postdoctoral Fellowship; US National Heart, Lung, and Blood Institute award [K08 HL089675-01A1]; Columbia University Irving Scholarship; Health Research Council of New Zealand; Brain Research New Zealand Centre of Research Excellence; "Ageing Well" Programme of the National Science Challenge, Ministry of Business, Innovation and Employment of New Zealand FX This research was supported by the Bill & Melinda Gates Foundation, an American Heart Association Postdoctoral Fellowship to GAR; US National Heart, Lung, and Blood Institute award K08 HL089675-01A1 and a Columbia University Irving Scholarship; and Health Research Council of New Zealand to VLF, RK, and PP. VLF was also partly funded by the Brain Research New Zealand Centre of Research Excellence and the "Ageing Well" Programme of the National Science Challenge, Ministry of Business, Innovation and Employment of New Zealand. The views expressed in this Article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, National Institutes of Health, or the US Department of Health and Human Services. NR 44 TC 27 Z9 27 U1 19 U2 21 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 AUG PY 2016 VL 15 IS 9 BP 913 EP 924 DI 10.1016/S1474-4422(16)30073-4 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA DT1YY UT WOS:000381279200011 PM 27291521 ER PT J AU Gratzinger, D Jaffe, ES AF Gratzinger, Dita Jaffe, Elaine S. TI Mucocutaneous ulcer: a mimic of EBV plus diffuse large B cell lymphoma in the immunodeficiency setting SO LEUKEMIA & LYMPHOMA LA English DT Letter ID LYMPHOPROLIFERATIVE DISORDERS C1 [Gratzinger, Dita] Stanford Univ, Dept Pathol, Sch Med, 300 Pasteur Dr L235, Stanford, CA 94305 USA. [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Gratzinger, D (reprint author), Stanford Univ, Dept Pathol, Sch Med, 300 Pasteur Dr L235, Stanford, CA 94305 USA. EM ditag@stanford.edu OI Gratzinger, Dita/0000-0002-9182-8123 NR 7 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2016 VL 57 IS 8 BP 1982 EP 1983 DI 10.3109/10428194.2016.1166492 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DT2DI UT WOS:000381290600037 PM 27071493 ER PT J AU Wang, F Dai, JC Li, MJ Chan, WC Kwok, CCH Leung, SL Wu, C Li, WT Yu, WC Tsang, KH Law, SH Lee, PMY Wong, CKM Shen, HB Wong, SYS Yang, XHR Tse, LA AF Wang, Feng Dai, Juncheng Li, Mengjie Chan, Wing-cheong Kwok, Carol Chi-hei Leung, Siu-lan Wu, Cherry Li, Wentao Yu, Wai-cho Tsang, Koon-ho Law, Sze-hong Lee, Priscilla Ming-yi Wong, Carmen Ka-man Shen, Hongbing Wong, Samuel Yeung-shan Yang, Xiaohong R. Tse, Lap Ah TI Risk assessment model for invasive breast cancer in Hong Kong women SO MEDICINE LA English DT Article DE breast cancer; estrogen receptor; LASSO model; light at night; menopause; risk assessment ID PROJECTING INDIVIDUALIZED PROBABILITIES; SHIFT-WORK; CIRCADIAN DISRUPTION; ALCOHOL-CONSUMPTION; SLEEP DURATION; CHINESE WOMEN; CARCINOGENICITY; METAANALYSIS; VALIDATION; PREVENTION AB No risk assessment tool is available for identifying high risk population of breast cancer (BCa) in Hong Kong. A case-control study including 918 BCa cases and 923 controls was used to develop the risk assessment model among Hong Kong Chinese women. Each participant received an in-depth interview to obtain their lifestyle and environmental risk factors. Least absolute shrinkage and selection operator (LASSO) selection model was used to select the optimal risk factors (LASSO-model). A risk score system was constructed to evaluate the cumulative effects of selected factors. Bootstrap simulation was used to test the internal validation of the model. Model performance was evaluated by receiver-operator characteristic curves and the area under the curve (AUC). Age, number of parity, number of BCa cases in 1st-degree relatives, exposure to light at night, and sleep quality were the common risk factors for all women. Alcohol drinking was included for premenopausal women; body mass index, age at menarche, age at 1st give birth, breast feeding, using of oral contraceptive, hormone replacement treatment, and history of benign breast diseases were included for postmenopausal women. The AUCs were 0.640 (95% CI, 0.598-0.681) and 0.655 (95% CI, 0.621-0.653) for pre- and postmenopausal women, respectively. Further subgroup evaluation revealed that the model performance was better for women aged 50 to 70 years or ER-positive. This BCa risk assessment tool in Hong Kong Chinese women based on LASSO selection is promising, which shows a slightly higher discriminative accuracy than those developed in other populations. C1 [Wang, Feng; Dai, Juncheng; Li, Mengjie; Li, Wentao; Lee, Priscilla Ming-yi; Wong, Carmen Ka-man; Wong, Samuel Yeung-shan; Tse, Lap Ah] Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Sha Tin, Hong Kong, Peoples R China. [Dai, Juncheng; Shen, Hongbing] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Collaborat Innovat Ctr Canc Personalized Med, Dept Epidemiol & Biostat,Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China. [Chan, Wing-cheong] North Dist Hosp, Dept Surg, Kowloon, Hong Kong, Peoples R China. [Kwok, Carol Chi-hei] Princess Margaret Hosp, Dept Oncol, Kowloon, Hong Kong, Peoples R China. [Leung, Siu-lan] Pamela Youde Nethersole Eastern Hosp, Dept Surg, Kowloon, Hong Kong, Peoples R China. [Wu, Cherry] North Dist Hosp, Dept Pathol, Kowloon, Hong Kong, Peoples R China. [Yu, Wai-cho] Princess Margaret Hosp, Dept Med & Geriatr, Kowloon, Hong Kong, Peoples R China. [Tsang, Koon-ho] Yan Chai Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Law, Sze-hong] Yan Chai Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Yang, Xiaohong R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Tse, LA (reprint author), Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Sha Tin, Hong Kong, Peoples R China. EM shelly@cuhk.edu.hk FU Research Grants Council of Hong Kong [474811] FX This work was supported by Research Grants Council of Hong Kong (Grant number 474811). NR 42 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 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD AUG PY 2016 VL 95 IS 32 AR e4515 DI 10.1097/MD.0000000000004515 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DU5IX UT WOS:000382246500036 PM 27512870 ER PT J AU Clemons, PA Shamji, A Hon, C Wagner, BK Schreiber, SL Krasnitz, A Sordella, R Sander, C Lowe, SW Powers, S Smith, K Aburi, M Lavarone, A Lasorella, A Silva, J Stockwell, B Califano, A Boehm, JS Vazquez, F Weir, BA Golub, TR Hahn, WC Khuri, FR Moreno, CS Du, YH Cooper, L Ivanov, AA Johns, MA Fu, HA Nikolova, O Mendez, E Gadi, VK Margolin, AA Grandori, C Kemp, CJ Warren, EH Riddell, SR McIntosh, MW Gevaert, O Ji, HP Kuo, CJ Dhruv, H Finlay, D Kiefer, J Kim, S Vuori, K Berens, ME Weissman, J Bivona, T Bandyopadhyay, S Hangauer, M Boettcher, M McManus, M McCormick, F Aksoy, O Simonds, EF Zheng, TN Chen, J An, ZY Balmain, A Weiss, WA Chen, K Liang, H Scott, KL Mills, GB Posner, BA MacMillan, J Minna, J White, MA Roth, MG Jagu, S Mazerik, JN Gerhard, DS AF Clemons, Paul A. Shamji, Alykhan Hon, Cindy Wagner, Bridget K. Schreiber, Stuart L. Krasnitz, Alex Sordella, Raffaella Sander, Chris Lowe, Scott W. Powers, Scott Smith, Kenneth Aburi, Mahalaxmi Lavarone, Antonio Lasorella, Anna Silva, Jose Stockwell, Brent Califano, Andrea Boehm, Jesse S. Vazquez, Francisca Weir, Barbara A. Golub, Todd R. Hahn, William C. Khuri, Fadlo R. Moreno, Carlos S. Du, Yuhong Cooper, Lee Ivanov, Andrey A. Johns, Margaret A. Fu, Haian Nikolova, Olga Mendez, Eduardo Gadi, Vijayakrishna K. Margolin, Adam A. Grandori, Carla Kemp, Christopher J. Warren, Edus H. Riddell, Stanley R. McIntosh, Martin W. Gevaert, Olivier Ji, Hanlee P. Kuo, Calvin J. Dhruv, Harshil Finlay, Darren Kiefer, Jeffrey Kim, Seungchan Vuori, Kristiina Berens, Michael E. Weissman, Jonathan Bivona, Trever Bandyopadhyay, Sourav Hangauer, Matt Boettcher, Michael McManus, Michael McCormick, Frank Aksoy, Ozlem Simonds, Erin F. Zheng, Tina Chen, Justin An, Zhenyi Balmain, Allan Weiss, William A. Chen, Ken Liang, Han Scott, Kenneth L. Mills, Gordon B. Posner, Bruce A. MacMillan, John Minna, John White, Michael A. Roth, Michael G. Jagu, Subhashini Mazerik, Jessica N. Gerhard, Daniela S. CA Canc Target Discovery Dev Network TI Transforming Big Data into Cancer-Relevant Insight: An Initial, Multi-Tier Approach to Assess Reproducibility and Relevance The Cancer Target Discovery and Development Network SO MOLECULAR CANCER RESEARCH LA English DT Article ID DRUG-SENSITIVITY; INHIBITION; LANDSCAPE; TBK1 AB The Cancer Target Discovery and Development (CTD2) Network was established to accelerate the transformation of "Big Data" into novel pharmacologic targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding. This article represents a first attempt to delineate the challenges of supporting and confirming discoveries arising from the systematic analysis of large-scale data resources in a collaborative work environment and to provide a framework that would begin a community discussion to resolve these challenges. The Network implemented a multi-tier framework designed to substantiate the biological and biomedical relevance as well as the reproducibility of data and insights resulting from its collaborative activities. The same approach can be used by the broad scientific community to drive development of novel therapeutic and biomarker strategies for cancer. (C) 2016 AACR. C1 [Jagu, Subhashini; Mazerik, Jessica N.; Gerhard, Daniela S.] NCI, 31 Ctr Dr, Bethesda, MD 20892 USA. [Clemons, Paul A.; Shamji, Alykhan; Hon, Cindy; Wagner, Bridget K.; Schreiber, Stuart L.] Broad Inst, Cambridge, MA USA. [Krasnitz, Alex; Sordella, Raffaella; Sander, Chris; Lowe, Scott W.; Powers, Scott] Cold Springs Harbor Lab, Cold Springs Harbor, NY USA. [Smith, Kenneth; Aburi, Mahalaxmi; Lavarone, Antonio; Lasorella, Anna; Silva, Jose; Stockwell, Brent; Califano, Andrea] Columbia Univ, New York, NY USA. [Boehm, Jesse S.; Vazquez, Francisca; Weir, Barbara A.; Golub, Todd R.; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khuri, Fadlo R.; Moreno, Carlos S.; Du, Yuhong; Cooper, Lee; Ivanov, Andrey A.; Johns, Margaret A.; Fu, Haian] Emory Univ, Atlanta, GA 30322 USA. [Nikolova, Olga; Mendez, Eduardo; Gadi, Vijayakrishna K.; Margolin, Adam A.; Grandori, Carla; Kemp, Christopher J.; Warren, Edus H.; Riddell, Stanley R.; McIntosh, Martin W.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Nikolova, Olga; Mendez, Eduardo; Gadi, Vijayakrishna K.; Margolin, Adam A.; Grandori, Carla; Kemp, Christopher J.] Cure First, Seattle, WA USA. [Nikolova, Olga; Mendez, Eduardo; Gadi, Vijayakrishna K.; Margolin, Adam A.; Grandori, Carla; Kemp, Christopher J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nikolova, Olga; Mendez, Eduardo; Gadi, Vijayakrishna K.; Margolin, Adam A.; Grandori, Carla; Kemp, Christopher J.] Univ Washington, Seattle, WA 98195 USA. [Gevaert, Olivier; Ji, Hanlee P.; Kuo, Calvin J.] Stanford Univ, Stanford, CA 94305 USA. [Dhruv, Harshil; Finlay, Darren; Kiefer, Jeffrey; Kim, Seungchan; Vuori, Kristiina; Berens, Michael E.] Translat Genom Res Inst, Phoenix, AZ USA. [Weissman, Jonathan; Bivona, Trever; Bandyopadhyay, Sourav; Hangauer, Matt; Boettcher, Michael; McManus, Michael; McCormick, Frank; Aksoy, Ozlem; Simonds, Erin F.; Zheng, Tina; Chen, Justin; An, Zhenyi; Balmain, Allan; Weiss, William A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chen, Ken; Liang, Han; Scott, Kenneth L.; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Posner, Bruce A.; MacMillan, John; Minna, John; White, Michael A.; Roth, Michael G.] Univ Texas Southwestern, Dallas, TX USA. RP Gerhard, DS (reprint author), NCI, 31 Ctr Dr, Bethesda, MD 20892 USA. EM gerhardd@mail.nih.gov RI Moreno, Carlos/B-3863-2009 OI Moreno, Carlos/0000-0002-5582-0028 FU NIH [CA176152, CA168409, CA168426, CA176058, CA168449, CA176303, CA176270, CA176299, CA168397, CA168370, CA176287, CA168394, CA176284] FX S.L. Schreiber was supported by NIH CA176152, S. Powers was supported by NIH CA168409, A. Califano was supported by NIH CA168426, W.C. Hahn was supported by NIH CA176058, H. Fu was supported by NIH CA168449, C.J. Kemp was supported by NIH CA176303, M. Mcintosh was supported by NIH CA176270, C.J. Kuo was supported by NIH CA176299, M. E. Berens was supported by NIH CA168397, M.T. Mcmanus was supported by NIH CA168370, W.A. Weiss was supported by NIH CA176287, G.B. Mills was supported by NIH CA168394, and M.G. Roth was supported by NIH CA176284. NR 20 TC 0 Z9 0 U1 12 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2016 VL 14 IS 8 BP 675 EP 682 DI 10.1158/1541-7786.MCR-16-0090 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DU5WJ UT WOS:000382283900001 ER PT J AU Shah, N Guo, YJ Wendelsdorf, KV Lu, Y Sparks, R Tsang, JS AF Shah, Naisha Guo, Yongjian Wendelsdorf, Katherine V. Lu, Yong Sparks, Rachel Tsang, John S. TI A crowdsourcing approach for reusing and meta analyzing gene expression data SO NATURE BIOTECHNOLOGY LA English DT Letter ID ENRICHMENT ANALYSIS; SIGNATURES; PROFILES; DISEASE; UPDATE C1 [Shah, Naisha; Wendelsdorf, Katherine V.; Lu, Yong; Sparks, Rachel; Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Guo, Yongjian] NIAID, Off Chief Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Tsang, JS (reprint author), NIAID, Syst Genom & Bioinformat Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM john.tsang@nih.gov NR 22 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2016 VL 34 IS 8 BP 803 EP 806 DI 10.1038/nbt.3603 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DT2VJ UT WOS:000381339600010 PM 27323300 ER PT J AU Wang, MX Carver, JJ Phelan, VV Sanchez, LM Garg, N Peng, Y Nguyen, DD Watrous, J Kapono, CA Luzzatto-Knaan, T Porto, C Bouslimani, A Melnik, AV Meehan, MJ Liu, WT Criisemann, M Boudreau, PD Esquenazi, E Sandoval-Calderon, M Kersten, RD Pace, LA Quinn, RA Duncan, KR Hsu, CC Floros, DJ Gavilan, RG Kleigrewe, K Northen, T Dutton, RJ Parrot, D Carlson, EE Aigle, B Michelsen, CF Jelsbak, L Sohlenkamp, C Pevzner, P Edlund, A McLean, J Piel, J Murphy, BT Gerwick, L Liaw, CC Yang, YL Humpf, HU Maansson, M Keyzers, RA Sims, AC Johnson, AR Sidebottom, AM Sedio, BE Klitgaard, A Larson, CB Boya, CA Torres-Mendoza, D Gonzalez, DJ Silva, DB Marques, LM Demarque, DP Pociute, E O'Neill, EC Briand, E Helfrich, EJN Granatosky, EA Glukhov, E Ryffel, F Houson, H Mohimani, H Kharbush, JJ Zeng, Y Vorholt, JA Kurita, KL Charusanti, P McPhail, KL Nielsen, KF Vuong, L Elfeki, M Traxler, MF Engene, N Koyama, N Vining, OB Baric, R Silva, RR Mascuch, SJ Tomasi, S Jenkins, S Macherla, V Hoffman, T Agarwal, V Williams, PG Dai, JQ Neupane, R Gurr, J Rodriguez, AMC Lamsa, A Zhang, C Dorrestein, K Duggan, BM Almaliti, J Allard, PM Phapale, P Nothias, LF Alexandrovr, T Litaudon, M Wolfender, JL Kyle, JE Metz, TO Peryea, T Nguyen, DT VanLeer, D Shinn, P Jadhav, A Muller, R Waters, KM Shi, WY Liu, XT Zhang, LX Knight, R Jensen, PR Palsson, BO Pogliano, K Linington, RG Gutierrez, M Lopes, NP Gerwick, WH Moore, BS Dorrestein, PC Bandeira, N AF Wang, Mingxun Carver, Jeremy J. Phelan, Vanessa V. Sanchez, Laura M. Garg, Neha Peng, Yao Don Duy Nguyen Watrous, Jeramie Kapono, Clifford A. Luzzatto-Knaan, Tal Porto, Carla Bouslimani, Amina Melnik, Alexey V. Meehan, Michael J. Liu, Wei -Ting Criisemann, Max Boudreau, Paul D. Esquenazi, Eduardo Sandoval-Calderon, Mario Kersten, Roland D. Pace, Laura A. Quinn, Robert A. Duncan, Katherine R. Hsu, Cheng-Chih Floros, Dimitrios J. Gavilan, Ronnie G. Kleigrewe, Karin Northen, Trent Dutton, Rachel J. Parrot, Delphine Carlson, Erin E. Aigle, Bertrand Michelsen, Charlotte F. Jelsbak, Lars Sohlenkamp, Christian Pevzner, Pavel Edlund, Anna McLean, Jeffrey Piel, Jorn Murphy, Brian T. Gerwick, Lena Liaw, Chih-Chuang Yang, Yu-Liang Humpf, Hans-Ulrich Maansson, Maria Keyzers, Robert A. Sims, Amy C. Johnson, Andrew R. Sidebottom, Ashley M. Sedio, Brian E. Klitgaard, Andreas Larson, Charles B. Boya P, Cristopher A. Torres-Mendoza, Daniel Gonzalez, David J. Silva, Denise B. Marques, Lucas M. Demarque, Daniel P. Pociute, Egle O'Neill, Ellis C. Briand, Enora Helfrich, Eric J. N. Granatosky, Eve A. Glukhov, Evgenia Ryffel, Florian Houson, Hailey Mohimani, Hosein Kharbush, Jenan J. Zeng, Yi Vorholt, Julia A. Kurita, Kenji L. Charusanti, Pep McPhail, Kerry L. Nielsen, Kristian Fog Vuong, Lisa Elfeki, Maryam Traxler, Matthew F. Engene, Niclas Koyama, Nobuhiro Vining, Oliver B. Baric, Ralph Silva, Ricardo R. Mascuch, Samantha J. Tomasi, Sophie Jenkins, Stefan Macherla, Venkat Hoffman, Thomas Agarwal, Vinayak Williams, Philip G. Dai, Jingqui Neupane, Ram Gurr, Joshua Rodriguez, Andres M. C. Lamsa, Anne Zhang, Chen Dorrestein, Kathleen Duggan, Brendan M. Almaliti, Jehad Allard, Pierre-Marie Phapale, Prasad Nothias, Louis-Felix Alexandrovr, Theodore Litaudon, Marc Wolfender, Jean-Luc Kyle, Jennifer E. Metz, Thomas O. Peryea, Tyler Dac-Trung Nguyen VanLeer, Danielle Shinn, Paul Jadhav, Ajit Muller, Rolf Waters, Katrina M. Shi, Wenyuan Liu, Xueting Zhang, Lixin Knight, Rob Jensen, Paul R. Palsson, Bernhard O. Pogliano, Kit Linington, Roger G. Gutierrez, Marcelino Lopes, Norberto P. Gerwick, William H. Moore, Bradley S. Dorrestein, Pieter C. Bandeira, Nuno TI Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking SO NATURE BIOTECHNOLOGY LA English DT Article ID SPECTRAL DATABASE; GENE-CLUSTER; GENOME; DEREPLICATION; METABOLOMICS; IDENTIFICATION; TECHNOLOGIES; REPOSITORY; DISCOVERY; RESOURCE AB The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data. C1 [Wang, Mingxun; Carver, Jeremy J.; Pevzner, Pavel] Univ Calif San Diego, Comp Sci & Engn, La Jolla, CA 92093 USA. [Wang, Mingxun; Carver, Jeremy J.; Pevzner, Pavel; Mohimani, Hosein; Bandeira, Nuno] Univ Calif San Diego, Ctr Computat Mass Spectrometry, La Jolla, CA USA. [Phelan, Vanessa V.; Sanchez, Laura M.; Garg, Neha; Watrous, Jeramie; Luzzatto-Knaan, Tal; Porto, Carla; Bouslimani, Amina; Melnik, Alexey V.; Meehan, Michael J.; Pace, Laura A.; Gonzalez, David J.; Koyama, Nobuhiro; Dorrestein, Kathleen; Duggan, Brendan M.; Almaliti, Jehad; Gerwick, William H.; Moore, Bradley S.; Dorrestein, Pieter C.; Bandeira, Nuno] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Collaborat Mass Spectrometry Innovat Ctr, La Jolla, CA USA. [Peng, Yao; Don Duy Nguyen; Kapono, Clifford A.; Hsu, Cheng-Chih; Floros, Dimitrios J.; Zeng, Yi] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA USA. [Liu, Wei -Ting] Stanford Univ, Dept Microbiol & Immunol, Palo Alto, CA 94304 USA. [Criisemann, Max; Boudreau, Paul D.; Duncan, Katherine R.; Kleigrewe, Karin; Gerwick, Lena; Larson, Charles B.; O'Neill, Ellis C.; Briand, Enora; Glukhov, Evgenia; Kharbush, Jenan J.; Mascuch, Samantha J.; Jensen, Paul R.; Gerwick, William H.; Moore, Bradley S.; Dorrestein, Pieter C.] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA USA. [Esquenazi, Eduardo; Pociute, Egle; Houson, Hailey; Vuong, Lisa; Macherla, Venkat] Sirenas Marine Discovery, San Diego, CA USA. [Sandoval-Calderon, Mario; Sohlenkamp, Christian] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca, Morelos, Mexico. [Kersten, Roland D.] Salk Inst Biol Studies, La Jolla, CA USA. [Quinn, Robert A.] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. [Duncan, Katherine R.] Scottish Marine Inst, Scottish Assoc Marine Sci, Oban, Argyll, Scotland. [Gavilan, Ronnie G.; Sedio, Brian E.; Boya P, Cristopher A.; Torres-Mendoza, Daniel; Gutierrez, Marcelino] INDICASAT, Ctr Drug Discovery & Biodivers, City Of Knowledge, Panama. [Northen, Trent; Jenkins, Stefan] Lawrence Berkeley Natl Lab, Genome Dynam, Berkeley, CA USA. [Dutton, Rachel J.] Harvard, FAS Ctr Syst Biol, Cambridge, MA USA. [Parrot, Delphine; Tomasi, Sophie] Univ Rennes 1, Prod Nat Synth Chim Med, Rennes, France. [Carlson, Erin E.] Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA. [Aigle, Bertrand] Univ Lorraine, Dynam Genomes & Adaptat Microbienne, Vandoeuvre Les Nancy, France. [Michelsen, Charlotte F.; Jelsbak, Lars; Maansson, Maria; Klitgaard, Andreas; Nielsen, Kristian Fog] Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark. [Edlund, Anna] J Craig Venter Inst, Microbial & Environm Genom, La Jolla, CA USA. [Edlund, Anna; McLean, Jeffrey; Shi, Wenyuan] UC Los Angeles, Sch Dent, Los Angeles, CA USA. [McLean, Jeffrey] Univ Washington, Dept Periodont, Seattle, WA 98195 USA. [Piel, Jorn; Helfrich, Eric J. N.; Ryffel, Florian; Vorholt, Julia A.] Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland. [Murphy, Brian T.; Elfeki, Maryam] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA. [Liaw, Chih-Chuang] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung, Taiwan. [Yang, Yu-Liang] Acad Sinica, Agr Biotechnol Res Ctr, Taipei, Taiwan. [Humpf, Hans-Ulrich] Univ Munster, Inst Food Chem, Munster, Germany. [Keyzers, Robert A.] Victoria Univ Wellington, Sch Chem & Phys Sci, Wellington, New Zealand. [Keyzers, Robert A.] Victoria Univ Wellington, Ctr Biodiscovery, Wellington, New Zealand. [Sims, Amy C.; Baric, Ralph] Univ North Carolina Chapel Hill, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Johnson, Andrew R.; Sidebottom, Ashley M.] Indiana Univ, Dept Chem, Bloomington, IN USA. [Sedio, Brian E.] Smithsonian Trop Res Inst, Ancon, Panama. [Larson, Charles B.; Gonzalez, David J.; Dorrestein, Pieter C.; Bandeira, Nuno] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA USA. [Silva, Denise B.; Marques, Lucas M.; Demarque, Daniel P.; Silva, Ricardo R.; Rodriguez, Andres M. C.; Lopes, Norberto P.] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil. [Silva, Denise B.] Univ Fed Mato Grosso do Sul, Ctr Ciencias Biol & Saude, Campo Grande, Brazil. [Briand, Enora] Univ Rennes 1, CNRS, UMR 6553, ECOBIO, Rennes, France. [Granatosky, Eve A.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Kurita, Kenji L.; Linington, Roger G.] UC Santa Cruz, PBSci Chem & Biochem Dept, Santa Cruz, CA USA. [Charusanti, Pep; Palsson, Bernhard O.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA USA. [McPhail, Kerry L.; Vining, Oliver B.] Oregon State Univ, Coll Pharm, Dept Pharmaceut Sci, Corvallis, OR 97331 USA. [Traxler, Matthew F.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA USA. [Engene, Niclas] Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. [Hoffman, Thomas; Muller, Rolf] Helmholtz Inst Pharmaceut Res Saarland, Dept Pharmaceut Biotechnol, Saarbrucken, Germany. [Agarwal, Vinayak; Moore, Bradley S.] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Oceans & Human Hlth, La Jolla, CA USA. [Williams, Philip G.; Dai, Jingqui; Neupane, Ram; Gurr, Joshua] Univ Hawaii Manoa, Dept Chem, Honolulu, HI 96822 USA. [Lamsa, Anne; Pogliano, Kit] Univ Calif San Diego, Div Biol Sci, La Jolla, CA USA. [Zhang, Chen] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA USA. [Allard, Pierre-Marie; Wolfender, Jean-Luc] Univ Geneva, Sch Pharmaceut Sci, Geneva, Switzerland. [Phapale, Prasad; Alexandrovr, Theodore] European Mol Biol Lab, Struct & Computat Biol, Heidelberg, Germany. [Nothias, Louis-Felix; Litaudon, Marc] Univ Paris Saclay, Labex CEBA, ICSN, CNRS,UPR 2301, Gif Sur Yvette, France. [Kyle, Jennifer E.; Metz, Thomas O.; Waters, Katrina M.] Pacific NW Natl Lab, Biol Sci, Richland, WA 99352 USA. [Peryea, Tyler; Dac-Trung Nguyen; VanLeer, Danielle; Shinn, Paul; Jadhav, Ajit] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Liu, Xueting] Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China. [Knight, Rob] Univ Calif San Diego, Dept Pediat, La Jolla, CA USA. RP Bandeira, N (reprint author), Univ Calif San Diego, Ctr Computat Mass Spectrometry, La Jolla, CA USA.; Dorrestein, PC; Bandeira, N (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Collaborat Mass Spectrometry Innovat Ctr, La Jolla, CA USA.; Dorrestein, PC (reprint author), Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA USA.; Dorrestein, PC; Bandeira, N (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA USA. EM pdorrestein@ucsd.edu; bandeira@ucsd.edu RI Nielsen, Kristian/C-7233-2011; Vorholt, Julia/K-3514-2016; Porto, Carla/D-6888-2013; Demarque, Daniel/K-7325-2014; Briand, Enora/P-6074-2016; almaliti, jehad/R-7507-2016; Muller, Rolf/B-1559-2008; O'Neill, Ellis/N-3805-2014; OI Nielsen, Kristian/0000-0002-5848-0911; Porto, Carla/0000-0001-8331-2760; Demarque, Daniel/0000-0002-3576-5148; Briand, Enora/0000-0001-8996-0072; almaliti, jehad/0000-0002-3562-0846; Muller, Rolf/0000-0002-1042-5665; O'Neill, Ellis/0000-0002-5941-2806; Torres-Mendoza, Daniel/0000-0002-3540-4238; Duncan, Katherine R./0000-0002-3670-4849; Klitgaard, Andreas/0000-0002-2533-570X; Phelan, Vanessa/0000-0001-7156-9294; Northen, Trent/0000-0001-8404-3259; PHAPALE, PRASAD/0000-0002-9487-597X; Keyzers, Rob/0000-0002-7658-7421 FU US National Institutes of Health (NIH) [5P41GM103484-07, GM094802, AI095125, GM097509, S10RR029121, UL1RR031980, GM085770, U01TW0007401, U01AI12316-01]; National Institute of Allergy and Infectious Diseases (NIAID), NIH; Department of Health and Human Services [HHSN272200800060C]; NIH [K01 GM103809, T32 GM075762, K99DE024543, 1F32GM089044, 5R21AI085540, U01TW006634-06]; NIH IRACDA [K12 GM068524]; United States-Israel Binational Agricultural Research and Development Fund Vaadia-BARD [FI-494-13]; Science without Borders Program from CNPq; Sao Paulo Research Foundation (FAPESP) [2014/01651-8, 2012/18031-7]; German Academic Exchange Service (DAAD); Deutsche Forschungsgemeinschaft (D.F.G.); Marie Curie IOF Fellowship within the 7th European Community Framework Program (FP7-PEOPLE-IOF) [301244-CYANOMIC]; Ministry of Science and Technology of Taiwan [MOST103-2628-B-110-001-MY3]; Novo Nordisk Foundation; National Program on Key Basic Research Project [2013BC734000]; National Natural Science Foundation of China [81102369, 31125002]; INSA grant, Rennes; FAPESP [2012/18031-7, 2014/01884-2, 2014/18052-0, 2013/16496-5, 2014/50265-3]; CAPES/PNPD; CNPq-INCT_if; Notre Dame Chemistry-Biochemistry-Biology Interface (CBBI) program; National Institutes of Health [1R01DE023810-01, 1R01GM095373]; Villum Foundation [VKR023113]; Augustinus Foundation [13-4656]; Aase & Ejnar Danielsens Foundation [10-001120]; UC MEXUS-CONACYT Collaborative Grant [CN-12-552]; NSF [DEB 1010816]; Smithsonian Institution Grand Challenges Award; DFG (Forschergruppe 854); SNF [IZLSZ3_149025]; Danish Council for Independent Research, Technology, and Production Sciences [09-064967]; Agilent Thought Leader Program; NIH/NIAID [U19-AI106772]; Department of Defense [W81XWH-13-1-0171]; Oregon Sea Grant [NA10OAR4170059/R/BT-48]; NSF; Research Corporation for Science Advancement (Cottrell Scholar Award); Indiana University Quantitative Chemical Biology trainee fellowship; Danish Research Council for Technology and Production Science; Sapere Aude [116262]; FNS [200020_146200]; [CNPq-PQ 480 306385/2011-2] FX This work was partially supported by US National Institutes of Health (NIH) grants 5P41GM103484-07, GM094802, AI095125, GM097509, S10RR029121, UL1RR031980, GM085770, U01TW0007401, and U01AI12316-01; N.B. was also partially supported as an Alfred P. Sloan Fellow. In addition, this work was supported by the National Institute of Allergy and Infectious Diseases (NIAID), NIH, and the Department of Health and Human Services, under Contract Number HHSN272200800060C. V.V.P. is supported by the NIH grant K01 GM103809. L.M.S. is supported by NIH IRACDA K12 GM068524 award. T.L.-K. is supported by the United States-Israel Binational Agricultural Research and Development Fund Vaadia-BARD No. FI-494-13. C.P. is supported by Science without Borders Program from CNPq. A.M.C.R. is supported by Sao Paulo Research Foundation (FAPESP) grant#2014/01651-8, 2012/18031-7. K.K. was supported by a fellowship within the Postdoc-Programme of the German Academic Exchange Service (DAAD). M.C. was supported by a Deutsche Forschungsgemeinschaft (D.F.G.) postdoctoral fellowship. E.B. is supported by a Marie Curie IOF Fellowship within the 7th European Community Framework Program (FP7-PEOPLE-2011-IOF, grant number 301244-CYANOMIC). C.-C.L. was supported by a grant from the Ministry of Science and Technology of Taiwan (MOST103-2628-B-110-001-MY3). P.C. and B.O.P. were supported by the Novo Nordisk Foundation. Lixin Zhang and Xueting Liu are supported by the National Program on Key Basic Research Project (2013BC734000) and the National Natural Science Foundation of China (81102369 and 31125002). D.P. is supported by an INSA grant, Rennes. R.R.S. is supported by FAPESP grant#2014/01884-2. D.P.D. is supported by FAPESP grant#2014/18052-0. L.M.M. is supported by FAPESP grant#2013/16496-5. D.B.S. is supported by FAPESP grant#2012/18031-7. N.P.L. is supported by FAPESP(2014/50265-3), CAPES/PNPD, CNPq-PQ 480 306385/2011-2, and CNPq-INCT_if. E.A.G. is supported by the Notre Dame Chemistry-Biochemistry-Biology Interface (CBBI) program and NIH T32 GM075762. W.S. and J.S.M. are supported by grants from the National Institutes of Health 1R01DE023810-01 and 1R01GM095373. A.E. is supported by a grant from the NIH K99DE024543. C.F.M. and L.J. are supported by the Villum Foundation VKR023113, the Augustinus Foundation 13-4656, and the Aase & Ejnar Danielsens Foundation 10-001120. M.S.-C. was supported by UC MEXUS-CONACYT Collaborative Grant CN-12-552. M.F.T. was supported by NIH grant 1F32GM089044. Contributions by B.E.S. were supported by NSF grant DEB 1010816 and a Smithsonian Institution Grand Challenges Award. E.J.N.H. and J.P. are supported by the DFG (Forschergruppe 854) and by SNF grant IZLSZ3_149025. K.F.N. and A.K. are supported by the Danish Council for Independent Research, Technology, and Production Sciences (09-064967) and the Agilent Thought Leader Program. A.C.S. and R.S.B. were supported by NIH/NIAID U19-AI106772. B.T.M. and M.E. were supported under Department of Defense grant #W81XWH-13-1-0171. Contributions by O.B.V. and K.L.M. were supported by Oregon Sea Grant NA10OAR4170059/R/BT-48, NIH 5R21AI085540, and U01TW006634-06. E.E.C., A.M.S., and A.R.J. were supported by an NSF CAREER Award, a Pew Biomedical Scholar Award (E.E.C.), a Sloan Research Fellow Award (E.E.C.), the Research Corporation for Science Advancement (Cottrell Scholar Award; E.E.C.) and an Indiana University Quantitative Chemical Biology trainee fellowship (A.R.J.). M.M. was supported by the Danish Research Council for Technology and Production Science with Sapere Aude (116262). P.-M. A.; was supported by FNS for fellowship on Subside (200020_146200). We thank V. Paul, R. Taylor, L. Aluwihare, F. Rohwer, B. Pullman, J. Fang, M. Overgaard, M. Katze, R.D. Smith, S.K. Mazmanian, W. Fenical, E. Macagno, X. He, and C. Neubauer for feedback and support for their laboratory personnel to contribute to the work. We thank B. Gust and co-workers at the University of Tuebingen for assisting us to obtain Streptomyces sp. DSM5940. NR 54 TC 26 Z9 26 U1 37 U2 50 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2016 VL 34 IS 8 BP 828 EP 837 DI 10.1038/nbt.3597 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DT2VJ UT WOS:000381339600019 PM 27504778 ER PT J AU Bhattacharya, P Dey, R Dagur, PK Joshi, AB Ismail, N Gannavaram, S Debrabant, A Akue, AD KuKuruga, MA Selvapandiyan, A McCoy, JP Nakhasi, HL AF Bhattacharya, Parna Dey, Ranadhir Dagur, Pradeep K. Joshi, Amritanshu B. Ismail, Nevien Gannavaram, Sreenivas Debrabant, Alain Akue, Adovi D. KuKuruga, Mark A. Selvapandiyan, Angamuthu McCoy, John Philip, Jr. Nakhasi, Hira L. TI Live Attenuated Leishmania donovani Centrin Knock Out Parasites Generate Non-inferior Protective Immune Response in Aged Mice against Visceral Leishmaniasis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID CD8(+) T-CELLS; DENDRITIC CELLS; NITRIC-OXIDE; ELDERLY INDIVIDUALS; DELETED PARASITES; VARICELLA VACCINE; PERIPHERAL-BLOOD; INNATE IMMUNITY; TH1 RESPONSE; IN-VIVO AB Background Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania donovani causes severe disease. Age appears to be critical in determining the clinical outcome of VL and at present there is no effective vaccine available against VL for any age group. Previously, we showed that genetically modified live attenuated L. donovani parasites (LdCen-/-) induced a strong protective innate and adaptive immune response in young mice. In this study we analyzed LdCen-/- parasite mediated modulation of innate and adaptive immune response in aged mice (18 months) and compared to young (2 months) mice. Methodology Analysis of innate immune response in bone marrow derived dendritic cells (BMDCs) from both young and aged mice upon infection with LdCen-/- parasites, showed significant enhancement of innate effector responses, which consequently augmented CD4(+) Th1 cell effector function compared to LdWT infected BMDCs in vitro. Similarly, parasitized splenic dendritic cells from LdCen-/- infected young and aged mice also revealed induction of proinflammatory cytokines (IL-12, IL-6, IFN-gamma and TNF) and subsequent down regulation of anti- inflammatory cytokine (IL-10) genes compared to LdWT infected mice. We also evaluated in vivo protection of the LdCen-/- immunized young and aged mice against virulent L. donovani challenge. Immunization with LdCen-/- induced higher IgG2a antibodies, lympho-proliferative response, pro- and anti-inflammatory cytokine responses and stimulated splenocytes for heightened leishmanicidal activity associated with nitric oxide production in young and aged mice. Furthermore, upon virulent L. donovani challenge, LdCen-/- immunized mice from both age groups displayed multifunctional Th1-type CD4 and cytotoxic CD8 T cells correlating to a significantly reduced parasite burden in the spleen and liver compared to naive mice. It is interesting to note that even though there was no difference in the LdCen-/-induced innate response in dendritic cells between aged and young mice; the adaptive response specifically in terms of T cell and B cell activation in aged animals was reduced compared to young mice which correlated with less protection in old mice compared to young mice. Conclusions Taken together, LdCen-/-immunization induced a significant but diminished host protective response in aged mice after challenge with virulent L. donovani parasites compared to young mice. C1 [Bhattacharya, Parna; Dey, Ranadhir; Joshi, Amritanshu B.; Ismail, Nevien; Gannavaram, Sreenivas; Debrabant, Alain; Nakhasi, Hira L.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. [Dagur, Pradeep K.; McCoy, John Philip, Jr.] NHLBI, Flow Cytometry Core, NIH, Bldg 10, Bethesda, MD 20892 USA. [Akue, Adovi D.; KuKuruga, Mark A.] Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Silver Spring, MD USA. [Selvapandiyan, Angamuthu] Inst Mol Med, New Delhi, India. RP Bhattacharya, P; Nakhasi, HL (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. EM Parna.Bhattacharya@fda.hhs.gov; Hira.Nakhasi@fda.hhs.gov FU Intramural Research Program at the Center for Biologics Evaluation and Research, FDA FX This research was supported in part by the Intramural Research Program at the Center for Biologics Evaluation and Research, FDA (PB, RD, NI, ABJ, SG, AD, HLN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 0 Z9 0 U1 5 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2016 VL 10 IS 8 AR e0004963 DI 10.1371/journal.pntd.0004963 PG 28 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DU7JR UT WOS:000382390800079 PM 27580076 ER PT J AU Denis, ACS Leitner, WW Wali, T James, S AF Denis, Adriana Costero-Saint Leitner, Wolfgang W. Wali, Tonu James, Stephanie TI Meeting Report: Translational Considerations of Novel Vector Management Approaches SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID FIELD TRIALS; MOSQUITOS; WORKING C1 [Denis, Adriana Costero-Saint; Wali, Tonu] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Leitner, Wolfgang W.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD USA. [James, Stephanie] Fdn Natl Inst Hlth, Bethesda, MD 20892 USA. RP James, S (reprint author), Fdn Natl Inst Hlth, Bethesda, MD 20892 USA. EM sjames@fnih.org RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 12 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2016 VL 10 IS 8 AR e0004800 DI 10.1371/journal.pntd.0004800 PG 5 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DU7JR UT WOS:000382390800006 ER PT J AU Ellis, EM Sharp, TM Perez-Padilla, J Gonzalez, L Poole-Smith, BK Lebo, E Baker, C Delorey, MJ Torres-Velasquez, B Ochoa, E Rivera-Garcia, B Diaz-Pinto, H Clavell, L Puig-Ramos, A Janka, GE Tomashek, KM AF Ellis, Esther M. Sharp, Tyler M. Perez-Padilla, Janice Gonzalez, Liza Poole-Smith, B. Katherine Lebo, Emmaculate Baker, Charlotte Delorey, Mark J. Torres-Velasquez, Brenda Ochoa, Eduardo Rivera-Garcia, Brenda Diaz-Pinto, Hector Clavell, Luis Puig-Ramos, Anabel Janka, Gritta E. Tomashek, Kay M. TI Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008-2013 SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID RARE CASE-REPORT; HEMORRHAGIC-FEVER; VIRUS-INFECTION AB Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 20122013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008-2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH casefatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012-2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p <= 0.02). Conclusions/Significance During this cluster of dengue-associated HLH cases that was temporally associated with the 2012-2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury. C1 [Ellis, Esther M.; Sharp, Tyler M.; Perez-Padilla, Janice; Poole-Smith, B. Katherine; Torres-Velasquez, Brenda; Tomashek, Kay M.] Ctr Dis Control & Prevent, Dengue Branch, San Juan, PR 00920 USA. [Ellis, Esther M.; Lebo, Emmaculate; Baker, Charlotte] Ctr Dis Control & Prevent, Div Sci Educ & Profess Dev, Atlanta, GA USA. [Gonzalez, Liza] Ponce Hlth Sci Univ, Ponce, PR USA. [Delorey, Mark J.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO USA. [Ochoa, Eduardo; Diaz-Pinto, Hector] Puerto Rico Childrens Hosp, Bayamon, PR USA. [Rivera-Garcia, Brenda] Puerto Rico Dept Hlth, San Juan, PR USA. [Clavell, Luis] San Jorge Childrens Hosp, San Juan, PR USA. [Puig-Ramos, Anabel] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Janka, Gritta E.] Univ Med Ctr, Hamburg, Germany. [Tomashek, Kay M.] NIH, Off Clin Res Resources, Div Microbiol & Infect Dis, Bldg 10, Bethesda, MD 20892 USA. RP Sharp, TM (reprint author), Ctr Dis Control & Prevent, Dengue Branch, San Juan, PR 00920 USA. EM tsharp@cdc.gov 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 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2016 VL 10 IS 8 AR e0004939 DI 10.1371/journal.pntd.0004939 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DU7JR UT WOS:000382390800073 PM 27556807 ER PT J AU Zheng, YL Zhang, X Fu, HX Guo, M Shukla, V Amin, ND Jing, E Bao, L Luo, HY Li, B Lu, XH Gao, YC AF Zheng, Ya-Li Zhang, Xia Fu, Hai-Xia Guo, Mei Shukla, Varsha Amin, Niranjana D. Jing, E. Bao, Li Luo, Hong-Yan Li, Bo Lu, Xiao-Hua Gao, Yong-Cai TI Knockdown of Expression of Cdk5 or p35 (a Cdk5 Activator) Results in Podocyte Apoptosis SO PLOS ONE LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; GLOMERULOSCLEROSIS; DIFFERENTIATION; CELLS; NEURODEGENERATION; GLOMERULI; REGULATOR; DEPLETION; PEPTIDE; NEURONS AB Podocytes are terminally differentiated glomerular epithelial cells. Podocyte loss has been found in many renal diseases. Cdk5 is a cyclin-dependent protein kinase which is predominantly regulated by p35. To study the role of Cdk5/p35 in podocyte survival, we first applied western blotting (WB) analysis to confirm the time-course expression of Cdk5 and p35 during kidney development and in cultured immortalized mouse podocytes. We also demonstrated that p35 plays an important role in promoting podocyte differentiation by overexpression of p35 in podocytes. To deregulate the expression of Cdk5 or p35 in mouse podocytes, we used RNAi and analyzed cell function and apoptosis assaying for podocyte specific marker Wilms Tumor 1 (WT1) and cleaved caspase 3, respectively. We also counted viable cells using cell counting kit-8. We found that depletion of Cdk5 causes decreased expression of WT1 and apoptosis. It is noteworthy, however, that downregulation of p35 reduced Cdk5 activity, but had no effect on cleaved caspase 3 expression. It did, however, reduce expression of WT1, a transcription factor, and produced podocyte dysmorphism. On the other hand increased apoptosis could be detected in p35-deregulated podocytes using the TUNEL analysis and immunofluorescent staining with cleaved caspase3 antibody. Viability of podocytes was decreased in both Cdk5 and p35 knockdown cells. Knocking down Cdk5 or p35 gene by RNAi does not affect the cycline I expression, another Cdk5 activator in podocyes. We conclude that Cdk5 and p35 play a crucial role in maintaining podocyte differentiation and survival, and suggest these proteins as targets for therapeutic intervention in podocyte-damaged kidney diseases. C1 [Zheng, Ya-Li; Zhang, Xia; Jing, E.; Bao, Li; Luo, Hong-Yan; Li, Bo; Lu, Xiao-Hua; Gao, Yong-Cai] Northwest Univ Nationalities, Coll Med, Affiliated Hosp 1, Dept Nephrol,Ningxia Peoples Hosp, Yinchuan 750002, Ningxia, Peoples R China. [Fu, Hai-Xia] Cent Hosp Rizhao City, Ctr Blood Purificat, Rizhao 276800, Shangdong, Peoples R China. [Shukla, Varsha; Amin, Niranjana D.] NINDS, Lab Neurochem, Bethesda, MD 20814 USA. [Guo, Mei] Fudan Univ, Zhongshan Xuhui Hosp, Shanghai 200031, Peoples R China. RP Zheng, YL (reprint author), Northwest Univ Nationalities, Coll Med, Affiliated Hosp 1, Dept Nephrol,Ningxia Peoples Hosp, Yinchuan 750002, Ningxia, Peoples R China. EM yalinew@yahoo.com FU National Natural Science Foundation of China [81160093, 81460161]; Natural Science Foundation of Ningxia Province [NZ14160]; Department of Science and Technology of Ningxia Province [2011ZYH169, 2013ZYS103] FX This work was supported by the following grant sponsors: National Natural Science Foundation of China, grant no. 81160093 and 81460161; Natural Science Foundation of Ningxia Province, grant no. NZ14160; and Department of Science and Technology of Ningxia Province, grant no. 2013ZYS103 and 2011ZYH169 (international collaboration with the intramural funds of NIH/NINDS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 0 Z9 0 U1 2 U2 2 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 AUG 1 PY 2016 VL 11 IS 8 AR e0160252 DI 10.1371/journal.pone.0160252 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS9NO UT WOS:000381110300035 PM 27479491 ER PT J AU Carvalho, AF Kohler, CA Fernandes, BS Quevedo, J Miskowiak, KW Brunoni, AR Machado-Vieira, R Maes, M Vieta, E Berk, M AF Carvalho, A. F. Kohler, C. A. Fernandes, B. S. Quevedo, J. Miskowiak, K. W. Brunoni, A. R. Machado-Vieira, R. Maes, M. Vieta, E. Berk, M. TI Bias in emerging biomarkers for bipolar disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Bias; biomarkers; bipolar disorder; meta-analysis; psychiatry; review ID NEUROTROPHIC FACTOR; OXIDATIVE STRESS; METAANALYSIS; HETEROGENEITY; PSYCHIATRY; EXCESS; RDOC; PSYCHOPATHOLOGY; SCHIZOPHRENIA; ASSOCIATIONS AB Background To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. Method The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included. Results Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of positive' nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I-2 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%. Conclusions Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of positive' results and selective reporting of outcomes are possible mechanisms. C1 [Carvalho, A. F.; Kohler, C. A.] Univ Fed Ceara, Dept Psychiat, Fac Med, Fortaleza, Ceara, Brazil. [Carvalho, A. F.; Kohler, C. A.] Univ Fed Ceara, Translat Psychiat Res Grp, Fac Med, Fortaleza, Ceara, Brazil. [Fernandes, B. S.; Maes, M.; Berk, M.] Deakin Univ, IMPACT Strateg Res Ctr, Sch Med, Geelong, Vic, Australia. [Fernandes, B. S.; Maes, M.; Berk, M.] Barwon Hlth, Geelong, Vic, Australia. [Fernandes, B. S.] Univ Fed Rio Grande do Sul, Dept Biochem, Lab Calcium Binding Prot Cent Nervous Syst, Porto Alegre, RS, Brazil. [Quevedo, J.] Univ Texas Med Sch Houston, Dept Psychiat & Behav Sci, Ctr Expt Models Psychiat, Houston, TX USA. [Quevedo, J.] Univ Southern Santa Catarina, Lab Neurosci, Grad Program Hlth Sci, Hlth Sci Unit, Criciuma, SC, Brazil. [Miskowiak, K. W.] Rigshosp, Psychiat Ctr Copenhagen, Copenhagen Univ Hosp, Copenhagen, Denmark. [Brunoni, A. R.] Univ Sao Paulo, Interdisciplinary Ctr Appl Neuromodulat CINA, Univ Hosp, Sao Paulo, Brazil. [Brunoni, A. R.] Univ Sao Paulo, Dept & Inst Psychiat, SIN, Lab Neurosci LIM 27, Sao Paulo, Brazil. [Machado-Vieira, R.] Univ Sao Paulo, Lab Neurosci, LIM 27, Inst & Dept Psychiat, Sao Paulo, Brazil. [Machado-Vieira, R.] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, Brazil. [Machado-Vieira, R.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Vieta, E.] Univ Barcelona, Bipolar Disorders Unit, Inst Neurosci, Hosp Clin,IDIBAPS,CIBERSAM, Barcelona, Catalonia, Spain. [Berk, M.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Dept Psychiat, Natl Ctr Excellence Youth Mental Hlth, Parkville, Vic, Australia. [Berk, M.] Univ Melbourne, Orygen Youth Hlth Res Ctr, Parkville, Vic, Australia. RP Carvalho, AF (reprint author), Univ Fed Ceara, Dept Clin Med, Fac Med, Rua Prof Costa Mendes 1608,4 Andar, BR-60430040 Fortaleza, Ceara, Brazil. EM andrefc7@terra.com.br RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Vieta, Eduard/0000-0002-0548-0053; Russowsky Brunoni, Andre/0000-0002-6310-3571 FU CNPq (Brazil); CAPES (Brazil); CNPq, Brazil [MCTI/CNPQ/Universal 14/2014461833/2014-0]; NARSAD Young Investigator from the Brain & Behavior Research Foundation [20493]; FAPESP Young Researcher from the Sao Paulo State Foundation [20911-5]; National Council for Scientific and Technological Development (CNPq) [470904]; NHMRC Senior Principal Research Fellowship [1059660] FX A.F.C. and J.Q. are supported by research fellowship awards from CNPq (Brazil). C.A.K. is supported by a postdoctoral fellowship from CAPES (Brazil). B.S.F. is supported by a scholarship and by a research grant MCTI/CNPQ/Universal 14/2014461833/2014-0, both from CNPq, Brazil. A.R.B. is supported by the following grants: 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation (grant no. 20493), 2012 FAPESP Young Researcher from the Sao Paulo State Foundation (grant no. 20911-5) and National Council for Scientific and Technological Development (CNPq, grant no. 470904). M.B. is supported by a NHMRC Senior Principal Research Fellowship (1059660). NR 56 TC 1 Z9 1 U1 7 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2016 VL 46 IS 11 BP 2287 EP 2297 DI 10.1017/S0033291716000957 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DT1FZ UT WOS:000381228400005 PM 27193198 ER PT J AU Shaw, P Weingart, D Bonner, T Watson, B Park, MTM Sharp, W Lerch, JP Chakravarty, MM AF Shaw, P. Weingart, D. Bonner, T. Watson, B. Park, M. T. M. Sharp, W. Lerch, J. P. Chakravarty, M. M. TI Defining the neuroanatomic basis of motor coordination in children and its relationship with symptoms of attention-deficit/hyperactivity disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Attention-deficit; hyperactivity disorder; brain imaging; cerebellum; cortex; motor coordination ID OF-THE-LITERATURE; HUMAN BRAIN; SEX-DIFFERENCES; ADHD; CORTEX; PERFORMANCE; CEREBELLUM; ACTIVATION; VOLUME; SKILLS AB Background When children have marked problems with motor coordination, they often have problems with attention and impulse control. Here, we map the neuroanatomic substrate of motor coordination in childhood and ask whether this substrate differs in the presence of concurrent symptoms of attention-deficit/hyperactivity disorder (ADHD). Method Participants were 226 children. All completed Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-based assessment of ADHD symptoms and standardized tests of motor coordination skills assessing aiming/catching, manual dexterity and balance. Symptoms of developmental coordination disorder (DCD) were determined using parental questionnaires. Using 3 Tesla magnetic resonance data, four latent neuroanatomic variables (for the cerebral cortex, cerebellum, basal ganglia and thalamus) were extracted and mapped onto each motor coordination skill using partial least squares pathway modeling. Results The motor coordination skill of aiming/catching was significantly linked to latent variables for both the cerebral cortex (t = 4.31, p < 0.0001) and the cerebellum (t = 2.31, p = 0.02). This effect was driven by the premotor/motor cortical regions and the superior cerebellar lobules. These links were not moderated by the severity of symptoms of inattention, hyperactivity and impulsivity. In categorical analyses, the DCD group showed atypical reduction in the volumes of these regions. However, the group with DCD alone did not differ significantly from those with DCD and co-morbid ADHD. Conclusions The superior cerebellar lobules and the premotor/motor cortex emerged as pivotal neural substrates of motor coordination in children. The dimensions of these motor coordination regions did not differ significantly between those who had DCD, with or without co-morbid ADHD. C1 [Shaw, P.; Weingart, D.; Bonner, T.; Watson, B.; Sharp, W.] NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bldg 31,B1 B37, Bethesda, MD 20892 USA. [Park, M. T. M.] Western Univ, Schulich Sch Med & Dent, London, ON, Canada. [Park, M. T. M.; Chakravarty, M. M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ, Canada. [Lerch, J. P.] Univ Toronto, Program Neurosci & Mental Hlth, Hosp Sick Children, Toronto, ON, Canada. [Lerch, J. P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Chakravarty, M. M.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Chakravarty, M. M.] McGill Univ, Dept Biol & Biomed Engn, Montreal, PQ, Canada. RP Shaw, P (reprint author), NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bldg 31,B1 B37, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov FU National Human Genome Research Institute; National Institute of Mental Health; Canadian Institutes of Health Research; National Sciences and Engineering Research Council of Canada; Weston Brian Institute; Michael J. Fox Foundation for Parkinson's Research; Alzheimer's Society; Fond de Recherches Sante Quebec FX P.S. is funded by the intramural programs of the National Human Genome Research Institute and National Institute of Mental Health. M.M.C. is funded by the Canadian Institutes of Health Research, National Sciences and Engineering Research Council of Canada, Weston Brian Institute, Michael J. Fox Foundation for Parkinson's Research, and Alzheimer's Society. M.M.C. also receives salary and research support from the Fond de Recherches Sante Quebec. NR 62 TC 0 Z9 0 U1 9 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2016 VL 46 IS 11 BP 2363 EP 2373 DI 10.1017/S0033291716000660 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DT1FZ UT WOS:000381228400011 PM 27282929 ER PT J AU Goldstein, RB Smith, SM Chou, SP Saha, TD Jung, J Zhang, HT Pickering, RP Ruan, WJ Huang, BJ Grant, BF AF Goldstein, Rise B. Smith, Sharon M. Chou, S. Patricia Saha, Tulshi D. Jung, Jeesun Zhang, Haitao Pickering, Roger P. Ruan, W. June Huang, Boji Grant, Bridget F. TI The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Posttraumatic stress disorder; Epidemiology; Comorbidity ID COMORBIDITY SURVEY-REPLICATION; GENERAL-POPULATION SAMPLE; MENTAL-HEALTH; LIFETIME PREVALENCE; HOUSEHOLD DYSFUNCTION; PERSONALITY-DISORDERS; PROCEDURAL VALIDITY; ANXIETY DISORDERS; SUBSTANCE USE; IV DISORDERS AB To present current, nationally representative US findings on the past-year and lifetime prevalences, sociodemographic correlates, psychiatric comorbidity, associated disability, and treatment of DSM-5 posttraumatic stress disorder (PTSD). Face-to-face interviews with 36,309 adults in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III. PTSD, alcohol and drug use disorders, and selected mood, anxiety, and personality disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Past-year and lifetime prevalences were 4.7 and 6.1 %, higher for female, white, Native American, younger, and previously married respondents, those with < high school education and lower incomes, and rural residents. PTSD was significantly associated with a broad range of substance use, mood, anxiety, and personality disorders, and past-month disability. Among respondents with lifetime PTSD, 59.4 % sought treatment; an average of 4.5 years elapsed from disorder onset to first treatment. DSM-5 PTSD is prevalent, highly comorbid, disabling, and associated with delayed help seeking. Additional research is needed to elucidate relationships identified herein, estimate PTSD-related costs, investigate hypotheses regarding etiology, course, and treatment, and support decisions about resource allocation to service delivery and research. Initiatives are needed to destigmatize PTSD, educate the public about its treatment, and encourage affected individuals to seek help. C1 [Goldstein, Rise B.; Smith, Sharon M.; Chou, S. Patricia; Saha, Tulshi D.; Jung, Jeesun; Zhang, Haitao; Pickering, Roger P.; Ruan, W. June; Huang, Boji; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,MS 9304, Bethesda, MD 20892 USA. [Goldstein, Rise B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13C, Bethesda, MD 20892 USA. [Smith, Sharon M.] NHLBI, Translat Blood Sci & Resources Branch, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,MS 9304, Bethesda, MD 20892 USA.; Goldstein, RB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13C, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov; smithsh1@mail.nih.gov; pchou@mail.nih.gov; sahatd@mail.nih.gov; jungj3@mail.nih.gov; zhangh13@mail.nih.gov; rpickeri@mail.nih.gov; ruanj@mail.nih.gov; huangbo@mail.nih.gov; bgrant@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug Abuse; 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. All authors are employees of the National Institutes of Health. NR 72 TC 6 Z9 6 U1 18 U2 19 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD AUG PY 2016 VL 51 IS 8 BP 1137 EP 1148 DI 10.1007/s00127-016-1208-5 PG 12 WC Psychiatry SC Psychiatry GA DT3UU UT WOS:000381407500008 PM 27106853 ER PT J AU Halpern, WG Ameri, M Bowman, CJ Elwell, MR Mirsky, ML Oliver, J Regan, KS Remick, AK Sutherland, VL Thompson, KE Tremblay, C Yoshida, M Tomlinson, L AF Halpern, Wendy G. Ameri, Mehrdad Bowman, Christopher J. Elwell, Michael R. Mirsky, Michael L. Oliver, Julian Regan, Karen S. Remick, Amera K. Sutherland, Vicki L. Thompson, Kary E. Tremblay, Claudine Yoshida, Midori Tomlinson, Lindsay TI Scientific and Regulatory Policy Committee Points to Consider Review: Inclusion of Reproductive and Pathology End Points for Assessment of Reproductive and Developmental Toxicity in Pharmaceutical Drug Development SO TOXICOLOGIC PATHOLOGY LA English DT Article DE preclinical research and development; reproductive system; safety assessment; toxicologic pathology; teratology; clinical pathology; developmental pathology ID SPRAGUE-DAWLEY RATS; PRECLINICAL JUVENILE TOXICITY; MONKEYS MACACA-FASCICULARIS; REPEAT-DOSE TOXICITY; CYNOMOLGUS MONKEYS; MAMMARY-GLAND; MONOCLONAL-ANTIBODY; CIRCULATING HORMONES; METABOLIZING-ENZYMES; POSITION PAPER AB Standard components of nonclinical toxicity testing for novel pharmaceuticals include clinical and anatomic pathology, as well as separate evaluation of effects on reproduction and development to inform clinical development and labeling. General study designs in regulatory guidances do not specifically mandate use of pathology or reproductive end points across all study types; thus, inclusion and use of these end points are variable. The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) formed a Working Group to assess the current guidelines and practices on the use of reproductive, anatomic pathology, and clinical pathology end points in general, reproductive, and developmental toxicology studies. The Working Group constructed a survey sent to pathologists and reproductive toxicologists, and responses from participating organizations were collected through the STP for evaluation by the Working Group. The regulatory context, relevant survey results, and collective experience of the Working Group are discussed and provide the basis of each assessment by study type. Overall, the current practice of including specific end points on a case-by-case basis is considered appropriate. Points to consider are summarized for inclusion of reproductive end points in general toxicity studies and for the informed use of pathology end points in reproductive and developmental toxicity studies. C1 [Halpern, Wendy G.] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. [Ameri, Mehrdad] GlaxoSmithKline, King Of Prussia, PA USA. [Bowman, Christopher J.; Mirsky, Michael L.] Pfizer, Groton, CT USA. [Elwell, Michael R.] Covance, Chantilly, VA USA. [Oliver, Julian] Incyte, Wilmington, DE USA. [Regan, Karen S.] Regan Path Tox Serv, Ashland, OH USA. [Remick, Amera K.] WIL Res, Hillsborough, NC USA. [Sutherland, Vicki L.] NIEHS NTP, Res Triangle Pk, NC USA. [Thompson, Kary E.] Bristol Myers Squibb, New Brunswick, NJ USA. [Tremblay, Claudine] Charles River Labs, Senneville, PQ, Canada. [Yoshida, Midori] Food Safety Commiss Japan, Minato Ku, Tokyo, Japan. [Tomlinson, Lindsay] Pfizer, Cambridge, MA USA. RP Halpern, WG (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM halpern.wendy@gene.com FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported [in part] by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 104 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2016 VL 44 IS 6 BP 789 EP 809 DI 10.1177/0192623316650052 PG 21 WC Pathology; Toxicology SC Pathology; Toxicology GA DS7ZE UT WOS:000381001300001 PM 27235322 ER PT J AU Dunnick, JK Merrick, BA Brix, A Morgan, DL Gerrish, K Wang, Y Flake, G Foley, J Shockley, KR AF Dunnick, June K. Merrick, B. Alex Brix, Amy Morgan, Daniel L. Gerrish, Kevin Wang, Yu Flake, Gordon Foley, Julie Shockley, Keith R. TI Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure SO TOXICOLOGIC PATHOLOGY LA English DT Article DE N, N-dimethyl-p-toluidine; nasal cavity toxicity; molecular markers ID STEM-CELL ANTIGEN; OXIDATIVE-STRESS; SIGNALING PATHWAY; GROWTH-FACTOR; SKIN-LESIONS; PROBE LEVEL; F344 RATS; GENE; EXPRESSION; CANCER AB N, N-dimethyl-p-toluidine (DMPT; Cas No. 99-97-8), an accelerant for methyl methacrylate monomers in medical devices, is a nasal cavity carcinogen according to a 2-yr cancer study of male and female F344/N rats, with the nasal tumors arising from the transitional cell epithelium. In this study, we exposed male F344/N rats for 5 days to DMPT (0, 1, 6, 20, 60, or 120 mg/kg [oral gavage]) to explore the early changes in the nasal cavity after short-term exposure. Lesions occurred in the nasal cavity including hyperplasia of transitional cell epithelium (60 and 120 mg/kg). Nasal tissue was rapidly removed and preserved for subsequent laser capture microdissection and isolation of the transitional cell epithelium (0 and 120 mg/kg) for transcriptomic studies. DMPT transitional cell epithelium gene transcript patterns were characteristic of an antioxidative damage response (e.g., Akr7a3, Maff, and Mgst3), cell proliferation, and decrease in signals for apoptosis. The transcripts of amino acid transporters were upregulated (e.g., Slc7a11). The DMPT nasal transcript expression pattern was similar to that found in the rat nasal cavity after formaldehyde exposure, with over 1,000 transcripts in common. Molecular changes in the nasal cavity after DMPT exposure suggest that oxidative damage is a mechanism of the DMPT toxic and/or carcinogenic effects. C1 [Dunnick, June K.] NIEHS, Toxicol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. [Merrick, B. Alex] NIEHS, Biomol Screening Branch, POB 12233, Res Triangle Pk, NC 27709 USA. [Brix, Amy] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. [Morgan, Daniel L.] NIEHS, NTP Lab, POB 12233, Res Triangle Pk, NC 27709 USA. [Gerrish, Kevin] NIEHS, Mol Genom Core, POB 12233, Res Triangle Pk, NC 27709 USA. [Wang, Yu; Flake, Gordon; Foley, Julie] NIEHS, Cellular & Mol Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. [Shockley, Keith R.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RP Dunnick, JK (reprint author), NIEHS, Toxicol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The intramural program of the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, supported this work. NR 75 TC 0 Z9 0 U1 3 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2016 VL 44 IS 6 BP 835 EP 847 DI 10.1177/0192623316637708 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA DS7ZE UT WOS:000381001300004 PM 27099258 ER PT J AU Yamashita, H Hoenerhoff, MJ Peddada, SD Sills, RC Pandiri, AR AF Yamashita, Haruhiro Hoenerhoff, Mark J. Peddada, Shyamal D. Sills, Robert C. Pandiri, Arun R. TI Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays SO TOXICOLOGIC PATHOLOGY LA English DT Article DE F344/N rat; ocular phototoxicity; retinal degeneration; light-induced exacerbation; carcinogenicity bioassay; NTP database survey; retinal atrophy ID ORDER-RESTRICTED INFERENCE; HUMAN INFANT FORMULA; ALBINO RATS; TAURINE DEFICIENCY; VISUAL DYSFUNCTION; FISCHER-344 RATS; GANGLION-CELLS; VISIBLE-LIGHT; LONG-TERM; DAMAGE AB Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light-induced retinal degeneration has a central/hemispherical localization whereas chemical-induced retinal degeneration has a diffuse localization. This study was conducted to identify and characterize treatment-related retinal degeneration in National Toxicology Program rodent bioassays. A total of 3 chronic bioassays in F344/N rats (but not in B6C3F1/N mice) were identified that had treatment-related increases in retinal degeneration (kava kava extract, acrylamide, and leucomalachite green). A retrospective light microscopic evaluation of the retinas from rats in these 3 studies showed a dose-related increase in the frequencies of retinal degeneration, beginning with the loss of photoreceptor cells, followed by the inner nuclear layer cells. These dose-related increased frequencies of degenerative retinal lesions localized within the central/hemispherical region are suggestive of exacerbation of light-induced retinal degeneration. C1 [Yamashita, Haruhiro; Hoenerhoff, Mark J.; Sills, Robert C.; Pandiri, Arun R.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, 111 TW Alexander Dr MD B306, Res Triangle Pk, NC 27709 USA. [Yamashita, Haruhiro] Taisho Pharmaceut Co Ltd, Saitama, Japan. [Hoenerhoff, Mark J.] Univ Michigan, Sch Med, Unit Lab Anim Med, In Vivo Anim Core, Ann Arbor, MI USA. [Peddada, Shyamal D.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RP Pandiri, AR (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, 111 TW Alexander Dr MD B306, Res Triangle Pk, NC 27709 USA. EM pandiriak@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 67 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 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2016 VL 44 IS 6 BP 892 EP 903 DI 10.1177/0192623316650050 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA DS7ZE UT WOS:000381001300009 PM 27230502 ER PT J AU Hussain, S Ji, ZX Taylor, AJ DeGraff, LM George, M Tucker, CJ Chang, CH Li, RB Bonner, JC Garantziotis, S AF Hussain, Salik Ji, Zhaoxia Taylor, Alexia J. DeGraff, Laura M. George, Margaret Tucker, Charles J. Chang, Chong Hyun Li, Ruibin Bonner, James C. Garantziotis, Stavros TI Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury SO ACS NANO LA English DT Article DE multiwalled carbon nanotubes; hyaluronan; lung; inflammation; fibrosis; mucous metaplasia; differentiated human bronchial epithelia ID PREDICTIVE TOXICOLOGICAL APPROACH; ALLERGIC AIRWAY INFLAMMATION; LUNG FIBROGENIC ACTIVITY; EPITHELIAL-CELLS; CANCER-CELLS; FIBROTIC RESPONSE; TARGETED DELIVERY; FIBROSIS; EXPOSURE; NANOPARTICLES AB Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury. C1 [Hussain, Salik; George, Margaret; Garantziotis, Stavros] NIEHS, Clin Res Unit, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Ji, Zhaoxia; Chang, Chong Hyun; Li, Ruibin] Univ Calif Los Angeles, UC Ctr Environm Implicat Nanotechnol, Los Angeles, CA 90095 USA. [Li, Ruibin] Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Suzhou 215123, Peoples R China. [DeGraff, Laura M.] NIEHS, Immun Inflammat & Dis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. [Tucker, Charles J.] NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA. [Taylor, Alexia J.; Bonner, James C.] North Carolina State Univ, Toxicol Program, Dept Biol Sci, Raleigh, NC 27695 USA. RP Hussain, S (reprint author), NIEHS, Clin Res Unit, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM salik.hussain@nih.gov RI Hussain, Salik/O-1687-2016; Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU NIH, National institute of Environmental Health Sciences (NIEHS); NIEHS [R01-ES020897]; National Science Foundation; Environmental Protection Agency [DBI-1266377]; U.S. Public Health Service [R01 ES016746, U19 ES019528] FX We want to thank Schantel Bouknight for scoring of lung sections. We also wish to gratefully acknowledge the excellent technical assistance provided by Dave Brar, Natasha Clayton, Eli Ney, Connie Cummings, Deloris Sutton, Annette Rice, Jamie Marshburn, and the NIEHS Core facilities for flow cytometry and florescent imaging. This work was supported by the Intramural Research Program of the NIH, National institute of Environmental Health Sciences (NIEHS) and NIEHS grant R01-ES020897 awarded to J.C.B. Partial support was also provided by the National Science Foundation and the Environmental Protection Agency to University of California at Los Angeles under cooperative agreement number DBI-1266377 and U.S. Public Health Service Grants (R01 ES016746 and U19 ES019528). Any opinions, findings, conclusions, or recommendations expressed herein are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the Environmental Protection Agency. NR 79 TC 1 Z9 1 U1 21 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD AUG PY 2016 VL 10 IS 8 BP 7675 EP 7688 DI 10.1021/acsnano.6b03013 PG 14 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DU1HP UT WOS:000381959100051 PM 27459049 ER PT J AU Rutten, LJF Hesse, BW St Sauver, JL Wilson, P Chawla, N Hartigan, DB Moser, RP Taplin, S Glasgow, R Arora, NK AF Rutten, Lila J. Finney Hesse, Bradford W. St Sauver, Jennifer L. Wilson, Patrick Chawla, Neetu Hartigan, Danielle B. Moser, Richard P. Taplin, Stephen Glasgow, Russell Arora, Neeraj K. TI Health Self-Efficacy Among Populations with Multiple Chronic Conditions: the Value of Patient-Centered Communication SO ADVANCES IN THERAPY LA English DT Article DE Multi-morbidity; Multiple chronic conditions; Patient-centered communication; Self-efficacy; Survey ID CHRONIC DISEASE; MANAGEMENT PROGRAM; PRIMARY-CARE; MENTAL-ILLNESS; DEPRESSION; OUTCOMES; SYSTEM; RISK; MULTIMORBIDITY; PERSPECTIVES AB Introduction: Using cross-sectional survey data, we assessed the association between chronic illness burden and health-related self-efficacy, evaluating whether patient-centered communication is associated with self-efficacy and if that relationship varies by chronic illness burden. Methods: Data were from the Health Information National Trends Survey, a cross-sectional survey of the US adult population collected in 2012-2013 (n = 3630). Health-related self-efficacy was measured with the item: "Overall, how confident are you about your ability to take good care of your health?" and the prevalence of six chronic conditions and depression/anxiety was assessed. Patient-centered communication was measured as the frequency with which respondents perceived their healthcare providers allowed them to ask questions, gave attention to their emotions, involved them in decisions, made sure they understood how to take care of their health, helped them to deal with uncertainty, and if they felt they could rely on their healthcare providers to take care of their healthcare needs. Results: Health-related self-efficacy was significantly lower among individuals with greater illness burden. In adjusted analysis, individuals who experienced more positive patient-centered communication reported higher levels of self-efficacy (beta = 0.26, P < 0.0001); this association was strongest among those with greater illness burden. Conclusion: Higher levels of self-efficacy were observed among patients reporting more positive patient-centered communication; the observed association was stronger among those with greater chronic illness burden. C1 [Rutten, Lila J. Finney; St Sauver, Jennifer L.; Wilson, Patrick] Mayo Clin, Dept Hlth Sci, Rochester, MN 55905 USA. [Hesse, Bradford W.; Moser, Richard P.; Taplin, Stephen] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Chawla, Neetu] Kaiser Permanente, Div Res, Oakland, CA USA. [Hartigan, Danielle B.] Bentley Univ, Dept Nat & Appl Sci, Waltham, MA USA. [Glasgow, Russell] Univ Colorado, Dept Family Med, Denver, CO 80202 USA. [Glasgow, Russell] Univ Colorado, Adult & Child Consortium Hlth Outcomes Res & Deli, Denver, CO 80202 USA. [Arora, Neeraj K.] Patient Centered Outcomes Res Inst, Washington, DC USA. RP Rutten, LJF (reprint author), Mayo Clin, Dept Hlth Sci, Rochester, MN 55905 USA. EM rutten.lila@mayo.edu FU National Cancer Institute [HHSN261201000064C]; Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery FX HINTS was funded by contract # HHSN261201000064C from the National Cancer Institute. This study was funded, in part, by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. This work was completed, while Dr. Arora was employed at the National Cancer Institute and does not reflect the policy or position of the Patient-Centered Outcomes Research Institute. The article processing charges for this publication were funded by the authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. NR 43 TC 0 Z9 0 U1 5 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X EI 1865-8652 J9 ADV THER JI Adv. Ther. PD AUG PY 2016 VL 33 IS 8 BP 1440 EP 1451 DI 10.1007/s12325-016-0369-7 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DS9AG UT WOS:000381073600012 ER PT J AU Kirkpatrick, AR Patel, EU Celum, CL Moore, RD Blankson, JN Mehta, SH Kirk, GD Margolick, JB Quinn, TC Eshleman, SH Laeyendecker, O AF Kirkpatrick, Allison R. Patel, Eshan U. Celum, Connie L. Moore, Richard D. Blankson, Joel N. Mehta, Shruti H. Kirk, Gregory D. Margolick, Joseph B. Quinn, Thomas C. Eshleman, Susan H. Laeyendecker, Oliver TI Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID RECENT HIV-INFECTIONS; ANTIRETROVIRAL THERAPY; AVIDITY INDEX; TYPE-1; COHORT; ASSAY; SPECIFICITY; LOAD AB Background: Accurate methods for cross-sectional incidence estimation are needed for HIV surveillance and prevention research. We developed an avidity assay based on the fourth-generation Genetic Systems HIV Combo Ag/Ab EIA (Bio-Rad Combo assay) and evaluated its performance. Materials and Methods: The Bio-Rad Combo assay was modified incubating samples with and without 0.025M diethylamine (DEA). The avidity index (AI) was calculated as the ratio of the DEA-treated to untreated result for a specific sample. We analyzed 2,140 samples from 808 individuals from the United States with known duration of HIV infection. The mean duration of recent infection (MDRI) and the false-recent rate (FRR, fraction of samples from individuals known to be infected >2 years misclassified as recent) were calculated for AI cutoffs of 20%-90% for the avidity assay alone and in combination with a viral load assay (VL, limit of detection 400 copies/ml). Factors associated with misclassification of samples collected >= 2 years after infections were also evaluated. Results: The MDRI for the Bio-Rad Combo Avidity assay ranged from 50 days using an AI cutoff of 20% to 276 days using an AI cutoff of 90%; the FRR ranged from 0% to 9%. When samples with a VL <400 copies/ml were classified as nonrecent, the FRRs were reduced approximately twofold and the MDRI estimates were reduced by similar to 20%. An AI cutoff of 50% provided an MDRI of 135 days with an FRR of 2.1%. All samples from elite suppressors had an AI >80%. In adjusted analysis, viral suppression and low CD4 cell count were significantly associated with misclassification among individuals infected >2 years. Conclusions: This modified Bio-Rad Combo Avidity assay may be a useful tool for cross-sectional HIV incidence estimation. Further research is needed to evaluate use of this assay in combination with other assays to accurately estimate population-level HIV incidence. C1 [Kirkpatrick, Allison R.; Patel, Eshan U.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, 855 North Wolfe St,Rangos Bldg,Room 538A, Baltimore, MD 21205 USA. [Celum, Connie L.] Univ Washington, Dept Med, Seattle, WA USA. [Moore, Richard D.; Blankson, Joel N.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Laeyendecker, O (reprint author), NIAID, Immunoregulat Lab, Div Intramural Res, NIH, 855 North Wolfe St,Rangos Bldg,Room 538A, Baltimore, MD 21205 USA. EM olaeyen1@jhmi.edu OI Patel, Eshan/0000-0003-2174-5004 FU HIV Prevention Trials Network (HPTN) - National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Office of AIDS Research of the National Institutes of Health (NIH), Department of Health and Human Services (DHHS) [UM1AI068613]; NIAID [R01 AI095068]; Division of Intramural Research, NIAID, NIH FX This work was supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of the National Institutes of Health (NIH), Department of Health and Human Services (DHHS) (UM1AI068613), and by R01 AI095068 (NIAID). Additional funding was provided by the Division of Intramural Research, NIAID, NIH. NR 35 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 2016 VL 32 IS 8 BP 756 EP 762 DI 10.1089/aid.2015.0198 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DS1ZS UT WOS:000380504800004 PM 26988426 ER PT J AU Hall, KD Chen, KY Guo, J Lam, YY Leibel, RL Mayer, LES Reitman, ML Rosenbaum, M Smith, SR Walsh, BT Ravussin, E AF Hall, Kevin D. Chen, Kong Y. Guo, Juen Lam, Yan Y. Leibel, Rudolph L. Mayer, Laurel E. S. Reitman, Marc L. Rosenbaum, Michael Smith, Steven R. Walsh, B. Timothy Ravussin, Eric TI Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; energy expenditure; ketogenic diet; insulin; carbohydrate; fat; macronutrients ID HIGH-FAT DIET; RANDOMIZED CONTROLLED-TRIAL; METABOLIC ADAPTATION; CALORIC RESTRICTION; ADIPOSE-TISSUE; HIGH-PROTEIN; WEIGHT-GAIN; CARBOHYDRATE; BALANCE; HUMANS AB Background: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. Objective: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. Design: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). Results: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of similar to 300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 +/- 13 kcal/d, P = 0.0004) and SEE (89 +/- 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 +/- 0.003, P < 0.0001). EEDLW increased by 151 +/- 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. Conclusion: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. C1 [Hall, Kevin D.; Chen, Kong Y.; Guo, Juen; Reitman, Marc L.] NIDDK, Bethesda, MD 20892 USA. [Lam, Yan Y.; Ravussin, Eric] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. [Leibel, Rudolph L.; Mayer, Laurel E. S.; Rosenbaum, Michael; Walsh, B. Timothy] Columbia Univ, New York, NY 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 OI Chen, Kong/0000-0002-0306-1904; Reitman, Marc/0000-0002-0426-9475 FU Nutrition Sciences Initiative; Intramural Research Program of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases; NIH [UL1 TR00040]; Nutrition Obesity Research Center Grant [P30DK072476] FX Supported by the Nutrition Sciences Initiative. This work was also supported in part by the Intramural Research Program of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (KDH, KYC, and MLR), NIH grant UL1 TR00040 (Columbia Clinical and Translational Science Award; MR and RL), and Nutrition Obesity Research Center Grant P30DK072476 (ER). NR 46 TC 10 Z9 10 U1 23 U2 35 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 AUG 1 PY 2016 VL 104 IS 2 BP 324 EP 333 DI 10.3945/ajcn.116.133561 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DU0CZ UT WOS:000381870200012 PM 27385608 ER PT J AU Schleicher, RL Sternberg, MR Lacher, DA Sempos, CT Looker, AC Durazo-Arvizu, RA Yetley, EA Chaudhary-Webb, M Maw, KL Pfeiffer, CM Johnson, CL AF Schleicher, Rosemary L. Sternberg, Maya R. Lacher, David A. Sempos, Christopher T. Looker, Anne C. Durazo-Arvizu, Ramon A. Yetley, Elizabeth A. Chaudhary-Webb, Madhulika Maw, Khin L. Pfeiffer, Christine M. Johnson, Clifford L. TI The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE standardization; survey; vitamin D; trend; NHANES; supplements ID TANDEM MASS-SPECTROMETRY; D DEFICIENCY; CLINICAL-PRACTICE; HYPOVITAMINOSIS-D; HEALTH; PREVALENCE; TRENDS; ADULTS; PREVENTION; OBESITY AB Background: Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D [25(OH)D] measurements. Objective: To accurately assess vitamin D status trends among those aged >= 12 y, we used data from the cross-sectional NHANESs. Design: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D-3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446). Weighted arithmetic means and the prevalence of 25(OH)D above or below cutoff concentrations were calculated to evaluate long-term trends. Results: Overall, mean predicted 25(OH)D showed no time trend from 1988 to 2006, but during 2007-2010 the mean measured 25(OH)D was 5-6 nmol/L higher. Those groups who showed the largest 25(OH)D increases (7-11 nmol/L) were older, female, non-Hispanic white, and vitamin D supplement users. During 19882010, the proportions of persons with 25(OH)D,40 nmol/L were 14-18% (overall), 46-60% (non-Hispanic blacks), 21-28% (Mexican Americans), and 6-10% (non-Hispanic whites). Conclusions: An accurate method for measuring 25(OH)D showed stable mean concentrations in the US population (1988-2006) and recent modest increases (2007-2010). Although it is unclear to what extent supplement usage compared with different laboratory methods explain the increases in 25(OH)D, the use of higher vitamin D supplement dosages coincided with the increase. Marked race-ethnic differences in 25(OH)D concentrations were apparent. These data provide the first standardized information about temporal trends in the vitamin D status of the US population. C1 [Schleicher, Rosemary L.; Sternberg, Maya R.; Chaudhary-Webb, Madhulika; Maw, Khin L.; Pfeiffer, Christine M.] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. [Lacher, David A.; Looker, Anne C.; Johnson, Clifford L.] CDC, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. [Sempos, Christopher T.; Durazo-Arvizu, Ramon A.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. EM cfp8@cdc.gov FU CDC; NIH/Office of Dietary Supplements FX Data collection and laboratory analyses of vitamin D were funded by the CDC and the NIH/Office of Dietary Supplements. NR 55 TC 6 Z9 6 U1 5 U2 6 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 AUG 1 PY 2016 VL 104 IS 2 BP 454 EP 461 DI 10.3945/ajcn.115.127985 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DU0CZ UT WOS:000381870200026 PM 27385610 ER PT J AU Terry, AL Cogswell, ME Wang, CY Chen, TC Loria, CM Wright, JD Zhang, XL Lacher, DA Merritt, RK Bowman, BA AF Terry, Ana L. Cogswell, Mary E. Wang, Chia-Yih Chen, Te-Ching Loria, Catherine M. Wright, Jacqueline D. Zhang, Xinli Lacher, David A. Merritt, Robert K. Bowman, Barbara A. TI Feasibility of collecting 24-h urine to monitor sodium intake in the National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE 24-hour urine; sodium excretion; NHANES; biomarker; hypertension; sodium intake ID AMINO BENZOIC-ACID; BLOOD-PRESSURE; UNITED-STATES; SALT INTAKE; COMPLETENESS; POTASSIUM; BIOMARKERS; EXCRETION AB Background: Twenty-four-hour urine sodium excretion is recommended for monitoring population sodium intake. Because of concerns about participation and completion, sodium excretion has not been collected previously in US nationally representative surveys. Objective: We assessed the feasibility of implementing 24-h urine collections as part of a nationally representative survey. Design: We selected a random half sample of nonpregnant US adults aged 20-69 y in 3 geographic locations of the 2013 NHANES. Participants received explicit instructions, started and ended the urine collection in a urine study mobile examination center, and answered questions about their collection. Among those with a complete 24-h urine collection, a random one-half were asked to collect a second 24-h urine sample. Sodium, potassium, chloride, and creatinine excretion were analyzed. Results: The final NHANES examination response rate for adults aged 20-69 y in these 3 study locations was 71%. Of those examined (n = 476), 282 (59%) were randomly selected to participate in the 24-h urine collection. Of these, 212 persons [75% of those selected for 24-h urine collection; 53% (equal to 71% x 75% of those selected for the NHANES)] collected a complete initial 24-h specimen and 92 persons (85% of 108 selected) collected a second complete 24-h urine sample. Moremen than women completed an initial collection (P = 0.04); otherwise, completion did not vary by sociodemographic characteristics, body mass index, education, or employment status for either collection. Mean 24-h urine volume and sodium excretion were 1964 +/- 1228 mL and 3657 +/- 2003 mg, respectively, for the first 24-h urine sample, and 2048 +/- 1288 mL and 3773 +/- 1891 mg, respectively, for the second collection. Conclusion: Given the 53% final component response rate and 75% completion rate, 24-h urine collections were deemed feasible and implemented in the NHANES 2014 on a subsample of adults aged 20-69 y to assess population sodium intake. C1 [Terry, Ana L.; Wang, Chia-Yih; Chen, Te-Ching; Zhang, Xinli; Lacher, David A.] CDC, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Cogswell, Mary E.; Merritt, Robert K.; Bowman, Barbara A.] CDC, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Loria, Catherine M.; Wright, Jacqueline D.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [Zhang, Xinli] Harris IT Serv Corp, Herndon, VA USA. RP Terry, AL (reprint author), CDC, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. EM auc5@cdc.gov FU CDC and NIH FX The data collection and laboratory analyses were funded by the CDC and the NIH. NR 27 TC 0 Z9 0 U1 1 U2 1 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 AUG 1 PY 2016 VL 104 IS 2 BP 480 EP 488 DI 10.3945/ajcn.115.121954 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DU0CZ UT WOS:000381870200029 PM 27413136 ER PT J AU Fox, AR Gordon, LK Heckenlively, JR Davis, JL Goldstein, DA Lowder, CY Nussenblatt, RB Butler, NJ Dalal, M Jayasundera, T Smith, WM Lee, RW Adamus, G Chan, CC Hooks, JJ Morgans, CW Detrick, B Sen, HN AF Fox, Austin R. Gordon, Lynn K. Heckenlively, John R. Davis, Janet L. Goldstein, Debra A. Lowder, Careen Y. Nussenblatt, Robert B. Butler, Nicholas J. Dalal, Monica Jayasundera, Thiran Smith, Wendy M. Lee, Richard W. Adamus, Grazyna Chan, Chi-Chao Hooks, John J. Morgans, Catherine W. Detrick, Barbara Sen, H. Nida TI Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ANTIRETINAL ANTIBODY DETECTION; STANDARDIZATION; NEED AB PURPOSE: To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN: Modified Delphi process. METHODS: A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. RESULTS: There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS: Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study. Published by Elsevier Inc. C1 [Fox, Austin R.; Nussenblatt, Robert B.; Chan, Chi-Chao; Hooks, John J.; Sen, H. Nida] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA. [Heckenlively, John R.; Jayasundera, Thiran] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Davis, Janet L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Goldstein, Debra A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA. [Lowder, Careen Y.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA. [Butler, Nicholas J.] Harvard Med Sch, Massachusetts Eye & Ear, Boston, MA USA. [Butler, Nicholas J.] Vet Affairs Boston Healthcare Syst, Jamaica Plain, MA USA. [Dalal, Monica] George Washington Univ, Dept Ophthalmol, Washington, DC USA. [Lee, Richard W.] Univ Bristol, Bristol Eye Hosp, Bristol, Avon, England. [Adamus, Grazyna] Casey Eye Inst, Ocular Immunol Lab, Astoria, OR USA. [Morgans, Catherine W.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Sen, HN (reprint author), 10 Ctr Dr 10D45, Bethesda, MD 20892 USA. EM senh@nei.nih.gov RI Lee, Richard/A-3116-2017 OI Lee, Richard/0000-0002-9480-6843 FU NEI INTRAMURAL RESEARCH PROGRAM, THE NIH OFFICE OF RARE DISeases Research (ORDR); NIH Medical Research Scholars Program; NIH FX THIS WORK IS SUPPORTED BY THE NEI INTRAMURAL RESEARCH PROGRAM, THE NIH OFFICE OF RARE DISeases Research (ORDR), and the NIH Medical Research Scholars Program. The NIH Medical Research Scholars Program is 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. Financial disclosures: Janet L. Davis, Consultant: AbbVie Inc (Chicago, IL); Debra A. Goldstein, Consultant: Bausch & Lomb (Bridgewater, NJ), Xoma (Berkeley, CA), Clearside Biomedical (Alpharetta, GA), Independent Data Monitoring Committee: AbbVie Inc (Chicago, IL); Careen Y. Lowder, Data and safety monitoring committee: Allergan (Dublin, Ireland); Richard W. Lee, Consultant: Roche-Genentech(South San Francisco, CA), EMD Serono (Darmstadt, Germany); Barbara Detrick, Consultant: Siemens Healthcare Diagnostics Inc (Tarrytown, NY), Abbott Laboratories (Chicago, IL). The following authors have no financial disclosures: Austin R. Fox, Lynn K. Gordon, John R. Heckenlively, Robert B. Nussenblatt, Nicholas J. Butler, Monica Dalal, Thiran Jayasundera, Wendy M. Smith, Grazyna Adamus, Chi-Chao Chan, John J. Hooks, Catherine W. Morgans, and H. Nida Sen. All authors attest that they meet the current ICMJE criteria for authorship. NR 15 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2016 VL 168 BP 183 EP 190 DI 10.1016/j.ajo.2016.05.013 PG 8 WC Ophthalmology SC Ophthalmology GA DT0IG UT WOS:000381166600020 PM 27210277 ER PT J AU Ciencewicki, JM Verhein, KC Gerrish, K Mccaw, ZR Li, JY Bushel, PR Kleeberger, SR AF Ciencewicki, Jonathan M. Verhein, Kirsten C. Gerrish, Kevin Mccaw, Zachary R. Li, Jianying Bushel, Pierre R. Kleeberger, Steven R. TI Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE neutrophils; genome-wide transcriptomics; pattern recognition analysis; tumor necrosis factor-alpha; innate immunity ID INDUCED LUNG INFLAMMATION; REPERFUSION INJURY; DENDRITIC CELLS; VIRUS-INFECTION; AIR-POLLUTION; IN-VITRO; RECEPTORS; MICE; SUSCEPTIBILITY; INHIBITION AB Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-nduced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proin-flammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl (+/+)) and MBL-deficient (Mbl (-/-)) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoal-veolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [Cxcl2 (major intrinsic protein 2)] and 5 [Cxcl5 (limb expression, LIX)] in the bronchoal-veolar lavage fluid were significantly lower in Mbl (+/+) than Mbl (-/-) mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl (+/+) and Mbl (-/-) mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS(2) data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at baseline and after exposure to ozone and significantly reduced pulmonary inflammation, thus indicating an important innate immunomodulatory role of the gene in this model. C1 [Ciencewicki, Jonathan M.; Verhein, Kirsten C.; Mccaw, Zachary R.; Kleeberger, Steven R.] NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. [Gerrish, Kevin] NIEHS, Signal Transduct Lab, POB 12233, Res Triangle Pk, NC 27709 USA. [Li, Jianying; Bushel, Pierre R.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RP Kleeberger, SR (reprint author), NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov FU Intramural Research Program of the National Institute of Environmental Health Sciences; Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences and Department of Health and Human Services. NR 57 TC 0 Z9 0 U1 4 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG 1 PY 2016 VL 311 IS 2 BP L280 EP L291 DI 10.1152/ajplung.00205.2015 PG 12 WC Physiology; Respiratory System SC Physiology; Respiratory System GA DT6XP UT WOS:000381628600009 PM 27106289 ER PT J AU Brown, J AF Brown, Jeremy TI National Institutes of Health Support for Clinical Emergency Care Research, 2011 to 2014 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID BIG DATA; MEDICINE AB Study objective: I report on the results of a portfolio analysis of National Institutes of Health (NIH) support for clinical emergency care research. Methods: A targeted query was created with data-mining techniques that accessed the NIH database for 2011 to 2014. The search was constructed to have a clinical focus; animal and bench research projects, as well as career development grants, were excluded. The search results were manually reviewed for appropriateness and then analyzed. Results: Six-hundred eighty-eight applications were analyzed. During the study period, the number of new emergency care projects submitted to NIH increased from 62 in 2011 to 153 in 2014. A total of 112 new applications were funded for $100 million, with an overall success rate of 23%. The total amount of support for both new and existing projects during the 4-year study period was $263 million. One third of the funded principal investigators were emergency medicine faculty, and their success rate for R01 funding was twice the NIH average. Conclusion: Emergency care research makes up 0.7% of NIH spending on new research project grants. The success rate is high for emergency medicine principal investigators conducting clinical work. The overall success rate for emergency medicine RO1s is similar to that of other clinical specialties. C1 [Brown, Jeremy] NIGMS, Off Emergency Care Res, NIH, Bethesda, MD 20892 USA. RP Brown, J (reprint author), NIGMS, Off Emergency Care Res, NIH, Bethesda, MD 20892 USA. EM jeremy.brown@nih.gov NR 8 TC 2 Z9 2 U1 4 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2016 VL 68 IS 2 BP 164 EP 171 DI 10.1016/j.annemergmed.2016.01.039 PG 8 WC Emergency Medicine SC Emergency Medicine GA DT0II UT WOS:000381166800006 PM 26973176 ER PT J AU Anantpadma, M Kouznetsova, J Wang, H Huang, RL Kolokoltsov, A Guha, R Lindstrom, AR Shtanko, O Simeonov, A Maloney, DJ Maury, W LaCount, DJ Jadhav, A Davey, RA AF Anantpadma, Manu Kouznetsova, Jennifer Wang, Hang Huang, Ruili Kolokoltsov, Andrey Guha, Rajarshi Lindstrom, Aaron R. Shtanko, Olena Simeonov, Anton Maloney, David J. Maury, Wendy LaCount, Douglas J. Jadhav, Ajit Davey, Robert A. TI Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NIEMANN-PICK C1; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; IN-VITRO; GLYCOPROTEIN; INFECTION; CELLS; MACROPINOCYTOSIS; PROTEIN; FILOVIRIDAE AB Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. C1 [Anantpadma, Manu; Shtanko, Olena; Davey, Robert A.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78227 USA. [Kouznetsova, Jennifer; Wang, Hang; Huang, Ruili; Guha, Rajarshi; Simeonov, Anton; Maloney, David J.; Jadhav, Ajit] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Lindstrom, Aaron R.; LaCount, Douglas J.] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN USA. [Maury, Wendy] Univ Iowa, Dept Microbiol, Iowa City, IA USA. [Kolokoltsov, Andrey] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. [Kolokoltsov, Andrey] Pharmeco LLC, Moscow, Russia. RP Davey, RA (reprint author), Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78227 USA. EM rdavey@txbiomed.org FU Cowles Fellowship Program at Texas Biomedical Research Institute; Southwest Foundation Forum Grant; Ewing Halsell Foundation; HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [5R21AI115082-02, 5R03MH086850-02, AI077519]; DOD \ Defense Threat Reduction Agency (DTRA) [HDTRA1-12-1-0002] FX This work, including the efforts of Manu Anantpadma, was funded by Cowles Fellowship Program at Texas Biomedical Research Institute. This work, including the efforts of Manu Anantpadma, was funded by Southwest Foundation Forum Grant. This work, including the efforts of Robert A. Davey, was funded by Ewing Halsell Foundation. This work, including the efforts of Robert A. Davey, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (5R21AI115082-02 and 5R03MH086850-02). This work, including the efforts of Wendy Maury, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (AI077519). This work, including the efforts of Robert A. Davey, was funded by DOD vertical bar Defense Threat Reduction Agency (DTRA) (HDTRA1-12-1-0002). NR 54 TC 2 Z9 2 U1 6 U2 10 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 AUG PY 2016 VL 60 IS 8 BP 4471 EP 4481 DI 10.1128/AAC.00543-16 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DS5AJ UT WOS:000380792600005 PM 27161622 ER PT J AU Hardiman, CA Weingarten, RA Conlan, S Khil, P Dekker, JP Mathers, AJ Sheppard, AE Segre, JA Frank, KM AF Hardiman, C. A. Weingarten, R. A. Conlan, S. Khil, P. Dekker, J. P. Mathers, A. J. Sheppard, A. E. Segre, J. A. Frank, K. M. TI Horizontal Transfer of Carbapenemase-Encoding Plasmids and Comparison with Hospital Epidemiology Data SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SEQUENCE TYPE 258; KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI; RESISTANT ENTEROBACTERIACEAE; MOLECULAR EPIDEMIOLOGY; BETA-LACTAMASE; NEW-JERSEY; GENE; DISSEMINATION; CONJUGATION AB Carbapenemase-producing organisms have spread worldwide, and infections with these bacteria cause significant morbidity. Horizontal transfer of plasmids carrying genes that encode carbapenemases plays an important role in the spread of multidrug-resistant Gram-negative bacteria. Here we investigate parameters regulating conjugation using an Escherichia coli laboratory strain that lacks plasmids or restriction enzyme modification systems as a recipient and also using patient isolates as donors and recipients. Because conjugation is tightly regulated, we performed a systematic analysis of the transfer of Klebsiella pneumoniae carbapenemase (bla(KPC))encoding plasmids into multiple strains under different environmental conditions to investigate critical variables. We used four bla(KPC)-carrying plasmids isolated from patient strains obtained from two hospitals: pKpQIL and pKPC-47e from the National Institutes of Health, and pKPC_UVA01 and pKPC_UVA02 from the University of Virginia. Plasmid transfer frequency differed substantially between different donor and recipient pairs, and the frequency was influenced by plasmid content, temperature, and substrate, in addition to donor and recipient strain. pKPC-47e was attenuated in conjugation efficiency across all conditions tested. Despite its presence in multiple clinical species, pKPC_UVA01 had lower conjugation efficiencies than pKpQIL into recipient strains. The conjugation frequency of these plasmids into K. pneumoniae and E. coli patient isolates ranged widely without a clear correlation with clinical epidemiological data. Our results highlight the importance of each variable examined in these controlled experiments. The in vitro models did not reliably predict plasmid mobilization observed in a patient population, indicating that further studies are needed to understand the most important variables affecting horizontal transfer in vivo. C1 [Hardiman, C. A.; Weingarten, R. A.; Khil, P.; Dekker, J. P.; Frank, K. M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Conlan, S.; Segre, J. A.] NHGRI, Bethesda, MD 20892 USA. [Mathers, A. J.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Sheppard, A. E.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Modernizing Med Microbiol Consortium, Oxford, England. RP Frank, KM (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM karen.frank@nih.gov FU Biotechnology and Biological Sciences Research Council (BBSRC); National Institutes of Health Director's Challenge Innovation Award; NIHR Oxford Biomedical Research Centre; Wellcome Trust [087646/Z/08/Z]; HHS \ NIH \ National Human Genome Research Institute (NHGRI); Medical Research Council (MRC); DH \ National Institute for Health Research (NIHR) [G0800778]; HHS \ NIH \ NIH Clinical Center (Clinical Center) FX This work, including the efforts of A. J. Mathers and A. E. Sheppard, was funded by Biotechnology and Biological Sciences Research Council (BBSRC). This work, including the efforts of C. A. Hardiman, R. A. Weingarten, S. Conlan, J. A. Segre, and K. M. Frank, was funded by National Institutes of Health Director's Challenge Innovation Award. This work, including the efforts of A. J. Mathers and A. E. Sheppard, was funded by NIHR Oxford Biomedical Research Centre. This work, including the efforts of A. J. Mathers and A. E. Sheppard, was funded by Wellcome Trust (087646/Z/08/Z). This work, including the efforts of S. Conlan and J. A. Segre, was funded by HHS vertical bar NIH vertical bar National Human Genome Research Institute (NHGRI). This work, including the efforts of A. J. Mathers and A. E. Sheppard, was funded by Medical Research Council (MRC). This work, including the efforts of A. J. Mathers and A. E. Sheppard, was funded by DH vertical bar National Institute for Health Research (NIHR) (G0800778). This work, including the efforts of C. A. Hardiman, R. A. Weingarten, P. Khil, J. P. Dekker, and K. M. Frank, was funded by HHS vertical bar NIH vertical bar NIH Clinical Center (Clinical Center). NR 56 TC 2 Z9 2 U1 6 U2 6 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 AUG PY 2016 VL 60 IS 8 BP 4910 EP 4919 DI 10.1128/AAC.00014-16 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DS5AJ UT WOS:000380792600056 PM 27270289 ER PT J AU Afonso, CL Amarasinghe, GK Banyai, K Bao, YM Basler, CF Bavari, S Bejerman, N Blasdell, KR Briand, FX Briese, T Bukreyev, A Calisher, CH Chandran, K Cheng, JS Clawson, AN Collins, PL Dietzgen, RG Dolnik, O Domier, LL Durrwald, R Dye, JM Easton, AJ Ebihara, H Farkas, SL Freitas-Astua, J Formenty, P Fouchier, RAM Fu, YP Ghedin, E Goodin, MM Hewson, R Horie, M Hyndman, TH Jiang, DH Kitajima, EW Kobinger, GP Kondo, H Kurath, G Lamb, RA Lenardon, S Leroy, EM Li, CX Lin, XD Liu, LJ Longdon, B Marton, S Maisner, A Muhlberger, E Netesov, SV Nowotny, N Patterson, JL Payne, SL Paweska, JT Randall, RE Rima, BK Rota, P Rubbenstroth, D Schwemmle, M Shi, M Smither, SJ Stenglein, MD Stone, DM Takada, A Terregino, C Tesh, RB Tian, JH Tomonaga, K Tordo, N Towner, JS Vasilakis, N Verbeek, M Volchkov, VE Wahl-Jensen, V Walsh, JA Walker, PJ Wang, D Wang, LF Wetzel, T Whitfield, AE Xie, JT Yuen, KY Zhang, YZ Kuhn, JH AF Afonso, Claudio L. Amarasinghe, Gaya K. Banyai, Krisztian Bao, Yiming Basler, Christopher F. Bavari, Sina Bejerman, Nicolas Blasdell, Kim R. Briand, Francois-Xavier Briese, Thomas Bukreyev, Alexander Calisher, Charles H. Chandran, Kartik Cheng, Jiasen Clawson, Anna N. Collins, Peter L. Dietzgen, Ralf G. Dolnik, Olga Domier, Leslie L. Duerrwald, Ralf Dye, John M. Easton, Andrew J. Ebihara, Hideki Farkas, Szilvia L. Freitas-Astua, Juliana Formenty, Pierre Fouchier, Ron A. M. Fu, Yanping Ghedin, Elodie Goodin, Michael M. Hewson, Roger Horie, Masayuki Hyndman, Timothy H. Jiang, Daohong Kitajima, Elliot W. Kobinger, Gary P. Kondo, Hideki Kurath, Gael Lamb, Robert A. Lenardon, Sergio Leroy, Eric M. Li, Ci-Xiu Lin, Xian-Dan Liu, Lijiang Longdon, Ben Marton, Szilvia Maisner, Andrea Muhlberger, Elke Netesov, Sergey V. Nowotny, Norbert Patterson, Jean L. Payne, Susan L. Paweska, Janusz T. Randall, Rick E. Rima, Bertus K. Rota, Paul Rubbenstroth, Dennis Schwemmle, Martin Shi, Mang Smither, Sophie J. Stenglein, Mark D. Stone, David M. Takada, Ayato Terregino, Calogero Tesh, Robert B. Tian, Jun-Hua Tomonaga, Keizo Tordo, Noel Towner, Jonathan S. Vasilakis, Nikos Verbeek, Martin Volchkov, Viktor E. Wahl-Jensen, Victoria Walsh, John A. Walker, Peter J. Wang, David Wang, Lin-Fa Wetzel, Thierry Whitfield, Anna E. Xie, Jiatao Yuen, Kwok-Yung Zhang, Yong-Zhen Kuhn, Jens H. TI Taxonomy of the order Mononegavirales: update 2016 SO ARCHIVES OF VIROLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; PARROT BORNAVIRUS 5; AVIAN PARAMYXOVIRUS; INTERNATIONAL COMMITTEE; FELINE MORBILLIVIRUS; RATIFICATION VOTE; DOMESTIC CATS; VIRUS; IDENTIFICATION; PROPOSALS AB In 2016, the order Mononegavirales was emended through the addition of two new families (Mymonaviridae and Sunviridae), the elevation of the paramyxoviral subfamily Pneumovirinae to family status (Pneumoviridae), the addition of five free-floating genera (Anphevirus, Arlivirus, Chengtivirus, Crustavirus, and Wastrivirus), and several other changes at the genus and species levels. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV). C1 [Afonso, Claudio L.] ARS, Southeast Poultry Res Lab, USDA, Athens, GA 30602 USA. [Amarasinghe, Gaya K.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Banyai, Krisztian; Farkas, Szilvia L.; Marton, Szilvia] Hungarian Acad Sci, Vet Med Res Inst, Agr Res Ctr, Budapest, Hungary. [Bao, Yiming] NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Basler, Christopher F.] Georgia State Univ, Ctr Microbial Pathogenesis, Inst Biomed Sci, Atlanta, GA 30303 USA. [Bavari, Sina; Dye, John M.] United States Army Med Res Inst Infect Dis, Frederick, MD USA. [Bejerman, Nicolas; Lenardon, Sergio] Inst Nacl Tecnol Agr, Inst Patol Vegetal, Ctr Invest Agr, Cordoba, Argentina. [Bejerman, Nicolas] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina. [Blasdell, Kim R.; Walker, Peter J.] CSIRO Hlth & Biosecur, Australian Anim Hlth Lab, Geelong, Vic, Australia. [Briand, Francois-Xavier] French Agcy Food Environm & Occupat Hlth & Safety, Avian & Rabbit Virol Immunol & Parasitol Unit, Ploufragan, France. [Briese, Thomas] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA. [Bukreyev, Alexander; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston Natl Lab, Galveston, TX 77555 USA. [Bukreyev, Alexander; Tesh, Robert B.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston Natl Lab, Galveston, TX 77555 USA. [Calisher, Charles H.] Colorado State Univ, Arthropod Borne & Infect Dis Lab, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA. [Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Cheng, Jiasen; Fu, Yanping; Jiang, Daohong; Liu, Lijiang; Xie, Jiatao] Huazhong Agr Univ, State Key Lab Agr Microbiol, Prov Key Lab Plant Pathol Hubei Prov, Coll Plant Sci & Technol, Wuhan, Peoples R China. [Clawson, Anna N.; Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. [Collins, Peter L.] NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 21702 USA. [Dietzgen, Ralf G.] Univ Queensland, Queensland Alliance Agr & Food Innovat, St Lucia, Qld, Australia. [Dolnik, Olga; Maisner, Andrea] Univ Marburg, Inst Virol, Marburg, Germany. [Domier, Leslie L.] Univ Illinois, Dept Crop Sci, Champaign, IL 61820 USA. [Duerrwald, Ralf] IDT Biol, Dessau Rosslau, Germany. [Easton, Andrew J.; Walsh, John A.] Univ Warwick, Sch Life Sci, Coventry, W Midlands, England. [Ebihara, Hideki] NIAID, Rocky Mt Labs, Integrated Res Facil, NIH, Hamilton, MT 59840 USA. [Freitas-Astua, Juliana] Embrapa Cassava & Fruits, Cruz Das Almas, BA, Brazil. [Formenty, Pierre] WHO, Geneva, Switzerland. [Fouchier, Ron A. M.] Erasmus Univ, Med Ctr, Dept Virosci, Postgrad Sch Mol Med, Rotterdam, Netherlands. [Ghedin, Elodie] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Goodin, Michael M.] Univ Kentucky, Plant Pathol, Lexington, KY 40506 USA. [Hewson, Roger] Publ Hlth England, Salisbury, Wilts, England. [Horie, Masayuki] Kagoshima Univ, Joint Fac Vet Med, Transboundary Anim Dis Res Ctr, Kagoshima, Japan. [Hyndman, Timothy H.] Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA, Australia. [Kitajima, Elliot W.] Univ Sao Paulo, Nucleo Apoio Pesquisa Microscopia Eletr Aplicada, Escola Super Agr Luiz de Queiroz, Sao Paulo, Brazil. [Kobinger, Gary P.] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. [Kondo, Hideki] Okayama Univ, Inst Plant Sci & Resources, Kurashiki, Okayama, Japan. [Kurath, Gael] US Geol Survey, Western Fisheries Res Ctr, Seattle, WA 98115 USA. [Lamb, Robert A.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Lamb, Robert A.] Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA. [Leroy, Eric M.] Ctr Int Rech Med Franceville, Inst Rech Dev, Franceville, Gabon. [Shi, Mang; Zhang, Yong-Zhen] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Inst Communicable Dis Control & Prevent, Beijing, Peoples R China. [Li, Ci-Xiu] Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou, Zhejiang, Peoples R China. [Lin, Xian-Dan] Wenzhou Ctr Dis Control & Prevent, Wenzhou, Peoples R China. [Longdon, Ben] Univ Cambridge, Dept Genet, Cambridge, England. [Muhlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Muhlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA. [Netesov, Sergey V.] Novosibirsk State Univ, Novosibirsk, Novosibirsk Obl, Russia. [Nowotny, Norbert] Univ Vet Med, Inst Virol, Vienna, Austria. [Nowotny, Norbert] Mohammed Bin Rashid Univ Med & Hlth Sci, Dept Basic Med Sci, Coll Med, Dubai, U Arab Emirates. [Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78227 USA. [Payne, Susan L.] Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. [Paweska, Janusz T.] Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Natl Hlth Lab Serv, Sandringham Johannesburg, Gauteng, South Africa. [Randall, Rick E.] Univ St Andrews, Biomed Sci Res Complex, St Andrews, Fife, Scotland. [Rima, Bertus K.] Queens Univ Belfast, Ctr Med Expt, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. [Rota, Paul] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Rubbenstroth, Dennis; Schwemmle, Martin] Univ Freiburg, Inst Virol, Fac Med, Med Ctr, Freiburg, Germany. [Smither, Sophie J.] CBR Div, Dstl, Salisbury, Wilts, England. [Stenglein, Mark D.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Stone, David M.] Ctr Environm Fisheries & Aquaculture Sci, Weymouth, Dorset, England. [Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan. [Terregino, Calogero] OIE Collaborating Ctr Dis Human Anim Interface, Ist Zooprofilatt Sperimentale Venezie,FAO Referen, Dept Comparat Biomed Sci, Natl OIE Reference Lab Newcastle Dis & Avian Infl, Padua, Italy. [Tian, Jun-Hua] Wuhan Ctr Dis Control & Prevent, Wuhan, Peoples R China. [Tomonaga, Keizo] Kyoto Univ, Inst Virus Res, Kyoto, Japan. [Tordo, Noel] Inst Pasteur, Unite Strategies Antivirales, Paris, France. [Tordo, Noel] Inst Pasteur Guinee, Conakry, Guinea. [Towner, Jonathan S.] Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Div High Consequence Pathogens Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Vasilakis, Nikos] Univ Texas Med Branch, Ctr Biodefense & Emerging Infect Dis, Dept Pathol, Galveston, TX 77555 USA. [Vasilakis, Nikos] Univ Texas Med Branch, Ctr Trop Dis, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Verbeek, Martin] Wageningen Univ & Res, Wageningen, Netherlands. [Volchkov, Viktor E.] Univ Lyon 1, Mol Basis Viral Pathogen, CIRI, INSERM,U1111,CNRS,UMR5308,Ecole Normal Super Lyon, Lyon, France. [Wahl-Jensen, Victoria] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD 21702 USA. [Wang, David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Wang, David] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Wang, Lin-Fa] Biosecur Queensland, Dept Agr & Fisheries, Brisbane, Qld, Australia. [Wang, Lin-Fa] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Singapore, Singapore. [Wetzel, Thierry] DLR Rheinpfalz, Inst Plant Protect, Neustadt, Germany. [Whitfield, Anna E.] Kansas State Univ, Plant Pathol, Manhattan, KS 66506 USA. [Yuen, Kwok-Yung] Univ Hong Kong, State Key Lab Emerging Infect Dis, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. EM kuhnjens@mail.nih.gov RI Netesov, Sergey/A-3751-2013; Fouchier, Ron/A-1911-2014; Verbeek, Martin/D-1445-2017; Stenglein, Mark/E-3541-2017; LEROY, Eric/I-4347-2016; OI Netesov, Sergey/0000-0002-7786-2464; Fouchier, Ron/0000-0001-8095-2869; Verbeek, Martin/0000-0002-8973-3803; Stenglein, Mark/0000-0002-0993-813X; LEROY, Eric/0000-0003-0022-0890; Freitas-Astua, Juliana/0000-0002-0506-6880; Blasdell, Kim/0000-0003-2121-0376; Banyai, Krisztian/0000-0002-6270-1772 FU Battelle Memorial Institute; US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I]; DHS ST [HSHQDC-07-C-00020]; National Institutes of Health (NIH) [HHSN272201000040I/HHSN27200004/D04]; NIH, National Library of Medicine FX This work was supported in part through Battelle Memorial Institute's prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I. A subcontractor to Battelle Memorial Institute who performed this work is: J. H. K., an employee of Tunnell Government Services, Inc. This work was also funded in part under Contract No. HSHQDC-07-C-00020 awarded by DHS S&T for the management and operation of the National Biodefense Analysis and Countermeasures Center (NBACC), a Federally Funded Research and Development Center (V. W.-J.); and National Institutes of Health (NIH) contract HHSN272201000040I/HHSN27200004/D04 (N. V., R. B. T.). Y. B. was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 31 TC 32 Z9 32 U1 7 U2 9 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD AUG PY 2016 VL 161 IS 8 BP 2351 EP 2360 DI 10.1007/s00705-016-2880-1 PG 10 WC Virology SC Virology GA DR8FZ UT WOS:000380135100037 PM 27216929 ER PT J AU Lu, MT Park, J Ghemigian, K Mayrhofer, T Puchner, SB Liu, T Fleg, JL Udelson, JE Truong, QA Ferencik, M Hoffmann, U AF Lu, Michael T. Park, Jakob Ghemigian, Khristine Mayrhofer, Thomas Puchner, Stefan B. Liu, Ting Fleg, Jerome L. Udelson, James E. Truong, Quynh A. Ferencik, Maros Hoffmann, Udo TI Epicardial and paracardial adipose tissue volume and attenuation - Association with high-risk coronary plaque on computed tomographic angiography in the ROMICAT II trial SO ATHEROSCLEROSIS LA English DT Article DE Coronary CT angiography; High-risk coronary plaque; Coronary atherosclerosis; Epicardial adipose tissue; Paracardial adipose tissue ID ACUTE CHEST-PAIN; VISCERAL ABDOMINAL FAT; NAPKIN-RING SIGN; PERICARDIAL FAT; CT ANGIOGRAPHY; CARDIOVASCULAR-DISEASE; INTRATHORACIC FAT; ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC LESIONS AB Background and aims: To determine whether epicardial (EAT) and paracardial adipose tissue (PAT) volume and attenuation are associated with high-risk coronary plaque features. Methods: In subjects with suspected acute coronary syndrome (ACS) enrolled in the ROMICAT II trial, EAT and PAT volumes indexed to body surface area (BSA) and attenuation were measured on non-contrast coronary artery calcium score (CACS) CT. High-risk plaque features (napkin-ring sign, positive remodeling, low density plaque, spotty calcium) and stenosis were assessed on coronary CT angiography (CTA). The association of EAT and PAT volume and attenuation with high-risk plaque and whether this was independent of clinical risk assessment, CACS and significant coronary artery disease (CAD) was determined. Results: Of 467 (mean 54 +/- 8 yrs, 53% male) with CACS and CTA, 167 (36%) had high-risk plaque features. Those with high-risk plaque had significantly higher indexed EAT (median 59 (Q1-Q3: 45-75) cc/m(2) vs. 49 (35-65) cc/m(2), p < 0.001) and PAT volume (median: 51 (36-73) cc/m(2) vs. 33 (22-52) cc/m(2), p < 0.001). Higher indexed EAT volume was associated with high-risk plaque [univariate OR 1.02 (95%-CI: 1.01-1.03) per cc/m(2) of EAT, p < 0.001], which remained significant [univariate OR 1.04 (95%-CI: 1.00 -1.08) per cc/m(2) of EAT, p = 0.040] after adjustment for risk factors, CACS, and stenosis >= 50%. Higher indexed PAT volume was associated with high-risk plaque in univariate analysis [OR 1.02 (1.01-1.03) per cc/m(2) of PAT, p < 0.001], though this was not significant in multivariate analysis. At a threshold of > 62.3 cc/m(2), EAT volume was associated with high-risk plaque [univariate OR 2.50 (95%-CI: 1.69-3.72), p < 0.001)], which remained significant [OR 1.83 (95%-CI: 1.10-3.05), p = 0.020] after adjustment. Subjects with high-risk plaque had lower mean attenuation EAT (-88.1 vs. -86.9 HU, p = 0.008) and PAT (-106 vs. -103 HU, p < 0.001), though this was not significant in multivariable analysis. Conclusions: Greater volumes of EAT are associated with high-risk plaque independent of risk factors, CACS and obstructive CAD. This observation supports possible local influence of EAT on development of high-risk coronary plaque. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Lu, Michael T.; Park, Jakob; Ghemigian, Khristine; Mayrhofer, Thomas; Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Lu, Michael T.; Park, Jakob; Ghemigian, Khristine; Mayrhofer, Thomas; Ferencik, Maros; Hoffmann, Udo] Harvard Med Sch, Boston, MA USA. [Park, Jakob] Heidelberg Univ, Heidelberg, Germany. [Mayrhofer, Thomas] Stralsund Univ Appl Sci, Sch Business Studies, Stralsund, Germany. [Puchner, Stefan B.] Univ Hosp Vienna, Div Cardiovasc & Intervent Radiol, Vienna, Austria. [Liu, Ting] China Med Univ, Affiliated Hosp 1, Shenyang, Peoples R China. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Truong, Quynh A.] Weill Cornell Med Coll, New York, NY USA. [Ferencik, Maros] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Lu, MT (reprint author), Div Cardiovasc Imaging, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM mlu@mgh.harvard.edu FU American Roentgen Ray Society FX The authors acknowledge NIH 5T32HL076136, the MGH Executive Committee on Research and the American Roentgen Ray Society Scholarship (MTL), the German Cardiac Society and German National Academic Foundation (JP), the American Heart Association 13FTF16450001 (MF), Siemens Healthcare, NIH/NHLBI 5K24HL113128 and 5U01HL092040-04 (UH). NR 52 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2016 VL 251 BP 47 EP 54 DI 10.1016/j.atherosclerosis.2016.05.033 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DT1SJ UT WOS:000381262100008 PM 27266821 ER PT J AU Aberra, TM Joshi, AA Lerman, JB Rodante, JA Dahiya, AK Teague, HL Ng, Q Silverman, JI Sorokin, AV Salahuddin, T Lockshin, BN Ahlman, MA Playford, MP Chen, MY Gelfand, JM Mehta, NN AF Aberra, Tsion M. Joshi, Aditya A. Lerman, Joseph B. Rodante, Justin A. Dahiya, Asha K. Teague, Heather L. Ng, Qimin Silverman, Joanna I. Sorokin, Alexander V. Salahuddin, Taufiq Lockshin, Benjamin N. Ahlman, Mark A. Playford, Martin P. Chen, Marcus Y. Gelfand, Joel M. Mehta, Nehal N. TI Self-reported depression in psoriasis is associated with subclinical vascular diseases SO ATHEROSCLEROSIS LA English DT Article DE Psoriasis; Subclinical cardiovascular disease; Depression; Anxiety; Inflammation ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; FDG PET/CT; RISK; SYMPTOMS; COHORT; ATHEROSCLEROSIS; INFLAMMATION; METAANALYSIS AB Background and aims: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown. Methods: Patients were selected from within a larger psoriasis cohort. Those who reported a history of depression (N = 36) on survey were matched by age and gender to patients who reported no history of psychiatric illness (N = 36). Target-to-background ratio from FDG PET/CT was used to assess aortic vascular inflammation and coronary CT angiography scans were analyzed to determine coronary plaque burden. Multivariable linear regression was performed to understand the effect of self-reported depression on vascular inflammation and coronary plaque burden after adjustment for Framingham risk (standardized beta reported). Results: In unadjusted analyses, vascular inflammation and coronary plaque burden were significantly increased in patients with self-reported depression as compared to patients with psoriasis alone. After adjustment for Framingham Risk Score, vascular inflammation (beta = 0.26, p = 0.02), total plaque burden (beta = 0.17, p = 0.03), and non-calcified burden (beta = 0.17, p = 0.03) were associated with self-reported depression. Conclusions: Self-reported depression in psoriasis is associated with increased vascular inflammation and coronary plaque burden. Depression may play an important role in promoting subclinical atherosclerosis beyond traditional cardiovascular risk factors. Published by Elsevier Ireland Ltd. C1 [Aberra, Tsion M.; Joshi, Aditya A.; Lerman, Joseph B.; Rodante, Justin A.; Dahiya, Asha K.; Teague, Heather L.; Ng, Qimin; Silverman, Joanna I.; Sorokin, Alexander V.; Salahuddin, Taufiq; Playford, Martin P.; Chen, Marcus Y.; Mehta, Nehal N.] NHLBI, NIH, Bethesda, MD 20892 USA. [Lockshin, Benjamin N.] DermAssociates, Silver Spring, MD USA. [Ahlman, Mark A.] NIH, Mol Biomed Imaging Lab, Bethesda, MD 20892 USA. [Gelfand, Joel M.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Mehta, NN (reprint author), NHLBI, Cardiovasc & Pulm Branch, Clin Res Ctr, 10 Ctr Dr,Room 5-5140, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov FU National Heart, Lung and Blood Institute (NHLBI) [HL006193- 02]; National Psoriasis Foundation; NIH; [R01-HL111293]; [K24 AR064310] FX This study was supported by the National Heart, Lung and Blood Institute (NHLBI) Intramural Research Program (HL006193- 02), R01-HL111293, and K24 AR064310 and National Psoriasis Foundation Discovery Grant.; 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 the Doris Duke Charitable Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. NR 21 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2016 VL 251 BP 219 EP 225 DI 10.1016/j.atherosclerosis.2016.05.043 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DT1SJ UT WOS:000381262100032 PM 27376696 ER PT J AU Albers, JJ Slee, A Fleg, JL O'Brien, KD Marcovina, SM AF Albers, John J. Slee, April Fleg, Jerome L. O'Brien, Kevin D. Marcovina, Santica M. TI Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial SO ATHEROSCLEROSIS LA English DT Article DE Cardiovascular risk; Homogeneous assays; HDL3-cholesterol; HDL2-cholesterol; Small dense LDL; LDL-triglyceride ID CORONARY-HEART-DISEASE; GLOBAL HEALTH OUTCOMES; LIPOPROTEIN-CHOLESTEROL; HOMOGENEOUS ASSAY; ATHEROTHROMBOSIS INTERVENTION; METABOLIC SYNDROME; ARTERY-DISEASE; RISK; COHORT; ATHEROSCLEROSIS AB Background and aims: Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes. Methods: Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1500 to 2000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40-80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling. Results: Baseline HDL3-C was protective against CV events (HR: 0.84, p = 0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p = 0.369; HR: 1.07, p = 0.373; HR: 1.05, p = 0.492; HR: 1.03, p = 0.554, respectively). Conclusions: The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Albers, John J.; Marcovina, Santica M.] Univ Washington, Northwest Lipid Metab & Diabet Res Labs, 401 Queen Anne Ave N, Seattle, WA 98109 USA. [Slee, April] Axio Res, AIM HIGH Coordinating Ctr, 2601 Fourth Ave,Ste 200, Seattle, WA 98121 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, 6701 Rockledge Dr,Rm 8150, Bethesda, MD 20892 USA. [O'Brien, Kevin D.] Univ Washington, Div Cardiol, Dept Med, 1959 NE Pacific Ave,Box 356422, Seattle, WA 98195 USA. RP Marcovina, SM (reprint author), Univ Washington, Northwest Lipid Metab & Diabet Res Labs, 401 Queen Anne Ave N, Seattle, WA 98109 USA. EM jja@uw.edu; AprilS@axioresearch.com; flegj@nhlbi.nih.gov; cardiac@uw.edu; smm@uw.edu FU National Heart, Lung, and Blood Institute [U01 HL081616, U01 HL081649]; AbbVie, Inc. FX The Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health (AIM-HIGH) study was supported by the National Heart, Lung, and Blood Institute (U01 HL081616 and U01 HL081649) and by an unrestricted grant from AbbVie, Inc. AbbVie donated the extended-release niacin, the matching placebo, and the ezetimibe; Merck donated the simvastatin. Neither of these companies had any role in the oversight or design of the study or in the analysis or interpretation of the data. NR 27 TC 1 Z9 1 U1 4 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2016 VL 251 BP 454 EP 459 DI 10.1016/j.atherosclerosis.2016.06.019 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DT1SJ UT WOS:000381262100064 PM 27320173 ER PT J AU Ustun, C Gotlib, J Popat, U Artz, A Litzow, M Reiter, A Nakamura, R Kluin-Nelemans, HC Verstovsek, S Gajewskil, J Perales, MA George, T Shore, T Sperr, W Saber, W Kota, V Yavuz, AS Pullarkat, V Rogosheske, J Hogan, W Van Besien, K Hagglund, H Damaj, G Arock, M Horny, HP Metcalfe, DD Deeg, HJ Devine, S Weisdorfl, D Akin, C Valent, P AF Ustun, Celalettin Gotlib, Jason Popat, Uday Artz, Andrew Litzow, Mark Reiter, Andreas Nakamura, Ryotaro Kluin-Nelemans, Hanneke C. Verstovsek, Srdan Gajewskil, James Perales, Miguel-Angel George, Tracy Shore, Tsiporah Sperr, Wolfgang Saber, Wael Kota, Vamsi Yavuz, Akif Selim Pullarkat, Vinod Rogosheske, John Hogan, William Van Besien, Koen Hagglund, Hans Damaj, Gandhi Arock, Michel Horny, Hans-Peter Metcalfe, Dean D. Deeg, H. Joachim Devine, Steven Weisdorfl, Daniel Akin, Cem Valent, Peter TI Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; EUROPEAN COMPETENCE NETWORK; BONE-MARROW-TRANSPLANTATION; CURRENT TREATMENT OPTIONS; NEOPLASTIC MAST-CELLS; MYELOMASTOCYTIC LEUKEMIA; RESPONSE CRITERIA; TRYPTASE LEVELS; VENOOCCLUSIVE DISEASE C1 [Ustun, Celalettin; Rogosheske, John; Weisdorfl, Daniel] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Gotlib, Jason] Stanford Univ, Div Hematol, Stanford, CA USA. [Popat, Uday] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX USA. [Artz, Andrew] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL USA. [Litzow, Mark; Hogan, William] Mayo Clin, Dept Internal Med, Div Hematol, Minneapolis, MN USA. [Reiter, Andreas] Univ Med Ctr Mannheim, Dept Hematol & Oncol, Mannheim, Germany. [Nakamura, Ryotaro] City Hope Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA USA. [Kluin-Nelemans, Hanneke C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands. [Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. [Gajewskil, James] Oregon Hlth & Sci Univ, Dept Hematol, Portland, OR USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, New York, NY USA. [George, Tracy] Univ New Mexico, Dept Pathol, Albuquerque, NM USA. [Shore, Tsiporah] Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA. [Sperr, Wolfgang] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol & Ludwig Boltzmann Clus, Vienna, Austria. [Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI USA. [Kota, Vamsi] Emory Univ, Winship Canc Inst, Dept Hematol & Oncol, Div Hematol, Atlanta, GA USA. [Yavuz, Akif Selim] Istanbul Univ, Istanbul Med Sch, Div Hematol, Istanbul, Turkey. [Van Besien, Koen] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Hagglund, Hans] Uppsala Univ, Dept Med Sci, Div Hematol, Uppsala, Sweden. [Damaj, Gandhi] Univ Basse Normandie, Univ Hosp, Sch Med, Inst Hematol,Dept Hematol, Caen, France. [Arock, Michel] Ecole Normale Super, CNRS UMR 8113, Cellular & Mol Oncol Unit, Cachan, France. [Arock, Michel] Univ Pitie Salpetriere, Ctr Hosp, Hematol Lab, Paris, France. [Horny, Hans-Peter] LMU, Inst Pathol, Munich, Germany. [Metcalfe, Dean D.] NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD USA. [Deeg, H. Joachim] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Deeg, H. Joachim] Univ Washington, Sch Med, Seattle, WA USA. [Devine, Steven] Ohio State Univ, Dept Med, Div Hematol, Columbus, OH 43210 USA. [Devine, Steven] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Akin, Cem] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA USA. RP Ustun, C (reprint author), Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. EM custun@umn.edu OI Akin, Cem/0000-0001-6301-4520 FU NCI NIH HHS [P30 CA016672] NR 85 TC 4 Z9 4 U1 3 U2 3 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 AUG PY 2016 VL 22 IS 8 BP 1348 EP 1356 DI 10.1016/j.bbmt.2016.04.018 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DS1XC UT WOS:000380417400003 PM 27131865 ER PT J AU Pirsl, F Curtis, LM Steinberg, SM Tella, SH Katic, M Dobbin, M Hsu, J Hakim, FT Mays, JW Im, AP Pulanic, D Mitchell, SA Baruffaldi, J Masuch, L Halverson, DC Gress, RE Barsony, J Pavletic, SZ AF Pirsl, Filip Curtis, Lauren M. Steinberg, Seth M. Tella, Sri Harsha Katic, Masenjka Dobbin, Marnie Hsu, Jennifer Hakim, Fran T. Mays, Jacqueline W. Im, Annie P. Pulanic, Drazen Mitchell, Sandra A. Baruffaldi, Judy Masuch, Licia Halverson, David C. Gress, Ronald E. Barsony, Julianna Pavletic, Steven Z. TI Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Osteoporosis; Late effects; Supportive care; Platelets ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; MEAN PLATELET VOLUME; CLINICAL-TRIALS; CHRONIC GVHD; REPRODUCTIVE HEALTH; MINERAL DENSITY AB The National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients, and the guidelines are based on experience with other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD because of prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score <=-2.5) at 3 anatomic sites the femoral neck (FN), lumbar spine (LS), and total hip (TH) and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN, P <.0001; LS, P =.0002; TH, P <.0001), malnutrition (FN, P =.0002; LS, P =.03; TH, P =.0076), higher platelet count (FN, P =.0065; TH, P =.0025), higher average National Institutes of Health organ score (FN, P =.038), higher prednisone dose (LS, P =.032), lower complement component 3 (LS, P =.0073), and physical inactivity (FN, P =.01) were associated with osteoporosis in at least 1 site. T-scores were significantly lower in the FN compared with the LS or TH (P <.0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in patients with cGVHD and osteoporosis has not been reported previously and represents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Pirsl, Filip; Curtis, Lauren M.; Katic, Masenjka; Hsu, Jennifer; Hakim, Fran T.; Baruffaldi, Judy; Masuch, Licia; Halverson, David C.; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 3E-3330, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Tella, Sri Harsha] NICHHD, NIH, Bethesda, MD 20892 USA. [Dobbin, Marnie] NIH, Dept Clin Nutr, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Mays, Jacqueline W.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Im, Annie P.] Univ Pittsburgh, Med Ctr, Adult Hematopoiet Stem Cell Transplant Program, Pittsburgh, PA USA. [Pulanic, Drazen] Univ Hosp Ctr Zagreb, Dept Internal Med, Div Hematol, Zagreb, Croatia. [Pulanic, Drazen] Univ Zagreb, Sch Med, Zagreb, Croatia. [Pulanic, Drazen] JJ Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia. [Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Barsony, Julianna] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. RP Curtis, LM (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 3E-3330, Bethesda, MD 20892 USA. EM curtislm@mail.nih.gov OI Katic, Masenjka/0000-0001-7237-697X FU Intramural NIH HHS [Z99 CA999999] NR 52 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 2016 VL 22 IS 8 BP 1517 EP 1524 DI 10.1016/j.bbmt.2016.04.012 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DS1XC UT WOS:000380417400026 PM 27118572 ER PT J AU Schoemans, H Goris, K Durm, RV Vanhoof, J Wolff, D Greinix, H Pavletic, S Lee, SJ Maertens, J Geest, SD Dobbels, F Duarte, RF AF Schoemans, H. Goris, K. Durm, R. V. Vanhoof, J. Wolff, D. Greinix, H. Pavletic, S. Lee, S. J. Maertens, J. Geest, S. D. Dobbels, F. Duarte, R. F. CA EBMT Complications Quality Life TI Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App' to support GvHD assessment according to NIH criteria-a proof of concept SO BONE MARROW TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CLINICAL-TRIALS; DIAGNOSIS AB The EBMT Complications and Quality of Life Working Party has developed a computer-based algorithm, the 'eGVHD App', using a user-centered design process. Accuracy was tested using a quasi-experimental crossover design with four expert-reviewed case vignettes in a convenience sample of 28 clinical professionals. Perceived usefulness was evaluated by the technology acceptance model (TAM) and User satisfaction by the Post-Study System Usability Questionnaire (PSSUQ). User experience was positive, with a median of 6 TAM points (interquartile range: 1) and beneficial median total, and subscale PSSUQ scores. The initial standard practice assessment of the vignettes yielded 65% correct results for diagnosis and 45% for scoring. The 'eGVHD App' significantly increased diagnostic and scoring accuracy to 93% (+ 28%) and 88% (+ 43%), respectively (both P < 0.05). The same trend was observed in the repeated analysis of case 2: accuracy improved by using the App (+ 31% for diagnosis and + 39% for scoring), whereas performance tended to decrease once the App was taken away. The 'eGVHD App' could dramatically improve the quality of care and research as it increased the performance of the whole user group by about 30% at the first assessment and showed a trend for improvement of individual performance on repeated case evaluation. C1 [Schoemans, H.; Goris, K.; Maertens, J.] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Hematol, 49 Herestr, B-3000 Leuven, Belgium. [Durm, R. V.] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Informat Technol, Leuven, Belgium. [Vanhoof, J.; Geest, S. D.; Dobbels, F.] Univ Leuven, Acad Ctr Nursing & Midwifery, Leuven, Belgium. [Wolff, D.] Univ Med Ctr Regensburg, Dept Internal Med Hematol & Oncol 3, Regensburg, Germany. [Greinix, H.] Med Univ Graz, Div Hematol, Graz, Austria. [Pavletic, S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Geest, S. D.; Dobbels, F.] Univ Basel, Inst Nursing Sci, Basel, Switzerland. [Duarte, R. F.] Hosp Univ Puerta de Hierro Majadahonda, Calle Joaquin Rodrigo 2, Madrid, Spain. RP Schoemans, H (reprint author), Katholieke Univ Leuven, Univ Hosp Leuven, Dept Hematol, 49 Herestr, B-3000 Leuven, Belgium. EM helene.schoemans@uzleuven.be FU Sofhea (Sociaal Fonds voor Hematologische Aandoeningen of Bloedziekten) FX We would like to acknowledge and thank the whole Department of Hematology of UZ Leuven for participating in this study. We also deeply thank Sofhea (Sociaal Fonds voor Hematologische Aandoeningen of Bloedziekten) for funding this research project. NR 8 TC 1 Z9 1 U1 3 U2 5 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 AUG PY 2016 VL 51 IS 8 BP 1062 EP 1065 DI 10.1038/bmt.2016.26 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DS4WB UT WOS:000380781200005 PM 27042834 ER PT J AU Anandi, P Jain, NA Tian, X Wu, CO Pophali, PA Koklanaris, E Ito, S Savani, BN Barrett, J Battiwalla, M AF Anandi, P. Jain, N. A. Tian, X. Wu, C. O. Pophali, P. A. Koklanaris, E. Ito, S. Savani, B. N. Barrett, J. Battiwalla, M. TI Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors SO BONE MARROW TRANSPLANTATION LA English DT Article ID LONG-TERM SURVIVORS; ZOLEDRONIC ACID; AVASCULAR NECROSIS; FRACTURE RISK; FOLLOW-UP; OSTEOPOROSIS; RECIPIENTS; PAMIDRONATE; MECHANISMS; PREVENTION AB Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but similar to 50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment-and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery. C1 [Anandi, P.; Jain, N. A.; Pophali, P. A.; Koklanaris, E.; Ito, S.; Barrett, J.; Battiwalla, M.] NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 5-3581,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. [Tian, X.; Wu, C. O.] NHLBI, Off Biostat Res, NIH, Bldg 10 CRC,Room 5-3581,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Battiwalla, M (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bldg 10 CRC,Room 5-3581,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM minoo.battiwalla@nih.gov RI Pophali, Priyanka/P-8646-2016 FU NHLBI, NIH FX This work was supported by the Intramural Research Program of the NHLBI, NIH. NR 34 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2016 VL 51 IS 8 BP 1101 EP 1106 DI 10.1038/bmt.2016.85 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DS4WB UT WOS:000380781200014 PM 27042843 ER PT J AU Srour, SA Devesa, SS Morton, LM Check, DP Curtis, RE Linet, MS Dores, GM AF Srour, Samer A. Devesa, Susan S. Morton, Lindsay M. Check, David P. Curtis, Rochelle E. Linet, Martha S. Dores, Graca M. TI Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloproliferative neoplasm; epidemiology; incidence; survival ID CHRONIC MYELOID-LEUKEMIA; JUVENILE MYELOMONOCYTIC LEUKEMIA; ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; HEMATOLOGICAL MALIGNANCY; PRIMARY MYELOFIBROSIS; PROGNOSTIC-FACTORS; LIFE EXPECTANCY; MYELODYSPLASTIC SYNDROMES; DIAGNOSTIC-CRITERIA AB Descriptive epidemiological information on myeloproliferative neoplasms (MPNs) and myelodysplastic (MDS)/MPNs is largely derived from single institution and European population-based studies. Data obtained following adoption of the World Health Organization classification of haematopoietic neoplasms and JAK2 V617F mutation testing are sparse. Using population-based data, we comprehensively assessed subtype-specific MPN and MDS/MPN incidence rates (IRs), IR ratios (IRRs) and relative survival (RS) in the United States (2001-12). IRs were highest for polycythaemia vera (PV) (IR=109) and essential thrombocythaemia (ET) (IR=96). Except for ET and mastocytosis, overall IRs were significantly higher among males (IRRs=14-23). All evaluable MPNs were associated with lower IRs among Hispanic whites than non-Hispanic whites (NHWs), with the exception of BCR-ABL1-positive chronic myeloid leukaemia (CML), chronic eosinophilic leukaemia (CEL) and juvenile myelomonocytic leukaemia. Except for CEL, Asians/Pacific Islanders had significantly lower MPN IRs than NHWs. ET, MPN-unclassifiable and CEL IRs were 18%, 19% and 60% higher, respectively, among blacks than NHWs. Five-year RS was more favourable for younger (< 60years) than older individuals and for women compared with men, except for PV at older ages. RS was highest (> 90%) for younger PV and ET patients and lowest (< 20%) for older chronic myelomonocytic leukaemia and atypical BCR-ABL1-negative CML patients. Varying MPN and MDS/MPN incidence patterns by subtype support distinct aetiologies and/or susceptible populations. Decreased survival rates as compared to that expected in the general population were associated with every MPN subtype, highlighting the need for new treatments, particularly among older individuals. C1 [Srour, Samer A.; Dores, Graca M.] Oklahoma City VA Hlth Care Syst, 921 NE 13th St, Oklahoma City, OK 73104 USA. [Srour, Samer A.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Med, Oklahoma City, OK 73190 USA. [Devesa, Susan S.; Morton, Lindsay M.; Check, David P.; Curtis, Rochelle E.; Linet, Martha S.; Dores, Graca M.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Srour, SA (reprint author), Oklahoma City VA Hlth Care Syst, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM samer-srour@ouhsc.edu FU Oklahoma City Veterans Affairs Health Care System in Oklahoma City; Intramural Research Program, National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Oklahoma City Veterans Affairs Health Care System in Oklahoma City; and the Intramural Research Program, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 64 TC 4 Z9 4 U1 1 U2 2 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 AUG PY 2016 VL 174 IS 3 BP 382 EP 396 DI 10.1111/bjh.14061 PG 15 WC Hematology SC Hematology GA DS4CO UT WOS:000380729200005 PM 27061824 ER PT J AU Shiels, MS Pfeiffer, RM Besson, C Clarke, CA Morton, LM Nogueira, L Pawlish, K Yanik, EL Suneja, G Engels, EA AF Shiels, Meredith S. Pfeiffer, Ruth M. Besson, Caroline Clarke, Christina A. Morton, Lindsay M. Nogueira, Leticia Pawlish, Karen Yanik, Elizabeth L. Suneja, Gita Engels, Eric A. TI Trends in primary central nervous system lymphoma incidence and survival in the US SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Lymphoma; central nervous system; incidence; survival; human immunodeficiency virus; transplant ID PRIMARY CNS LYMPHOMA; NON-HODGKINS-LYMPHOMA; UNITED-STATES; CANCER-RISK; IMMUNOCOMPETENT PATIENTS; HIV; SURVEILLANCE; PEOPLE; AIDS AB It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)-infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992-2011). HIV-infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV-infected; 09% transplant recipients). HIV prevalence in PCNSL cases declined from 641% (1992-1996) to 127% (2007-2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20-39 year-old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (17% and 16%/year), but remained stable in other age groups. Five-year survival was poor, particularly among HIV-infected cases (90%). Among HIV-uninfected cases, 5-year survival increased from 191% (1992-1994) to 301% (2004-2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV-infected and HIV-uninfected PCNSL patients. C1 [Shiels, Meredith S.; Pfeiffer, Ruth M.; Morton, Lindsay M.; Yanik, Elizabeth L.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Besson, Caroline] Bicetre Univ Hosp, Le Kremlin Bicetre, France. [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA. [Nogueira, Leticia] Texas Dept State Hlth Serv, Austin, TX USA. [Pawlish, Karen] New Jersey Dept Hlth, Trenton, NJ USA. [Suneja, Gita] Univ Utah, Dept Radiat Oncol, Salt Lake City, UT USA. RP Shiels, MS (reprint author), NCI, NIH, 9609 Med Ctr Dr,Room 6E-218 MSC 9767, Bethesda, MD 20892 USA. EM shielsms@mail.nih.gov OI Besson, Caroline/0000-0003-4364-7173; Yanik, Elizabeth/0000-0002-5835-0201 FU Intramural Research Program of the National Cancer Institute; Minneapolis Medical Research Foundation, Minneapolis, MN [HHSH250201000018C]; Arbor Research Collaborative for Health in Ann Arbor, MI [HHSH234200537009C]; 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 [HHSN261201 000037C, N01-PC-35137, N01-PC-35139]; SEER Program of the National Cancer Institute: Iowa [HSN 261201000032C, N01-PC-35143]; SEER Program of the National Cancer Institute: New Jersey [HHSN261201300021I, N01-PC-2013-00021]; 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 [1U58 DP000807-01, U58 DP000848-04, 5U58DP003875-01, 5U58DP003883-03, U58DP12-1205 3919-03, 5U58DP003921-03, 5U58/DP003931-02, U58DP 003879, U58DP000832, 5U58DP000824-04]; Massachusetts Cancer Prevention and Control Cooperative Agreement [5458DP003920]; New Jersey (Memorandum of Agreement) [5-100-046-4220-496-6140]; University of Utah; Fred Hutchinson Cancer Research Center in Seattle, WA FX This work was supported by the Intramural Research Program of the National Cancer Institute.; 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 (HHSN261201 000037C, N01-PC-35137, and N01-PC-35139), Iowa (HSN 261201000032C and N01-PC-35143), New Jersey (HHSN261201300021I, N01-PC-2013-00021), 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), New Jersey (5U58/ DP003931-02), New York (U58DP 003879), 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 (Memorandum of Agreement 5-100-046-4220-496-6140), 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 30 TC 0 Z9 0 U1 2 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 AUG PY 2016 VL 174 IS 3 BP 417 EP 424 DI 10.1111/bjh.14073 PG 8 WC Hematology SC Hematology GA DS4CO UT WOS:000380729200008 PM 27018254 ER PT J AU Reusing, SB Manser, AR Enczmann, J Mulder, A Claas, FH Carrington, M Fischer, JC Borkhardt, A Babor, F Uhrberg, M AF Reusing, Sarah B. Manser, Angela R. Enczmann, Juergen Mulder, Arend Claas, Frans H. Carrington, Mary Fischer, Johannes C. Borkhardt, Arndt Babor, Florian Uhrberg, Markus TI Selective downregulation of HLA-C and HLA-E in childhood acute lymphoblastic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE NK cells; HLA class I; KIR; childhood leukaemia; ALL ID E SURFACE EXPRESSION; CELLS C1 [Reusing, Sarah B.; Manser, Angela R.; Enczmann, Juergen; Fischer, Johannes C.; Uhrberg, Markus] Univ Dusseldorf, Inst Transplantat Diagnost & Cell Therapeut, Dusseldorf, Germany. [Mulder, Arend; Claas, Frans H.] Leiden Univ, Dept Immunohaematol & Bloodtransfus, Med Ctr, Leiden, Netherlands. [Carrington, Mary] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Borkhardt, Arndt; Babor, Florian] Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, Ctr Child & Adolescent Hlth, Dusseldorf, Germany. RP Uhrberg, M (reprint author), Univ Dusseldorf, Inst Transplantat Diagnost & Cell Therapeut, Dusseldorf, Germany. EM markus.uhrberg@med.uni-duesseldorf.de OI Fischer, Johannes/0000-0002-2079-1845 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E] NR 9 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2016 VL 174 IS 3 BP 477 EP 480 DI 10.1111/bjh.13777 PG 4 WC Hematology SC Hematology GA DS4CO UT WOS:000380729200016 PM 26527563 ER PT J AU Gonzales, FA Taplin, SH Yu, MD Breen, N Cronin, KA AF Gonzales, Felisa A. Taplin, Stephen H. Yu, Mandi Breen, Nancy Cronin, Kathy A. TI Receipt of mammography recommendations among White and non-White women before and after the 2009 United States Preventive Services Task Force recommendation change SO CANCER CAUSES & CONTROL LA English DT Article DE Mammography; Breast cancer screening; Disparities; United States Preventive Services Task Force; Practice guidelines ID BREAST-CANCER-TREATMENT; SHARED DECISION-MAKING; OF-THE-LITERATURE; SCREENING MAMMOGRAPHY; RACIAL/ETHNIC DISPARITIES; MULTIPLE-IMPUTATION; TRENDS; IMPACT; RATES; AGE AB Receipt of a mammography recommendation from a physician is a strong predictor of obtaining a mammogram. In 2009, the United States Preventive Services Task Force (USPSTF) recommended routine biennial mammography for women aged 50-74 but not for women aged 40-49. We examined changes in reports of clinician recommendations for mammography among White and non-White women after these age-specific recommendations were issued. Data from women aged 40-49 and 50-74 were drawn from the 2008 and 2013 National Health Interview Surveys. We used linear probability models to determine whether the proportions of women reporting a mammography recommendation changed after the USPSTF recommendation was issued and whether any changes observed differed across White and non-White women. All analyses were stratified by age groups and mammography history. Among women without a recent mammogram, reported clinician recommendations did not change for White women, but they decreased by 13-percentage points (95 % CI -0.22, -0.03) among non-White women aged 40-49 (p = 0.01) and increased by 9-percentage points (95 % CI 0.01, 0.17) among non-White women aged 50-74 (p = 0.04). Among women with a mammogram in the past 2 years, reported mammography recommendation from a clinician did not change for White or non-White women. Recommendations to reduce screening may be differentially implemented across racial/ethnic groups. Changes in reports of mammography recommendation from a clinician after the USPSTF breast cancer screening recommendation change were observed only among non-White women without a recent history of mammography. It is unclear whether these differences are due to the clinician, the women, or both. C1 [Gonzales, Felisa A.] NCI, Div Canc Control & Populat Sci, BG 9609 RM 3E502 MSC 9712,9609 Med Ctr Dr, Rockville, MD 20850 USA. [Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, BG 9609 RM 3E342 MSC 9761,9609 Med Ctr Dr, Rockville, MD 20850 USA. [Yu, Mandi] NCI, Div Canc Control & Populat Sci, BG 9609 RM 4E544 MSC 9765,9609 Med Ctr Dr, Rockville, MD 20850 USA. [Breen, Nancy] NCI, Div Canc Control & Populat Sci, BG 2DEM RM 800 MSC 5465,6707 Democracy Blvd, Bethesda, MD 20892 USA. [Cronin, Kathy A.] NCI, Div Canc Control & Populat Sci, BG 9609 RM 4E454 MSC 9765,9609 Med Ctr Dr, Rockville, MD 20850 USA. RP Gonzales, FA (reprint author), NCI, Div Canc Control & Populat Sci, BG 9609 RM 3E502 MSC 9712,9609 Med Ctr Dr, Rockville, MD 20850 USA. EM Felisa.gonzales@nih.gov; taplins@mail.nih.gov; Yum3@mail.nih.gov; breenn@mail.nih.gov; cronink@mail.nih.gov NR 66 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 AUG PY 2016 VL 27 IS 8 BP 977 EP 987 DI 10.1007/s10552-016-0775-9 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DS9RK UT WOS:000381120800003 PM 27351918 ER PT J AU Falk, RT Staff, AC Bradwin, G Karumanchi, SA Troisi, R AF Falk, Roni T. Staff, Annetine Cathrine Bradwin, Gary Karumanchi, S. Ananth Troisi, Rebecca TI A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial SO CANCER CAUSES & CONTROL LA English DT Article DE Breast cancer risk; Angiogenesis; VEGF sFlt-1; PlGF ID ENDOTHELIAL GROWTH-FACTOR; CLINICAL-USEFULNESS; PROGNOSTIC VALUE; MENSTRUAL-CYCLE; PLASMA-LEVELS; VEGF LEVELS; SERUM; PREGNANCY; PREECLAMPSIA; RECEPTORS AB Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33-2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1. C1 [Falk, Roni T.] NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20852 USA. [Staff, Annetine Cathrine] Oslo Univ Hosp, Women & Childrens Div, Dept Gynecol & Obstet, N-0424 Oslo, Norway. [Bradwin, Gary] Boston Childrens Hosp, Dept Lab Med, Clin & Epidemiol Res Lab, Boston, MA USA. [Karumanchi, S. Ananth] Harvard Med Sch, Ctr Vasc Biol, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Karumanchi, S. Ananth] Harvard Med Sch, Ctr Vasc Biol, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA USA. [Karumanchi, S. Ananth] Harvard Med Sch, Ctr Vasc Biol, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA USA. [Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20852 USA. RP Falk, RT (reprint author), NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20852 USA. EM falkr@mail.nih.gov; UXNNAF@ous-hf.no; Gary.Bradwin@childrens.harvard.edu; sananth@bidmc.harvard.edu; troisir@mail.nih.gov FU National Cancer Institute, NIH, U.S. Department of Health and Human Services [HHSN261201200327P] FX This study was supported by the National Cancer Institute, NIH, U.S. Department of Health and Human Services through contract # HHSN261201200327P. NR 43 TC 0 Z9 0 U1 4 U2 4 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 AUG PY 2016 VL 27 IS 8 BP 1009 EP 1017 DI 10.1007/s10552-016-0779-5 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DS9RK UT WOS:000381120800006 PM 27357932 ER PT J AU Yang, BY Petrick, JL Chen, J Hagberg, KW Sahasrabuddhe, VV Graubard, BI Jick, S McGlynn, KA AF Yang, Baiyu Petrick, Jessica L. Chen, Jie Hagberg, Katrina Wilcox Sahasrabuddhe, Vikrant V. Graubard, Barry I. Jick, Susan McGlynn, Katherine A. TI Associations of NSAID and paracetamol use with risk of primary liver cancer in the Clinical Practice Research Datalink SO CANCER EPIDEMIOLOGY LA English DT Article DE Analgesics; Liver cancer; Case-control study; Medical records database ID PRACTICE RESEARCH DATABASE; HEPATOCELLULAR-CARCINOMA; DATA RESOURCE; CELL-GROWTH; MORTALITY; ACETAMINOPHEN; INHIBITION; INDUCTION; APOPTOSIS; DISEASE AB Liver cancer incidence has been rising rapidly in Western countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely-used analgesics that may modulate the risk of liver cancer, but population-based evidence is limited. We conducted a case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink to examine the association between the use of prescription NSAIDs and paracetamol and development of liver cancer. Multivariable-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Overall, ever-use of NSAIDs was not associated with risk of liver cancer (aOR = 1.05, 95% CI = 0.88-1.24), regardless of recency and intensity of use. Use of paracetamol was associated with a slightly increased risk of liver cancer (aOR = 1.18, 95% CI = 1.00-1.39), particularly among individuals with body mass index < 25 kg/m(2) (aOR = 1.56, 95% CI = 1.17-2.09). Our results suggest that NSAID use was not associated with liver cancer risk in this population. Ever-use of paracetamol may be associated with slightly higher liver cancer risk, but results should be interpreted cautiously due to methodological limitations. Given that paracetamol is a widely-used analgesic, further examination of its relationship with liver cancer is warranted. Published by Elsevier Ltd. C1 [Yang, Baiyu; Petrick, Jessica L.; Chen, Jie; Sahasrabuddhe, Vikrant V.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hagberg, Katrina Wilcox; Jick, Susan] Boston Collaborat Drug Surveillance Program, Lexington, MA 02421 USA. [Hagberg, Katrina Wilcox; Jick, Susan] Boston Univ, Sch Publ Hlth, Lexington, MA 02421 USA. [Sahasrabuddhe, Vikrant V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Yang, BY (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM baiyu.yang@nih.gov RI CPRD, CPRD/B-9594-2017 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The authors thank Dr. Marie Bradley for her insightful comments, and Ms. Megan Braunlin for her help with the analyses. NR 28 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 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD AUG PY 2016 VL 43 BP 105 EP 111 DI 10.1016/j.canep.2016.06.009 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DT8KS UT WOS:000381739700016 PM 27420633 ER PT J AU Mutlu, E Gao, L Collins, LB Walker, NJ Hartwell, HJ Olson, JR Sun, W Gold, A Ball, LM Swenberg, JA AF Mutlu, Esra Gao, Lina Collins, Leonard B. Walker, Nigel J. Hartwell, Hadley J. Olson, James R. Sun, Wei Gold, Avram Ball, Louise M. Swenberg, James A. TI Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HEPATIC LIPID-PEROXIDATION; OXYGEN SPECIES PRODUCTION; TOXIC EQUIVALENCY FACTORS; CEREBELLAR GRANULE CELLS; MEMBRANE-BOUND ATPASES; PROTECTIVE ROLE; IN-VIVO; CHEMICAL CARCINOGENESIS; SUBCHRONIC EXPOSURE; CYTOCHROME-P450 1A AB Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N-6-ethenodeoxyadenosine (1,N-6-epsilon dA), N-2,3-ethenoguanine (N-2,3-epsilon G), 1,N-2-ethenodeoxyguanosine (1,N-2-epsilon dG), as well as malondialdehyde (M(1)dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-nydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG. and 1,N-6-epsilon dA. concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 mu g/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 mu g/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N-6-epsilon dA, AcrdG, and M1dG. Exposure to PCB 153 (1000 mu g/kg/day) for 53 wks increased 8-oxo-dG, and 1,N-6-epsilon dA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N-6-epsilon dA., AcrdG, 1,N-2-epsilon dG, and N-2,3-epsilon G significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153; or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and carcinogenesis in female Sprague Dawley rats. C1 [Mutlu, Esra; Walker, Nigel J.] NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Gao, Lina; Collins, Leonard B.; Hartwell, Hadley J.; Gold, Avram; Ball, Louise M.; Swenberg, James A.] Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Olson, James R.] SUNY Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. [Sun, Wei] Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC 27599 USA. [Swenberg, James A.] Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Campus Box 7431, Chapel Hill, NC 27599 USA. RP Swenberg, JA (reprint author), Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.; Swenberg, JA (reprint author), Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Campus Box 7431, Chapel Hill, NC 27599 USA. EM jswenber@email.unc.edu RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS Superfund Basic Research Program [P42-ES05948]; NIEHS Center for Environmental Health and Susceptibility [P30 ES 10126] FX This work was supported by the NIEHS Superfund Basic Research Program P42-ES05948 and the NIEHS Center for Environmental Health and Susceptibility P30 ES 10126. NR 87 TC 0 Z9 0 U1 11 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 2016 VL 29 IS 8 BP 1335 EP 1344 DI 10.1021/acs.chemrestox.6b00146 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA DT6KQ UT WOS:000381593500010 PM 27436759 ER PT J AU Yao, XL Gordon, EM Barochia, AV Remaley, AT Levine, SJ AF Yao, Xianglan Gordon, Elizabeth M. Barochia, Amisha V. Remaley, Alan T. Levine, Stewart J. TI The A's Have It Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma SO CHEST LA English DT Article DE airway hyperresponsiveness; airway inflammation; asthma; lipids ID NEUTROPHILIC AIRWAY INFLAMMATION; REVERSE CHOLESTEROL TRANSPORT; CARDIOVASCULAR-DISEASE; ENDOTOXIN EXPOSURE; UNITED-STATES; HDL; ACTIVATION; CELLS; ABCA1; MICE AB New treatments are needed for patients with asthma who are refractory to standard therapies, such as individuals with a phenotype of "type 2-low" inflammation. This important clinical problem could potentially be addressed by the development of apolipoprotein A-I (apoA-I) mimetic peptides. ApoA-I interacts with its cellular receptor, the ATP-binding cassette subfamily A, member 1 (ABCA1), to facilitate cholesterol efflux out of cells to form nascent high-density lipoprotein particles. The ability of the apoA-I/ABCA1 pathway to promote cholesterol efflux from cells that mediate adaptive immunity, such as antigen-presenting cells, can attenuate their function. Data from experimental murine models have shown that the apoA-I/ABCA1 pathway can reduce neutrophilic airway inflammation, primarily by suppressing the production of granulocyte-colony stimulating factor. Furthermore, administration of apoA-I mimetic peptides to experimental murine models of allergic asthma has decreased both neutrophilic and eosinophilic airway inflammation, as well as airway hyperresponsiveness and mucous cell metaplasia. Higher serum levels of apoA-I have also been associated with less severe airflow obstruction in patients with asthma. Collectively, these results suggest that the apoA-I/ABCA1 pathway may have a protective effect in asthma, and support the concept of advancing inhaled apoA-I mimetic peptides to clinical trials that can assess their safety and effectiveness. Thus, we propose that the development of inhaled apoA-I mimetic peptides as a new treatment could represent a clinical advance for patients with severe asthma who are unresponsive to other therapies. C1 [Yao, Xianglan; Gordon, Elizabeth M.; Barochia, Amisha V.; Levine, Stewart J.] NHLBI, Lab Asthma & Lung Inflammat, Cardiovasc & Pulm Branch, Div Intramural Res,NIH, Bldg 10, Bethesda, MD 20892 USA. [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc & Pulm Branch, Div Intramural Res,NIH, Bldg 10, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health [1ZIAHL006054-06] FX This work was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (project number 1ZIAHL006054-06). NR 49 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2016 VL 150 IS 2 BP 283 EP 288 DI 10.1016/j.chest.2016.05.035 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DS7AG UT WOS:000380934100016 PM 27327118 ER PT J AU Harari, S Elia, D Torre, O Bulgheroni, E Provasi, E Moss, J AF Harari, Sergio Elia, Davide Torre, Olga Bulgheroni, Elisabetta Provasi, Elena Moss, Joel TI Sirolimus Therapy for Patients With Lymphangioleiomyomatosis Leads to Loss of Chylous Ascites and Circulating LAM Cells SO CHEST LA English DT Editorial Material ID TUBEROUS SCLEROSIS COMPLEX; EFFICACY; TSC2 AB A young woman received a diagnosis of abdominal, sporadic lymphangioleiomyomatosis (LAM) and multiple abdominal lymphangioleiomyomas and was referred for recurrent chylous ascites responding only to a fat-free diet. On admission, pulmonary function test (PFT) results showed a moderate reduction in the transfer factor for carbon monoxide with normal exercise performance. The serum vascular endothelial growth factor D (VEGF-D) level was 2,209 pg/mL. DNA sequences, amplified at loci kg8, D16S3395, D16S3024, D16S521, and D16S291 on chromosome 16p13.3, showed a loss of heterozygosity (LOH) only for kg8. Fat-free total parenteral nutrition in association with sirolimus (2 mg po daily) was initiated. Serum sirolimus levels were maintained at concentrations between 5 and 15 ng/mL. After 1 month, reintroduction of a low-fat oral feeding was achieved without recurrence of ascites. PFT results were stable. Interestingly, clinical improvement was associated with a reduction in the VEGF-D serum level (1,558 pg/mL). LOH at the kg8 biomarker in blood LAM cells was no longer detected. C1 [Harari, Sergio; Elia, Davide; Torre, Olga] Osped San Giuseppe, MultiMed, Serv Fisiopatol Resp & Emoodinam Polmonare, Unita Pneumol & Terapia Semiintens Resp,IRCCS, Via S Vittore 12, I-20142 Milan, Italy. [Bulgheroni, Elisabetta; Provasi, Elena] Ist Nazl Genet Mol Romeo & Enrica Invernizzi, Milan, Italy. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Elia, D (reprint author), Osped San Giuseppe, MultiMed, Serv Fisiopatol Resp & Emoodinam Polmonare, Unita Pneumol & Terapia Semiintens Resp,IRCCS, Via S Vittore 12, I-20142 Milan, Italy. EM davide.elia@multimedica.it OI Harari, Sergio/0000-0001-8629-7391 FU Intramural Research Program, NIH, NHLBI FX The authors have reported to CHEST the following: J. M. was supported by the Intramural Research Program, NIH, NHLBI. None declared (S. H., D. E., O. T., E. B., E. P.). NR 11 TC 0 Z9 0 U1 2 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2016 VL 150 IS 2 BP E29 EP E32 DI 10.1016/j.chest.2016.02.654 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DS7AG UT WOS:000380934100001 PM 27502989 ER PT J AU Izzi, JM Beck, SE Adams, RJ Pate, KAM Hutchinson, EK AF Izzi, Jessica M. Beck, Sarah E. Adams, Robert J. Pate, Kelly A. Metcalf Hutchinson, Eric K. TI Serum Cobalamin (Vitamin B-12) Concentrations in Rhesus Macaques (Macaca mulatta) and Pigtailed Macaques (Macaca nemestrina) with Chronic Idiopathic Diarrhea SO COMPARATIVE MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; BABOON PAPIO-CYNOCEPHALUS; GASTROINTESTINAL-DISEASE; RISK-FACTORS; THERAPEUTIC IMPLICATIONS; ACID-CONCENTRATIONS; METHYLMALONIC ACID; DEFICIENCY STATES; CROHNS-DISEASE; CATS AB Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B-12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques. Here we measured serum cobalamin concentrations in both rhesus and pigtailed macaques with CID and compared them with those of healthy controls. Serum cobalamin levels were 2.5-fold lower in pigtailed macaques with CID than control animals but did not differ between rhesus macaques with CID and their controls. This finding supports the use of serum cobalamin concentration as an adjunct diagnostic tool in pigtailed macaques that present with clinical symptoms of chronic gastrointestinal disease. This use of serum vitamin B-12 levels has implications for the future use of parenteral cobalamin supplementation to improve clinical outcomes in this species. C1 [Izzi, Jessica M.; Beck, Sarah E.; Adams, Robert J.; Pate, Kelly A. Metcalf] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21218 USA. [Izzi, Jessica M.; Hutchinson, Eric K.] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. RP Izzi, JM (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21218 USA.; Izzi, JM (reprint author), NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. EM jizzi13@gmail.com FU NIH ORIP grants [R25 OD10913, P40 OD013117, K01 OD018244] FX We thank our fellow laboratory animal medicine trainees, especially Cassandra Moats, Anna Goodroe, Peter Otovic, Theresa Meade, and Meghan Vermillion, and the veterinary technical staff at the Johns Hopkins University Research Farm for their aid in sample collection throughout the study. This study was funded in part by NIH ORIP grants R25 OD10913, P40 OD013117, and K01 OD018244. NR 55 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2016 VL 66 IS 4 BP 324 EP 332 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA DT1KV UT WOS:000381242500007 PM 27538863 ER PT J AU Connolly, MA Trentalange, M Zeiss, CJ AF Connolly, Meghan A. Trentalange, Mark Zeiss, Caroline J. TI Long-Term Clinical Outcomes in Diabetic Rhesus Macaques (Macaca mulatta) Treated with Medroxyprogesterone Acetate for Endometriosis SO COMPARATIVE MEDICINE LA English DT Article ID CONDITION SCORING SYSTEM; ORAL-CONTRACEPTIVES; WEIGHT-GAIN; MELLITUS; METABOLISM; GLUCOSE; WOMEN; MODEL; USERS; RISK AB Depot medroxyprogesterone acetate (DMPA) is a common medical treatment for endometriosis in NHP. Because DMPA reportedly impairs glucoregulatory function in humans and rhesus macaques, as well as predisposes humans to diabetes mellitus (DM), we performed a retrospective study to further investigate its potential long-term clinical effects in animals with and without DM. Using a cohort of 29 rhesus macaques, we explored the hypotheses that DMPA treatment accelerates the onset of DM and that its use in rhesus macaques with endometriosis worsens clinical outcome measures (lifespan, body weight and body condition score). For both body weight and body condition score, a declining and statistically significant trend in mean values was evident as macaques developed either DM, or endometriosis or both. The addition of DMPA did not significantly alter this pattern. The presence of DM, endometriosis, or DMPA treatment statistically but not clinically significantly increased risk of death. Similarly, the presence of the 2 highly correlated variables endometriosis and DMPA treatment statistically but not clinically significantly increased the risk of incident DM. These results indicate that DMPA treatment was associated with worsening trends in lifespan and incident DM, however these trends did not achieve clinical significance in this cohort. C1 [Connolly, Meghan A.] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. [Trentalange, Mark] Yale Univ, Yale Program Aging, Biostat Core, New Haven, CT USA. [Zeiss, Caroline J.] Yale Univ, Comparat Med Sect, New Haven, CT USA. RP Connolly, MA (reprint author), NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. EM meghan.connolly@nih.gov NR 44 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2016 VL 66 IS 4 BP 343 EP 348 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA DT1KV UT WOS:000381242500009 PM 27538865 ER PT J AU MacAllister, RP McCully, CML Bacher, J Thomas, ML Cruz, R Wangari, S Warren, KE AF MacAllister, Rhonda Pung McCully, Cynthia M. Lester Bacher, John Thomas, Marvin L., III Cruz, Rafael Wangari, Solomon Warren, Katherine E. TI Minimally Invasive Lumbar Port System for the Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta) SO COMPARATIVE MEDICINE LA English DT Article ID MONKEYS; DRUGS; MODEL AB Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter reservoir for CSF collection is an intensive model to create and maintain and thus may not be feasible or practical for short-term studies. Furthermore, previous NHP lumbar port models require laminectomy for catheter placement. The new model uses a minimally invasive technique for percutaneous placement of a lumbar catheter to create a closed, subcutaneous system for effective, repeated CSF sample collection. None of the rhesus macaques (Macaca mulatta; n = 10) implanted with our minimally invasive lumbar port (MILP) system experienced neurologic deficits, postoperative infection of the surgical site, or skin erosion around the port throughout the 21.7-mo study. Functional MILP systems were maintained in 70% of the macaques, with multiple, high-quality, 0.5- to 1.0-mL samples of CSF collected for an average of 3 mo by using aspiration or gravitational flow. Among these macaques, 57% had continuous functionality for a mean of 19.2 mo; 50% of the cohort required surgical repair for port repositioning and replacement during the study. The MILP was unsuccessful in 2 macaques, at an average of 9.5 d after surgery. Nonpatency in these animals was attributed to the position of the lumbar catheter. The MILP system is an appropriate replacement for temporary catheterization and previous models requiring laminectomy and is a short-term alternative for ventricular CSF collection systems in NHP. C1 [MacAllister, Rhonda Pung; McCully, Cynthia M. Lester; Cruz, Rafael; Wangari, Solomon; Warren, Katherine E.] NCI, Bethesda, MD 20892 USA. [MacAllister, Rhonda Pung] Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. [Bacher, John; Thomas, Marvin L., III] NIH, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA. RP MacAllister, RP (reprint author), NCI, Bethesda, MD 20892 USA.; MacAllister, RP (reprint author), Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. EM macallis@ohsu.edu FU Nonhuman Primate Division (Laboratory Animal Science Program, National Cancer Institute) FX We thank the Nonhuman Primate Division (Laboratory Animal Science Program, National Cancer Institute) for their support and excellence in animal care. NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2016 VL 66 IS 4 BP 349 EP 352 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA DT1KV UT WOS:000381242500010 PM 27538866 ER PT J AU Chackerian, B Remaley, A AF Chackerian, Bryce Remaley, Alan TI Vaccine strategies for lowering LDL by immunization against proprotein convertase subtilisin/kexin type 9 SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE atherosclerosis; cholesterol; proprotein convertase subtilisin; kexin type 9; vaccine ID DENSITY-LIPOPROTEIN-RECEPTOR; VIRUS-LIKE PARTICLES; HIGH-RISK PATIENTS; STATIN THERAPY; CARDIOVASCULAR EVENTS; CHRONIC DISEASES; REDUCING LIPIDS; PCSK9; CHOLESTEROL; EFFICACY AB Purpose of reviewmAbs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have the potential to become groundbreaking therapies for the treatment of hypercholesterolemia. However, one major drawback of mAb-based therapy for a chronic condition like dyslipidemia is its relatively high cost. This review summarizes two recent studies describing novel vaccine approaches for lowering LDL-cholesterol by active immunization against PCSK9.Recent findingsPCSK9 is a plasma protein secreted by the liver that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the LDL receptor. Two PCSK9 inhibitory mAbs (evolocumab and alirocumab) have recently been approved by the Food and Drug Administration and a third mAb (bococizumab) is in late stage clinical trials. Treatment with PCSK9 mAbs, in combination with statins, reduces LDL-cholesterol levels by as much as 40-60%. As an alternative to mAbs, there have been two recent studies describing the development of vaccines that target PCSK9. These studies have shown that PCSK9 vaccines can effectively induce high-titer antibody responses that reduce proatherogenic lipoproteins in animal models.SummaryA PCSK9 vaccine-based approach could serve as a more widely applicable and a more cost-effective approach than mAb therapy for controlling hypercholesteremia and associated cardiovascular disease. C1 [Chackerian, Bryce] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Remaley, Alan] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Chackerian, B (reprint author), Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. EM BChackerian@salud.unm.edu FU National Heart, Lung and Blood Institute; NIH [R01 AI083305]; Intramural Research Program of NHLBI FX This work was supported in part by intramural research funds from the National Heart, Lung and Blood Institute. Research was also funded by NIH grant R01 AI083305 (to BC) and by the Intramural Research Program of NHLBI. NR 35 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 0957-9672 EI 1473-6535 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD AUG PY 2016 VL 27 IS 4 BP 345 EP 350 DI 10.1097/MOL.0000000000000312 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA DS8NQ UT WOS:000381040500004 PM 27389630 ER PT J AU Goodman, MF McDonald, JP Jaszczur, MM Woodgate, R AF Goodman, Myron F. McDonald, John P. Jaszczur, Malgorzata M. Woodgate, Roger TI Insights into the complex levels of regulation imposed on Escherichia coli DNA polymerase V SO DNA REPAIR LA English DT Review DE Translesion DNA synthesis; Posttranslational regulation; Proteolysis; Y-family DNA polymerase ID UMUD MUTAGENESIS PROTEIN; SOS MUTAGENESIS; RECA PROTEIN; UV MUTAGENESIS; ERROR-PRONE; EVOLUTIONARY FITNESS; ULTRAVIOLET-LIGHT; CLPXP PROTEASE; BINDING-SITES; IN-VITRO AB It is now close to 40 years since the isolation of non-mutable umu/uvm strains of Escherichia coli and the realization that damage induced mutagenesis in E.coli is not a passive process. Early models of mutagenesis envisioned the Umu proteins as accessory factors to the cell's replicase that not only reduced its normally high fidelity, but also allowed the enzyme to traverse otherwise replication-blocking lesions in the genome. However, these models underwent a radical revision approximately 15 years ago, with the discovery that the Umu proteins actually encode for a DNA polymerase, E.coli pol V. The polymerase lacks 3' -> 5' exonucleolytic proofreading activity and is inherently error-prone when replicating both undamaged and damage DNA. So as to limit any "gratuitous" mutagenesis, the activity of pol V is strictly regulated in the cell at multiple levels. This review will summarize our current understanding of the myriad levels of regulation imposed on pol V including transcriptional control, posttranslational modification, targeted proteolysis, activation of the catalytic activity of pol V through protein-protein interactions and the very recently described intracellular spatial regulation of pol V. Remarkably, despite the multiple levels at which pol V is regulated, the enzyme is nevertheless able to contribute to the genetic diversity and evolutionary fitness of E.coli. Published by Elsevier B.V. C1 [Goodman, Myron F.] Univ Southern Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA. [Goodman, Myron F.] Univ Southern Calif, Dept Chem, Univ Pk, Los Angeles, CA 90089 USA. [McDonald, John P.; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Jaszczur, Malgorzata M.] Univ Southern Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA. RP Goodman, MF (reprint author), Univ Southern Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA.; Goodman, MF (reprint author), Univ Southern Calif, Dept Chem, Univ Pk, Los Angeles, CA 90089 USA.; Woodgate, R (reprint author), 9800 Med Ctr Dr,Bldg C,Rm 320, Bethesda, MD 20892 USA. EM mgoodman@usc.edu; woodgate@mail.nih.gov FU NIH/NICHD Intramural Research Program [ES012259, GM21422] FX This study was made possible by funding from the NIH/NICHD Intramural Research Program to R.W. and ES012259, GM21422 to M.F.G. We thank Alexandra Vaisman for generating the figures shown in this review article. NR 73 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD AUG PY 2016 VL 44 BP 42 EP 50 DI 10.1016/j.dnarep.2016.05.005 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA DT0KA UT WOS:000381171200006 PM 27236212 ER PT J AU Mattingly, CJ Boyles, R Lawler, CP Haugen, AC Dearry, A Haendel, M AF Mattingly, Carolyn J. Boyles, Rebecca Lawler, Cindy P. Haugen, Astrid C. Dearry, Allen Haendel, Melissa TI Laying a Community-Based Foundation for Data-Driven Semantic Standards in Environmental Health Sciences SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID ANTIBIOTIC-RESISTANCE; ONTOLOGY; BIOLOGY; UNIFICATION; KNOWLEDGE; PROJECT; DISEASE AB BACKGROUND: Despite increasing availability of environmental health science (EHS) data, development, and implementation of relevant semantic standards, such as ontologies or hierarchical vocabularies, has lagged. Consequently, integration and analysis of information needed to better model environmental influences on human health remains a significant challenge. OBJECTIVES: We aimed to identify a committed community and mechanisms needed to develop EHS semantic standards that will advance understanding about the impacts of environmental exposures on human disease. METHODS: The National Institute of Environmental Health Sciences sponsored the "Workshop for the Development of a Framework for Environmental Health Science Language" hosted at North Carolina State University on 15-16 September 2014. Through the assembly of data generators, users, publishers, and funders, we aimed to develop a foundation for enabling the development of community-based and data-driven standards that will ultimately improve standardization, sharing, and interoperability of EHS information. DISCUSSION: Creating and maintaining an EHS common language is a continuous and iterative process, requiring community building around research interests and needs, enabling integration and reuse of existing data, and providing a low barrier of access for researchers needing to use or extend such a resource. CONCLUSIONS: Recommendations included developing a community-supported web-based toolkit that would enable a) collaborative development of EHS research questions and use cases, b) construction of user-friendly tools for searching and extending existing semantic resources, c) education and guidance about standards and their implementation, and d) creation of a plan for governance and sustainability. C1 [Mattingly, Carolyn J.] North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA. [Mattingly, Carolyn J.] North Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC USA. [Boyles, Rebecca; Lawler, Cindy P.; Haugen, Astrid C.; Dearry, Allen] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. [Haendel, Melissa] Oregon Hlth & Sci Univ, Lib, Portland, OR 97201 USA. [Haendel, Melissa] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Mattingly, CJ (reprint author), North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA. EM cjmattin@ncsu.edu OI Boyles, Rebecca/0000-0003-0073-6854 FU National Institutes of Health, NIEHS; Office of the Associate Director for Data Science FX This work was supported by the National Institutes of Health, the NIEHS, and the Office of the Associate Director for Data Science. NR 29 TC 1 Z9 1 U1 4 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 AUG PY 2016 VL 124 IS 8 BP 1136 EP 1140 DI 10.1289/ehp.1510438 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900011 PM 26871594 ER PT J AU Auerbach, S Filer, D Reif, D Walker, V Holloway, AC Schlezinger, J Srinivasan, S Svoboda, D Judson, R Bucher, JR Thayer, KA AF Auerbach, Scott Filer, Dayne Reif, David Walker, Vickie Holloway, Alison C. Schlezinger, Jennifer Srinivasan, Supriya Svoboda, Daniel Judson, Richard Bucher, John R. Thayer, Kristina A. TI Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast (TM) High-Throughput Data SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID PANCREATIC BETA-CELLS; INSULIN-SECRETION; RODENTICIDE VACOR; MATERNAL SMOKING; WEIGHT-GAIN; C-ELEGANS; FORMAMIDINE PESTICIDE; TRIPHENYLTIN IMPAIRS; OBESOGEN TRIBUTYLTIN; GLUCOSE-INTOLERANCE AB BACKGROUND: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast (TM) high-throughput screening (HTS) program. OBJECTIVES: Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes-or obesity-related outcomes using high-throughput screening data. METHODS: We identified ToxCast (TM) assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. DISCUSSION: The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast (TM) data will also help assess the predictive utility of this HTS platform. CONCLUSIONS: More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. C1 [Auerbach, Scott; Walker, Vickie; Bucher, John R.; Thayer, Kristina A.] NIEHS, Div Natl Toxicol Program, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. [Filer, Dayne; Judson, Richard] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Reif, David] North Carolina State Univ, Bioinformat Res Ctr, Dept Biol Sci, Raleigh, NC USA. [Holloway, Alison C.] McMaster Univ, Dept Obstet & Gynecol, Hamilton, ON, Canada. [Schlezinger, Jennifer] Boston Univ, Sch Med, Dept Environm Hlth, Boston, MA 02118 USA. [Srinivasan, Supriya] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Svoboda, Daniel] SciOme LLC, Res Triangle Pk, NC USA. RP Thayer, KA (reprint author), NIEHS, NTP Off Hlth Assessment & Translat OHAT, NTP, 530 Davis Dr,Room 2150 Mail Drop K2-04, Morrisville, NC 27560 USA. EM thayer@niehs.nih.gov FU National Institute of Environmental Health Sciences/National Institutes of Health; U.S. Environmental Protection Agency (EPA) FX This research was supported by the National Institute of Environmental Health Sciences/National Institutes of Health and the U.S. Environmental Protection Agency (EPA). NR 96 TC 2 Z9 2 U1 6 U2 10 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 AUG PY 2016 VL 124 IS 8 BP 1141 EP 1154 DI 10.1289/ehp.1510456 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900012 PM 26978842 ER PT J AU Aaron, CP Chervona, Y Kawut, SM Roux, AVD Shen, MW Bluemke, DA Van Hee, VC Kaufman, JD Barr, RG AF Aaron, Carrie P. Chervona, Yana Kawut, Steven M. Roux, Ana V. Diez Shen, Mingwu Bluemke, David A. Van Hee, Victor C. Kaufman, Joel D. Barr, R. Graham TI Particulate Matter Exposure and Cardiopulmonary Differences in the Multi-Ethnic Study of Atherosclerosis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID LEFT-VENTRICULAR MASS; POLLUTION MESA AIR; OBSTRUCTIVE-PULMONARY-DISEASE; SUBCLINICAL ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; PERCENT EMPHYSEMA; FLOW OBSTRUCTION; TERM EXPOSURE; PRESSURE; LUNG AB BACKGROUND: Particulate matter (PM) exposure may directly affect the pulmonary vasculature. Although the pulmonary vasculature is not easily measurable, differential associations for right ventricular (RV) and left ventricular (LV) mass may provide an indirect assessment of pulmonary vascular damage. OBJECTIVES: We tested whether long-term exposure to PM < 2.5 mu m (PM2.5) is associated with greater RV mass and RV mass/end-diastolic volume ratio relative to the LV. METHODS: The Multi-Ethnic Study of Atherosclerosis performed cardiac magnetic resonance (CMR) imaging among participants 45-84 years old without clinical cardiovascular disease in 2000-2002 in six U.S. cities. A fine-scale spatiotemporal model estimated ambient PM2.5 exposure in the year before CMR; individually weighted estimates accounted for indoor exposure to ambient PM2.5. Linear regression models were adjusted for demographics, anthropometrics, smoking status, cardiac risk factors, and LV parameters, with additional adjustment for city. RESULTS: The 4,041 included participants had a mean age of 61.5 years, and 47% were never smokers. The mean ambient PM2.5 was 16.4 mu g/m(3) and individually weighted PM2.5 was 11.0 mu g/m(3). PM2.5 exposure was associated with greater RV mass [ambient: 0.11 g per 5 mu g/m(3) (95% CI: -0.05, 0.27); individually weighted: 0.20 g per 5 mu g/m(3) (95% CI: 0.04, 0.36)] and a greater RV mass/end-diastolic volume ratio conditional on LV parameters. City-adjusted results for RV mass were of greater magnitude and were statistically significant for both measures of PM2.5, whereas those for RV mass/end-diastolic volume ratio were attenuated. CONCLUSIONS: Long-term PM2.5 exposures were associated with greater RV mass and RV mass/end-diastolic volume ratio conditional on the LV; however, additional adjustment for city attenuated the RV mass/end-diastolic volume findings. These findings suggest that PM2.5 exposure may be associated with subclinical cardiopulmonary differences in this general population sample. C1 [Aaron, Carrie P.; Chervona, Yana; Barr, R. Graham] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA. [Chervona, Yana] NYU, Dept Environm Med, 550 1St Ave, New York, NY 10016 USA. [Kawut, Steven M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Roux, Ana V. Diez; Shen, Mingwu] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. [Van Hee, Victor C.; Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Van Hee, Victor C.; Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA USA. [Van Hee, Victor C.; Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Barr, R. Graham] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Aaron, CP (reprint author), Columbia Univ, Coll Phys & Surg, PH 9 East Room 105,630 West 168th St, New York, NY 10032 USA. EM cp2346@columbia.edu RI Kaufman, Joel/B-5761-2008; OI Kaufman, Joel/0000-0003-4174-9037; Bluemke, David/0000-0002-8323-8086 FU National Heart, Blood, and Lung Institute, National Institutes of Health (NHBLI/NIH) [N01-HC-95159, N01-HC-95169, R01-HL077612, RC1-HL100543, R01-HL086719]; U.S. Environmental Protection Agency (EPA) [R830543, R831697, K24-HL103844]; MESA Investigators; U.S. EPA; Actelion Pharmaceuticals US, Inc; United Therapeutics Corporation; Gilead Sciences, Inc.; Lung Biotechnology PBC; Pfizer Inc.; Ikaria, Inc.; Pulmonary Hypertension Association; Merck Co., Inc.; GeNO LLC; Bayer AG; European Respiratory Journal and Insmed Incorporated; Alpha1 Foundation FX The MESA study is conducted and supported by the National Heart, Blood, and Lung Institute, National Institutes of Health (NHBLI/NIH) (N01-HC-95159 through N01-HC-95165 and N01-HC-95169, R01-HL077612, RC1-HL100543, and R01-HL086719) and by the U.S. Environmental Protection Agency (EPA) (R830543, R831697, and K24-HL103844) and MESA Investigators. This publication was also developed under a STAR research assistance agreement, No. RD831697 (MESA Air), awarded by the U.S. EPA.; Y.C. reports employment by SafeBridge Consultants, Inc. since September 2013. S.M.K. reports grant support from Actelion Pharmaceuticals US, Inc; United Therapeutics Corporation; Gilead Sciences, Inc.; Lung Biotechnology PBC; Pfizer Inc.; Ikaria, Inc.; the Pulmonary Hypertension Association; Merck & Co., Inc.; GeNO LLC; and Bayer AG; travel reimbursement from the American College of Chest Physicians and the American Thoracic Society; and personal fees from the European Respiratory Journal and Insmed Incorporated. R.G.B. reports grant funding from the Alpha1 Foundation, travel reimbursement from the COPD Foundation and royalties from UpToDate, Inc. These funding sources did not influence the design, collection, analysis, interpretation of the data, or decision to publish this work. The other authors declare they have no actual or potential competing financial interests. NR 50 TC 1 Z9 1 U1 6 U2 8 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 AUG PY 2016 VL 124 IS 8 BP 1166 EP 1173 DI 10.1289/ehp.1409451 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900014 PM 26859533 ER PT J AU Gassman, NR Coskun, E Jaruga, P Dizdaroglu, M Wilson, SH AF Gassman, Natalie R. Coskun, Erdem Jaruga, Pawel Dizdaroglu, Miral Wilson, Samuel H. TI Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BASE EXCISION-REPAIR; OXIDATIVE DNA-DAMAGE; ENDOCRINE DISRUPTORS; ESTROGEN RESPONSE; NA+/H+ EXCHANGER; INTRACELLULAR PH; LIVING CELLS; CANCER CELLS; MALE RATS; STRESS AB BACKGROUND: Exposure to bisphenol A (BPA) has been reported to alter global gene expression, induce epigenetic modifications, and interfere with complex regulatory networks of cells. In addition to these reprogramming events, we have demonstrated that BPA exposure generates reactive oxygen species and promotes cellular survival when co-exposed with the oxidizing agent potassium bromate (KBrO3). OBJECTIVES: We determined the cellular microenvironment changes induced by co-exposure of BPA and KBrO3 versus either agent alone. Methods: Ku70-deficient cells were exposed to 150 mu M BPA, 20 mM KBrO3, or co-exposed to both agents. Four and 24 hr post-damage initiation by KBrO3, with BPA-only samples timed to coincide with these designated time points, we performed whole-genome microarray analysis and evaluated chromatin structure, DNA lesion load, glutathione content, and intracellular pH. RESULTS: We found that 4 hr post-damage initiation, BPA exposure and co-exposure transiently condensed chromatin compared with untreated and KBrO3-only treated cells; the transcription of DNA repair proteins was also reduced. At this time point, BPA exposure and co-exposure also reduced the change in intracellular pH observed after treatment with KBrO3 alone. Twenty-four hours post-damage initiation, BPA-exposed cells showed less condensed chromatin than cells treated with KBrO3 alone; the intracellular pH of the co-exposed cells was significantly reduced compared with untreated and KBrO3-treated cells; and significant up-regulation of DNA repair proteins was observed after co-exposure. CONCLUSION: These results support the induction of an adaptive response by BPA co-exposure that alters the microcellular environment and modulates DNA repair. Further work is required to determine whether BPA induces similar DNA lesions in vivo at environmentally relevant doses; however, in the Ku70-deficient mouse embryonic fibroblasts, exposure to a high dose of BPA was associated with changes in the cellular microenvironment that may promote survival. C1 [Gassman, Natalie R.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. [Coskun, Erdem; Jaruga, Pawel; Dizdaroglu, Miral] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA. [Coskun, Erdem] Gazi Univ, Fac Pharm, Ankara, Turkey. [Gassman, Natalie R.] Univ S Alabama, Dept Oncol Sci, Mitchell Canc Inst, Mobile, AL 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 National Institutes of Health, NIEHS [Z01-ES050158, Z01-ES050159]; NIEHS [1K99ES023813-01] FX This research was supported by research project numbers Z01-ES050158 and Z01-ES050159 (S.H.W.) in the intramural research program of the National Institutes of Health, NIEHS. N.R.G. is funded by NIEHS grant 1K99ES023813-01. NR 56 TC 2 Z9 2 U1 3 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 AUG PY 2016 VL 124 IS 8 BP 1241 EP 1252 DI 10.1289/EHP237 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900023 PM 27082013 ER PT J AU Cui, YX Balshaw, DM Kwok, RK Thompson, CL Collman, GW Birnbaum, LS AF Cui, Yuxia Balshaw, David M. Kwok, Richard K. Thompson, Claudia L. Collman, Gwen W. Birnbaum, Linda S. TI The Exposome: Embracing the Complexity for Discovery in Environmental Health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID DISEASE; LIFE; EPIDEMIOLOGY; POLLUTANTS; CHALLENGE; RISK AB Environmental exposures are ubiquitous and play a fundamental role in the development of complex human diseases. The exposome, which is defined as the totality of environmental exposures over the life course, allows for systematic evaluation of the relationship between exposures and associated biological consequences, and represents a powerful approach for discovery in environmental health research. However, implementing the exposome concept is challenged by the ability to accurately assess multiple exposures and the ability to integrate information across the exposure-disease continuum. On 14-15 January 2015, the National Institute of Environmental Health Sciences (NIEHS) held the Exposome Workshop where a group of international and U.S. scientists from different disciplines gathered to review the state of the science in research areas related to the exposome and to provide recommendations for incorporating the exposome concept into each research area. To move the field forward, the NIEHS is establishing a Children's Health Exposure Analysis Resource (CHEAR) to provide infrastructure support for access to laboratory and statistical analyses to children's health studies. It is recognized that incorporating the exposome concept into exposure and environmental health research will be a long journey and will require significant collaborative efforts from different scientific disciplines, nations, and stakeholders. C1 [Cui, Yuxia; Balshaw, David M.] NIEHS, Exposure Response & Technol Branch, Div Extramural Res & Training, NIH,US DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Kwok, Richard K.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Thompson, Claudia L.] NIEHS, Populat Hlth Branch, Div Extramural Res & Training, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Collman, Gwen W.] NIEHS, Div Extramural Res & Training, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIEHS, Off Director, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. RP Balshaw, DM (reprint author), NIEHS, NIH, US Dept HHS, POB 12233,Mail Drop K3-04, Res Triangle Pk, NC 27709 USA. EM balshaw@niehs.nih.gov RI Kwok, Richard/B-6907-2017 OI Kwok, Richard/0000-0002-6794-8360 FU NIEHS, NIH FX The NIEHS Exposome Workshop was supported by the NIEHS, NIH. NR 25 TC 2 Z9 2 U1 6 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 AUG PY 2016 VL 124 IS 8 BP A137 EP A140 DI 10.1289/EHP412 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900003 PM 27479988 ER PT J AU Darney, SP AF Darney, Sally Perreault TI EHP Highlights of the Past Year SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Darney, Sally Perreault] NIEHS, Environm Hlth Perspect, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. RP Darney, SP (reprint author), NIEHS, Environm Hlth Perspect, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM sally.darney@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 124 IS 8 BP A132 EP A132 DI 10.1289/EHP777 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DS4KL UT WOS:000380749900001 PM 27479990 ER PT J AU Mason, JL Johnston, E Berndt, S Segal, K Lei, M Wiest, JS AF Mason, Julie L. Johnston, Elizabeth Berndt, Sam Segal, Katie Lei, Ming Wiest, Jonathan S. TI Labor and skills gap analysis of the biomedical research workforce SO FASEB JOURNAL LA English DT Article DE training; education; occupation; graduate students; postdoctoral fellows AB The United States has experienced an unsustainable increase of the biomedical research workforce over the past 3 decades. This expansion has led to a myriad of consequences, including an imbalance in the number of researchers and available tenure-track faculty positions, extended postdoctoral training periods, increasing age of investigators at first U.S. National Institutes of Health R01 grant, and exodus of talented individuals seeking careers beyond traditional academe. Without accurate data on the biomedical research labor market, challenges will remain in resolving these problems and in advising trainees of viable career options and the skills necessary to be productive in their careers. We analyzed workforce trends, integrating both traditional labor market information and real-time job data. We generated a profile of the current biomedical research workforce, performed labor gap analyses of occupations in the workforce at regional and national levels, and assessed skill transferability between core and complementary occupations. We conclude that although supply into the workforce and the number of job postings for occupations within that workforce have grown over the past decade, supply continues to outstrip demand. Moreover, we identify practical skill sets from real-time job postings to optimally equip trainees for an array of careers to effectively meet future workforce demand. C1 [Mason, Julie L.; Lei, Ming; Wiest, Jonathan S.] NCI, Ctr Canc Training, NIH, Bethesda, MD 20892 USA. [Johnston, Elizabeth; Segal, Katie] ICF Int, Cambridge, MA USA. [Berndt, Sam] ICF Int, Fairfax, VA USA. RP Mason, JL (reprint author), NCI, Ctr Canc Training, 9609 Med Ctr Dr,2W-120, Bethesda, MD 20892 USA. EM masonjl@mail.nih.gov FU NCI/NIH; NIH [HHSN261201200010I, HHSN261201500149P] FX The authors thank Misty Heggeness [U.S. National Institutes of Health (NIH) Office of the Director, Division of Biomedical Research Workforce), Patricia Labosky (NIH Office of the Director, Office of Strategic Coordination), and Randall Ribaudo (Human Workflows, LLC) for guidance and suggestions on this analysis, and Erika Ginsburg [NIH National Cancer Institute (NCI) Center for Cancer Training] for critically reviewing the manuscript. This research was supported by the Office of the Director, NCI/NIH. All authors are employees or contractors of NIH. ICF International acknowledges support from NIH Contract HHSN261201200010I. Access to Labor Insight, Burning Glass Technologies, was available through NIH Contract HHSN261201500149P. Any views expressed are those of the authors and not necessarily those of the NIH. The authors declare no conflicts of interest. NR 32 TC 1 Z9 1 U1 1 U2 1 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 AUG PY 2016 VL 30 IS 8 BP 2673 EP 2683 DI 10.1096/fj.201500067R PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DS7WP UT WOS:000380994000005 PM 27075242 ER PT J AU Almuzzaini, B Sarshad, AA Rahmanto, AS Hansson, ML Von Euler, A Sangfelt, O Visa, N Farrants, AKO Percipalle, P AF Almuzzaini, Bader Sarshad, Aishe A. Rahmanto, Aldwin S. Hansson, Magnus L. Von Euler, Anne Sangfelt, Olle Visa, Neus Farrants, Ann-Kristin Ostlund Percipalle, Piergiorgio TI In beta-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects SO FASEB JOURNAL LA English DT Article DE genome-wide analysis; NM1; nuclear actin; rRNA synthesis ID POLYMERASE-I TRANSCRIPTION; RIBOSOMAL-RNA GENES; NUCLEOLAR TRANSCRIPTION; NUCLEAR ACTIN; CELL-GROWTH; FACTOR UBF; FACTOR SL1; MYOSIN-I; PROMOTER; COMPLEX AB Actin and nuclear myosin 1 (NM1) are regulators of transcription and chromatin organization. Using a genome-wide approach, we report here that beta-actin binds intergenic and genic regions across the mammalian genome, associated with both protein-coding and rRNA genes. Within the rDNA, the distribution of beta-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In beta-actin(-/-) mouse embryonic fibroblasts (MEFs), we found that rRNA synthesis levels decreased concomitantly with drops in RNA polymerase I (Pol I) and NM1 occupancies across the rRNA gene. Reintroduction of wild-type beta-actin, in contrast to mutated forms with polymerization defects, efficiently rescued rRNA synthesis underscoring the direct role for a polymerization-competent form of beta-actin in Pol I transcription. The rRNA synthesis defects in the beta-actin(-/-) MEFs are a consequence of epigenetic reprogramming with up-regulation of the repressive mark H3K4me1 (mono-methylation of lys4 on histone H3) and enhanced chromatin compaction at promoter-proximal enhancer (T0 sequence), which disturb binding of the transcription factor TTF1. We propose a novel genome-wide mechanism where the polymerase-associated beta-actin synergizes with NM1 to coordinate permissive chromatin with Pol I transcription, cell growth, and proliferation. C1 [Almuzzaini, Bader; Sarshad, Aishe A.; Rahmanto, Aldwin S.; Hansson, Magnus L.; Sangfelt, Olle; Percipalle, Piergiorgio] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden. [Almuzzaini, Bader] King Abdullah Int Med Res Ctr, Natl Guard Hlth Affairs, Riyadh, Saudi Arabia. [Von Euler, Anne; Visa, Neus; Farrants, Ann-Kristin Ostlund; Percipalle, Piergiorgio] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden. [Percipalle, Piergiorgio] New York Univ Abu Dhabi, Dept Biol, Div Sci, Abu Dhabi, U Arab Emirates. [Sarshad, Aishe A.] NIAMSD, NIH, Bethesda, MD USA. RP Percipalle, P (reprint author), New York Univ Abu Dhabi, Saadyiat Campus, Abu Dhabi 129188, U Arab Emirates. EM pp69@nyu.edu FU Swedish Research Council; Swedish Cancer Society; National Guard Health Affairs-King Abdullah International Medical Research Center; Karolinska Institute doctoral fellowship; Swedish Society for Medical Research; Radiumhemmets Forskningsfonder FX The authors thank C. Ampe (University of Ghent, Ghent, Belgium) and R. Treissman (London Research Institute, London, United Kingdom) for kindly providing the beta-actin+/+ MEFs, beta-actin-/- MEFs, and beta-actin constructs. The authors also thank M. Corcoran and M. Rahman (both from the Karolinska Institute) for technical help. This work was supported by grants from the Swedish Research Council and the Swedish Cancer Society to P.P., O.S., and N.V. B.A.M. was cofunded by National Guard Health Affairs-King Abdullah International Medical Research Center, and A.A.S. was cofunded by a Karolinska Institute doctoral fellowship. M.H. was supported by a postdoctoral fellowship from the Swedish Society for Medical Research. A.S.R. was supported by funds from Radiumhemmets Forskningsfonder. NR 48 TC 1 Z9 1 U1 2 U2 2 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 AUG PY 2016 VL 30 IS 8 BP 2860 EP 2873 DI 10.1096/fj.201600280R PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DS7WP UT WOS:000380994000021 PM 27127100 ER PT J AU Karzai, FH Madan, RA Dahut, WL AF Karzai, Fatima H. Madan, Ravi A. Dahut, William L. TI Metabolic syndrome in prostate cancer: impact on risk and outcomes SO FUTURE ONCOLOGY LA English DT Review DE androgen-deprivation therapy; androgen receptor; cardiovascular risk; diabetes; gonadotropin-releasing hormone agonist/antagonist; hypertriglyceridemia; insulin resistance; metabolic syndrome; prostate cancer ID ANDROGEN-DEPRIVATION THERAPY; INSULIN-RESISTANCE; CARDIOVASCULAR MORTALITY; PELVIC LYMPHADENECTOMY; RADICAL PROSTATECTOMY; MEN; ASSOCIATION; CHEMOTHERAPY; BLOCKADE; ESTROGEN AB Androgen-deprivation therapy (ADT) is a fundamental element of treatment for nonlocalized prostate cancer and for patients with high-risk disease who are not candidates for radical treatment. ADT has been linked to metabolic syndrome, which involves changes in metabolic factors. While distinct from classic metabolic syndrome, this type does include changes in body composition, lipid profiles and insulin resistance. The constellation of risk factors may be associated with cardiovascular morbidity and the onset of diabetes mellitus. Physicians should discuss in detail the risk and benefits of ADT, as well as any needed lifestyle modifications with patients before beginning therapy. C1 [Karzai, Fatima H.; Madan, Ravi A.; Dahut, William L.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov NR 55 TC 0 Z9 0 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD AUG PY 2016 VL 12 IS 16 BP 1947 EP 1955 DI 10.2217/fon-2016-0061 PG 9 WC Oncology SC Oncology GA DS8JS UT WOS:000381030000011 PM 27067408 ER PT J AU Bunch, H Lawney, BP Burkholder, A Ma, DD Zheng, XF Motola, S Fargo, DC Levine, SS Wang, YYE Hue, G AF Bunch, Heeyoun Lawney, Brian P. Burkholder, Adam Ma, Duanduan Zheng, Xiaofeng Motola, Shmulik Fargo, David C. Levine, Stuart S. Wang, Yaoyu E. Hue, Guang TI RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes SO GENOMICS LA English DT Article DE Long non-coding RNAs; RNA polymerase II promoter-proximal pausing; TRIM28 ID POL-II; TRANSCRIPTIONAL ELONGATION; DIVERGENT TRANSCRIPTION; MEDIATOR COMPLEX; PREPARES GENES; P-TEFB; EXPRESSION; INITIATION; DROSOPHILA; RELEASE AB Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are less clear. Here, our genomic study has shown that a significant number of long non-coding RNAs (lncRNAs, >1000 nucleotides) harbor RNA polymerase II (Pol II) engaged with the transcriptional start site. A pausing and transcriptional elongation factor for protein-coding genes, tripartite motif-containing 28 (TRIM28) regulates the transcription of a subset of lncRNAs in mammalian cells. In addition, the majority of lncRNAs in human and murine cells regulated by Pol II promoter-proximal pausing appear to function in stimulus-inducible biological pathways. Our findings suggest an important role of Pol II pausing for the transcription of mammalian lncRNA genes. (C) 2016 Elsevier Inc. All rights reserved. C1 [Bunch, Heeyoun] Harvard Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Lawney, Brian P.; Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02130 USA. [Burkholder, Adam; Fargo, David C.] NIEHS, Integrat Bioinformat, NIH, Res Triangle Pk, NC 27705 USA. [Ma, Duanduan; Motola, Shmulik; Levine, Stuart S.] MIT, BioMicro Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Zheng, Xiaofeng; Hue, Guang] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27705 USA. RP Bunch, H (reprint author), Harvard Med Sch, Dept Genet & Complex Dis, Harvard Sch Publ Hlth, Goldenson Bldg,Room 559,220 Longwood Ave, Boston, MA 02115 USA. EM heeyounbunch@gmail.com OI Bunch, Heeyoun/0000-0003-0038-1985 FU Harvard Joint Center for Radiation Therapy FX We appreciate S. K. Calderwood in Beth Israel Deaconess Medical Center & Harvard Medical School for discussions and reading the manuscript and P. J. Park and L. Jung in Brigham Women Hospital & Harvard Medical School for providing initial bioinformatics analysis and discussions. We are grateful to D. J. Taatjes in the University of Colorado, Boulder and to J. Rinn in the Broad Institute for their critical reading and helpful comments of the manuscript. H.B. is grateful to D. Bunch, Joy, R. Baker, M. Seaquist, K. Perkins, D. Verrengia, G. Hugenberger, and P.S.C. for their loving support and encouragement throughout the work. This study was supported by grants from the Harvard Joint Center for Radiation Therapy to H.B. NR 59 TC 0 Z9 0 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 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD AUG PY 2016 VL 108 IS 2 BP 64 EP 77 DI 10.1016/j.ygeno.2016.07.003 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DT4UX UT WOS:000381477700003 PM 27432546 ER PT J AU Baydyuk, M Xu, JH Wu, LG AF Baydyuk, Maryna Xu, Jianhua Wu, Ling-Gang TI The calyx of Held in the auditory system: Structure, function, and development SO HEARING RESEARCH LA English DT Review ID SYNAPTIC VESICLE ENDOCYTOSIS; PRESYNAPTIC CALCIUM CURRENT; READILY RELEASABLE POOL; SHORT-TERM DEPRESSION; RAT MEDIAL NUCLEUS; FAST CNS SYNAPSE; VENTRAL COCHLEAR NUCLEUS; BUSHY CELL AXONS; TRAPEZOID BODY; TRANSMITTER RELEASE AB The calyx of Held synapse plays an important role in the auditory system, relaying information about. sound localization via fast and precise synaptic transmission, which is achieved by its specialized structure and giant size. During development, the calyx of Held undergoes anatomical, morphological, and physiological changes necessary for performing its functions. The large dimensions of the calyx of Held nerve terminal are well suited for direct electrophysiological recording of many presynaptic events that are difficult, if not impossible to record at small conventional synapses. This unique accessibility has been used to investigate presynaptic ion channels, transmitter release, and short-term plasticity, providing invaluable information about basic presynaptic mechanisms of transmission at a central synapse. Here, we review anatomical and physiological specializations of the calyx of Held, summarize recent studies that provide new mechanisms important for calyx development and reliable synaptic transmission, and examine fundamental presynaptic mechanisms learned from studies using calyx as a model nerve terminal. This article is part of a Special Issue entitled . (C) 2016 Elsevier B.V. All rights reserved. C1 [Baydyuk, Maryna; Wu, Ling-Gang] NINDS, 35 Convent Dr,Bldg 35, Bethesda, MD 20892 USA. [Xu, Jianhua] Augusta Univ, Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA. [Xu, Jianhua] Augusta Univ, Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. [Baydyuk, Maryna] Georgetown Univ, Dept Biol, 3700 O St NW, Washington, DC 20057 USA. RP Baydyuk, M (reprint author), NINDS, 35 Convent Dr,Bldg 35, Bethesda, MD 20892 USA.; Baydyuk, M (reprint author), Georgetown Univ, Dept Biol, 3700 O St NW, Washington, DC 20057 USA. EM mb339@georgetown.edu FU NINDS Intramural Research Program FX This work was supported by the NINDS Intramural Research Program. NR 151 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD AUG PY 2016 VL 338 SI SI BP 22 EP 31 DI 10.1016/j.heares.2016.03.009 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DT9RQ UT WOS:000381840400003 PM 27018297 ER PT J AU Singh, A Blaskovic, D Joo, J Yang, Z Jackson, SH Coleman, WG Yan, M AF Singh, Aparna Blaskovic, Dusan Joo, Jungsoo Yang, Zhen Jackson, Sharon H. Coleman, William G., Jr. Yan, Ming TI Investigating the Role of Helicobacter pylori PriA Protein SO HELICOBACTER LA English DT Article DE Helicobacter pylori; DNA helicase; replication fork stabilization ID VIVO EXPRESSION TECHNOLOGY; T-ANTIGEN GENE; ESCHERICHIA-COLI; DELAYED PHAGOCYTOSIS; GASTRIC SURFACE; DNA-REPAIR; GNOTOBIOTIC PIGLETS; BACTERIAL VIRULENCE; EPITHELIAL-CELLS; VIRAL-DNA AB BackgroundIn bacteria, PriA protein, a conserved DEXH-type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA binding property allows it to recognize and stabilize stalled forks and the structures derived from them. PriA plays a very critical role in replication fork stabilization and DNA repair in E. coli and N. gonorrhoeae. In our in vivo expression technology screen, priA gene was induced in vivo when Helicobacter pylori infects mouse stomach. Materials and MethodsWe decided to elucidate the role of H. pylori PriA protein in survival in mouse stomach, survival in gastric epithelial cells and macrophage cells, DNA repair, acid stress, and oxidative stress. ResultsThe priA null mutant strain was unable to colonize mice stomach mucosa after long-term infections. Mouse colonization was observed after 1 week of infection, but the levels were much lower than the wild-type HpSS1 strain. PriA protein was found to be important for intracellular survival of epithelial cell-/macrophage cell-ingested H. pylori. Also, a priA null mutant was more sensitive to DNA-damaging agents and was much more sensitive to acid and oxidative stress as compared to the wild-type strain. ConclusionsThese data suggest that the PriA protein is needed for survival and persistence of H. pylori in mice stomach mucosa. C1 [Singh, Aparna; Blaskovic, Dusan; Joo, Jungsoo; Yang, Zhen; Coleman, William G., Jr.; Yan, Ming] NIDDK, NIH, Bethesda, MD 20892 USA. [Jackson, Sharon H.; Coleman, William G., Jr.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. RP Jackson, SH (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA.; Yan, M (reprint author), NIH, Kidney Dis, Bldg 10, Bethesda, MD 20892 USA. EM sjackson@mail.nih.gov; yanming@niddk.nih.gov FU intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases; intramural research program of the National Institute on Minority Health and Health Disparities FX This research was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, and the intramural research program of the National Institute on Minority Health and Health Disparities. We are thankful to Dr. Reed B. Wickner, NIDDK, NIH, for critical reading of the manuscript. NR 57 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD AUG PY 2016 VL 21 IS 4 BP 295 EP 304 DI 10.1111/hel.12283 PG 10 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA DS0EU UT WOS:000380269000006 PM 26817518 ER PT J AU Talarico, S Safaeian, M Gonzalez, P Hildesheim, A Herrero, R Porras, C Cortes, B Larson, A Fang, FC Salama, NR AF Talarico, Sarah Safaeian, Mahboobeh Gonzalez, Paula Hildesheim, Allan Herrero, Rolando Porras, Carolina Cortes, Bernal Larson, Ann Fang, Ferric C. Salama, Nina R. TI Quantitative Detection and Genotyping of Helicobacter pylori from Stool using Droplet Digital PCR Reveals Variation in Bacterial Loads that Correlates with cagA Virulence Gene Carriage SO HELICOBACTER LA English DT Article DE Droplet digital PCR; stool-based assay; bacterial load; cagA gene; H; pylori ID POLYMERASE-CHAIN-REACTION; COMPLETE GENOME SEQUENCE; TYROSINE PHOSPHORYLATION; INFECTION; CHILDREN; DISEASE; PROTEIN; SAMPLES; CANCER; RISK AB BackgroundEpidemiologic studies of the carcinogenic stomach bacterium Helicobacter pylori have been limited by the lack of noninvasive detection and genotyping methods. We developed a new stool-based method for detection, quantification, and partial genotyping of H. pylori using droplet digital PCR (ddPCR), which allows for increased sensitivity and absolute quantification by PCR partitioning. Materials and MethodsStool-based ddPCR assays for H. pylori 16S gene detection and cagA virulence gene typing were tested using a collection of 50 matched stool and serum samples from Costa Rican volunteers and 29 H. pylori stool antigen-tested stool samples collected at a US hospital. ResultsThe stool-based H. pylori 16S ddPCR assay had a sensitivity of 84% and 100% and a specificity of 100% and 71% compared to serology and stool antigen tests, respectively. The stool-based cagA genotyping assay detected cagA in 22 (88%) of 25 stools from CagA antibody-positive individuals and four (16%) of 25 stools from CagA antibody-negative individuals from Costa Rica. All 26 of these samples had a Western-type cagA allele. Presence of serum CagA antibodies was correlated with a significantly higher load of H. pylori in the stool. ConclusionsThe stool-based ddPCR assays are a sensitive, noninvasive method for detection, quantification, and partial genotyping of H. pylori. The quantitative nature of ddPCR-based H. pylori detection revealed significant variation in bacterial load among individuals that correlates with presence of the cagA virulence gene. These stool-based ddPCR assays will facilitate future population-based epidemiologic studies of this important human pathogen. C1 [Talarico, Sarah; Salama, Nina R.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Safaeian, Mahboobeh; Hildesheim, Allan] NCI, NIH, Rockville, MD USA. [Gonzalez, Paula; Herrero, Rolando; Porras, Carolina; Cortes, Bernal] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica. [Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, Lyon, France. [Larson, Ann; Fang, Ferric C.] Harborview Med Ctr, Clin Microbiol Lab, Seattle, WA USA. [Larson, Ann; Fang, Ferric C.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Fang, Ferric C.; Salama, Nina R.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Salama, NR (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Mailstop C3-168, Seattle, WA 98109 USA. EM nsalama@fredhutch.org FU NIH [K01DK090103, R01AI054423]; NIH Intramural Research Program FX This work was supported by grants K01DK090103 and R01AI054423 from the NIH and by the NIH Intramural Research Program. We would like to thank Yoshio Yamaoka for providing Japanese H. pylori strains for testing of the cagA assays. We would also like to thank Tina Gall and Jennifer Taylor for their assistance in constructing the figures. NR 41 TC 1 Z9 1 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD AUG PY 2016 VL 21 IS 4 BP 325 EP 333 DI 10.1111/hel.12289 PG 9 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA DS0EU UT WOS:000380269000009 PM 26667241 ER PT J AU Hoye, BJ Munster, VJ Huig, N de Vries, P Oosterbeek, K Tijsen, W Klaassen, M Fouchier, RAM van Gils, JA AF Hoye, Bethany J. Munster, Vincent J. Huig, Naomi de Vries, Peter Oosterbeek, Kees Tijsen, Wim Klaassen, Marcel Fouchier, Ron A. M. van Gils, Jan A. TI Hampered Performance of Migratory Swans: Intra- and Inter-Seasonal Effects of Avian Influenza Virus SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Article ID WILD BIRDS; NATURAL INFECTION; BLOOD PARASITES; BODY CONDITION; BEWICKS SWANS; DEER MICE; A VIRUS; HOST; POPULATION; SURVIVAL AB The extent to which animal migrations shape parasite transmission networks is critically dependent on a migrant's ability to tolerate infection and migrate successfully. Yet, sub-lethal effects of parasites can be intensified through periods of increased physiological stress. Long-distance migrants may, therefore, be especially susceptible to negative effects of parasitic infection. Although a handful of studies have investigated the short-term, transmission-relevant behaviors of wild birds infected with low-pathogenic avian influenza viruses (LPAIV), the ecological consequences of LPAIV for the hosts themselves remain largely unknown. Here, we assessed the potential effects of naturally-acquired LPAIV infections in Bewick's swans, a long-distance migratory species that experiences relatively low incidence of LPAIV infection during early winter. We monitored both foraging and movement behavior in the winter of infection, as well as subsequent breeding behavior and inter-annual resighting probability over 3 years. Incorporating data on infection history we hypothesized that any effects would be most apparent in naive individuals experiencing their first LPAIV infection. Indeed, significant effects of infection were only seen in birds that were infected but lacked antibodies indicative of prior infection. Swans that were infected but had survived a previous infection were indistinguishable from uninfected birds in each of the ecological performance metrics. Despite showing reduced foraging rates, individuals in the naive-infected category had similar accumulated body stores to re-infected and uninfected individuals prior to departure on spring migration, possibly as a result of having higher scaled mass at the time of infection. And yet individuals in the naive-infected category were unlikely to be resighted 1 year after infection, with 6 out of 7 individuals that never resighted again compared to 20 out of 63 uninfected individuals and 5 out of 12 individuals in the re-infected category. Collectively, our findings indicate that acute and superficially harmless infection with LPAIV may have indirect effects on individual performance and recruitment in migratory Bewick's swans. Our results also highlight the potential for infection history to play an important role in shaping ecological constraints throughout the annual cycle. C1 [Hoye, Bethany J.; Huig, Naomi; de Vries, Peter; Tijsen, Wim; Klaassen, Marcel] Netherlands Inst Ecol NIOO KNAW, Dept Anim Ecol, Wageningen, Netherlands. [Hoye, Bethany J.; Klaassen, Marcel] Deakin Univ, Sch Life & Environm Sci, Ctr Integrat Ecol, Geelong, Vic, Australia. [Munster, Vincent J.; Fouchier, Ron A. M.] Erasmus MC, Dept Virosci, Rotterdam, Netherlands. [Munster, Vincent J.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Oosterbeek, Kees] SOVON Texel, Dutch Ctr Field Ornithol, Den Burg, Texel, Netherlands. [van Gils, Jan A.] NIOZ Royal Netherlands Inst Sea Res, Dept Coastal Syst, Den Burg, Texel, Netherlands. [van Gils, Jan A.] Univ Utrecht, Den Burg, Texel, Netherlands. RP Hoye, BJ (reprint author), Netherlands Inst Ecol NIOO KNAW, Dept Anim Ecol, Wageningen, Netherlands.; Hoye, BJ (reprint author), Deakin Univ, Sch Life & Environm Sci, Ctr Integrat Ecol, Geelong, Vic, Australia. EM hoye.bethany@gmail.com RI Klaassen, Marcel/B-4325-2008; Fouchier, Ron/A-1911-2014; van Gils, Jan/B-5544-2008; OI Klaassen, Marcel/0000-0003-3907-9599; Fouchier, Ron/0000-0001-8095-2869; van Gils, Jan/0000-0002-4132-8243; KNAW, NIOO-KNAW/0000-0002-3835-159X NR 79 TC 1 Z9 1 U1 8 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD AUG PY 2016 VL 56 IS 2 BP 317 EP 329 DI 10.1093/icb/icw038 PG 13 WC Zoology SC Zoology GA DT1YX UT WOS:000381279100018 PM 27252210 ER PT J AU Wang, GY Hu, FB Mistry, KB Zhang, CL Ren, FZ Huo, Y Paige, D Bartell, T Hong, XM Caruso, D Ji, ZC Chen, Z Ji, YL Pearson, C Ji, HK Zuckerman, B Cheng, TL Wang, XB AF Wang, Guoying Hu, Frank B. Mistry, Kamila B. Zhang, Cuilin Ren, Fazheng Huo, Yong Paige, David Bartell, Tami Hong, Xiumei Caruso, Deanna Ji, Zhicheng Chen, Zhu Ji, Yuelong Pearson, Colleen Ji, Hongkai Zuckerman, Barry Cheng, Tina L. Wang, Xiaobin TI Association Between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations With Child Metabolic Health SO JAMA PEDIATRICS LA English DT Article ID NEURAL-TUBE DEFECTS; GESTATIONAL WEIGHT-GAIN; FOLIC-ACID; INSULIN-RESISTANCE; OFFSPRING OBESITY; CHILDBEARING AGE; UNITED-STATES; BIRTH-WEIGHT; PREGNANCY; PREVENTION AB IMPORTANCE Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. To our knowledge, the role of maternal folate concentrations, alone or in combination with maternal OWO, in child metabolic health has not been examined in a prospective birth cohort. OBJECTIVE To test the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that sufficient maternal folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk. DESIGN, SETTING, AND PARTICIPANTS This prospective birth cohort study was conducted at the Boston Medical Center, Boston, Massachusetts. It included 1517 mother-child dyads recruited at birth from 1998 to 2012 and followed up prospectively up to 9 years from 2003 to 2014. MAIN OUTCOMES AND MEASURES Child body mass index z score calculated according to US reference data, OWO defined as a body mass index in the 85th percentile or greater for age and sex, and metabolic biomarkers (leptin, insulin, and adiponectin). RESULTS The mean (SD) age was 28.6 (6.5) years for mothers and 6.2 (2.4) years for the children. An L-shaped association between maternal folate concentrations and child OWO was observed: the risk for OWO was higher among those in the lowest quartile (Q1) as compared with those in Q2 through Q4, with an odds ratio of 1.45 (95% CI, 1.13-1.87). The highest risk for child OWO was found among children of obese mothers with low folate concentrations (odds ratio, 3.05; 95% CI, 1.91-4.86) compared with children of normal-weight mothers with folate concentrations in Q2 through Q4 after accounting for multiple covariables. Among children of obese mothers, their risk for OWO was associated with a 43% reduction (odds ratio, 0.57; 95% CI, 0.34-0.95) if their mothers had folate concentrations in Q2 through Q4 compared with Q1. Similar patterns were observed for child metabolic biomarkers. CONCLUSIONS AND RELEVANCE In this urban low-income prospective birth cohort, we demonstrated an L-shaped association between maternal plasma folate concentrations and child OWO and the benefit of sufficient folate concentrations, especially among obese mothers. The threshold concentration identified in this study exceeded the clinical definition of folate deficiency, which was primarily based on the hematological effect of folate. Our findings underscore the need to establish optimal rather than minimal folate concentrations for preventing adverse metabolic outcomes in the offspring. C1 [Wang, Guoying; Zhang, Cuilin; Bartell, Tami; Hong, Xiumei; Caruso, Deanna; Chen, Zhu; Ji, Yuelong; Cheng, Tina L.; Wang, Xiaobin] Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Bloomberg Sch Publ Hlth, Ctr Early Life Origins Dis, 615 N Wolfe St, Baltimore, MD 21205 USA. [Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hu, Frank B.] Harvard Med Sch, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Mistry, Kamila B.; Cheng, Tina L.; Wang, Xiaobin] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Gen Pediat & Adolescent Med, Baltimore, MD 21205 USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. [Ren, Fazheng] China Agr Univ, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing, Peoples R China. [Huo, Yong] Peking Univ, Hosp 1, Dept Cardiol, Beijing, Peoples R China. [Bartell, Tami] Ann & Robert H Lurie Childrens Hosp Chicago, Stanley Manne Childrens Res Inst, Chicago, IL 60611 USA. [Ji, Zhicheng; Ji, Hongkai] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Pearson, Colleen; Zuckerman, Barry] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Pearson, Colleen; Zuckerman, Barry] Boston Med Ctr, Boston, MA USA. RP Wang, XB (reprint author), Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Bloomberg Sch Publ Hlth, Ctr Early Life Origins Dis, 615 N Wolfe St, Baltimore, MD 21205 USA. EM xwang82@jhu.edu FU PERI grants from March of Dimes [20-FY02-56, 21-FY07-605]; National Institutes of Health [R21ES011666, R21HD066471, R01HD041702, U01AI090727, R21AI079872, R01HD086013]; Maternal and Child Health Bureau [R40MC27443]; intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX The Boston Birth Cohort is supported in part by the PERI grants 20-FY02-56 and 21-FY07-605 from the March of Dimes; grants R21ES011666, R21HD066471, R01HD041702, U01AI090727, R21AI079872, and R01HD086013 from the National Institutes of Health; and grant R40MC27443 from the Maternal and Child Health Bureau. 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 37 TC 1 Z9 1 U1 7 U2 7 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 AUG PY 2016 VL 170 IS 8 AR e160845 DI 10.1001/jamapediatrics.2016.0845 PG 9 WC Pediatrics SC Pediatrics GA DS9XW UT WOS:000381137800002 PM 27295011 ER PT J AU McGowan, EC Peng, RD Salo, PM Zeldin, DC Keet, CA AF McGowan, Emily C. Peng, Roger D. Salo, Paivi M. Zeldin, Darryl C. Keet, Corinne A. TI Changes in Food-Specific IgE Over Time in the National Health and Nutrition Examination Survey (NHANES) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Food allergy; NHANES; Food sensitization; Epidemiology ID PEANUT ALLERGEN; UNITED-STATES; PREVALENCE; CHILDREN; ANAPHYLAXIS; DIAGNOSIS; RISK; SENSITIZATION; ASTHMA; TRENDS AB BACKGROUND: Food allergy prevalence appears to have recently risen, with larger increases among non-Hispanic blacks. However, it is unclear whether these trends represent shifts in recognition of food allergy or in sensitization. OBJECTIVE: The objective of this study was to determine whether sensitization to common food allergens increased in US children from 1988-1994 to 2005-2006 and whether these trends differed by race and/or ethnicity. METHODS: Food-specific immunoglobulin E (IgE; to peanut, milk, egg, and shrimp) was measured by ImmunoCAP in stored sera from subjects aged 6-19 in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and was compared with NHANES 2005-2006. Sensitization to foods was defined as overall (IgE >= 0.35 kU/L), moderate level (IgE >= 2 kU/L), and high level (IgE >= commonly used 95% predictive values). Sensitization to individual and combined foods was compared between surveys, with analyses further stratified by race and/or ethnicity. RESULTS: A total of 7896 subjects (NHANES III: n [4995, NHANES 2005-2006: n[2901) were included. In NHANES III, the prevalence of food sensitization was 24.3% (95% confidence interval [CI]: 22.1-26.5) compared with 21.6% (95% CI: 19.523.7) in NHANES 2005-2006. There were no significant changes in the prevalence of any level of milk, egg, or peanut sensitization, but shrimp sensitization at all levels decreased markedly; overall sensitization NHANES III: 11.2% (95% CI: 10.0-12.5) versus NHANES 2005-2006: 6.1% (95% CI: 4.5-7.7). There was a trend toward the increased prevalence of moderate-and high-level sensitization to the combination of milk, egg, and peanut among non-Hispanic blacks but not other groups. CONCLUSIONS: In contrast to our expectations, sensitization to common food allergens did not increase between the late 1980s/early 1990s and the mid-2000s among US 6-19 year olds, and in fact decreased to shrimp. (C) 2016 American Academy of Allergy, Asthma & Immunology C1 [McGowan, Emily C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD USA. [McGowan, Emily C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Peng, Roger D.] 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. [Keet, Corinne A.] Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD USA. RP Keet, CA (reprint author), Johns Hopkins Univ Hosp, CMSC 1102,600 N Wolfe St, Baltimore, MD 21202 USA. EM ckeet1@jhmi.edu FU National Institutes of Health (NIH) [1K23AI103187, 1KL2TR001077, R21AI107085]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01 ES025041] FX This work was funded by the National Institutes of Health (NIH) through the following grants: (National Institute of Allergy and Infectious Diseases [NIAID]) 1K23AI103187, (National Center for Research Resources) 1KL2TR001077, and (NIAID) R21AI107085, and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES025041). The funders had no role in the design, analysis, or interpretation of this work. NR 38 TC 5 Z9 5 U1 5 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD AUG PY 2016 VL 4 IS 4 BP 713 EP 720 DI 10.1016/j.jaip.2016.01.017 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA DU0SZ UT WOS:000381916100022 PM 27133095 ER PT J AU Bernabe-Rubio, M Andres, G Casares-Arias, J Fernandez-Barrera, J Rangel, L Reglero-Real, N Gershlick, DC Fernandez, JJ Millan, J Correas, I Miguez, DG Alonso, MA AF Bernabe-Rubio, Miguel Andres, German Casares-Arias, Javier Fernandez-Barrera, Jaime Rangel, Laura Reglero-Real, Natalia Gershlick, David C. Fernandez, Jose J. Millan, Jaime Correas, Isabel Miguez, David G. Alonso, Miguel A. TI Novel role for the midbody in primary ciliogenesis by polarized epithelial cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PRIMARY CILIUM; INTRAFLAGELLAR TRANSPORT; ASYMMETRIC INHERITANCE; CYTOKINETIC ABSCISSION; MEDIATED ABSCISSION; NEURAL PROGENITORS; MARKER PROMININ-1; CILIARY MEMBRANE; ANIMAL-CELLS; RAB8 GTPASE AB The primary cilium is a membrane protrusion that is crucial for vertebrate tissue homeostasis and development. Here, we investigated the uncharacterized process of primary ciliogenesis in polarized epithelial cells. We show that after cytokinesis, the midbody is inherited by one of the daughter cells as a remnant that initially locates peripherally at the apical surface of one of the daughter cells. The remnant then moves along the apical surface and, once proximal to the centrosome at the center of the apical surface, enables cilium formation. The physical removal of the remnant greatly impairs ciliogenesis. We developed a probabilistic cell population-based model that reproduces the experimental data. In addition, our model explains, solely in terms of cell area constraints, the various observed transitions of the midbody, the beginning of ciliogenesis, and the accumulation of ciliated cells. Our findings reveal a biological mechanism that links the three microtubule-based organelles-the midbody, the centrosome, and the cilium-in the same cellular process. C1 [Bernabe-Rubio, Miguel; Casares-Arias, Javier; Fernandez-Barrera, Jaime; Rangel, Laura; Reglero-Real, Natalia; Millan, Jaime; Correas, Isabel; Alonso, Miguel A.] CSIC, Ctr Biol Mol Severo Ochoa, Dept Cell Biol & Immunol, Madrid 28049, Spain. [Andres, German] CSIC, Ctr Biol Mol Severo Ochoa, Electron Microscopy Unit, Madrid 28049, Spain. Univ Autonoma Madrid, E-28049 Madrid, Spain. [Gershlick, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA. [Fernandez, Jose J.] CSIC, Ctr Nacl Biotecnol, Madrid 28049, Spain. [Miguez, David G.] Univ Autonoma Madrid, Dept Condensed Matter Phys, Inst Ciencias Mat Nicolas Cabrera, E-28049 Madrid, Spain. [Miguez, David G.] Univ Autonoma Madrid, Inst Fis Mat Condensada, E-28049 Madrid, Spain. RP Alonso, MA (reprint author), CSIC, Ctr Biol Mol Severo Ochoa, Dept Cell Biol & Immunol, Madrid 28049, Spain. EM maalonso@cbm.csic.es RI Alonso, Miguel/J-3945-2016; Fernandez, Jose-Jesus/A-5084-2008; Andres, German/E-2632-2016; OI Alonso, Miguel/0000-0002-7001-8826; Fernandez, Jose-Jesus/0000-0003-2222-3355; Andres, German/0000-0003-0265-5409; Casares Arias, Javier/0000-0003-3147-5730; Gershlick, David/0000-0002-0602-210X; Miguez Gomez, David/0000-0001-8065-1142 FU Spanish Ministerio de Economia y Competitividad/Fondo Europeo de Desarrollo Regional [BFU2012-32532, BFU2015-67266-R, BFU2014-53299-P, TIN-2012-37483-C03-02]; Comunidad de Madrid [S2010/BMD-2305]; Instituto de Investigaciones Sanitarias Jimenez Diaz; Ministerio de Economia y Competitividad [RYC-2010-07450]; Amarouto Program from the Comunidad de Madrid FX This work was supported by the following grants from the Spanish Ministerio de Economia y Competitividad/Fondo Europeo de Desarrollo Regional: BFU2012-32532 and BFU2015-67266-R to M.A. Alonso, BFU2014-53299-P to D.G. Miguez, and TIN-2012-37483-C03-02 to J.F. Fernandez. Grants from the Comunidad de Madrid (S2010/BMD-2305) to I. Correas and from Instituto de Investigaciones Sanitarias Jimenez Diaz to J. Millan are also acknowledged. M. Bernabe-Rubio and D.G. Miguez are the holders of a fellowship and a Ramon y Cajal contract (RYC-2010-07450), respectively, from the Ministerio de Economia y Competitividad. G. Andres was supported by the Amarouto Program from the Comunidad de Madrid. NR 68 TC 1 Z9 1 U1 3 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD AUG 1 PY 2016 VL 214 IS 3 BP 259 EP 273 DI 10.1083/jcb.201601020 PG 15 WC Cell Biology SC Cell Biology GA DS5OO UT WOS:000380831800007 PM 27458130 ER PT J AU Lippincott, MF Chan, YM Delaney, A Rivera-Morales, D Butler, JP Seminara, SB AF Lippincott, Margaret F. Chan, Yee-Ming Delaney, Angela Rivera-Morales, Dianali Butler, James P. Seminara, Stephanie B. TI Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; KISS-1 PEPTIDE; GPR54; SECRETION; RECEPTOR; WOMEN AB Context: Some patients with idiopathic hypogonadotropic hypogonadism (IHH) undergo spontaneous activation of their hypothalamic-pituitary-gonadal axis resulting in normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: To assess the responsiveness of the GnRH neuronal network to exogenous kisspeptin administration in IHH patients who have undergone reversal. Participants: Six men with congenital IHH and evidence for reversal. Intervention: Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to iv boluses of kisspeptin (0.24-2.4 nmol/kg) and GnRH (75 ng/kg). Results: Individuals with sustained reversal of their hypogonadotropism (spontaneous LH pulses) responded to exogenous kisspeptin with a GnRH-induced LH pulse. Individuals who had reversal but then subsequently suffered relapse of their IHH (loss of spontaneous LH pulsatility) did not respond to kisspeptin. Conclusions: The ability of kisspeptin to stimulate a GnRH-induced LH pulse correlates with the presence of endogenous LH pulses. These data suggest that reversal of hypogonadotropism, and by extension sexual maturation, may be due to the acquisition of kisspeptin responsiveness. C1 [Lippincott, Margaret F.; Chan, Yee-Ming; Rivera-Morales, Dianali; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Lippincott, Margaret F.; Chan, Yee-Ming; Rivera-Morales, Dianali; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Butler, James P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA 02115 USA. [Delaney, Angela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Genet Puberty & Reprod, Bethesda, MD 20892 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,BHX 5, Boston, MA 02114 USA. EM Seminara.Stephanie@mgh.harvard.edu FU Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01 HD043341, P50 HD028138]; Harvard Catalyst Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health) [UL1 RR 025758, UL1 TR000170]; Harvard Catalyst Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 RR 025758, UL1 TR000170]; Harvard Catalyst Harvard Clinical and Translational Science Center (Harvard University and its affiliated academic health care centers); NIH NICHD Grant [K24 HD067388, F32 HD078083]; Doris Duke Clinical Scientist Development Award [2013110]; Postdoctoral Fellowship Award for Clinical Research from the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery; NIH Intramural Research Program of NICHD FX This work was supported by grants R01 HD043341 and P50 HD028138 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) and the Harvard Catalyst Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Awards UL1 RR 025758 and UL1 TR000170 and financial contributions from Harvard University and its affiliated academic health care centers). S.B.S. was supported by the NIH NICHD Grant K24 HD067388. Y.-M.C. was supported by a Doris Duke Clinical Scientist Development Award (Grant 2013110). M.F.L. was supported by the NIH NICHD Grant F32 HD078083 and by a Postdoctoral Fellowship Award for Clinical Research from the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery. A.D. was supported by the NIH Intramural Research Program of NICHD. NR 44 TC 1 Z9 2 U1 3 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2016 VL 101 IS 8 BP 3061 EP 3069 DI 10.1210/jc.2016-1545 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0YF UT WOS:000381930200014 PM 27214398 ER PT J AU Hernandez-Ramirez, LC Martucci, F Morgan, RML Trivellin, G Tilley, D Ramos-Guajardo, N Iacovazzo, D D'Acquisto, F Prodromou, C Korbonits, M AF Hernandez-Ramirez, Laura C. Martucci, Federico Morgan, Rhodri M. L. Trivellin, Giampaolo Tilley, Daniel Ramos-Guajardo, Nancy Iacovazzo, Donato D'Acquisto, Fulvio Prodromou, Chrisostomos Korbonits, Marta TI Rapid Proteasomal Degradation of Mutant Proteins Is the Primary Mechanism Leading to Tumorigenesis in Patients With Missense AIP Mutations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-INTERACTING-PROTEIN; MULTIPLE ENDOCRINE NEOPLASIA; ISOLATED PITUITARY-ADENOMA; YOUNG-PATIENTS; GENE-MUTATIONS; MACROADENOMAS; PREVALENCE; DIAGNOSIS; SEQUENCE; FAMILIES AB Context: The pathogenic effect of mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene (AIPmuts) in pituitary adenomas is incompletely understood. We have identified the primary mechanism of loss of function for missense AIPmuts. Objective: This study sought to analyze the mechanism/speed of protein turnover of wild-type and missense AIP variants, correlating protein half-life with clinical parameters. Design and Setting: Half-life and protein-protein interaction experiments and cross-sectional analysis of AIPmut positive patients' data were performed in a clinical academic research institution. Patients: Data were obtained from our cohort of pituitary adenoma patients and literature-reported cases. Interventions: Protein turnover of endogenous AIP in two cell lines and fifteen AIP variants over-expressed in HEK293 cells was analyzed via cycloheximide chase and proteasome inhibition. Glutathione-S-transferase pull-down and quantitative mass spectrometry identified proteins involved in AIP degradation; results were confirmed by coimmunoprecipitation and gene knockdown. Relevant clinical data was collected. Main Outcome Measures: Half-life of wild-type and mutant AIP proteins and its correlation with clinical parameters. Results: Endogenous AIP half-life was similar in HEK293 and lymphoblastoid cells (43.5 and 32.7 h). AIP variants were divided into stable proteins (median, 77.7 h; interquartile range [IQR], 60.7-92.9 h), and those with short (median, 27 h; IQR, 21.6-28.7 h) or very short (median, 7.7 h; IQR, 5.6-10.5 h) half-life; proteasomal inhibition rescued the rapid degradation of mutant proteins. The experimental half-life significantly correlated with age at diagnosis of acromegaly/gigantism (r = 0.411; P = .002). The FBXO3-containing SKP1-CUL1-F-box protein complex was identified as the E3 ubiquitin-ligase recognizing AIP. Conclusions: AIP is a stable protein, driven to ubiquitination by the SKP1-CUL1-F-box protein complex. Enhanced proteasomal degradation is a novel pathogenic mechanism for AIPmuts, with direct implications for the phenotype. C1 [Hernandez-Ramirez, Laura C.; Martucci, Federico; Trivellin, Giampaolo; Tilley, Daniel; Ramos-Guajardo, Nancy; Iacovazzo, Donato; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Ctr Endocrinol, London EC1M 6BQ, England. [D'Acquisto, Fulvio] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Ctr Biochem Pharmacol, London EC1M 6BQ, England. [Morgan, Rhodri M. L.; Prodromou, Chrisostomos] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, Falmer, England. [Hernandez-Ramirez, Laura C.; Trivellin, Giampaolo] Eunice Kennedy Shriver Natl Inst Child Hlth andHu, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Morgan, Rhodri M. L.] Imperial Coll London, Dept Life Sci, Struct Biol Ctr, Prot Crystallog Facil, Flowers Bldg, London SW7 2AZ, England. RP Korbonits, M (reprint author), Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Ctr Endocrinol,Endocrinol & Metab, London EC1M 6BQ, England. EM m.korbonits@qmul.ac.uk OI Trivellin, Giampaolo/0000-0003-2384-4153; Korbonits, Marta/0000-0002-4101-9432; Hernandez-Ramirez, Laura C./0000-0002-6599-6406 FU Medical Research Council of the United Kingdom; Wellcome Trust [095605/Z11/Z]; National Institute of Health Research; Royal Society; Pfizer; National Council of Science and Technology; Secretariat of Public Education from the Mexican Government; Barts and The London Charity FX This work was supported by the Medical Research Council of the United Kingdom, Wellcome Trust, National Institute of Health Research, Barts and The London Charity, Royal Society, and Pfizer. L.C.H.-R. was supported by grants from the National Council of Science and Technology and the Secretariat of Public Education from the Mexican Government. C.P. is funded by the Wellcome Trust 095605/Z11/Z. NR 53 TC 1 Z9 1 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2016 VL 101 IS 8 BP 3144 EP 3154 DI 10.1210/jc.2016-1307 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0YF UT WOS:000381930200023 PM 27253664 ER PT J AU Sleiman, S Halliday, CL Chapman, B Brown, M Nitschke, J Lau, AF Chen, SCA AF Sleiman, Sue Halliday, Catriona L. Chapman, Belinda Brown, Mitchell Nitschke, Joanne Lau, Anna F. Chen, Sharon C. -A. TI Performance of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Aspergillus, Scedosporium, and Fusarium spp. in the Australian Clinical Setting SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SPECIES IDENTIFICATION; ACCURATE IDENTIFICATION; ROUTINE IDENTIFICATION; FILAMENTOUS FUNGI; MEDICAL MYCOLOGY; MOLDS; PSEUDALLESCHERIA; INFECTIONS; EPIDEMIOLOGY; BIOTYPER AB We developed an Australian database for the identification of Aspergillus, Scedosporium, and Fusarium species (n = 28) by matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF MS). In a challenge against 117 isolates, species identification significantly improved when the in-house-built database was combined with the Bruker Filamentous Fungi Library compared with that for the Bruker library alone (Aspergillus, 93% versus 69%; Fusarium, 84% versus 42%; and Scedosporium, 94% versus 18%, respectively). C1 [Sleiman, Sue; Halliday, Catriona L.; Brown, Mitchell; Nitschke, Joanne; Chen, Sharon C. -A.] Univ Sydney, Westmead Hosp, Inst Clin Pathol & Med Res, Ctr Infect Dis & Microbiol Lab Serv, Westmead, NSW, Australia. [Chapman, Belinda] Univ Sydney, Westmead Inst Med Res, Westmead, NSW, Australia. [Lau, Anna F.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Chen, Sharon C. -A.] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia. RP Chen, SCA (reprint author), Univ Sydney, Westmead Hosp, Inst Clin Pathol & Med Res, Ctr Infect Dis & Microbiol Lab Serv, Westmead, NSW, Australia.; Chen, SCA (reprint author), Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia. EM sharon.chen@health.nsw.gov.au FU Intramural Research Program of the National Institutes of Health FX A.F.L. was supported by the Intramural Research Program of the National Institutes of Health. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. NR 34 TC 2 Z9 2 U1 2 U2 2 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 AUG PY 2016 VL 54 IS 8 BP 2182 EP 2186 DI 10.1128/JCM.00906-16 PG 5 WC Microbiology SC Microbiology GA DT1YO UT WOS:000381278200037 PM 27252460 ER PT J AU Portier, CJ Armstrong, BK Baguley, BC Baur, X Belyaev, I Belle, R Belpoggi, F Biggeri, A Bosland, MC Bruzzi, P Budnik, LT Bugge, MD Burns, K Calaf, GM Carpenter, DO Carpenter, HM Lopez-Carrillo, L Clapp, R Cocco, P Consonni, D Comba, P Craft, E Dalvie, MA Davis, D Demers, PA De Roos, AJ DeWitt, J Forastiere, F Freedman, JH Fritschi, L Gaus, C Gohlke, JM Goldberg, M Greiser, E Hansen, J Hardell, L Hauptmann, M Huang, W Huff, J James, MO Jameson, CW Kortenkamp, A Kopp-Schneider, A Kromhout, H Larramendy, ML Landrigan, PJ Lash, LH Leszczynski, D Lynch, CF Magnani, C Mandrioli, D Martin, FL Merler, E Michelozzi, P Miligi, L Miller, AB Mirabelli, D Mirer, FE Naidoo, S Perry, MJ Petronio, MG Pirastu, R Portier, RJ Ramos, KS Robertson, LW Rodriguez, T Roosli, M Ross, MK Roy, D Rusyn, I Saldiva, P Sass, J Savolainen, K Scheepers, PTJ Sergi, C Silbergeld, EK Smith, MT Stewart, BW Sutton, P Tateo, F Terracini, B Thielmann, HW Thomas, DB Vainio, H Vena, JE Vineis, P Weiderpass, E Weisenburger, DD Woodruff, TJ Yorifuji, T Yu, IJ Zambon, P Zeeb, H Zhou, SF AF Portier, Christopher J. Armstrong, Bruce K. Baguley, Bruce C. Baur, Xaver Belyaev, Igor Belle, Robert Belpoggi, Fiorella Biggeri, Annibale Bosland, Maarten C. Bruzzi, Paolo Budnik, Lygia Therese Bugge, Merete D. Burns, Kathleen Calaf, Gloria M. Carpenter, David O. Carpenter, Hillary M. Lopez-Carrillo, Lizbeth Clapp, Richard Cocco, Pierluigi Consonni, Dario Comba, Pietro Craft, Elena Dalvie, Mohamed Aqiel Davis, Devra Demers, Paul A. De Roos, Anneclaire J. DeWitt, Jamie Forastiere, Francesco Freedman, Jonathan H. Fritschi, Lin Gaus, Caroline Gohlke, Julia M. Goldberg, Marcel Greiser, Eberhard Hansen, Johnni Hardell, Lennart Hauptmann, Michael Huang, Wei Huff, James James, Margaret O. Jameson, C. W. Kortenkamp, Andreas Kopp-Schneider, Annette Kromhout, Hans Larramendy, Marcelo L. Landrigan, Philip J. Lash, Lawrence H. Leszczynski, Dariusz Lynch, Charles F. Magnani, Corrado Mandrioli, Daniele Martin, Francis L. Merler, Enzo Michelozzi, Paola Miligi, Lucia Miller, Anthony B. Mirabelli, Dario Mirer, Franklin E. Naidoo, Saloshni Perry, Melissa J. Petronio, Maria Grazia Pirastu, Roberta Portier, Ralph J. Ramos, Kenneth S. Robertson, Larry W. Rodriguez, Theresa Roosli, Martin Ross, Matt K. Roy, Deodutta Rusyn, Ivan Saldiva, Paulo Sass, Jennifer Savolainen, Kai Scheepers, Paul T. J. Sergi, Consolato Silbergeld, Ellen K. Smith, Martyn T. Stewart, Bernard W. Sutton, Patrice Tateo, Fabio Terracini, Benedetto Thielmann, Heinz W. Thomas, David B. Vainio, Harri Vena, John E. Vineis, Paolo Weiderpass, Elisabete Weisenburger, Dennis D. Woodruff, Tracey J. Yorifuji, Takashi Yu, Il Je Zambon, Paola Zeeb, Hajo Zhou, Shu-Feng TI Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA) SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Editorial Material ID HISTORICAL CONTROL DATA; LYMPHOMA C1 [Portier, Christopher J.] Environm Hlth Consultant, CH-3600 Thun, Switzerland. [Armstrong, Bruce K.] Univ Sydney, Sydney, NSW, Australia. [Baguley, Bruce C.] Univ Auckland, Auckland, New Zealand. [Baur, Xaver] Charite, Berlin, Germany. [Belyaev, Igor] Canc Res Inst, Bratislava, Slovakia. [Belle, Robert] Univ Paris 06, Sorbonne Univ, UMR8227, UPMC, Roscoff, France. [Belpoggi, Fiorella; Mandrioli, Daniele] CesareMaltoni Canc Res Ctr, Bologna, Italy. [Biggeri, Annibale] Univ Florence, Inst Canc Prevent & Res, I-50121 Florence, Italy. [Bosland, Maarten C.] Univ Illinois, Chicago, IL USA. [Bruzzi, Paolo] San Martino IST Hosp, Natl Canc Res Inst, Genoa, Italy. [Budnik, Lygia Therese] Univ Hamburg, Hamburg, Germany. [Bugge, Merete D.] Natl Inst Occupat Hlth, STAMI, Oslo, Norway. [Burns, Kathleen] Sciencecorps, Lexington, MA USA. [Calaf, Gloria M.] Univ Tarapaca, Inst Alta Invest, Arica, Chile. [Carpenter, David O.] Univ Albany, Inst Hlth & Environm, Rensselaer, NY USA. [Carpenter, Hillary M.] Toxicologist, Maplewood, MN USA. [Lopez-Carrillo, Lizbeth] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Clapp, Richard] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy. [Consonni, Dario] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Prevent Med, Milan, Italy. [Comba, Pietro] Ist Super Sanita, Dept Environm & Primary Prevent, Rome, Italy. [Craft, Elena] Environm Def Fund, Austin, TX USA. [Dalvie, Mohamed Aqiel] Univ Cape Town, Ctr Environm & Occupat Hlth, Cape Town, South Africa. [Davis, Devra] Environm Hlth Trust, Jackson Hole, WY USA. [Davis, Devra] Hebrew Univ Jerusalem, Hadassah Med Sch, Jerusalem, Israel. [Demers, Paul A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [De Roos, Anneclaire J.] Drexel Univ, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [DeWitt, Jamie] E Carolina Univ, Brody Sch Med, Greenville, NC USA. [Forastiere, Francesco] Lazio Reg Hlth Serv, Dept Epidemiol, Rome, Italy. [Freedman, Jonathan H.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Fritschi, Lin] Curtin Univ, Sch Publ Hlth, Perth, WA, Australia. [Gaus, Caroline] Univ Queensland, Dept Environm Toxicol, Brisbane, Qld, Australia. [Gohlke, Julia M.] Virginia Tech, Dept Populat Hlth Sci, Blacksburg, VA USA. [Goldberg, Marcel] Paris Descartes Univ, Paris, France. [Greiser, Eberhard] Epi Consult GmbH, Musweiler, Germany. [Hansen, Johnni] Danish Canc Soc Res Ctr, Copenhagen, Denmark. [Hardell, Lennart] Univ Hosp, Orebra, Sweden. [Hauptmann, Michael] Netherlands Canc Inst, Biostat Branch, Amsterdam, Netherlands. [Huang, Wei] Peking Univ, Fac Dept Occupat & Environm Hlth, Sch Publ Hlth, Beijing, Peoples R China. [Huff, James] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [James, Margaret O.] Univ Florida, Gainesville, FL USA. [Jameson, C. W.] CWJ Consulting LLC, Cape Coral, FL USA. [Kortenkamp, Andreas] Brunel Univ London, Inst Environm Hlth & Soc, London, England. [Kopp-Schneider, Annette] German Canc Res Ctr, Div Biostat, Heidelberg, Germany. [Kromhout, Hans] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Larramendy, Marcelo L.] Natl Univ La Plata, Natl Council Sci & Technol Res, La Plata, Buenos Aires, Argentina. [Landrigan, Philip J.] Icahn Sch Med Mt Sinai, Arnhold Inst Global Hlth, New York, NY USA. [Lash, Lawrence H.] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Leszczynski, Dariusz] Univ Helsinki, Dept Biosci, Helsinki, Finland. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Magnani, Corrado] Univ Piemonte Orientale, Canc Epidemiol Unit, Novara, Italy. [Martin, Francis L.] Univ Lancaster, Ctr Biophoton, Lancaster LA1 4YW, England. [Merler, Enzo] Natl Hlth Serv, Occupat Hlth Unit, Dept Prevent, Padua, Italy. [Michelozzi, Paola] Dept Epidemiol Lazio Reg, Rome, Italy. [Miligi, Lucia] ISPO Canc Prevent & Res Inst, Occupat & Environm Epidemiol Unit, Florence, Italy. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Mirabelli, Dario] Univ Turin, Unit Canc Epidemiol, Turin, Italy. [Mirabelli, Dario] CPO Piemonte, Turin, Italy. [Mirer, Franklin E.] CUNY, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, New York, NY USA. [Naidoo, Saloshni] Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Durban, South Africa. [Perry, Melissa J.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC USA. [Petronio, Maria Grazia] Local Hlth Author Empoli, Hlth & Environm Dept Prevent, Florence, Italy. [Pirastu, Roberta] Sapienza Rome Univ, Dept Biol & Biotechnol Charles Darwin, Rome, Italy. [Portier, Ralph J.] Louisiana State Univ, Dept Environm Sci, Sch Coast & Environm, Los Angeles, CA USA. [Ramos, Kenneth S.] Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med, Tucson, AZ USA. [Robertson, Larry W.] Univ Iowa, Iowa Superfund Res Program, Iowa City, IA USA. [Robertson, Larry W.] Univ Iowa, Interdisciplinary Grad Program Human Toxicol, Iowa City, IA USA. [Rodriguez, Theresa] Natl Autonomous Univ Nicaragua UNAN Leon, Ctr Res Hlth Work & Environm CISTA, Leon, Nicaragua. [Roosli, Martin] Univ Basel, Swiss Trop & Publ Hlth Inst, Associated Inst, Basel, Switzerland. [Ross, Matt K.] Mississippi State Univ, Coll Vet Med, Mississippi State, MS 39762 USA. [Roy, Deodutta] Florida Int Univ, Dept Environm & Occupat Hlth, Miami, FL 33199 USA. [Rusyn, Ivan] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. [Saldiva, Paulo] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Sass, Jennifer] Nat Resources Def Council, Washington, DC USA. [Sass, Jennifer] George Washington Univ, Washington, DC USA. [Savolainen, Kai] Finnish Inst Occupat Hlth, Nanosafety Res Ctr, Helsinki, Finland. [Scheepers, Paul T. J.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands. [Sergi, Consolato] Univ Alberta, Dept Pathol, Edmonton, AB, Canada. [Silbergeld, Ellen K.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Stewart, Bernard W.] Univ New South Wales, Fac Med, Randwick, NSW, Australia. [Sutton, Patrice] Univ Calif San Francisco, Program Reprod Hlth & Environm, San Francisco, CA 94143 USA. [Tateo, Fabio] Ist Geosce Georisorse CNR, Padua, Italy. [Terracini, Benedetto] Univ Turin, Turin, Italy. [Thielmann, Heinz W.] German Canc Res Ctr, Heidelberg, Germany. [Thielmann, Heinz W.] Heidelberg Univ, Fac Pharm, Bergheimer Str 58, D-69115 Heidelberg, Germany. [Thomas, David B.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Vainio, Harri] Kuwait Univ, Fac Publ Hlth, Kuwait, Kuwait. [Vena, John E.] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC USA. Imperial Coll London, Dept Environm Epidemiol, London, England. [Weiderpass, Elisabete] Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, Oslo, Norway. [Weiderpass, Elisabete] Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland. [Weisenburger, Dennis D.] City Hope Med Ctr, Dept Pathol, Duarte, CA USA. [Woodruff, Tracey J.] Univ Calif San Francisco, Program Reprod Hlth & Environm, San Francisco, CA 94143 USA. [Yorifuji, Takashi] Okayama Univ, Okayama, Japan. [Yu, Il Je] Hoseo Univ, Inst Nanoprod Safety Res, Asan, South Korea. [Zambon, Paola] Univ Padua, Padua, Italy. [Zeeb, Hajo] Leibniz Inst Prevent Res & Epidemiol, Dept Prevent & Evaluat, Bremen, Germany. [Zhou, Shu-Feng] Univ S Florida, Coll Pharm, Tampa, FL USA. RP Portier, CJ (reprint author), Environm Hlth Consultant, CH-3600 Thun, Switzerland. EM cportier@me.com RI Michelozzi, Paola/J-8608-2016; Consonni, Dario/K-7943-2016; Natarajan, Meena/J-9167-2012; Roosli, Martin/A-2658-2008; Weiderpass, Elisabete/M-4029-2016; Forastiere, Francesco/J-9067-2016; OI L Martin, Francis/0000-0001-8562-4944; Michelozzi, Paola/0000-0002-1646-2555; Consonni, Dario/0000-0002-8935-3843; Gohlke, Julia/0000-0002-6984-2893; DeWitt, Jamie/0000-0002-0440-4059; Natarajan, Meena/0000-0001-5652-9681; Roosli, Martin/0000-0002-7475-1531; Weiderpass, Elisabete/0000-0003-2237-0128; Forastiere, Francesco/0000-0002-9162-5684; Gaus, Caroline/0000-0002-0585-8511; Bruzzi, Paolo/0000-0002-7874-2077 FU NCI NIH HHS [P30 CA086862] NR 27 TC 4 Z9 4 U1 24 U2 34 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 AUG PY 2016 VL 70 IS 8 BP 741 EP 745 DI 10.1136/jech-2015-207005 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR8MS UT WOS:000380152600002 PM 26941213 ER PT J AU Pan, BF Liu, XP Asai, Y Kurima, K Griffith, AJ Holt, JR AF Pan, Bifeng Liu, Xiao-Ping Asai, Yukako Kurima, Kiyoto Griffith, Andrew J. Holt, Jeffrey R. TI Cysteine Mutagenesis Reveals TMC1 Residues that Contribute to Mechanotransduction SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the Society-of-General-Physiologists - Genetic and Animal Models for Ion Channel Function in Physiology and Disease CY SEP 07-11, 2016 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiologists HO Marine Biol Lab C1 [Pan, Bifeng; Liu, Xiao-Ping; Asai, Yukako; Holt, Jeffrey R.] Harvard Med Sch, Dept Otolaryngol, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Kurima, Kiyoto; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1295 EI 1540-7748 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 2016 VL 148 IS 2 MA 65 BP 28A EP 28A PG 1 WC Physiology SC Physiology GA DS5OT UT WOS:000380832300074 ER PT J AU Rehermann, B AF Rehermann, Barbara TI Peptide-dependent HLA-KIR-mediated regulation of NK cell function SO JOURNAL OF HEPATOLOGY LA English DT Article ID INHIBITORY RECEPTOR; DIRECT BINDING; RECOGNITION; SELECTIVITY; ACTIVATION; INFECTION C1 [Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, DHHS,NIH, 10 Ctr Dr,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, DHHS,NIH, 10 Ctr Dr,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov FU NIDDK, NIH FX This work was supported by the intramural research program of NIDDK, NIH. NR 20 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD AUG PY 2016 VL 65 IS 2 BP 237 EP 239 DI 10.1016/j.jhep.2016.03.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DS2AH UT WOS:000380516900002 PM 27212248 ER PT J AU Lunemann, S Martrus, G Holzemer, A Chapel, A Ziegler, M Korner, C Beltran, WG Carrington, M Wedemeyer, H Altfeld, M AF Lunemann, Sebastian Martrus, Gloria Hoelzemer, Angelique Chapel, Anais Ziegler, Maja Koerner, Christian Beltran, Wilfredo Garcia Carrington, Mary Wedemeyer, Heiner Altfeld, Marcus TI Sequence variations in HCV core-derived epitopes alter binding of KIR2DL3 to HLA-C*03:04 and modulate NK cell function SO JOURNAL OF HEPATOLOGY LA English DT Article DE HCV; KIR; HLA; NK ID NATURAL-KILLER-CELLS; HEPATITIS-C VIRUS; MHC CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTOR; CRYSTAL-STRUCTURE; INHIBITION; INFECTION; HLA; RECOGNITION; ACTIVATION AB Background & Aims: Both natural killer (NK) cells and human leukocyte antigen (HLA)/killer cell immunoglobulin like receptor (KIR) interactions have been shown to play an important role in the control, clearance and progression of hepatitis C virus (HCV) disease. Here we aimed at elucidating the effects of viral peptides derived from HCV on HLA stabilization, changes in KIR binding and primary NK cell function. Methods: Transporter for antigen presentation-deficient 722.221 cells stably transfected with HLA-C*03: 04 were used to screen 200 overlapping peptides, covering the non-structural protein 3 (NS3) and core protein of HCV genotype 1, for their ability to bind and stabilize HLA-C*03: 04. Binding of KIR2DL3 to the HLA-peptide complex was assessed using a KIR2DL3-IgG fusion construct. Primary NK cells were isolated from healthy donors to investigate the effects of identified peptides on KIR2DL3(+) NK cell function. Results: Thirty-one peptides able to stabilize HLA-C*03: 04 were identified. One 9mer peptide, YIPLVGAPL, resulted in significantly higher KIR2DL3 binding to HLA-C*03:04(+) 722.221 cells and suppression of primary KIR2DL3+ NK cell function. Interestingly this sequence exhibited a high frequency of mutations in different HCV genotypes. These genotype-specific peptides showed lower HLA-C*03: 04 stabilization, decreased binding of the inhibitory KIR2DL3 and lower inhibition of NK cell function. Conclusions: Taken together we show that a viral peptide derived from the core protein of HCV genotype 1 binding to HLA-C*03: 04 results in a sequence-dependent engagement of the inhibitory NK cell receptor KIR2DL3, while the large majority of the remain-ing 30 HLA-C*03: 04 binding HCV core peptides did not. These data show that sequence variations within HCV can modulate NK cell function, providing potential pathways for viral escape. Lay summary: We identified a HCV peptide that dampens NK cell responses, and thereby possibly prevents killing of infected cells through this part of the innate immune system. This is facilitated via presentation of the viral peptide on HLA*03: 04 to the inhibitory KIR receptor KIR2DL3 on NK cells. Naturally occurring sequence mutations in the peptide alter these interactions making the inhibition less efficient. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Lunemann, Sebastian; Martrus, Gloria; Chapel, Anais; Ziegler, Maja; Koerner, Christian; Altfeld, Marcus] Heinrich Pette Inst, Dept Virol Immunol, Hamburg, Germany. [Hoelzemer, Angelique] Univ Hosp Eppendorf, Dept Internal Med, Hamburg, Germany. [Wedemeyer, Heiner] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. [Beltran, Wilfredo Garcia; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Carrington, Mary] Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Altfeld, M (reprint author), Martinistr 52, D-20251 Hamburg, Germany. EM marcus.altfeld@hpi.uni-hamburg.de FU Deutsche Forschungsgemeinschaft [SFB841] FX This study was supported by the Deutsche Forschungsgemeinschaft (SFB841). NR 30 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD AUG PY 2016 VL 65 IS 2 BP 252 EP 258 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DS2AH UT WOS:000380516900007 PM 27057987 ER PT J AU Ouchi, T Nakato, G Udey, MC AF Ouchi, Takeshi Nakato, Gaku Udey, Mark C. TI EpCAM Expressed by Murine Epidermal Langerhans Cells Modulates Immunization to an Epicutaneously Applied Protein Antigen SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ADHESION MOLECULE EPCAM; DERMAL DENDRITIC CELLS; SCALDED-SKIN SYNDROME; TIGHT JUNCTION; EP-CAM; CONTACT HYPERSENSITIVITY; BULLOUS IMPETIGO; IN-VIVO; DISTINCT; IDENTIFICATION AB Langerhans cells (LCs) induce type 2 antibodies reactive with protein antigens that are applied to murine skin in the absence of adjuvant after extending their dendrites through tight junctions to acquire antigens and migrating to regional lymph nodes. In response to contact sensitizers, epithelial cell adhesion molecule (EpCAM) on LCs promotes LC dendrite mobility and LC migration. In epithelial cells, EpCAM regulates expression and distribution of selected tight junctions-associated claudins. To determine if EpCAM regulates claudins in LC and immune responses to externally applied proteins, we studied conditional knockout mice with EpCAM-deficient LCs. Although LC claudin-1 levels were dramatically reduced in the absence of EpCAM, conditional knockout mice with EpCAM-deficient LCs and control LC dendrites docked with epidermal tight junctions with equal efficiencies and ingested surface proteins. Topical immunization of conditional knockout mice with EpCAM-deficient LCs with ovalbumin led to increased induction of type 2 Ova-specific antibodies and enhanced proliferation of ovalbumin-reactive T cells associated with increased accumulation of LCs in lymph nodes. These results suggest that, in the absence of strong adjuvants, EpCAM-deficient LCs exhibit increased migration to regional lymph nodes. EpCAM appears to differentially regulate LC mobility/migration in the setting of limited inflammation as compared with the intense inflammation triggered by contact sensitizers. C1 [Ouchi, Takeshi; Nakato, Gaku; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 4,Room 4N222, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 4,Room 4N222, Bethesda, MD 20892 USA. EM udeym@mail.nih.gov FU Intramural NIH HHS [Z01 SC003669-19, Z99 CA999999, Z01 SC003669-18] NR 44 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2016 VL 136 IS 8 BP 1627 EP 1635 DI 10.1016/j.jid.2016.04.005 PG 9 WC Dermatology SC Dermatology GA DS2HE UT WOS:000380585200088 PM 27106675 ER PT J AU Ishitsuka, Y Huebner, AJ Rice, RH Koch, PJ Speransky, VV Steven, AC Roop, DR AF Ishitsuka, Yosuke Huebner, Aaron J. Rice, Robert H. Koch, Peter J. Speransky, Vladislav V. Steven, Alasdair C. Roop, Dennis R. TI Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CORNIFIED CELL-ENVELOPE; ANTIOXIDANT RESPONSIVE ELEMENTS; NF-E2-RELATED FACTOR-2; STRUCTURAL PROTEINS; BINDING PROTEINS; BARRIER FUNCTION; NRF2; ACTIVATION; IDENTIFICATION; PSORIASIS AB Loricrin is a major component of the cornified cell envelope, a highly insoluble structure composed of covalently cross-linked proteins. Although loricrin knockout mice only exhibit a mild transient phenotype at birth, they show a marked delay in the formation of an epidermal barrier in utero. We recently discovered that induction of a compensatory response to repair the defective barrier is initiated by amniotic fluid via activation of NF-E2-related factor 2 and identified Sprr2d and Sprr2h as direct transcriptional targets. Proteomic analysis suggested that other proteins were also incorporated into the loricrin knockout cell envelope, in addition to the small proline rich proteins. Here we present evidence suggesting that the late cornified envelope 1 proteins are also compensatory components as determined by their localization within the loricrin knockout cell envelope via immunoelectron microscopy. We also demonstrate that late cornified envelope 1 genes are upregulated at the transcriptional level in loricrin knockout mouse skin and confirm that late cornified envelope 1 genes are transcriptional targets of NRF2. Our present study further highlights the complexity and importance of a compensatory mechanism that evolved in terrestrial animals to ensure the formation of a functional epidermal barrier. C1 [Ishitsuka, Yosuke; Huebner, Aaron J.; Koch, Peter J.; Roop, Dennis R.] Univ Colorado, Dept Dermatol, Anschutz Med Campus,Res Complex 1 North, Aurora, CO 80045 USA. [Ishitsuka, Yosuke; Huebner, Aaron J.; Koch, Peter J.; Roop, Dennis R.] Univ Colorado, Charles C Gates Ctr Regenerat Med, Anschutz Med Campus,Res Complex 1 North, Aurora, CO 80045 USA. [Rice, Robert H.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. [Speransky, Vladislav V.] Ted Pella, Life Sci, Redding, CA USA. [Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Roop, DR (reprint author), Univ Colorado, Dept Dermatol, Anschutz Med Campus,Res Complex 1 North, Aurora, CO 80045 USA.; Roop, DR (reprint author), Univ Colorado, Charles C Gates Ctr Regenerat Med, Anschutz Med Campus,Res Complex 1 North, Aurora, CO 80045 USA. EM dennis.roop@ucdenver.edu FU NIBIB; NIAMS [AR47898] FX We thank Michal Jarnik for his contribution to the EM studies. This research was supported in part by the Intramural Research Programs of NIAMS and NIBIB, and a grant from NIAMS (AR47898) to DRR. We also thank the University of Colorado Skin Disease Research Center (P30AR057212) Morphology Phenotyping Core for assistance. NR 40 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2016 VL 136 IS 8 BP 1656 EP 1663 DI 10.1016/j.jid.2016.04.022 PG 8 WC Dermatology SC Dermatology GA DS2HE UT WOS:000380585200091 PM 27167730 ER PT J AU Li, L Kim, J Flowers, B Cataisson, C Yuspa, S AF Li, L. Kim, J. Flowers, B. Cataisson, C. Yuspa, S. TI Rho-associated protein kinase (ROCK) controls cellular homeostasis of mouse primary keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 11-14, 2016 CL Scottsdale, AZ SP Soc Investigat Dermatol C1 [Li, L.; Kim, J.; Flowers, B.; Cataisson, C.; Yuspa, S.] NCI, Lab Canc Biol & Genet, 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2016 VL 136 IS 8 MA LB793 BP B8 EP B8 PG 1 WC Dermatology SC Dermatology GA DS2HE UT WOS:000380585200040 ER PT J AU Nemeth, K Gorog, A Mezey, E Harsing, J Kuroli, E Rady, P Fischer, M Kovacs, L Sillo, P Tyring, SK Karpati, S AF Nemeth, K. Gorog, A. Mezey, E. Harsing, J. Kuroli, E. Rady, P. Fischer, M. Kovacs, L. Sillo, P. Tyring, S. K. Karpati, S. TI Detection of hair follicle-associated Merkel Cell Polyomavirus in an immunocompromised host with follicular spicules and alopecia and successful treatment with valganciclovir SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 11-14, 2016 CL Scottsdale, AZ SP Soc Investigat Dermatol C1 [Nemeth, K.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Nemeth, K.; Gorog, A.; Harsing, J.; Kuroli, E.; Sillo, P.; Karpati, S.] Semmelweis Univ, Dept Dermatol, Budapest, Hungary. [Mezey, E.] NIDCR, NIH, Bethesda, MD USA. [Fischer, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kovacs, L.] Semmelweis Univ, Dept Pediat 1, Budapest, Hungary. [Rady, P.; Tyring, S. K.] UTHlth Med Sch, Dept Dermatol, Houston, TX 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2016 VL 136 IS 8 MA LB807 BP B10 EP B10 PG 1 WC Dermatology SC Dermatology GA DS2HE UT WOS:000380585200053 ER PT J AU Nguyen, KD Lee, EE Tyring, SK North, JP Cockerell, CJ Buck, CB Wang, RC AF Nguyen, K. D. Lee, E. E. Tyring, S. K. North, J. P. Cockerell, C. J. Buck, C. B. Wang, R. C. TI A novel strain of HPyV7 causing a HIV/AIDS-associated pruritic rash SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 11-14, 2016 CL Scottsdale, AZ SP Soc Investigat Dermatol C1 [Nguyen, K. D.; Lee, E. E.; Cockerell, C. J.; Wang, R. C.] Univ Texas Southwestern Med Ctr, Dept Dermatol, Dallas, TX USA. [Tyring, S. K.] Univ Texas Hlth Sci Ctr Houston, Dept Dermatol, Houston, TX 77030 USA. [North, J. P.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [North, J. P.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Buck, C. B.] NCI, Bethesda, MD 20892 USA. NR 0 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 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2016 VL 136 IS 8 MA LB806 BP B10 EP B10 PG 1 WC Dermatology SC Dermatology GA DS2HE UT WOS:000380585200050 ER PT J AU Kim, SYH Wilson, R De Vries, R Ryan, KA Holloway, RG Kieburtz, K AF Kim, Scott Y. H. Wilson, Renee De Vries, Raymond Ryan, Kerry A. Holloway, Robert G. Kieburtz, Karl TI Are patients with amyotrophic lateral sclerosis at risk of a therapeutic misconception? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID ONCOLOGY TRIALS; CLINICAL-TRIALS; DOUBLE-BLIND; BENEFIT AB Objectives To assess whether persons with amyotrophic lateral sclerosis (ALS) are at risk of a therapeutic misconception (TM) in which they misconceive research as treatment or overestimate the likelihood of its benefit. Methods 72 patients with ALS recruited via academic and patient organisations were surveyed using a hypothetical first-in-human intervention study scenario. We elicited their understanding of the purpose of the study ('purpose-of-research question') and then asked how they interpreted the question. We then asked for an estimate of the likelihood that their ALS would improve by participating and asked them to explain the meaning of their estimates. Results Although 10 of 72 (14%) subjects incorrectly said that the intervention study was 'mostly intending to help [me]' in response to the purpose-of-research question, 7 of those 10 thought that the question was asking them about their own motivations for participating. Overall, only one of 72 respondents (1.4%) both understood the purpose-of-research question as intended and gave the incorrect response. Subjects' mean estimate of likelihood of benefit was 31% (SD 26). This was due to 29 of 72 of respondents providing high estimates (50%-54% likelihood), which they said were expressions of hope and need for a positive attitude; among those who said their estimates meant 'those are the facts' or 'there is a lot of uncertainty', the estimates were much lower (12.6% and 18.5%, respectively). Conclusions In this group of patients with ALS considering a hypothetical first-in-human intervention study, apparent TM responses have alternative explanations and the risk of true TM appears low. C1 [Kim, Scott Y. H.] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. [Wilson, Renee] Univ Rochester, Ctr Human Expt Therapeut, Rochester, NY USA. [De Vries, Raymond] Univ Michigan, Dept Learning Hlth Sci, Ann Arbor, MI 48109 USA. [De Vries, Raymond; Ryan, Kerry A.] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA. [Holloway, Robert G.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Kieburtz, Karl] Univ Rochester, Clin & Translat Sci Inst, Rochester, NY USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA. EM scott.kim@nih.gov FU National Institute for Neurological Disorders and Stroke [R01-NS062770]; CTSA award from the National Center for Research Resources [UL1 RR024160]; National Center for Advancing Translational Sciences; Intramural Research Program; National Institutes of Health, USA FX This work was supported in part by the National Institute for Neurological Disorders and Stroke (R01-NS062770), a CTSA award (UL1 RR024160) from the National Center for Research Resources and the National Center for Advancing Translational Sciences and the Intramural Research Program, all of the National Institutes of Health, USA. NR 27 TC 1 Z9 1 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD AUG PY 2016 VL 42 IS 8 BP 514 EP 518 DI 10.1136/medethics-2015-103319 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DS7YG UT WOS:000380998600008 PM 26964569 ER PT J AU Kim, SYH De Vries, R Holloway, RG Kieburtz, K AF Kim, Scott Y. H. De Vries, Raymond Holloway, Robert G. Kieburtz, Karl TI Understanding the 'therapeutic misconception' from the research participant's perspective SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material ID TRIALS C1 [Kim, Scott Y. H.] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. [De Vries, Raymond] Univ Michigan, Ctr Bioeth & Social Sci, Ann Arbor, MI 48109 USA. [De Vries, Raymond] Univ Michigan, Dept Learning Hlth Sci, Ann Arbor, MI 48109 USA. [Holloway, Robert G.; Kieburtz, Karl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Kieburtz, Karl] Univ Rochester, Ctr Human Expt Therapeut, Rochester, NY USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA. EM scott.kim@nih.gov NR 13 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 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD AUG PY 2016 VL 42 IS 8 BP 522 EP 523 DI 10.1136/medethics-2016-103597 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DS7YG UT WOS:000380998600011 PM 27145809 ER PT J AU Hristovski, D Kastrin, A Dinevski, D Burgun, A Ziberna, L Rindflesch, TC AF Hristovski, Dimitar Kastrin, Andrej Dinevski, Dejan Burgun, Anita Ziberna, Lovro Rindflesch, Thomas C. TI Using Literature-Based Discovery to Explain Adverse Drug Effects SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE Literature-based discovery; Text mining; Pharmacovigilance; Adverse drug effects; Adverse drug reactions; Pharmacogenomics ID PATIENT; RHABDOMYOLYSIS; PANCREATITIS; GENERATION; IRINOTECAN; KNOWLEDGE; IDENTIFY; TEXT; RATS AB We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects. C1 [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Ljubljana, Slovenia. [Kastrin, Andrej] Novo Mesto, Fac Informat Studies, Ljubljana, Slovenia. [Dinevski, Dejan] Univ Maribor, Fac Med, Maribor, Slovenia. [Burgun, Anita] Paris Descartes Univ, Georges Pompidou European Hosp, APHP, INSERM,UMRS 1138,Eq 22, Paris, France. [Ziberna, Lovro] Univ Ljubljana, Fac Med, Inst Pharmacol & Expt Toxicol, Ljubljana, Slovenia. [Rindflesch, Thomas C.] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Hristovski, D (reprint author), Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Ljubljana, Slovenia. EM dimitar.hristovski@mf.uni-lj.si FU Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine FX This work was supported in part by the Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine. Authors would like to thank Celine Narjoz and Marie-Anne Loriot for suggesting the additional adverse drug reactions, which we used in this study. We are also grateful for the contribution of the medical students (Faculty of Medicine, University of Maribor) in the evaluation of the extracted relations. NR 26 TC 0 Z9 0 U1 6 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0148-5598 EI 1573-689X J9 J MED SYST JI J. Med. Syst. PD AUG PY 2016 VL 40 IS 8 AR 185 DI 10.1007/s10916-016-0544-z PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA DS3QG UT WOS:000380697200005 PM 27318993 ER PT J AU Ryerson, LZ Frohman, TC Foley, J Kister, I Weinstock-Guttman, B Tornatore, C Pandey, K Donnelly, S Pawate, S Bomprezzi, R Smith, D Kolb, C Qureshi, S Okuda, D Kalina, J Rimler, Z Green, R Monson, N Hoyt, T Bradshaw, M Fallon, J Chamot, E Bucello, M Beh, S Cutter, G Major, E Herbert, J Frohman, EM AF Ryerson, L. Zhovtis Frohman, T. C. Foley, J. Kister, I. Weinstock-Guttman, B. Tornatore, C. Pandey, K. Donnelly, S. Pawate, S. Bomprezzi, R. Smith, D. Kolb, C. Qureshi, S. Okuda, D. Kalina, J. Rimler, Z. Green, R. Monson, N. Hoyt, T. Bradshaw, M. Fallon, J. Chamot, E. Bucello, M. Beh, S. Cutter, G. Major, E. Herbert, J. Frohman, E. M. TI Extended interval dosing of natalizumab in multiple sclerosis SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID RECONSTITUTION INFLAMMATORY SYNDROME; TREATMENT INTERRUPTION; CONTROLLED TRIAL; DISEASE-ACTIVITY; MS PATIENTS; JC VIRUS; WITHDRAWAL; THERAPY; HOLIDAY; SAFETY AB Background Natalizumab (NTZ), a monoclonal antibody to human alpha(4)beta(1)/beta(7) integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days. Methods A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks. Results 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. Conclusions Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID. C1 [Ryerson, L. Zhovtis; Kister, I.; Kalina, J.; Rimler, Z.; Fallon, J.; Herbert, J.] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Frohman, T. C.; Qureshi, S.; Okuda, D.; Monson, N.; Beh, S.; Frohman, E. M.] Univ Texas Southwestern Med Ctr, Dept Neurol, Dallas, TX USA. [Frohman, T. C.; Qureshi, S.; Okuda, D.; Monson, N.; Beh, S.; Frohman, E. M.] Univ Texas Southwestern Med Ctr, Dept Neurotherapeut, Dallas, TX USA. [Foley, J.; Hoyt, T.] Rocky Mt MS Clin, Salt Lake City, UT USA. [Weinstock-Guttman, B.; Kolb, C.; Bucello, M.] Univ Buffalo, Buffalo, NY USA. [Tornatore, C.] Georgetown Univ, Washington, DC USA. [Pandey, K.; Green, R.] Barnabas Hlth MS Ctr, Livingston, NJ USA. [Donnelly, S.] CUNY, Grad Ctr, New York, NY USA. [Pawate, S.; Bradshaw, M.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Bomprezzi, R.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Smith, D.] Multiple Sclerosis Ctr Connecticut, Norwich, CT USA. [Chamot, E.; Cutter, G.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA. [Major, E.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Frohman, E. M.] Univ Texas Southwestern Med Ctr, Dept Ophthalmol, Dallas, TX USA. [Frohman, E. M.] Univ Texas Dallas, Dept Bioengn, Dallas, TX 75230 USA. [Frohman, E. M.] Univ Texas Dallas, Dept Behav & Brain Sci, Dallas, TX 75230 USA. RP Frohman, EM (reprint author), Univ Texas Southwestern Sch Med, Dept Neurol & Neurotherapeut, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Elliot.frohman@utsouthwesternen.edu OI Ryerson , Lana/0000-0003-1868-3893; Kister, Ilya/0000-0003-3549-949X FU Biogen Idec; Novartis; Genzyme; Acorda; Guthy-Jackson Charitable Foundation; National Multiple Sclerosis Society; Serono; Navartis; Questcor Pharmaceuticals, Inc; Shire; TEVA; Biogen; EMD Serono; Acorda Therapeutics; TEVA Neuroscience; Genzyme Corp; Consortium of Multiple Sclerosis Centers; Cerespir Inc; Consortium of MS Centers; D3 (Drug Discovery and Development); Genentech; Innate Therapeutics; Jannsen Pharmaceuticals; Klein-Buendel Incorporated; Medimmune; Opexa Therapeutics; Receptos; Roche; Savara Inc; Spiniflex Pharmaceuticals; Somahlution; Teva pharmaceuticals; Transparency Life Sciences; PML Consortium; Takeda/Millennium Pharma; Glaxo Smith Klein; Genentech Roche; Sanofi Genzyme FX LZR has received research support from Biogen Idec. She has received compensation for advisory board and speaker activities from Biogen Idec and Teva. TCF has received speaker and consultant fees from Novartis, Genzyme and Acorda. IK is the member of scientific advisory board for Biogen Idec and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono and Navartis. JF has served as a consultant for and receives honoraria from Biogen, Genzyme, Teva, Novartis and Avanir. BW-G has participated in speaker's bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Acorda Therapeutics, Inc and Genentech. BW-G also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc and Shire. She serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs. CT has received speaker and consulting fees from Biogen Idec. KP has received speaker and consulting fees from Acorda, TEVA and Biogen. DS has received speaker and consulting fees from Biogen Idec. CK has received speaker and consulting fees from Biogen, Teva, EMD Serono and Acorda. DO received lecture fees from Acorda Therapeutics, Genzyme and TEVA Neuroscience, consulting and advisory board fees from Genzyme, Novartis and TEVA Neuroscience, and research support from Biogen. EC reports grants from Genzyme Corp, grants from Consortium of Multiple Sclerosis Centers, grants from Biogen Idec, grants from National Multiple Sclerosis Society, outside the submitted work. MBu has received speaker and consulting fees from Genzyme, Teva and EMD Serono. GC has received consulting, speaking fees and advisory boards: Cerespir Inc, Consortium of MS Centers (grant), D3 (Drug Discovery and Development), Genzyme, Genentech, Innate Therapeutics, Jannsen Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, Savara Inc, Spiniflex Pharmaceuticals, Somahlution, Teva pharmaceuticals, Transparency Life Sciences. EM reports personal fees from PML Consortium, personal fees from Takeda/Millennium Pharma, personal fees from Glaxo Smith Klein, personal fees from Genentech Roche, personal fees from Sanofi Genzyme, outside the submitted work. JH has received research support from Biogen Idec. EMF has received speaker and consultant fees from Novartis, Genzyme, TEVA and Acorda. NR 28 TC 4 Z9 4 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 2016 VL 87 IS 8 BP 885 EP 889 DI 10.1136/jnnp-2015-312940 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA DS1VP UT WOS:000380392200014 ER PT J AU Yucesoy, B Talzhanov, Y Barmada, MM Johnson, VJ Kashon, ML Baron, E Wilson, NW Frye, B Wang, W Fluharty, K Gharib, R Meade, J Germolec, D Luster, MI Nedorost, S AF Yucesoy, Berran Talzhanov, Yerkebulan Barmada, M. Michael Johnson, Victor J. Kashon, Michael L. Baron, Elma Wilson, Nevin W. Frye, Bonnie Wang, Wei Fluharty, Kara Gharib, Rola Meade, Jean Germolec, Dori Luster, Michael I. Nedorost, Susan TI Genetic Basis of Irritant Susceptibility in Health Care Workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; OF-FUNCTION MUTATIONS; CONTACT-DERMATITIS; ATOPIC-DERMATITIS; FACTOR RECEPTOR; JAPANESE POPULATION; PSORIASIS-VULGARIS; SKIN INFLAMMATION; FILAGGRIN GENE; IL22 GENE AB Objective: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within genes involved in inflammation, skin barrier integrity, signaling/pattern recognition, and antioxidant defense with irritant susceptibility in a group of health care workers. Methods: The 536 volunteer subjects were genotyped for selected SNPs and patch tested with three model irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH), and benzalkonium chloride (BKC). Genotyping was performed on genomic DNA using Illumina Goldengate custom panels. Results: The ACACB (rs2268387, rs16934132, rs2284685), NTRK2 (rs10868231), NTRK3 (rs1347424), IL22 (rs1179251), PLAU (rs2227564), EGFR (rs6593202), and FGF2 (rs308439) SNPs showed an association with skin response to tested irritants in different genetic models (all at P < 0.001). Functional annotations identified two SNPs in PLAU (rs2227564) and ACACB (rs2284685) genes with a potential impact on gene regulation. In addition, EGF (rs10029654), EGFR (rs12718939), CXCL12 (rs197452), and VCAM1 (rs3917018) genes showed an association with hand dermatitis (P < 0.005). Conclusions: The results demonstrate that genetic variations in genes related to inflammation and skin homeostasis can influence responses to irritants and may explain inter-individual variation in the development of subsequent contact dermatitis. C1 [Yucesoy, Berran; Kashon, Michael L.; Frye, Bonnie; Wang, Wei; Fluharty, Kara; Meade, Jean] NIOSH, Hlth Effects Lab Div, CDC, Morgantown, WV 26505 USA. [Talzhanov, Yerkebulan; Barmada, M. Michael] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. [Johnson, Victor J.] BRT, Morrisville, NY USA. [Baron, Elma; Nedorost, Susan] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Wilson, Nevin W.] Univ Nevada, Sch Med, Dept Pediat, Reno, NV 89557 USA. [Gharib, Rola] West Virginia Univ, Sch Med, Dept Dermatol, Morgantown, WV USA. [Germolec, Dori] NIEHS, Toxicol Branch, DNTP, POB 12233, Res Triangle Pk, NC 27709 USA. [Luster, Michael I.] West Virginia Univ, Sch Publ Hlth, Morgantown, WV USA. RP Yucesoy, B (reprint author), NIOSH, Hlth Effects Lab Div, Morgantown, WV 26505 USA. EM berranyucesoy@gmail.com OI Barmada, M Michael/0000-0002-3604-6460 FU NIOSH [AES12007001-1-0-6]; NIEHS [AES12007001-1-0-6] FX This study was supported in part by an inter-agency agreement between NIOSH and NIEHS (AES12007001-1-0-6) as a collaborative National Toxicology Program research activity. NR 68 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 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 2016 VL 58 IS 8 BP 753 EP 759 DI 10.1097/JOM.0000000000000784 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DT0DP UT WOS:000381153200010 PM 27206134 ER PT J AU Lim, YH Ovejero, D Derrick, KM Collins, MT Choate, KA AF Lim, Young H. Ovejero, Diana Derrick, Kristina M. Collins, Michael T. Choate, Keith A. CA Yale Ctr Mendelian Genomics TI Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE congenital melanocytic nevus; cutaneous skeletal hypophosphatemia syndrome; epidermal nevus; fibroblast growth factor-23; mosaicism; nevus syndrome; rickets ID EPIDERMAL NEVUS SYNDROME; D-RESISTANT RICKETS; X-LINKED HYPOPHOSPHATEMIA; VITAMIN-D METABOLISM; PHOSPHATE HOMEOSTASIS; PHAKOMATOSIS PIGMENTOKERATOTICA; POSTZYGOTIC HRAS; FGF23; PATHWAY; RAS AB Background: We recently demonstrated multilineage somatic mosaicism in cutaneous skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated fibroblast growth factor (FGF)-23, and hypophosphatemia, finding identical RAS mutations in affected skin and bone. Objective: We sought to: (1) provide an updated overview of CSHS; (2) review its pathobiology; (3) present a new patient with CSHS; and (4) discuss treatment modalities. Methods: We searched PubMed for ''nevus AND rickets,'' and ''nevus AND hypophosphatemia,'' identifying cases of nevi with hypophosphatemic rickets or elevated serum FGF-23. For our additional patient with CSHS, we performed histopathologic and radiographic surveys of skin and skeletal lesions, respectively. Sequencing was performed for HRAS, KRAS, and NRAS to determine causative mutations. Results: Our new case harbored somatic activating HRAS p.G13 R mutation in affected tissue, consistent with previous findings. Although the mechanism of FGF-23 dysregulation is unknown in CSHS, interaction between FGF and MAPK pathways may provide insight into pathobiology. Anti-FGF-23 antibody KRN-23 may be useful in managing CSHS. Limitations: Multilineage RAS mutation in CSHS was recently identified; further studies on mechanism are unavailable. Conclusion: Patients with nevi in association with skeletal disease should be evaluated for serum phosphate and FGF-23. Further studies investigating the role of RAS in FGF-23 regulation are needed. C1 [Lim, Young H.; Choate, Keith A.] Yale Univ, Sch Med, Dept Dermatol, 333 Cedar St, New Haven, CT 06510 USA. [Lim, Young H.; Choate, Keith A.] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06519 USA. [Lim, Young H.; Choate, Keith A.] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06519 USA. [Ovejero, Diana; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Ovejero, Diana] Univ Autonoma Barcelona, Dept Med, Barcelona, Spain. [Derrick, Kristina M.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Div Pediat Endocrinol, Bronx, NY 10467 USA. RP Choate, KA (reprint author), Yale Univ, Sch Med, Dept Dermatol, 333 Cedar St, New Haven, CT 06510 USA.; Choate, KA (reprint author), Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06519 USA.; Choate, KA (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06519 USA. EM keith.choate@yale.edu FU Doris Duke Charitable Foundation; Medical Scientist Training Program at Yale University (National Institutes of Health) [T32 GM007205]; Yale Center for Mendelian Genomics (National Institutes of Health) [U54HG006504] FX Supported in part by a Clinical Scientist Development Award (Dr Choate) and Medical Student Research Fellowship (Mr Lim) from the Doris Duke Charitable Foundation, the Medical Scientist Training Program at Yale University (National Institutes of Health T32 GM007205) (Mr Lim), and the Yale Center for Mendelian Genomics (National Institutes of Health U54HG006504). NR 48 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2016 VL 75 IS 2 BP 420 EP 427 DI 10.1016/j.jaad.2015.11.012 PG 8 WC Dermatology SC Dermatology GA DS4JV UT WOS:000380748300038 PM 27444071 ER PT J AU Pichard, DC Ombrello, AK Hoffmann, P Stone, DL Cowen, EW AF Pichard, Dominique C. Ombrello, Amanda K. Hoffmann, Patrycja Stone, Deborah L. Cowen, Edward W. TI Early-onset stroke, polyarteritis nodosa (PAN), and livedo racemosa SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material DE deficiency of adenosine deaminase 2; genodermatosis; livedo; polyarteritis nodosa; stroke ID DEAMINASE 2 DEFICIENCY; ADA2 DEFICIENCY; VASCULOPATHY; MUTATIONS; PHENOTYPE C1 [Pichard, Dominique C.; Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. [Ombrello, Amanda K.; Hoffmann, Patrycja; Stone, Deborah L.] NIH, Inflammatory Dis Sect, Natl Human Genome Res Inst, Bldg 10, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 15 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2016 VL 75 IS 2 BP 449 EP 453 DI 10.1016/j.jaad.2016.01.057 PG 5 WC Dermatology SC Dermatology GA DS4JV UT WOS:000380748300048 PM 27444081 ER PT J AU Snider, TH Babin, MC Jett, DA Platoff, GE Yeung, DT AF Snider, Thomas H. Babin, Michael C. Jett, David A. Platoff, Gennady E., Jr. Yeung, David T. TI Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig SO JOURNAL OF TOXICOLOGICAL SCIENCES LA English DT Article DE Nerve agent; Pesticide; Oxime; Therapy; ED50; Therapeutic index ID CHEMICAL-WARFARE; EFFICACY; ATTACK; RATS AB Anticholinesterases, such as organophosphorus pesticides and warfare nerve agents, present a significant health threat. Onset of symptoms after exposure can be rapid, requiring quick-acting, efficacious therapy to mitigate the effects. The goal of the current study was to identify the safest antidote with the highest therapeutic index (TI = oxime 24-hr LD50/oxime ED50) from a panel of four oximes deemed most efficacious in a previous study. The oximes tested were pralidoxime chloride (2-PAM CO, MMB4 DMS, HLo-7 DMS, and obidoxime Cl-2. The 24-hr median lethal dose (LD50) for the four by intramuscular (IM) injection and the median effective dose (ED50) were determined. In the ED50 study, male guinea pigs clipped of hair received 2x LD50 topical challenges of undiluted Russian VX (VR), VX, or phorate oxon (PHO) and, at the onset of cholinergic signs, IM therapy of atropine (0.4 mg/kg) and varying levels of oxime. Survival was assessed at 3 hr after onset clinical signs. The 3-hr 90th percentile dose (ED90) for each oxime was compared to the guinea pig pre-hospital human-equivalent dose of 2-PAM Cl, 149 mu mol/kg. The TI was calculated for each OP/oxime combination. Against VR, MMB4 DMS had a higher TI than HLo-7 DMS, whereas 2-PAM Cl and obidoxime Cl-2 were ineffective. Against VX, MMB4 DMS > HLo-7 DMS > 2-PAM Cl > obidoxime Cl. Against PHO, all performed better than 2-PAM Cl. MMB4 DMS was the most effective oxime as it was the only oxime with ED90 < 149 mu mol/kg against all three topical OPs tested. C1 [Snider, Thomas H.; Babin, Michael C.] Battelle Mem Inst, 505 King Ave,JM-7, Columbus, OH 43201 USA. [Jett, David A.; Yeung, David T.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Platoff, Gennady E., Jr.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Snider, TH (reprint author), Battelle Mem Inst, 505 King Ave,JM-7, Columbus, OH 43201 USA. EM snider-t@sbcglobal.net FU NIH Office of the Director (OD) [Y1-OD-0387-01]; NIH; NIAID; NINDS; DoD Defense Technical Information Center (DTIC) under the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program [SP0700-00-D-3180, 832/CB-10-0832, 0794, 689/CB-13-0689] FX This work was supported by the NIH Office of the Director through an interagency agreement (OD#: Y1-OD-0387-01) between the National Institute of Allergy and Infectious Diseases (NIAID) and Department of Defense (DoD) and prepared under the auspices of the NIH, NIAID, NINDS, and the DoD Defense Technical Information Center (DTIC) under the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program, Contract No. SP0700-00-D-3180, Delivery Order Number 0687, CBRNIAC Task 832/CB-10-0832 and SP0700-00-D-3180, Delivery Order Number 0794, CBRNIAC Task 689/CB-13-0689. NR 35 TC 1 Z9 1 U1 10 U2 10 PU JAPANESE SOC TOXICOLOGICAL SCIENCES PI TOKYO PA INTERNATIONAL MEDICAL INFORMATION CENTER, SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI, SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 0388-1350 EI 1880-3989 J9 J TOXICOL SCI JI J. Toxicol. Sci. PD AUG PY 2016 VL 41 IS 4 BP 511 EP 521 PG 11 WC Toxicology SC Toxicology GA DS8WZ UT WOS:000381065000007 PM 27432237 ER PT J AU Cajka, T Davis, R Austin, KJ Newman, JW German, JB Fiehn, O Smilowitz, JT AF Cajka, Tomas Davis, Ryan Austin, Kathryn J. Newman, John W. German, J. Bruce Fiehn, Oliver Smilowitz, Jennifer T. TI Using a lipidomics approach for nutritional phenotyping in response to a test meal containing gamma-linolenic acid SO METABOLOMICS LA English DT Article DE Dihomo-gamma-linolenic acid; Gammalinolenic acid; Lipidomics; Liquid chromatography-mass spectrometry; Phenotyping; SWATH ID POLYUNSATURATED FATTY-ACIDS; MASS-SPECTROMETRY; GENE-CLUSTER; EICOSAPENTAENOIC ACID; ARACHIDONIC-ACID; METABOLISM; BIOSYNTHESIS; LIPIDS; SUPPLEMENTATION; PHOSPHOLIPIDS AB Introduction Plasma fatty acids are derived from preformed sources in the diet and de novo synthesis through the action of desaturase and elongase enzymes. Objective This study was designed to examine the elongation of gamma-linolenic acid (GLA, 18:3n6) into dihomo-gamma-linolenic acid (DGLA, 20:3n6) over an 8-h period using both targeted gas chromatography-flame ionization detection and untargeted liquid chromatography-mass spectrometry-based lipidomics utilizing the sequential window acquisition of all theoretical fragmention spectra (SWATH). Methods In a single blind, placebo-controlled, crossover design, seven healthy subjects consumed a test meal that consisted of GLA fat (borage oil) or a control fat (a mixture of corn, safflower, sunflower and extra-virgin light olive oils) on three separate test days for each test meal. Results Total plasma fatty acid concentrations and 366 unique lipid species were measured at 0, 2, 4, 6 and 8 h in response to the test meals. Mean plasma 18:3n6 was 7-fold higher to the GLA challenge compared with baseline and the control meal. By 8 h, mean plasma 20:3n6 was significantly higher in response to the GLA test meal than baseline and the control group. Five of the seven subjects were "responders'' in converting GLA into DGLA, but two subjects did not show this conversion. The conversion was independent of physical activity level. Conclusion Using polyunsaturated fatty acid metabolism as an example, this study demonstrates inter-individual differences in enzymatic capacities to inform exact nutritional and metabolic phenotyping that could be used for precision medicine. C1 [Cajka, Tomas; Newman, John W.; Fiehn, Oliver] Univ Calif Davis, NIH, West Coast Metabol Ctr, Davis, CA 95616 USA. [Davis, Ryan] Lipomics, 3410 Ind Blvd,Suite 103, West Sacramento, CA USA. [Austin, Kathryn J.; German, J. Bruce; Smilowitz, Jennifer T.] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. [Austin, Kathryn J.; German, J. Bruce; Smilowitz, Jennifer T.] Univ Calif Davis, Foods Hlth Inst, Davis, CA 95616 USA. [Newman, John W.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. [Newman, John W.] USDA ARS, Obes & Metab Res Unit, Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Fiehn, Oliver] King Abdulaziz Univ, Dept Biochem, Fac Sci, POB 80203, Jeddah 21589, Saudi Arabia. RP Smilowitz, JT (reprint author), Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA.; Smilowitz, JT (reprint author), Univ Calif Davis, Foods Hlth Inst, Davis, CA 95616 USA. EM jensm@ucdavis.edu RI Cajka, Tomas/A-8914-2008 OI Cajka, Tomas/0000-0002-9728-3355 FU National Institute of Environmental Health Sciences (NIEHS) [P42ES004699]; NIEHS [R01 ES002710]; NIEHS Superfund Research Program [P42 ES011269]; CHARGE [P01 ES11269]; West Coast Metabolomics Center (NIH) [U24 DK097154]; NIH [1S10RR031630-01, P20 HL113452]; USDA Agricultural Research Service Projects [5306-51000-016-00D, 5306-51000-019-00D, 2032-51530-022-00D] FX This project was made possible in part by support from the National Institute of Environmental Health Sciences (NIEHS) (P42ES004699), NIEHS R01 ES002710, NIEHS Superfund Research Program P42 ES011269; the CHARGE study (P01 ES11269); West Coast Metabolomics Center (NIH U24 DK097154) and instrument support (NIH 1S10RR031630-01), cardiovascular research (NIH P20 HL113452) and USDA Agricultural Research Service Projects 5306-51000-016-00D, 5306-51000-019-00D and 2032-51530-022-00D. We would like to thank Dr. Vincent Ziboh in loving memory for his inspiration and insight for this project. We would like to thank the staff at the USDA, ARS, Western Human Nutrition Research Center, Davis, CA, for clinical, laboratory and kitchen support. The USDA is an equal opportunity provider and employer. We thank the study participants for their time efforts to commit to the study procedures. NR 43 TC 0 Z9 0 U1 7 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 EI 1573-3890 J9 METABOLOMICS JI Metabolomics PD AUG PY 2016 VL 12 IS 8 AR UNSP 127 DI 10.1007/s11306-016-1075-9 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DS9DO UT WOS:000381083100001 ER PT J AU Dropulic, LK Lederman, HM AF Dropulic, Lesia K. Lederman, Howard M. TI Overview of Infections in the Immunocompromised Host SO MICROBIOLOGY SPECTRUM LA English DT Article ID ORGAN-TRANSPLANT RECIPIENTS; STEM-CELL TRANSPLANTATION; EPSTEIN-BARR-VIRUS; TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BONE-MARROW-TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; RENAL-ALLOGRAFT RECIPIENTS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CHRONIC GRANULOMATOUS-DISEASE AB Understanding the components of the immune system that contribute to host defense against infection is key to recognizing infections that are more likely to occur in an immunocompromised patient. In this review, we discuss the integrated system of physical barriers and of innate and adaptive immunity that contributes to host defense. Specific defects in the components of this system that predispose to particular infections are presented. This is followed by a review of primary immunodeficiency diseases and secondary immunodeficiencies, the latter of which develop because of a specific illness or condition or are treatment-related. The effects of treatment for neoplasia, autoimmune diseases, solid organ and stem cell transplants on host defenses are reviewed and associated with susceptibility to particular infections. In conclusion, an approach to laboratory screening for a suspected immunodeficiency is presented. Knowledge of which host defects predispose to specific infections allows clinicians to prevent, diagnose, and manage infections in their immunocompromised patients most effectively. C1 [Dropulic, Lesia K.] NIAID, NIH, Div Intramural Res, Bethesda, MD 20892 USA. [Lederman, Howard M.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Lederman, Howard M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. [Lederman, Howard M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. RP Dropulic, LK (reprint author), NIAID, NIH, Div Intramural Res, Bethesda, MD 20892 USA. EM dropulicl@niaid.nih.gov NR 336 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA EI 2165-0497 J9 MICROBIOL SPECTR JI Microbiol. Spectr. PD AUG PY 2016 VL 4 IS 4 AR UNSP DMIH2-0026-2016 DI 10.1128/microbiolspec.DMIH2-0026-2016 PG 43 WC Microbiology SC Microbiology GA DT9GI UT WOS:000381804000015 ER PT J AU Schug, TT Johnson, AF Birnbaum, LS Colborn, T Guillette, LJ Crews, DP Collins, T Soto, AM vom Saal, FS McLachlan, JA Sonnenschein, C Heindel, JJ AF Schug, Thaddeus T. Johnson, Anne F. Birnbaum, Linda S. Colborn, Theo Guillette, Louis J., Jr. Crews, David P. Collins, Terry Soto, Ana M. vom Saal, Frederick S. McLachlan, John A. Sonnenschein, Carlos Heindel, Jerrold J. TI Minireview: Endocrine Disruptors: Past Lessons and Future Directions SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID NONMONOTONIC DOSE RESPONSES; TURTLE SEX DETERMINATION; PRENATAL BISPHENOL-A; IN-UTERO EXPOSURE; US POPULATION; POLYCHLORINATED-BIPHENYLS; REPRODUCTIVE HEALTH; JUVENILE ALLIGATORS; ESTROGENIC ACTIVITY; NEONATAL EXPOSURE AB Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health. C1 [Schug, Thaddeus T.; Heindel, Jerrold J.] NIEHS, NIH, Div Extramural Res, Res Triangle Pk, NC 27560 USA. [Johnson, Anne F.] MDB Inc, Durham, NC 27713 USA. [Birnbaum, Linda S.] NCI, NIH, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Colborn, Theo] Endocrine Disrupt Exchange, Paonia, CO 81428 USA. [Guillette, Louis J., Jr.] Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. [Guillette, Louis J., Jr.] Hollings Marine Lab, Charleston, SC 29425 USA. [Crews, David P.] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA. [Collins, Terry] Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. [Soto, Ana M.; Sonnenschein, Carlos] Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Medford, MA 02155 USA. [vom Saal, Frederick S.] Univ Missouri, Div Biol Sci & Dept, Columbia, MO 65211 USA. [McLachlan, John A.] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70118 USA. RP Schug, TT (reprint author), Div Extramural Res, 530 Davis Dr,Room 3041 Mail Drop K3-15, Morrisville, NC 27560 USA. EM schugt@niehs.nih.gov FU National Institutes of Health (NIH) Grants [ES023254, ES020662, ES08314]; National Science Foundation (NSF) Grant [IOS-1051623]; Avon Foundation FX This work was supported by National Institutes of Health (NIH) Grants ES023254 and ES020662 and the National Science Foundation (NSF) Grant IOS-1051623 (to D.C.) and by the NIH Grant ES08314, and the Avon Foundation (to A.M.S. and C.S.). NR 118 TC 6 Z9 6 U1 25 U2 41 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 2016 VL 30 IS 8 BP 833 EP 847 DI 10.1210/me.2016-1096 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU0ZB UT WOS:000381932700003 PM 27477640 ER PT J AU Radenkovic, D Kobayashi, H Remsey-Semmelweis, E Seifalian, AM AF Radenkovic, Dina Kobayashi, Hisataka Remsey-Semmelweis, Erno Seifalian, Alexander M. TI Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Quantum dots; Nanotechnology; Image-guided surgery; Cancer imaging; Nanoparticles; Breast cancer ID SENTINEL LYMPH-NODE; PRACTICE GUIDELINE UPDATE; VIVO REAL-TIME; IN-VIVO; BLUE-DYE; SILICA NANOPARTICLES; TOXICITY ASSESSMENT; AMERICAN SOCIETY; PHOTOTHERMAL THERAPY; ANTI-HER2 ANTIBODY AB Breast cancer is the most common cancer in the world. Sentinel lymph node (SLN) biopsy is used for staging of axillary lymph nodes. Organic dyes and radiocolloid are currently used for SLN mapping, but expose patients to ionizing radiation, are unstable during surgery and cause local tissue damage. Quantum dots (QD) could be used for SLN mapping without the need for biopsy. Surgical resection of the primary tumor is the optimal treatment for early-diagnosed breast cancer, but due to difficulties in defining tumor margins, cancer cells often remain leading to reoccurrences. Functionalized QD could be used for image-guided tumor resection to allow visualization of cancer cells. Near Infrared QD are photostable and have improved deep tissue penetration. Slow elimination of QD raises concerns of potential accumulation. Nevertheless, promising findings with cadmium-free QD in recent in vivo studies and first in-human trial suggest huge potential for cancer diagnostic and therapy. (C) 2016 Elsevier Inc. All rights reserved. C1 [Radenkovic, Dina; Seifalian, Alexander M.] UCL, UCL Med Sch, London, England. [Kobayashi, Hisataka] NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Remsey-Semmelweis, Erno; Seifalian, Alexander M.] NanoRegMed Ltd, London BioSci Innovat Ctr, London, England. RP Seifalian, AM (reprint author), UCL, London WC1E 6BT, England. EM a.seifalian@gmail.com OI seifalian, Alexander/0000-0002-8334-9376 NR 127 TC 3 Z9 3 U1 25 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD AUG PY 2016 VL 12 IS 6 BP 1581 EP 1592 DI 10.1016/j.nano.2016.02.014 PG 12 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA DT8DF UT WOS:000381718600015 PM 27013132 ER PT J AU Early, R Bradley, BA Dukes, JS Lawler, JJ Olden, JD Blumenthal, DM Gonzalez, P Grosholz, ED Ibanez, I Miller, LP Sorte, CJB Tatem, AJ AF Early, Regan Bradley, Bethany A. Dukes, Jeffrey S. Lawler, Joshua J. Olden, Julian D. Blumenthal, Dana M. Gonzalez, Patrick Grosholz, Edwin D. Ibanez, Ines Miller, Luke P. Sorte, Cascade J. B. Tatem, Andrew J. TI Global threats from invasive alien species in the twenty-first century and national response capacities SO NATURE COMMUNICATIONS LA English DT Article ID PLANT INVASIONS; UNITED-STATES; BIOLOGICAL INVASIONS; CLIMATE-CHANGE; GREAT-BRITAIN; TRADE; BIODIVERSITY; RISK; INTRODUCTIONS; RICHNESS AB Invasive alien species (IAS) threaten human livelihoods and biodiversity globally. Increasing globalization facilitates IAS arrival, and environmental changes, including climate change, facilitate IAS establishment. Here we provide the first global, spatial analysis of the terrestrial threat from IAS in light of twenty-first century globalization and environmental change, and evaluate national capacities to prevent and manage species invasions. We find that one-sixth of the global land surface is highly vulnerable to invasion, including substantial areas in developing economies and biodiversity hotspots. The dominant invasion vectors differ between high-income countries (imports, particularly of plants and pets) and low-income countries (air travel). Uniting data on the causes of introduction and establishment can improve early-warning and eradication schemes. Most countries have limited capacity to act against invasions. In particular, we reveal a clear need for proactive invasion strategies in areas with high poverty levels, high biodiversity and low historical levels of invasion. C1 [Early, Regan] Univ Exeter, Ctr Ecol & Conservat, Penryn Campus, Penryn TR10 9FE, Cornwall, England. [Bradley, Bethany A.] Univ Massachusetts, Dept Environm Conservat, Amherst, MA 01003 USA. [Dukes, Jeffrey S.] Purdue Univ, Dept Forestry & Nat Resources, W Lafayette, IN 47907 USA. [Dukes, Jeffrey S.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Lawler, Joshua J.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA. [Olden, Julian D.] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Blumenthal, Dana M.] USDA ARS, Rangeland Resources Res Unit, Ft Collins, CO USA. [Gonzalez, Patrick] Natl Pk Serv, Nat Resource Stewardship & Sci, Berkeley, CA 94720 USA. [Gonzalez, Patrick] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. [Grosholz, Edwin D.] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA. [Ibanez, Ines] Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA. [Miller, Luke P.] Stanford Univ, Hopkins Marine Stn, Pacific Grove, CA 93950 USA. [Sorte, Cascade J. B.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA. [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton SO17 1BJ, Hants, England. [Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Tatem, Andrew J.] Flowminder Fdn, SE-11355 Stockholm, Sweden. RP Early, R (reprint author), Univ Exeter, Ctr Ecol & Conservat, Penryn Campus, Penryn TR10 9FE, Cornwall, England. EM r.early@exeter.ac.uk RI Gonzalez, Patrick/B-9479-2013 OI Gonzalez, Patrick/0000-0002-7105-0561 FU University of California, Santa Barbara; State of California; National Center for Ecological Analysis and Synthesis - National Science Foundation [EF-0553768]; NERC GW4+ DTP PhD 'Unexplained limits on species distributions. What do they mean for conservation?' FX We thank Ricardo Dobrovolski, Andy Nelson, Ben Halpern, Catarina Meireles, Sarah Ayton and Ryan Bird Rafalski for supplying or collating data, and Rashid Al Badwawi, Olga Dmitrieva, Manar Maraqa and Nazmi Sellami for help with translation. The analysis was conducted as part of the Climate Change & Invasive Species Working Group supported by the National Center for Ecological Analysis and Synthesis, a Center funded by the National Science Foundation (grant #EF-0553768), the University of California, Santa Barbara, and the State of California. The work was supported by the NERC GW4+ DTP PhD 'Unexplained limits on species distributions. What do they mean for conservation?' NR 76 TC 1 Z9 1 U1 62 U2 84 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2016 VL 7 AR 12485 DI 10.1038/ncomms12485 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DU1DG UT WOS:000381947800001 PM 27549569 ER PT J AU Martinez-Picado, J McLaren, PJ Erkizia, I Martin, MP Benet, S Rotger, M Dalmau, J Ouchi, D Wolinsky, SM Penugonda, S Gunthard, HF Fellay, J Carrington, M Izquierdo-Useros, N Telenti, A AF Martinez-Picado, Javier McLaren, Paul J. Erkizia, Itziar Martin, Maureen P. Benet, Susana Rotger, Margalida Dalmau, Judith Ouchi, Dan Wolinsky, Steven M. Penugonda, Sudhir Gunthard, Huldrych F. Fellay, Jacques Carrington, Mary Izquierdo-Useros, Nuria Telenti, Amalio TI Identification of Siglec-1 null individuals infected with HIV-1 SO NATURE COMMUNICATIONS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DENDRITIC CELLS; TRANS-INFECTION; T-CELLS; PROTEIN; RECEPTORS; VARIANTS; CAPTURE; AIDS AB Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in B1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. C1 [Martinez-Picado, Javier; Erkizia, Itziar; Benet, Susana; Dalmau, Judith; Ouchi, Dan; Izquierdo-Useros, Nuria] Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona 08916, Spain. [Martinez-Picado, Javier] ICREA, Barcelona 08010, Spain. [Martinez-Picado, Javier] Univ Vic, Cent Univ Catalonia UVic UCC, Barcelona 08500, Spain. [McLaren, Paul J.] Publ Hlth Agcy Canada, Natl HIV & Retrovirol Lab, Winnipeg, MB R3E 0W3, Canada. [McLaren, Paul J.] Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB R3E 0J9, Canada. [Martin, Maureen P.; Carrington, Mary] Leidos Biomed Res Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Rotger, Margalida] Univ Hosp Ctr, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Rotger, Margalida] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Wolinsky, Steven M.; Penugonda, Sudhir] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Gunthard, Huldrych F.] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Gunthard, Huldrych F.] Univ Zurich, Inst Med Virol, CH-8057 Zurich, Switzerland. [Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland. [Fellay, Jacques] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Telenti, Amalio] J Craig Venter Inst, Genom Med, La Jolla, CA 92037 USA. RP Martinez-Picado, J; Izquierdo-Useros, N (reprint author), Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona 08916, Spain.; Martinez-Picado, J (reprint author), ICREA, Barcelona 08010, Spain.; Martinez-Picado, J (reprint author), Univ Vic, Cent Univ Catalonia UVic UCC, Barcelona 08500, Spain.; Telenti, A (reprint author), J Craig Venter Inst, Genom Med, La Jolla, CA 92037 USA. EM jmpicado@irsicaixa.es; nizquierdo@irsicaixa.es; atelenti@jcvi.org RI SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Izquierdo-Useros, Nuria/G-2534-2016; Martinez-Picado, Javier/G-5507-2012; Infektiologie, USZ/A-6921-2011; gunthard, huldrych/F-1724-2011; Fellay, Jacques/A-6681-2009 OI Izquierdo-Useros, Nuria/0000-0002-1039-1821; Martinez-Picado, Javier/0000-0002-4916-2129; gunthard, huldrych/0000-0002-1142-6723; Fellay, Jacques/0000-0002-8240-939X FU Spanish Secretariat of Science and Innovation [SAF2013-49042-R]; Gilead Fellowship Program [GLD1400271]; Mathilde Krim Fellowship [108676]; Spanish AIDS network 'Red Tematica Cooperativa de Investigacion en SIDA'; Swiss National Science Foundation [717, 148522]; SHCS research foundation; National Institute of Allergy and Infectious Diseases (NIAID) [U01-AI35042, U01-AI35039, U01-AI35040, U01-AI35041, UM1-AI35043]; National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research FX We thank the patients for participating in the SHCS and MACS. We thank Nimisha Chaturvedi and Victor Urrea for their excellent statistical assistance. The members of the SHCS are Aubert V., Battegay M., Bernasconi E., Boni J., Braun D.L., Bucher H.C., Burton-Jeangros C., Calmy A., Cavassini M., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Furrer H. (Chairman of the Clinical and Laboratory Committee), Fux C. A., Gorgievski M., Gunthard H. (President of the SHCS), Haerry D. (deputy of 'Positive Council'), Hasse B., Hirsch H.H., Hoffmann M., Hosli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kouyos R., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Marzolini C., Metzner K., Muller N., Nadal D., Nicca D., Pantaleo G., Rauch A. (Chairman of the Scientific Board), Regenass S., Rudin C. (Chairman of the Mother & Child Sub-study), Schoni-Affolter F. (Head of Data Centre), Schmid P., Speck R., Stockle M., Tarr P., Trkola A., Vernazza P., Weber R., Yerly S. MACS Principal Investigators are: Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson), UM1-AI35043. J.M.-P. and N.I.-U. are supported by the Spanish Secretariat of Science and Innovation through Grant SAF2013-49042-R. N.I.-U. is supported by the Gilead Fellowship Program GLD1400271 and the Mathilde Krim Fellowship in basic biomedical research 108676 founded by 'AmfAR' AIDS research Foundation. JMP is supported by the Spanish AIDS network 'Red Tematica Cooperativa de Investigacion en SIDA'. Work at the laboratory of A.T. was financed by the Swiss National Science Foundation. The genetic analyses were realized within the framework of the Swiss HIV Cohort Study (SHCS Project number 717), which is supported by the Swiss National Science Foundation (Grant Number 148522) and by the SHCS research foundation. Some data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042, U01-AI35039, U01-AI35040, U01-AI35041 and UM1-AI35043, with additional co-funding from the National Cancer Institute (NCI). This project has been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. NR 24 TC 0 Z9 0 U1 5 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2016 VL 7 AR 12412 DI 10.1038/ncomms12412 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT5MC UT WOS:000381526300001 PM 27510803 ER PT J AU Pankratz, N Schick, UM Zhou, Y Zhou, W Ahluwalia, TS Allende, ML Auer, PL Bork-Jensen, J Brody, JA Chen, MH Clavo, V Eicher, JD Grarup, N Hagedorn, EJ Hu, B Hunker, K Johnson, AD Leusink, M Lu, YC Lyytikainen, LP Manichaikul, A Marioni, RE Nalls, MA Pazoki, R Smith, AV van Rooij, FJA Yang, ML Zhang, XL Zhang, Y Asselbergs, FW Boerwinkle, E Borecki, IB Bottinger, EP Cushman, M de Bakker, PIW Deary, IJ Dong, LG Feitosa, MF Floyd, JS Franceschini, N Franco, OH Garcia, ME Grove, ML Gudnason, V Hansen, T Harris, TB Hofman, A Jackson, RD Jia, J Kahonen, M Launer, LJ Lehtimaki, T Liewald, DC Linneberg, A Liu, YM Loos, RJF Nguyen, VM Numans, ME Pedersen, O Psaty, BM Raitakari, OT Rich, SS Rivadeneira, F Di Sant, AMR Rotter, JI Starr, JM Taylor, KD Thuesen, BH Tracy, RP Uitterlinden, AG Wang, JS Wang, JD Dehghan, A Huo, Y Cupples, LA Wilson, JG Proia, RL Zon, LI O'Donnell, CJ Reiner, AP Ganesh, SK AF Pankratz, Nathan Schick, Ursula M. Zhou, Yi Zhou, Wei Ahluwalia, Tarunveer Singh Allende, Maria Laura Auer, Paul L. Bork-Jensen, Jette Brody, Jennifer A. Chen, Ming-Huei Clavo, Vinna Eicher, John D. Grarup, Niels Hagedorn, Elliott J. Hu, Bella Hunker, Kristina Johnson, Andrew D. Leusink, Maarten Lu, Yingchang Lyytikainen, Leo-Pekka Manichaikul, Ani Marioni, Riccardo E. Nalls, Mike A. Pazoki, Raha Smith, Albert Vernon van Rooij, Frank J. A. Yang, Min-Lee Zhang, Xiaoling Zhang, Yan Asselbergs, Folkert W. Boerwinkle, Eric Borecki, Ingrid B. Bottinger, Erwin P. Cushman, Mary de Bakker, Paul I. W. Deary, Ian J. Dong, Liguang Feitosa, Mary F. Floyd, James S. Franceschini, Nora Franco, Oscar H. Garcia, Melissa E. Grove, Megan L. Gudnason, Vilmundur Hansen, Torben Harris, Tamara B. Hofman, Albert Jackson, Rebecca D. Jia, Jia Kahonen, Mika Launer, Lenore J. Lehtimaki, Terho Liewald, David C. Linneberg, Allan Liu, Yongmei Loos, Ruth J. F. Nguyen, Vy M. Numans, Mattijs E. Pedersen, Oluf Psaty, Bruce M. Raitakari, Olli T. Rich, Stephen S. Rivadeneira, Fernando Di Sant, Amanda M. Rosa Rotter, Jerome I. Starr, John M. Taylor, Kent D. Thuesen, Betina Heinsbaek Tracy, Russell P. Uitterlinden, Andre G. Wang, Jiansong Wang, Judy Dehghan, Abbas Huo, Yong Cupples, L. Adrienne Wilson, James G. Proia, Richard L. Zon, Leonard I. O'Donnell, Christopher J. Reiner, Alex P. Ganesh, Santhi K. CA CHARGE Consortium Hematology TI Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SUSCEPTIBILITY LOCI; LYMPHOCYTE EGRESS; CROHNS-DISEASE; FUNCTIONAL PREDICTIONS; CHARGE CONSORTIUM; KIDNEY-FUNCTION; LARGE-SCALE; DIFFERENTIATION AB Hematologic measures such as hematocrit and white blood cell ( WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals ( 37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations ( CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count ( S1PR4), monocyte count ( BTBD8, NLRP12, and IL17RA), eosinophil count ( IRF1), and total WBC count ( MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury. C1 [Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Schick, Ursula M.; Lu, Yingchang; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA. [Schick, Ursula M.; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Zhou, Yi; Hagedorn, Elliott J.; Hu, Bella; Nguyen, Vy M.; Di Sant, Amanda M. Rosa; Zon, Leonard I.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. [Zhou, Wei] Univ Michigan, Dept Computat Med & Biostat, Ann Arbor, MI 48109 USA. [Ahluwalia, Tarunveer Singh; Bork-Jensen, Jette; Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer Singh] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Allende, Maria Laura; Proia, Richard L.] NIDDKD, Genet Dev & Dis Branch, US Natl Inst Hlth, Bethesda, MD USA. [Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA. [Brody, Jennifer A.; Floyd, James S.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Ming-Huei; Eicher, John D.; Johnson, Andrew D.; Zhang, Xiaoling; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Clavo, Vinna; Hunker, Kristina; Yang, Min-Lee; Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Clavo, Vinna; Hunker, Kristina; Yang, Min-Lee; Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Eicher, John D.; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Intramural Res Program, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. [Leusink, Maarten] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands. [Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere, Finland. [Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Marioni, Riccardo E.; Deary, Ian J.; Liewald, David C.; Starr, John M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Nalls, Mike A.] NIA, Neurogenet Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Pazoki, Raha; van Rooij, Frank J. A.; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, Kopavogur, Iceland. [Zhang, Xiaoling] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Zhang, Yan; Jia, Jia; Huo, Yong] Peking Univ, Hosp 1, Dept Cardiol, Beijing 100871, Peoples R China. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England. [Boerwinkle, Eric; Grove, Megan L.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Borecki, Ingrid B.; Feitosa, Mary F.; Wang, Judy] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Cushman, Mary] Univ Vermont, Dept Med, Div Hematol Oncol, Burlington, VT USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.; Numans, Mattijs E.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Dong, Liguang] Peking Univ, Shougang Hosp, Jin Ding St Community Hlth Ctr, Beijing, Peoples R China. [Franceschini, Nora] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kahonen, Mika] Univ Tampere, Sch Med, Tampere, Finland. [Linneberg, Allan; Thuesen, Betina Heinsbaek] Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark. [Linneberg, Allan] Rigshosp, Dept Clin Expt Res, Glostrup, Denmark. [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Numans, Mattijs E.] Leiden Univ, Med Ctr, Publ Hlth & Primary Care, Leiden, Netherlands. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Rotter, Jerome I.; Taylor, Kent D.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Rotter, Jerome I.; Taylor, Kent D.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh, Midlothian, Scotland. Univ Vermont, Coll Med, Dept Pathol & Lab Med, Colchester, VT USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Colchester, VT USA. [Wang, Jiansong] Peking Univ, Shougang Hosp, Chron Dis Res Ctr, Beijing, Peoples R China. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Intramural Res Program, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Boston Vet Adm Healthcare, Dept Med, Cardiol Sect, Boston, MA USA. [Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Pankratz, N (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.; Ganesh, SK (reprint author), Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.; Ganesh, SK (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. EM nathan.pankratz.rps@gmail.com; sganesh@umich.edu RI Floyd, James/G-7563-2015; Johnson, Andrew/G-6520-2013; Grarup, Niels/K-2807-2015; Feitosa, Mary/K-8044-2012; OI Grarup, Niels/0000-0001-5526-1070; Feitosa, Mary/0000-0002-0933-2410; Pazoki, Raha/0000-0002-5142-2348; Manichaikul, Ani/0000-0002-5998-795X; Ahluwalia, Tarunveer Singh/0000-0002-7464-3354; Dehghan, Abbas/0000-0001-6403-016X; Linneberg, Allan/0000-0002-0994-0184 FU NIDDK Division of Intramural Research; US National Institutes of Health [N01AG12100, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, HHSN268200800007C]; Clinical and Translational Science Institute [UL1TR000124]; Danish Heart Foundation [07-10-R61-A1754-B838-22392F]; Biobanking and BioMolecular resources Research Infrastructure-The Netherlands (BBMRI-NL) grant [NWO 184.021.007]; Health Insurance Foundation [2012B233]; Academy of Finland [134309, 126925, 121584, 124282, 129378, 117787, 41071]; US NIH [N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC25195, N02HL64278, N01AG62101, N01AG62103, N01AG62106]; NIH, US [HHSN268200782096C, HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, RR024156]; US, NIH [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, RC2HL102924, CA137088, 5RC2HL102419, HL080295, HL087652, HL103612, HL105756, HL120393]; NIH US [AG023629, DK063491, R01DK089256, R01HL087700, R01HL088215, R01HL117078, 1R01AG032098-01A1, U01-HG005152, R25CA094880, R01HL122684, R01HL04880, R01HL32262, R01DK49216, R01HL10001, R01DK092760, R01OD017870] FX This work was supported by the following grants and contracts: US National Institutes of Health contracts (N01AG12100, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC25195, N02HL64278, N01AG62101, N01AG62103, N01AG62106, HHSN268200782096C, HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, RR024156, N02HL64278, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, RC2HL102924, and CA137088); US National Institutes of Health grants (5RC2HL102419, HL080295, HL087652, HL103612, HL105756, HL120393, AG023629, DK063491, R01DK089256, R01HL087700, R01HL088215, R01HL117078, 1R01AG032098-01A1, U01-HG005152, R25CA094880, R01HL122684, R01HL04880, R01HL32262, R01DK49216, R01HL10001, R01DK092760, and R01OD017870); a Clinical and Translational Science Institute grant (UL1TR000124); a Danish Heart Foundation grant (07-10-R61-A1754-B838-22392F); a Biobanking and BioMolecular resources Research Infrastructure-The Netherlands (BBMRI-NL) grant (NWO 184.021.007); a Health Insurance Foundation grant (2012B233); and Academy of Finland grants (134309, 126925, 121584, 124282, 129378, 117787, and 41071).; This work was supported in part by the NIDDK Division of Intramural Research. NR 85 TC 2 Z9 2 U1 5 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 AUG PY 2016 VL 48 IS 8 BP 867 EP + DI 10.1038/ng.3607 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA DS4ML UT WOS:000380755100010 ER PT J AU Shin, HY Willi, M Yoo, KH Zeng, XK Wang, CC Metser, G Hennighausen, L AF Shin, Ha Youn Willi, Michaela Yoo, Kyung Hyun Zeng, Xianke Wang, Chaochen Metser, Gil Hennighausen, Lothar TI Hierarchy within the mammary STAT5-driven Wap super-enhancer SO NATURE GENETICS LA English DT Article ID WHEY ACIDIC PROTEIN; DISTAL REGULATORY ELEMENTS; TRANSGENIC MICE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; SIGNAL TRANSDUCER; GLAND DEVELOPMENT; CELL IDENTITY; T-CELLS; STAT5 AB Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes. C1 [Shin, Ha Youn; Willi, Michaela; Yoo, Kyung Hyun; Zeng, Xianke; Wang, Chaochen; Metser, Gil; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Willi, Michaela] Med Univ Innsbruck, Div Bioinformat, Bioctr, Innsbruck, Austria. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov OI Willi, Michaela/0000-0002-2248-1998 FU IPR of the NIDDK/NIH FX We thank H. Smith from the NIDDK genomics core for never-ending help with next-generation sequencing and C. Liu from the NHLBI transgenic core for generating the CRISPR/Cas9-based mouse mutants. M.W. is a graduate student of the Individual Graduate Partnership Program (GPP) between NIH/NIDDK and the Medical University of Innsbruck. This work was performed in partial fulfillment of the graduation requirements for M.W. We thank K. Kang and S. Oh for discussions in the early stage of this project and Z. Trajanoski for advising M.W. during her graduate studies. This research was funded by the IPR of the NIDDK/NIH. NR 78 TC 13 Z9 13 U1 5 U2 7 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 AUG PY 2016 VL 48 IS 8 BP 904 EP + DI 10.1038/ng.3606 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DS4ML UT WOS:000380755100014 PM 27376239 ER PT J AU Pearson, RD Amato, R Auburn, S Miotto, O Almagro-Garcia, J Amaratunga, C Suon, S Mao, S Noviyanti, R Trimarsanto, H Marfurt, J Anstey, NM William, T Boni, MF Dolecek, C Tran, HT White, NJ Michon, P Siba, P Tavul, L Harrison, G Barry, A Mueller, I Ferreira, MU Karunaweera, N Randrianarivelojosia, M Gao, Q Hubbart, C Hart, L Jeffery, B Drury, E Mead, D Kekre, M Campino, S Manske, M Cornelius, VJ MacInnis, B Rockett, KA Miles, A Rayner, JC Fairhurst, RM Nosten, F Price, RN Kwiatkowski, DP AF Pearson, Richard D. Amato, Roberto Auburn, Sarah Miotto, Olivo Almagro-Garcia, Jacob Amaratunga, Chanaki Suon, Seila Mao, Sivanna Noviyanti, Rintis Trimarsanto, Hidayat Marfurt, Jutta Anstey, Nicholas M. William, Timothy Boni, Maciej F. Dolecek, Christiane Hien Tinh Tran White, Nicholas J. Michon, Pascal Siba, Peter Tavul, Livingstone Harrison, Gabrielle Barry, Alyssa Mueller, Ivo Ferreira, Marcelo U. Karunaweera, Nadira Randrianarivelojosia, Milijaona Gao, Qi Hubbart, Christina Hart, Lee Jeffery, Ben Drury, Eleanor Mead, Daniel Kekre, Mihir Campino, Susana Manske, Magnus Cornelius, Victoria J. MacInnis, Bronwyn Rockett, Kirk A. Miles, Alistair Rayner, Julian C. Fairhurst, Rick M. Nosten, Francois Price, Ric N. Kwiatkowski, Dominic P. TI Genomic analysis of local variation and recent evolution in Plasmodium vivax SO NATURE GENETICS LA English DT Article ID DRUG-RESISTANCE GENES; DNA-SEQUENCING DATA; DUFFY-BLOOD-GROUP; MALARIA; FALCIPARUM; DIVERSITY; CHLOROQUINE; INFECTIONS; REVEALS; POLYMORPHISMS AB The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of > 200 clinical samples collected across the Asia-Pacific region and analyzed data on > 300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax. C1 [Pearson, Richard D.; Amato, Roberto; Miotto, Olivo; Drury, Eleanor; Mead, Daniel; Kekre, Mihir; Campino, Susana; Manske, Magnus; Cornelius, Victoria J.; MacInnis, Bronwyn; Rockett, Kirk A.; Miles, Alistair; Rayner, Julian C.; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Cambridge, England. [Pearson, Richard D.; Amato, Roberto; Miotto, Olivo; Almagro-Garcia, Jacob; Hubbart, Christina; Hart, Lee; Jeffery, Ben; Cornelius, Victoria J.; Rockett, Kirk A.; Miles, Alistair; Kwiatkowski, Dominic P.] Wellcome Trust Ctr Human Genet, MRC Ctr Genom & Global Hlth, Oxford, England. [Auburn, Sarah; Marfurt, Jutta; Anstey, Nicholas M.; Price, Ric N.] Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia. [Auburn, Sarah; Marfurt, Jutta; Price, Ric N.] Charles Darwin Univ, Darwin, NT, Australia. [Miotto, Olivo; White, Nicholas J.] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand. [Amaratunga, Chanaki] NIAID, NIH, Rockville, MD USA. [Suon, Seila] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. [Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia. [Noviyanti, Rintis; Trimarsanto, Hidayat] Eijkman Inst Mol Biol, Jakarta, Indonesia. [William, Timothy] Sabah Menzies Sch Hlth Res, Clin Res Unit, Infect Dis Soc, Kota Kinabalu, Sabah, Malaysia. [William, Timothy] Queen Elizabeth Hosp, Clin Res Ctr, Kota Kinabalu, Sabah, Malaysia. [Boni, Maciej F.; Dolecek, Christiane; Hien Tinh Tran] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam. [Michon, Pascal; Siba, Peter; Tavul, Livingstone] Papua New Guinea Inst Med Res, Madang, Papua N Guinea. [Michon, Pascal] Divine Word Univ, Fac Med & Hlth Sci, Madang, Papua N Guinea. [Harrison, Gabrielle; Barry, Alyssa; Mueller, Ivo] Walter & Eliza Hall Inst Med Res, Div Populat Hlth & Immun, Parkville, Vic, Australia. [Harrison, Gabrielle; Barry, Alyssa; Mueller, Ivo] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia. [Ferreira, Marcelo U.] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, Brazil. [Karunaweera, Nadira] Univ Colombo, Fac Med, Dept Parasitol, Colombo, Sri Lanka. [Randrianarivelojosia, Milijaona] Inst Pasteur Madagascar, Antananarivo, Madagascar. [Gao, Qi] Minist Hlth, Jiangsu Inst Parasit Dis, Key Lab Parasit Dis Control & Prevent, Prov Key Lab Parasite Mol Biol, Wuxi, Jiangsu, Peoples R China. [Nosten, Francois] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Shoklo Malaria Res Unit, Fac Trop Med, Mae Sot, Thailand. [Nosten, Francois; Price, Ric N.] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England. RP Kwiatkowski, DP (reprint author), Wellcome Trust Sanger Inst, Cambridge, England.; Kwiatkowski, DP (reprint author), Wellcome Trust Ctr Human Genet, MRC Ctr Genom & Global Hlth, Oxford, England. EM dominic@sanger.ac.uk RI Ferreira, Marcelo/G-8289-2011; OI Ferreira, Marcelo/0000-0002-5293-9090; Auburn, Sarah/0000-0002-4638-536X; Rayner, Julian/0000-0002-9835-1014; Trimarsanto, Hidayat/0000-0003-2436-8283; Kwiatkowski, Dominic/0000-0002-5023-0176; Mead, Daniel/0000-0001-7717-4330; Manske, Magnus/0000-0001-5916-0947; Price, Richard/0000-0003-2000-2874 FU Wellcome Trust [098051, 090770/Z/09/Z, 091625]; Medical Research Council [G0600718]; UK Department for International Development [M006212]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank the patients and communities that provided samples for this study, and our many colleagues who supported this work in the field. Sequencing, data analysis and project coordination were funded by the Wellcome Trust (098051, 090770/Z/09/Z), the Medical Research Council (G0600718) and the UK Department for International Development (M006212). A.B. and I.M. acknowledge the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Medical Research Institutes Infrastructure Support Scheme (NHMRC IRIISS). S.A. and R.N.P. are funded by the Wellcome Trust (Senior Fellowship in Clinical Science awarded to R.N.P., 091625). This study was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 53 TC 12 Z9 12 U1 4 U2 5 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 AUG PY 2016 VL 48 IS 8 BP 959 EP 964 DI 10.1038/ng.3599 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DS4ML UT WOS:000380755100022 PM 27348299 ER PT J AU Maguire, MG Martin, DF Ying, GS Jaffe, GJ Daniel, E Grunwald, JE Toth, CA Ferris, FL Fine, SL AF Maguire, Maureen G. Martin, Daniel F. Ying, Gui-shuang Jaffe, Glenn J. Daniel, Ebenezer Grunwald, Juan E. Toth, Cynthia A. Ferris, Frederick L., III Fine, Stuart L. CA Comparison Age-related Macular TI Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration The Comparison of Age-Related Macular Degeneration Treatments Trials SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2016 CL Seattle, WA SP Assoc Res Vis & Ophthalmol ID OPTICAL COHERENCE TOMOGRAPHY; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; LONG-TERM OUTCOMES; PHOTODYNAMIC THERAPY; INTRAVITREAL RANIBIZUMAB; RANDOMIZED-TRIAL; CLINICAL-TRIALS; VISUAL-ACUITY; BEVACIZUMAB; VERTEPORFIN AB Purpose: To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD). Design: Cohort study. Participants: Patients enrolled in the Comparison of AMD Treatments Trials. Methods: Patients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination. Main Outcome Measures: Visual acuity (VA) and morphologic retinal features. Results: Visual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was -3 letters from baseline and -11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm(2), a mean of 4.8 mm(2) larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% suberetinal pigment epithelium). Mean foveal total thickness was 278 mm, a decrease of 182 mm from baseline and 20 mm from 2 years. The retina was abnormally thin (<120 mm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (-4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups. Conclusions: Vision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming antievascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD. (C) 2016 by the American Academy of Ophthalmology. C1 [Maguire, Maureen G.; Ying, Gui-shuang; Daniel, Ebenezer; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. [Martin, Daniel F.] Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Jaffe, Glenn J.; Toth, Cynthia A.] Duke Univ, Dept Ophthalmol, Durham, NC USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Fine, Stuart L.] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA. RP Maguire, MG (reprint author), Univ Penn, Dept Ophthalmol, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM maguirem@mail.med.upenn.edu NR 40 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 2016 VL 123 IS 8 BP 1751 EP 1761 DI 10.1016/j.ophtha.2016.03.045 PG 11 WC Ophthalmology SC Ophthalmology GA DS4MC UT WOS:000380754200032 ER PT J AU Willis, JR Vitale, S Morse, L Parke, DW Rich, WL Lum, F Cantrell, RA AF Willis, Jeffrey R. Vitale, Susan Morse, Lawrence Parke, David W., II Rich, William L. Lum, Flora Cantrell, Ronald A. TI The Prevalence of Myopic Choroidal Neovascularization in the United States Analysis of the IRIS (R) Data Registry and NHANES SO OPHTHALMOLOGY LA English DT Article ID PATHOLOGICAL MYOPIA; REFRACTIVE ERROR; RISK-FACTORS; EPIDEMIOLOGY; RETINOPATHY; PROGRESSION; POPULATION; EYE AB Purpose: To determine the prevalence of high myopia (HM), progressive high (degenerative) myopia (PHM), and myopic choroidal neovascularization (mCNV) in the United States. Design: Cross-sectional study. Participants: Individuals aged 18 years and older participating in the National Health and Nutrition Examination Survey (NHANES) and patients aged 18 years and older seen in clinics participating in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS (R)) Registry. Methods: We analyzed NHANES data from 2005 to 2008 to determine the prevalence of HM in the United States. This prevalence was then applied to estimates from the US Population Census (2014) to arrive at a population burden of HM at the diopter level in the United States. Data from the IRIS Registry were used to calculate the real-world prevalence rates of PHM and mCNV among patients with HM at the diopter level. This was subsequently applied to this reference population with HM to calculate the diopter-adjusted prevalence and population burden of PHM and mCNV in the United States in 2014. Main Outcome Measures: High myopia was defined as myopic refractive error of <= 6.0 diopters in the right eye. Progressive HM was defined as HM with the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code of "360.21: Progressive High (Degenerative) Myopia." Myopic CNV was defined as HM with the presence of subretinal/choroidal neovascularization indicated by the ICD-9-CM diagnosis of "362.16: Retinal Neovascularization NOS." Results: The estimated diopter-adjusted prevalence of HM, PHM, and mCNV was 3.92% (95% confidence interval [CI], 2.82-5.60), 0.33% (95% CI, 0.21-0.55), and 0.017% (95% CI, 0.010-0.030), respectively, among adults in the United States aged 18 years and older in 2014. This translated into a population burden of approximately 9 614 719 adults with HM, 817 829 adults with PHM, and 41 111 adults with mCNV in the United States in 2014. Conclusions: Although HM and PHM impose a relatively large burden among adults in the United States, mCNV seems to be a rare disease. Relating data from the IRIS Registry and NHANES could be a novel method for assessing ophthalmic disease prevalence in the United States. Future studies should aim to better assess current treatment patterns and optimal management strategies of this condition. (C) 2016 by the American Academy of Ophthalmology. C1 [Willis, Jeffrey R.; Morse, Lawrence] Univ Calif Davis, Med Ctr, Dept Ophthalmol, Sacramento, CA 95817 USA. [Willis, Jeffrey R.; Cantrell, Ronald A.] Genentech Inc, San Francisco, CA 94080 USA. [Vitale, Susan] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Parke, David W., II; Rich, William L.; Lum, Flora] Amer Acad Ophthalmol, San Francisco, CA 94109 USA. RP Lum, F (reprint author), Amer Acad Ophthalmol, Div Qual & Data Sci, 655 Beach St, San Francisco, CA 94109 USA. EM flum@aao.org NR 26 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 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 2016 VL 123 IS 8 BP 1771 EP 1782 DI 10.1016/j.ophtha.2016.04.021 PG 12 WC Ophthalmology SC Ophthalmology GA DS4MC UT WOS:000380754200035 PM 27342789 ER PT J AU Datiles, MB Ferris, F Ansari, RR Zigler, JS AF Datiles, Manuel B., III Ferris, Frederick, III Ansari, Rafat R. Zigler, J. Samuel, Jr. TI Re: Datiles et al.: Longitudinal study of age-related cataract using dynamic light scattering: loss of alpha-crystallin leads to nuclear cataract development (Ophthalmology 2016;123:248-54) REPLY SO OPHTHALMOLOGY LA English DT Letter C1 [Datiles, Manuel B., III; Ferris, Frederick, III] NEI, Off Clin Director, NIH, 10 Ctr Dr,Bldg 10,Room 1, Bethesda, MD 20892 USA. [Ansari, Rafat R.] NASA, Glenn Res Ctr, Cleveland, OH USA. [Zigler, J. Samuel, Jr.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21287 USA. RP Datiles, MB (reprint author), NEI, Off Clin Director, NIH, 10 Ctr Dr,Bldg 10,Room 1, Bethesda, MD 20892 USA. EM Datilesm@nei.nih.gov NR 1 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 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 2016 VL 123 IS 8 BP E48 EP E48 PG 1 WC Ophthalmology SC Ophthalmology GA DS4MC UT WOS:000380754200005 PM 27450826 ER PT J AU Aggarwal, SK Ghosh, A Cheng, MJ Luton, K Lowet, PF Berger, A AF Aggarwal, Sunil K. Ghosh, Amrita Cheng, M. Jennifer Luton, Kathleen Lowet, Peter F. Berger, Ann TI Initiating pain and palliative care outpatient services for the suburban underserved in Montgomery County, Maryland: Lessons learned at the NIH Clinical Center and MobileMed SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Palliative care; Pain management; Underserved; Maryland; Suburbanization of poverty AB Objective: With the ongoing expansion of palliative care services throughout the United States, meeting the needs of socioeconomically marginalized populations, as in all domains of healthcare, continues to be a challenge. Our specific aim here was to help meet some of these needs through expanding delivery of pain and palliative care services by establishing a new clinic for underserved patients and collecting descriptive data about its operation. Method: In November of 2014, the National Institutes of Health Clinical Center's Pain and Palliative Care Service (PPCS) launched a bimonthly offsite pain and palliative care outpatient clinic in collaboration with Mobile Medical Care Inc. (MobileMed), a private not-for-profit primary care provider in Montgomery County, Maryland, serving underserved area residents since 1968. Staffed by NIH hospice and palliative medicine clinical fellows and faculty, the clinic provides specialty pain and palliative care consultation services to patients referred by their primary care healthcare providers. A patient log was maintained, charts reviewed, and referring providers surveyed on their satisfaction with the service. Results: The clinic had 27 patient encounters with 10 patients (6 males, 4 females, aged 23-67) during its first 7 months of operation. The reason for referral for all but one patient was chronic pain of multiple etiologies. Patients had numerous psychosocial stressors and comorbidities. All primary care providers who returned surveys (n = 4) rated their level of satisfaction with the consultation service as very satisfied or extremely satisfied. Significance of Results: This brief descriptive report outlines the steps taken and logistical issues addressed to launch and continue the clinic, the characteristics of patients treated, and the results of quality-improvement projects. Lessons learned are highlighted and future directions suggested for the clinic and others that may come along like it. C1 [Aggarwal, Sunil K.; Ghosh, Amrita; Cheng, M. Jennifer; Berger, Ann] NIH, Ctr Clin, Pain & Palliat Care Serv, 10 Ctr Dr,2-1733 MSC 1517, Bethesda, MD 20892 USA. [Luton, Kathleen; Lowet, Peter F.] Mobile Med Care Inc, Bethesda, MD USA. RP Aggarwal, SK (reprint author), NIH, Ctr Clin, Pain & Palliat Care Serv, 10 Ctr Dr,2-1733 MSC 1517, Bethesda, MD 20892 USA. EM sunila@uw.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD AUG PY 2016 VL 14 IS 4 BP 381 EP 386 DI 10.1017/S1478951515001030 PG 6 WC Health Policy & Services SC Health Care Sciences & Services GA DT2DH UT WOS:000381290500010 PM 26373835 ER PT J AU Adachi, K Klausner, JD Xu, JH Ank, B Bristow, CC Morgado, MG Watts, DH Weir, F Persing, D Mofenson, LM Veloso, VG Pilotto, JH Joao, E Gray, G Theron, G Santos, B Fonseca, R Kreitchmann, R Pinto, J Mussi-Pinhata, MM Ceriotto, M Machado, DM Bryson, YJ Grinsztejn, B Bastos, FI Siberry, G Nielsen-Saines, K AF Adachi, Kristina Klausner, Jeffrey D. Xu, Jiahong Ank, Bonnie Bristow, Claire C. Morgado, Mariza G. Watts, D. Heather Weir, Fred Persing, David Mofenson, Lynne M. Veloso, Valdilea G. Pilotto, Jose Henrique Joao, Esau Gray, Glenda Theron, Gerhard Santos, Breno Fonseca, Rosana Kreitchmann, Regis Pinto, Jorge Mussi-Pinhata, Marisa M. Ceriotto, Mariana Machado, Daisy Maria Bryson, Yvonne J. Grinsztejn, Beatriz Bastos, Francisco I. Siberry, George Nielsen-Saines, Karin CA NICHD HPTN 040 Study Team TI Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HIV; pregnancy; chlamydia; gonorrhea; sexually transmitted infections; adverse infant outcomes ID ACTIVE ANTIRETROVIRAL THERAPY; PRETERM BIRTH; PERINATAL-MORTALITY; ASSOCIATION; CHILDREN; SYPHILIS; TRANSMISSION; METAANALYSIS; MORBIDITY; DISEASE AB Background: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Methods: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Results: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76). Conclusions: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants. C1 [Adachi, Kristina; Klausner, Jeffrey D.; Ank, Bonnie; Bryson, Yvonne J.; Nielsen-Saines, Karin] David Geffen UCLA Sch Med, Los Angeles, CA USA. [Klausner, Jeffrey D.; Bristow, Claire C.] UCLA Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Xu, Jiahong] WESTAT Corp, Rockville, MD 20850 USA. [Morgado, Mariza G.; Veloso, Valdilea G.; Grinsztejn, Beatriz; Bastos, Francisco I.] Fundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, Brazil. [Watts, D. Heather] US Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USA. [Weir, Fred; Persing, David] Cepheid, Sunnyvale, CA USA. [Mofenson, Lynne M.; Siberry, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Pilotto, Jose Henrique] Hosp Geral Nova Iguacu, DST AIDS, Rio De Janeiro, Brazil. [Joao, Esau] Hosp Fed Servidores Estado, Rio De Janeiro, Brazil. [Gray, Glenda] Univ Witwatersrand, SAMRC, Cape Town, South Africa. [Gray, Glenda] Univ Witwatersrand, Perinatal HIV Res Unit, Cape Town, South Africa. [Theron, Gerhard] Univ Stellenbosch, Tygerberg Hosp, Dept Obstet & Gynecol, Cape Town, South Africa. [Santos, Breno] Hosp Conceicao, Serv Infectol, Porto Alegre, RS, Brazil. [Fonseca, Rosana] Hosp Femina, Porto Alegre, RS, Brazil. [Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil. [Pinto, Jorge] Univ Fed Minas Gerais, Dept Pediat, Belo Horizonte, MG, Brazil. [Mussi-Pinhata, Marisa M.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Sao Paulo, Brazil. [Ceriotto, Mariana] Fdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, Argentina. [Machado, Daisy Maria] Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil. RP Adachi, K (reprint author), David Geffen Sch Med UCLA, Dept Pediat, Div Infect Dis, 10833 Conte Ave,MDCC 22-442, Los Angeles, CA 90095 USA. EM kadachi@mednet.ucla.edu FU NICHD [HHSN267200800001C, N01-HD-8-0001, U01 AI047986]; National Institute of Allergy and Infectious Diseases (NIAID)/NIH; National Institutes of Health (NIH) [NIAIDU01 AI068632, UM1AI068632, UM1AI068616, UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health [AI068632]; Boehringer Ingelheim Pharmaceuticals Inc. (BIPI); GlaxoSmithKline on behalf of ViiV Healthcare; Cepheid, Sunnyvale, CA; UCLA Center for AIDS Research (CFAR) NIH/NIAID [AI028697] FX The NICHD HPTN 040 study was supported by NICHD Contract # HHSN267200800001C (NICHD Control # N01-HD-8-0001) and U01 AI047986 (Brazilian AIDS Prevention Trials International Network), National Institute of Allergy and Infectious Diseases (NIAID)/NIH. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers NIAIDU01 AI068632, UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH (AI068632). In addition, the parent study was supported in part by Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), and GlaxoSmithKline on behalf of ViiV Healthcare. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development. This particular sub-study was supported by Cepheid, Sunnyvale, CA, where CT and NG testing of specimens was performed. Support was also provided by the UCLA Center for AIDS Research (CFAR) NIH/NIAID AI028697. Support for Kristina Adachi's work on this sub-study was also provided in part by the UCLA Children's Discovery and Innovation Institute (CDI). The content, conclusions and opinions expressed in this article are those of the authors and do not necessarily represent those of the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. Department of State, affiliated universities, programs or companies of the authors. 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 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD AUG PY 2016 VL 35 IS 8 BP 894 EP 900 DI 10.1097/INF.0000000000001199 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA DS4MK UT WOS:000380755000018 PM 27164464 ER PT J AU Chew, EY Clemons, TE Harrington, M Bressler, SB Elman, MJ Kim, JE Garfinkel, R Heier, JS Brucker, A Boyer, D AF Chew, Emily Y. Clemons, Traci E. Harrington, Molly Bressler, Susan B. Elman, Michael J. Kim, Judy E. Garfinkel, Richard Heier, Jeffrey S. Brucker, Alexander Boyer, David CA AREDS2-HOME Study Res Grp TI EFFECTIVENESS OF DIFFERENT MONITORING MODALITIES IN THE DETECTION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION The Home Study, Report Number 3 SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; incident choroidal neovascularization; telemonitoring ID RANDOMIZED-TRIAL; EYE HOME; RANIBIZUMAB; DEVICE AB Purpose: To determine the effectiveness of different monitoring modalities to detect incident neovascularization associated with age-related macular degeneration (AMD). Methods: Secondary analyses compared the rates of detecting incident neovascular AMD in prescheduled office visits versus office visits triggered by monitoring device or by symptom realization in a randomized trial evaluating home telemonitoring device plus standard care (device arm) versus standard care alone. Results: At prescheduled office visits, neovascular AMD was detected in 14/1927 visits (0.7%, 95% confidence interval [CI]: 0.4%-1.1%) and 14/1949 visits (0.7%, 95% CI: 0.3%-1.1%) in the device and standard care alone arms, respectively. Thirty-seven participants with neovascular AMD were detected in 318 office visits (11.6%, 95% CI: 8.1%-15.2%) triggered by device or symptom realization and 17 neovascular AMD in 65 office visits (26%, 95% CI: 15.5%-36.8%) triggered by symptom realization in the device and standard care alone arms, respectively. The home device strategy had a higher neovascular-AMD detection rate than prescheduled office visits (relative risk = 16.0 [95% CI: 8.8-29.3]). Neovascular AMD detected at triggered visits were associated with less vision loss from baseline in the device arm versus standard care alone arm (-3 letters vs. -11.5 letters, respectively, P = 0.03). Conclusion: Telemonitoring may alter the management of patients with AMD and improve vision outcomes. C1 [Chew, Emily Y.] NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA. [Clemons, Traci E.; Harrington, Molly] EMMES Corp, Rockville, MD USA. [Bressler, Susan B.] Johns Hopkins Univ, Wilmer Eye Inst, Retina Div, Baltimore, MD 21218 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Kim, Judy E.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA. [Garfinkel, Richard] Retina Grp Washington, Washington, DC USA. [Heier, Jeffrey S.] Ophthalm Consultants Boston, Boston, MA USA. [Brucker, Alexander] Scheie Eye Inst, Philadelphia, PA USA. [Boyer, David] Retina Vitreous Associates Med Grp, Los Angeles, CA USA. RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Notal Vision Ltd; National Eye Institute, National Institutes of Health, Bethesda, Maryland (CTA) [CTA-00833]; National Eye Institute, National Institutes of Health [HHS-N-260-2005-00007-C, N01-EY-5-0007] FX Supported by Notal Vision Ltd through a clinical trial agreement with the National Eye Institute, National Institutes of Health, Bethesda, Maryland (CTA no: CTA-00833) and a service agreement with EMMES Corporation. The Age-Related Eye Disease Study 2 study is supported by the intramural program funds and contracts from the National Eye Institute, National Institutes of Health (contract nos: HHS-N-260-2005-00007-C, N01-EY-5-0007). NR 8 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 AUG PY 2016 VL 36 IS 8 BP 1542 EP 1547 PG 6 WC Ophthalmology SC Ophthalmology GA DS7MI UT WOS:000380967200033 PM 27243927 ER PT J AU Roux, A Jackson, SN Muller, L Barbacci, D O'Rourke, J Thanos, PK Volkow, ND Balaban, C Schultz, JA Woods, AS AF Roux, Aurelie Jackson, Sheller N. Muller, Ludovic Barbacci, Damon O'Rourke, Joseph Thanos, Panayotis K. Volkow, Nora D. Balaban, Carey Schultz, J. Albert Woods, Amina S. TI Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE lipids; alcohol; electrospray ionization; solid-phase extraction; mass spectrometry ID STIMULATES PHOSPHOLIPASE-D; INDUCED OXIDATIVE STRESS; PRIMARY RAT HEPATOCYTES; ADULT RATS; FATTY-ACIDS; INDUCED FLUIDIZATION; ALCOHOL-CONSUMPTION; PHYSICAL-PROPERTIES; CHOLESTEROL CONTENT; MEMBRANE-FLUIDITY AB Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell membranes, are involved in cell signaling, signal transduction, and energy storage. In this study, we analyzed lipid composition of chronically ethanol exposed mouse brains. Juvenile (JUV) and adult (ADU) mice were placed on a daily limited-access ethanol intake model for 52 days. After euthanasia, brains were harvested, and total lipids were extracted from brain homogenates. Samples were analyzed using high resolution mass spectrometry and processed by multivariate and univariate statistical analysis. Significant lipid changes were observed in different classes including sphingolipids, fatty acids, lysophosphatidylcholines, and other glycerophospholipids. C1 [Roux, Aurelie; Jackson, Sheller N.; Muller, Ludovic; Volkow, Nora D.; Woods, Amina S.] NIDA IRP, Struct Biol Unit, NIH, Baltimore, MD 21224 USA. [Muller, Ludovic] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [O'Rourke, Joseph; Thanos, Panayotis K.] Univ Buffalo, Dept Psychol, Behav Neuropharmacol & Neuroimaging Lab, Buffalo, NY 14260 USA. [Barbacci, Damon; Schultz, J. Albert] Ionwerks Inc, Houston, TX 77002 USA. [Balaban, Carey] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Balaban, Carey] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15260 USA. [Balaban, Carey] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Balaban, Carey] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Woods, AS (reprint author), NIDA IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU NIDA SBIR Phase II grants [5R44DA030853-04, 5R44DA036263-04] FX Ionwerks gratefully acknowledges partial support for this work from NIDA SBIR Phase II grants 5R44DA030853-04 and 5R44DA036263-04. NR 77 TC 0 Z9 0 U1 6 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD AUG PY 2016 VL 7 IS 8 BP 1148 EP 1156 DI 10.1021/acschemneuro.6b00120 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA DT8CS UT WOS:000381717300016 PM 27269520 ER PT J AU Pletneva, NV Pletnev, S Pakhomov, AA Chertkova, RV Martynov, VI Muslinkina, L Dauter, Z Pletnev, VZ AF Pletneva, Nadya V. Pletnev, Sergei Pakhomov, Alexey A. Chertkova, Rita V. Martynov, Vladimir I. Muslinkina, Liya Dauter, Zbigniew Pletnev, Vladimir Z. TI Crystal structure of the fluorescent protein from Dendronephthya sp in both green and photoconverted red forms SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY LA English DT Article DE fluorescent photoconvertible proteins; green fluorescent protein; red fluorescent protein; three-dimensional structure; chromophore; beta-barrel; structure-function relationships; DendFP; DendRFP; DendGFP; Dendronephthya ID PHOTOINDUCED PEPTIDE CLEAVAGE; MICROSCOPY; CONVERSION; DENDRA2; STATE; GFP; CHROMOPHORE; MECHANISM; EVOLUTION; CELLS AB The fluorescent protein from Dendronephthya sp. (DendFP) is a member of the Kaede-like group of photoconvertible fluorescent proteins with a His62-Tyr63-Gly64 chromophore-forming sequence. Upon irradiation with UV and blue light, the fluorescence of DendFP irreversibly changes from green (506 nm) to red (578 nm). The photoconversion is accompanied by cleavage of the peptide backbone at the C-alpha-N bond of His62 and the formation of a terminal carboxamide group at the preceding Leu61. The resulting double C-alpha=C-beta bond in His62 extends the conjugation of the chromophore pi system to include imidazole, providing the red fluorescence. Here, the three-dimensional structures of native green and photoconverted red forms of DendFP determined at 1.81 and 2.14 angstrom resolution, respectively, are reported. This is the first structure of photoconverted red DendFP to be reported to date. The structure-based mutagenesis of DendFP revealed an important role of positions 142 and 193: replacement of the original Ser142 and His193 caused a moderate red shift in the fluorescence and a considerable increase in the photoconversion rate. It was demonstrated that hydrogen bonding of the chromophore to the Gln116 and Ser105 cluster is crucial for variation of the photoconversion rate. The single replacement Gln116Asn disrupts the hydrogen bonding of Gln116 to the chromophore, resulting in a 30-fold decrease in the photoconversion rate, which was partially restored by a further Ser105Asn replacement. C1 [Pletneva, Nadya V.; Pakhomov, Alexey A.; Chertkova, Rita V.; Martynov, Vladimir I.; Pletnev, Vladimir Z.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. [Pletnev, Sergei; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA. [Pletnev, Sergei] Leidos Biomed Res Inc, Basic Res Program, Argonne, IL 60439 USA. [Muslinkina, Liya] Russian Acad Sci, Arbuzov Inst Organ & Phys Chem, Kazan, Russia. RP Pletneva, NV; Pletnev, VZ (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. EM nadin.plet@gmail.com; vzpletnev@gmail.com RI Pakhomov, Alexey/D-7199-2012; Pletneva, Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov, Vladimir/S-3483-2016 OI Martynov, Vladimir/0000-0003-4923-6842 FU Russian Science Foundation [14-14-00281]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; US Department of Energy, Office of Science and Office of Basic Energy Sciences [W-31-109-Eng-38] FX This research was supported by funding from the Russian Science Foundation (project 14-14-00281). X-ray data collection at the synchrotron station was supported in part by Federal funds from the National Cancer Institute, National Institutes of Health under contract No. HHSN261200800001E and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Diffraction experiments were carried out on synchrotron beamline 22-ID of the Southeast Regional Collaborative Access Team (SERCAT) located at the Advanced Photon Source, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy, Office of Science and Office of Basic Energy Sciences under Contract No.W-31-109-Eng-38. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government. NR 37 TC 0 Z9 0 U1 10 U2 15 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 2059-7983 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Struct. Biol. PD AUG PY 2016 VL 72 BP 922 EP 932 DI 10.1107/S205979831601038X PN 8 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA DS4TA UT WOS:000380773100003 PM 27487823 ER PT J AU Esser, L Shukla, S Zhou, F Ambudkar, SV Xia, D AF Esser, Lothar Shukla, Suneet Zhou, Fei Ambudkar, Suresh V. Xia, Di TI Crystal structure of the antigen-binding fragment of a monoclonal antibody specific for the multidrug-resistance-linked ABC transporter human P-glycoprotein SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS LA English DT Article DE monoclonal antibodies; UIC2/Fab; multidrug resistance; human ABC-dependent transporter P-glycoprotein; multidrug resistance ID DIFFERENTIAL IMMUNOREACTIVITY; CONFORMATIONAL-CHANGES; INSECT CELLS; COMPETITION; INHIBITION; EXPRESSION; MODE AB P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancers that plays important roles in the pharmacokinetics of a large number of drugs. The drug-resistance phenotype of P-gp can be modulated by the monoclonal antibody UIC2, which specifically recognizes human P-gp in a conformation-dependent manner. Here, the purification, sequence determination and high-resolution structure of the Fab fragment of UIC2 (UIC2/Fab) are reported. Purified UIC2/Fab binds human P-gp with a 1: 1 stoichiometry. Crystals of UIC2/Fab are triclinic (space group P1), with unit-cell parameters a = 40.67, b = 44.91, c = 58.09 angstrom, alpha = 97.62, beta = 99.10, gamma = 94.09 degrees, and diffracted X-rays to 1.6 angstrom resolution. The structure was determined by molecular replacement and refined to 1.65 angstrom resolution. The asymmetric unit contains one molecule of UIC2/Fab, which exhibits a positively charged antigen-binding surface, suggesting that it might recognize an oppositely charged extracellular epitope of P-gp. C1 [Esser, Lothar; Shukla, Suneet; Zhou, Fei; Ambudkar, Suresh V.; Xia, Di] NCI, NIH, 37 Convent Dr,Bldg 37, Bethesda, MD 20892 USA. RP Xia, D (reprint author), NCI, NIH, 37 Convent Dr,Bldg 37, Bethesda, MD 20892 USA. EM dixia@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX The authors wish to thank the staff of the SER-CAT beamline at APS, ANL for assistance in data collection. This study used the DNA Core of NCI and the high-performance Biowulf Linux cluster (http://hpc.nih.gov) at the NIH. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 23 TC 0 Z9 0 U1 8 U2 8 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 2053-230X J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Commun. PD AUG PY 2016 VL 72 BP 636 EP 641 DI 10.1107/S2053230X16009778 PN 8 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA DS4SV UT WOS:000380772600009 PM 27487928 ER PT J AU Veronezi, BP Moffa, AH Carvalho, AF Galhardoni, R Simis, M Bensenor, IM Lotufo, PA Machado-Vieira, R Daskalakis, ZJ Brunoni, AR AF Veronezi, B. P. Moffa, A. H. Carvalho, A. F. Galhardoni, R. Simis, M. Bensenor, I. M. Lotufo, P. A. Machado-Vieira, R. Daskalakis, Z. J. Brunoni, A. R. TI Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE major depressive disorder; glutamate; gamma-aminobutyric acid; motor cortex excitability; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; MAJOR DEPRESSION; CORTEX EXCITABILITY; PREFRONTAL CORTEX; MOOD DISORDERS; DSM-IV; FEATURES; ORGANIZATION; ADOLESCENTS; RELIABILITY AB Objective: Major depressive disorder (MDD) is a clinically heterogeneous condition. However, the role of cortical glutamate and gamma-aminobutyric acid (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not been explored in different MDD subtypes. Our aim was to assess the atypical and melancholic depression subtypes regarding potential differences in GABA and glutamate receptor-mediated activity through established transcranial magnetic stimulation (TMS) neurophysiological measures from the motor cortex. Method: We evaluated 81 subjects free of antidepressant medication, including 21 healthy controls and 20 patients with atypical, 20 with melancholic, and 20 with undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate intracortical facilitation (ICF), cortical silent period (CSP), and short intracortical inhibition (SICI), which index glutamate, GABA(B) receptor-, and GABA(A) receptor-mediated activity respectively. Results: Patients with MDD demonstrated significantly decreased mean CSP values than healthy controls (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression presented a distinct cortical excitability pattern of decreased cortical inhibition and increased cortical facilitation, that is, an increased mean ICF and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all comparisons). Conclusion: Different MDD subtypes may demonstrate different neurophysiology in relation to GABA(A) and glutamatergic activity. TMS as an investigational tool might be useful to distinguish between different MDD subtypes. C1 [Veronezi, B. P.; Moffa, A. H.; Bensenor, I. M.; Lotufo, P. A.; Brunoni, A. R.] Univ Sao Paulo, Univ Hosp, Interdisciplinary Ctr Appl Neuromodulat, Sao Paulo, Brazil. [Carvalho, A. F.] Univ Fed Ceara, Dept Psychiat, Fortaleza, Ceara, Brazil. [Moffa, A. H.] Univ Fed Ceara, Fac Med, Translat Psychiat Res Grp, Fortaleza, Ceara, Brazil. [Galhardoni, R.; Brunoni, A. R.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM 27, Serv Interdisciplinary Neuromodulat, Sao Paulo, Brazil. [Galhardoni, R.] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo, Brazil. [Galhardoni, R.] Univ Sao Paulo, Dept Neurol, Pain Ctr, Sao Paulo, Brazil. [Galhardoni, R.] Univ City Sao Paulo UNICID, Med Sch, Sao Paulo, Brazil. [Simis, M.] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Phys Med & Rehabil, Sao Paulo, Brazil. [Machado-Vieira, R.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Daskalakis, Z. J.] Univ Toronto, Temerty Ctr Therapeut Brain Intervent, Toronto, ON, Canada. [Daskalakis, Z. J.] Univ Toronto, Campbell Family Res Inst, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON, Canada. RP Brunoni, AR (reprint author), Interdisciplinary Ctr Appl Neuromodulat, Av Prof Lineu Prestes 2565,3o andar, BR-05508000 Sao Paulo, Brazil. EM brunoni@usp.br RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Lotufo, Paulo/A-9843-2008; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Lotufo, Paulo/0000-0002-4856-8450; Russowsky Brunoni, Andre/0000-0002-6310-3571 FU NARSAD Young Investigator from Brain & Behavior Research Foundation [20493]; Sao Paulo State Foundation [12/20911-5]; National Council for Scientific and Technological Development (CNPq) [470904]; CNPq scholarship grant; FAPESP scholarship grant [13/19759-7]; National Council for Scientific and Technological Development (CNPq; level II; Brazil) FX ARB is supported by the following grants: 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation (Grant Number 20493), 2012 FAPESP Young Researcher from the Sao Paulo State Foundation (Grant Number 12/20911-5), and National Council for Scientific and Technological Development (CNPq, Grant Number 470904). ARB also received equipment from the Soterix Company. AHM receives a CNPq scholarship grant. BPV receives a FAPESP scholarship grant (13/19759-7). AFC is the recipient of a research fellowship award from the National Council for Scientific and Technological Development (CNPq; level II; Brazil). NR 53 TC 0 Z9 0 U1 6 U2 7 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 AUG PY 2016 VL 134 IS 2 BP 172 EP 182 DI 10.1111/acps.12565 PG 11 WC Psychiatry SC Psychiatry GA DT7SY UT WOS:000381688700009 PM 27028276 ER PT J AU Grantz, KL Grewal, J Albert, PS Wapner, R D'Alton, ME Sciscione, A Grobman, WA Wing, DA Owen, J Newman, RB Chien, EK Gore-Langton, RE Kim, S Zhang, CL Louis, GMB Hediger, ML AF Grantz, Katherine L. Grewal, Jagteshwar Albert, Paul S. Wapner, Ronald D'Alton, Mary E. Sciscione, Anthony Grobman, William A. Wing, Deborah A. Owen, John Newman, Roger B. Chien, Edward K. Gore-Langton, Robert E. Kim, Sungduk Zhang, Cuilin Louis, Germaine M. Buck Hediger, Mary L. TI Dichorionic twin trajectories: the NICHD Fetal Growth Studies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE dichorionic; estimated fetal weight; fetal growth; twin ID BIRTH-WEIGHT; HEAD; GESTATIONS; RETARDATION; PREGNANCIES; PREDICTION; PATTERNS; DISEASE; HEALTH; RISK AB BACKGROUND: Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation that are performed in controlled clinical settings. Currently, there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated with the use of the same benchmarks as singleton growth. OBJECTIVES: Our objective was to define the trajectory of fetal growth in dichorionic twins empirically using longitudinal 2-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard that was developed by our group for singletons. STUDY DESIGN: A prospective cohort of 171 women with twin gestations was recruited from 8 US sites from 2012-2013. After an initial sonogram at 11 weeks 0 days-13 weeks 6 days of gestation during which dichorionicity was confirmed, women were assigned randomly to 1 of 2 serial ultrasonography schedules. Growth curves and percentiles were estimated with the use of linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education, and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories with the use of likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements in which there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests that were computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, which was defined as < 10th percentile that would be introduced if fetal growth estimation for twins was based on an unweighted singleton standard. RESULTS: Women underwent a median of 5 ultrasound scans. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks of gestation; biparietal diameter in twins was smaller from 34-36 weeks of gestation. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks of gestation, which indicated a comparatively asymmetric growth pattern. At 35 weeks of gestation, the average gestational age at delivery for twins, the estimated fetal weights for the 10th, 50th, and 90th percentiles were 1960, 2376, and 2879 g for dichorionic twins, respectively, and 2180, 2567, and 3022 g for the singletons, respectively. At 32 weeks of gestation, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age with the use of a singleton, non-Hispanic white standard. By 35 weeks of gestation, 38% of twins would be classified as small for gestational age. CONCLUSION: The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks of gestation, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard. C1 [Grantz, Katherine L.; Grewal, Jagteshwar; Albert, Paul S.; Kim, Sungduk; Zhang, Cuilin; Louis, Germaine M. Buck; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Wapner, Ronald; D'Alton, Mary E.] Columbia Univ, Med Ctr, New York, NY USA. [Sciscione, Anthony] Christiana Care Hlth Syst, Wilmington, DE USA. [Grobman, William A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Wing, Deborah A.] Calif State Univ Long Beach, Irvine & Long Beach Mem Med Ctr, Long Beach, CA 90840 USA. [Owen, John] Univ Alabama Birmingham, Birmingham, AL USA. [Newman, Roger B.] Med Univ South Carolina, Charleston, SC 29425 USA. [Chien, Edward K.] Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. [Gore-Langton, Robert E.] Emmes Corp, Rockville, MD USA. RP Grantz, KL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. EM katherine.grantz@nih.gov OI owen, john/0000-0001-8854-2346; Grewal, Jagteshwar/0000-0002-0141-4876; Buck Louis, Germaine/0000-0002-1774-4490; 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 [HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers: HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; HHSN275201000009C). NR 32 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2016 VL 215 IS 2 AR 221.e1-e16 DI 10.1016/j.ajog.2016.04.044 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DS5JN UT WOS:000380818200020 PM 27143399 ER PT J AU Hildesheim, A Gonzalez, P Kreimer, AR Wacholder, S Schussler, J Rodriguez, AC Porras, C Schiffman, M Sidawy, M Schiller, JT Lowy, DR Herrero, R AF Hildesheim, Allan Gonzalez, Paula Kreimer, Aimee R. Wacholder, Sholom Schussler, John Rodriguez, Ana C. Porras, Carolina Schiffman, Mark Sidawy, Mary Schiller, John T. Lowy, Douglas R. Herrero, Rolando CA Costa Rica HPV Vaccine Trial CVT TI Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical cancer; clinical trial; human papillomaviruses; prevention; vaccines ID POOLED ANALYSIS; BROAD-SPECTRUM; TRIAL; NEOPLASIA; EFFICACY; PCR; WOMEN; ASSAY AB BACKGROUND: Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. OBJECTIVES: To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN: We included 1711 women (18 +/- 25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS: Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were -5.4% (95% confidence interval -19,10) and 0.3% (95% confidence interval -69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval -131, 82) and -211% (95% confidence interval -2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval -43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. CONCLUSION: We find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies. C1 [Hildesheim, Allan; Kreimer, Aimee R.; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gonzalez, Paula; Rodriguez, Ana C.; Porras, Carolina; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Schussler, John] Informat Management Serv Inc, Silver Spring, MD USA. [Sidawy, Mary] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Schiller, John T.; Lowy, Douglas R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Hildesha@mail.nih.gov OI Schussler, John/0000-0002-8793-0766 FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on Women's Health; GlaxoSmithKline Biologicals (GSK) [FDA BB-IND 7920]; GlaxoSmithKline; Merck FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. The trial is sponsored and funded by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health. GlaxoSmithKline Biologicals (GSK) provided vaccine and support for aspects of the trial associated with regulatory submission needs of the company under a Clinical Trials Agreement (FDA BB-IND 7920) during the four-year, randomized blinded phase of our study. John T. Schiller and Douglas R. Lowy report that they are named inventors on US Government-owned HPV vaccine patents that are licensed to GlaxoSmithKline and Merck and for which the National Cancer Institute receives licensing fees. They are entitled to limited royalties as specified by federal law. The other authors declare that they have no conflicts of interest. The NCI and Costa Rica investigators are responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. Registered with Clinicaltrials.gov NCT00128661. NR 17 TC 2 Z9 2 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2016 VL 215 IS 2 AR 212.e1-e15 DI 10.1016/j.ajog.2016.02.021 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DS5JN UT WOS:000380818200016 PM 26892991 ER PT J AU Stern, JE McLain, AC Louis, GMB Luke, B Yeung, EH AF Stern, Judy E. McLain, Alexander C. Louis, Germaine M. Buck Luke, Barbara Yeung, Edwina H. TI Accuracy of self-reported survey data on assisted reproductive technology treatment parameters and reproductive history SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE assisted reproductive technology; intracytoplasmic sperm injection; participant self-report; patient communication; survey study ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; ASSESSMENT MONITORING-SYSTEM; BIRTH-DEFECTS; UNITED-STATES; UPSTATE KIDS; RISK; COHORT; CHILDREN; MASSACHUSETTS AB BACKGROUND: It is unknown whether data obtained from maternal self-report for assisted reproductive technology treatment parameters and reproductive history are accurate for use in research studies. OBJECTIVES: We evaluated the accuracy of self-reported in assisted reproductive technology treatment and reproductive history from the Upstate KIDS study in comparison with clinical data reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. STUDY DESIGN: Upstate KIDS maternal questionnaire data from deliveries between 2008 and 2010 were linked to data reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System. The 617 index deliveries were compared as to treatment type (frozen embryo transfer and donor egg or sperm) and use of intracytoplasmic sperm injection and assisted hatching. Use of injectable medications, self-report for assisted reproductive technology, or frozen embryo transfer prior to the index deliveries were also compared. We report agreement in which both sources had yes or both no and sensitivity of maternal report using Society for Assisted Reproductive Technology Clinic Outcome Reporting System as the gold standard. Significance was determined using chi(2) at P < 0.05. RESULTS: Universal agreement was not reached on any parameter but was best for treatment type of frozen embryo transfer (agreement, 96%; sensitivity, 93%) and use of donor eggs (agreement, 97%; sensitivity, 82%) or sperm (agreement, 98%; sensitivity, 82%). Use of intracytoplasmic sperm injection (agreement, 78%: sensitivity, 78%) and assisted hatching (agreement, 57%; sensitivity, 38%) agreed less well with self-reported use (P <.0001). In vitro fertilization (agreement, 82%) and frozen embryo transfer (agreement, 90%) prior to the index delivery were more consistently reported than was use of injectable medication (agreement, 76%) (P <.0001). CONCLUSION: Women accurately report in vitro fertilization treatment but are less accurate about procedures handled in the laboratory (intracytoplasmic sperm injection or assisted hatching). Clinics might better communicate with patients on the use of these procedures, and researchers should use caution when using self-reported treatment data. C1 [Stern, Judy E.] Dartmouth Coll, Geisel Sch Med, Dept Ostet & Gynecol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [McLain, Alexander C.] Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC USA. [Yeung, Edwina H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD USA. [Luke, Barbara] Michigan State Univ, Dept Obstet, E Lansing, MI 48824 USA. [Luke, Barbara] Michigan State Univ, Dept Gynecol, E Lansing, MI 48824 USA. [Luke, Barbara] Michigan State Univ, Dept Reprod Biol, E Lansing, MI 48824 USA. RP Stern, JE (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Ostet & Gynecol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM judy.e.stern@dartmouth.edu OI Yeung, Edwina/0000-0002-3851-2613; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201200005C, HHSN267200700019C] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts HHSN275201200005C and HHSN267200700019C). NR 32 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2016 VL 215 IS 2 AR 219.e1-e6 DI 10.1016/j.ajog.2016.02.010 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DS5JN UT WOS:000380818200019 PM 26875948 ER PT J AU Thirunavukkarasu, S Khan, NS Song, CY Ghafoor, HU Brand, DD Gonzalez, FJ Malik, KU AF Thirunavukkarasu, Shyamala Khan, Nayaab S. Song, Chi Young Ghafoor, Hafiz U. Brand, David D. Gonzalez, Frank J. Malik, Kafait U. TI Cytochrome P450 1B1 Contributes to the Development of Angiotensin II-Induced Aortic Aneurysm in Male Apoe(-/-) Mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Investigative-Pathology / Mini Symposium Sessions on Vascular Biology and Molecular Mechanisms of Diseases at Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Soc Investigat Pathol ID SMOOTH-MUSCLE-CELLS; E-DEFICIENT MICE; INDUCED HYPERTENSION; OXIDATIVE STRESS; T-CELLS; CARDIOVASCULAR-DISEASE; CLINICAL-IMPLICATIONS; GENE-EXPRESSION; PDGFR-BETA; PATHOGENESIS AB Cytochrome P450 (CYP) 1B1 is implicated in vascular smooth muscle cell migration, proliferation, and hypertension. We assessed the contribution of CYP1B1 to angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA). Male Apoe(-/-)/Cyp1b1(+/+) and Apoe(-/-)/Cyp1b1(-/-) mice were infused with Ang II or its vehicle for 4 weeks; another group of Apoe(-/-) /Cyp1b1(-/-) mice was coadministered the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS) every third day for 4 weeks. On day 28 of Ang II infusion, AAAs were analyzed by ultrasound and ex vivo by Vernier calipers, mice were euthanized, and tissues were harvested. Ang II produced AAAs in Apoe(-/-)/Cyp1b1(+/+) mice; mice treated with TMS or Apoe(-/-)/Cyp1b1(-/-) mice had reduced AAAs. Ang II enhanced infiltration of macrophages, T cells, and platelets and increased platelet derived growth factor D, Pdgfrb, Itga2, and matrix metalloproteinases 2 and 9 expression in aortic lesions; these changes were inhibited in mice treated with TMS and in Apoe(-/-)/Cyp1b1(-/-) mice. Oxidative stress resulted in cyclooxygenase-2 expression in aortic lesions. These effects were minimized in Apoe(-/-)/Cyp1b1+/+ mice treated with TMS and in Apoe(-/-)/Cyp1b1(-/-) mice and by concurrent treatment with the superoxide scavenger 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl. CYP1B1 contributed to the development of Ang II induced AAA and associated pathogenic events in mice, likely by enhancing oxidative stress and associated signaling events. Thus, CYP1B1 may serve as a target for therapeutic agents for AAA in males. C1 [Thirunavukkarasu, Shyamala; Khan, Nayaab S.; Song, Chi Young; Ghafoor, Hafiz U.; Malik, Kafait U.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA. [Brand, David D.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Med & Microbiol Immunol & Biochem, Memphis, TN USA. [Brand, David D.] Vet Affairs Med Ctr, Res Serv, Memphis, TN USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Malik, KU (reprint author), Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA. EM kmalik@uthsc.edu FU BLRD VA [I01 BX001193]; NHLBI NIH HHS [R01 HL079109] NR 60 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2016 VL 186 IS 8 BP 2204 EP 2219 DI 10.1016/j.ajpath.2016.04.005 PG 16 WC Pathology SC Pathology GA DS2ON UT WOS:000380623500020 PM 27301358 ER PT J AU Hughes, BL Clifton, RG Hauth, JC Leveno, KJ Myatt, L Reddy, UM Varner, MW Wapner, RJ Mercer, BM Peaceman, AM Ramin, SM Tolosa, JE Saade, G Sorokin, Y AF Hughes, Brenna L. Clifton, Rebecca G. Hauth, John C. Leveno, Kenneth J. Myatt, Leslie Reddy, Uma M. Varner, Michael W. Wapner, Ronald J. Mercer, Brian M. Peaceman, Alan M. Ramin, Susan M. Tolosa, Jorge E. Saade, George Sorokin, Yoram CA Eunice Kennedy Shriver Natl Inst TI Is Mid-trimester Insulin Resistance Predictive of Subsequent Puerperal Infection? A Secondary Analysis of Randomized Trial Data SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE insulin resistance; puerperal infection; pregnancy; predictor ID POLYCYSTIC-OVARY-SYNDROME; PRETERM PRELABOR RUPTURE; AMNIOTIC-FLUID; HISTOLOGICAL CHORIOAMNIONITIS; CEREBRAL-PALSY; TERM INFANTS; MEMBRANES; OBESITY; WOMEN; INTERLEUKIN-6 AB Objective The objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). Methods Secondary analysis of low-risk nulliparas enrolled in a multicenter preeclampsia prevention trial. HOMA: IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks' gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test. Logistic regression was used to control for potential confounders. Results Of 1,180 women with fasting glucose and insulin available, 121 (10.3%) had a puerperal infection. Median HOMA: IR was higher among those with subsequent puerperal infection (4.3 [interquartile, IQR: 2.2-20.5] vs. 2.6 [IQR: 1.5-6.7], p < 0.0001). After controlling for potentially confounding variables HOMA: IR was only marginally associated with an increased risk of development of puerperal infection, adjusted odds ratio: 1.01 (95% confidence interval: 1.00-1.02; p = 0.04) per unit increase. Elevated HOMA: IR performed poorly as a predictor of puerperal infection, with a positive predictive value of 15% and a negative predictive value of 92%. Conclusion Though associated with an increased risk of puerperal infection, insulin resistance, measured by HOMA: IR, is not a clinically useful predictor of puerperal infection. C1 [Hughes, Brenna L.] Brown Univ, Women & Infants Hosp, Dept Obstet & Gynecol, Providence, RI USA. [Clifton, Rebecca G.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Hauth, John C.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Leveno, Kenneth J.] Univ Texas Southwestern Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. [Myatt, Leslie] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Varner, Michael W.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Wapner, Ronald J.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Mercer, Brian M.] Case Western Reserve Univ, Dept Obstet & Gynecol, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Peaceman, Alan M.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Saade, George] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Hughes, BL (reprint author), Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, 101 Dudley St, Providence, RI 02905 USA. EM bhughes@wihri.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917, HD36801]; National Heart, Lung, and Blood Institute; National Center for Research Resources [M01 RR00080, UL1 RR024153, UL1 RR024989]; [K23HD062340-01] FX A portion of this work was funded by K23HD062340-01 (Hughes/Anderson). The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917, and HD36801); the National Heart, Lung, and Blood Institute; and the National Center for Research Resources (M01 RR00080, UL1 RR024153, UL1 RR024989). Comments and views of the authors do not necessarily represent the views of the NICHD. NR 30 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 AUG PY 2016 VL 33 IS 10 BP 983 EP 990 DI 10.1055/s-0036-1583188 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA DS4TN UT WOS:000380774600010 PM 27120478 ER PT J AU Aliaga, S Zhang, J Long, DL Herring, AH Laughon, M Boggess, K Reddy, UM Grantz, KL AF Aliaga, Sofia Zhang, Jun Long, D. Leann Herring, Amy H. Laughon, Matthew Boggess, Kim Reddy, Uma M. Grantz, Katherine Laughon TI Center Variation in the Delivery of Indicated Late Preterm Births SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE late preterm birth; preterm birth; center variation; practice variation ID REGIONAL-VARIATION; UNITED-STATES; INFANTS; CARE; GESTATIONS; OUTCOMES; RATES; MORTALITY; TERM AB Objective Evidence for optimal timing of delivery for some pregnancy complications at late preterm gestation is limited. The purpose of this study was to identify center variation of indicated late preterm births. Study design We performed an analysis of singleton late pretermand term births from a large U.S. retrospective obstetrical cohort. Births associated with spontaneous preterm labor, major congenital anomalies, chorioamnionitis, and emergency cesarean were excluded. We used modified Poisson fixed effects logistic regression with interaction terms to assess center variation of indicated late preterm births associated with four medical/obstetric comorbidities after adjusting for socio-demographics, comorbidities, and hospital/provider characteristics. Results We identified 150,055 births from 16 hospitals; 9,218 were indicated late preterm births. We found wide variation of indicated late preterm births across hospitals. The extent of center variation was greater for births associated with preterm premature rupture of membranes (risk ratio [RR] across sites: 0.45-3.05), hypertensive disorders of pregnancy (RR across sites: 0.36-1.27), and placenta previa/abruption (RR across sites: 0.48-1.82). We found less center variation for births associated with diabetes (RR across sites: 0.65-1.39). Conclusion Practice variation in the management of indicated late preterm deliveries might be a source of preventable late preterm birth. C1 [Aliaga, Sofia; Laughon, Matthew] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Zhang, Jun] Shanghai Jiao Tong Univ, Xinhua Hosp, MOE Shanghai Key Lab Childrens Environm Hlth, Sch Med, Shanghai, Peoples R China. [Long, D. Leann; Herring, Amy H.] West Virginia Univ, Dept Biostat, Morgantown, WV USA. [Herring, Amy H.] Carolina Populat Ctr, Chapel Hill, NC USA. [Boggess, Kim] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. RP Aliaga, S (reprint author), Pediat CB 7596,101 Manning Dr, Chapel Hill, NC 27599 USA. EM saliaga@med.unc.edu OI Grantz, Katherine/0000-0003-0276-8534 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C]; National Institute of General Medical Sciences [U54GM104942]; Faculty Development Award from North Carolina Children's Promise FX The data included in this article were obtained from the Consortium on Safe Labor, which was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract number HHSN267200603425C. Institutions involved in the Consortium include, in alphabetical order, the following: Baystate Medical Center, Springfield, MA; Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles, CA; Christiana Care Health System, Newark, DE; MedStar Georgetown University Hospital, Washington, DC; Indiana University Clarian Health, Indianapolis, IN; Intermountain Healthcare and the University of Utah, Salt Lake City, UT; Maimonides Medical Center, Brooklyn, NY; MetroHealth Medical Center, Cleveland, OH; Summa Health System, Akron City Hospital, Akron, OH; The EMMES Corporation, Rockville, MD (Data Coordinating System); University of Illinois at Chicago, Chicago, IL; University of Miami, Miami, FL; and University of Texas Health Science Center at Huston, Houston, TX. The named authors alone are responsible for the views expressed in this manuscript, which does not necessarily represent the decisions or the stated policy of the NICHD.; DL Long received support from a grant from the National Institute of General Medical Sciences (U54GM104942); her views expressed in this manuscript are not that of the NIH.; This study received supported from a Faculty Development Award from the North Carolina Children's Promise. NR 38 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 33 IS 10 BP 1008 EP 1016 DI 10.1055/s-0036-1582129 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA DS4TN UT WOS:000380774600014 PM 27120474 ER PT J AU Yao, XL Gordon, EM Figueroa, DM Barochia, AV Levine, SJ AF Yao, Xianglan Gordon, Elizabeth M. Figueroa, Debbie M. Barochia, Amisha V. Levine, Stewart J. TI Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Review DE apolipoprotein E; apolipoprotein A-I; lipid transport; lung disease ID APOE-DEFICIENT MICE; NEUTROPHILIC AIRWAY INFLAMMATION; DENSITY-LIPOPROTEIN RECEPTOR; INNATE IMMUNE-RESPONSES; MIMETIC PEPTIDE D-4F; PULMONARY-HYPERTENSION; KLEBSIELLA-PNEUMONIAE; BACTERIAL-INFECTIONS; ANTIGEN PRESENTATION; PEDIATRIC-PATIENTS AB Emerging roles are being recognized increasingly for apolipoproteins in the pathogenesis and treatment of lung diseases on the basis of their ability to suppress inflammation, oxidative stress, and tissue remodeling, and to promote adaptive immunity and host defense. Apolipoproteins, such as apolipoprotein E (apoE) and apolipoprotein A-I (apoA-I), are important components of lipoprotein particles that facilitate the transport of cholesterol, triglycerides, and phospholipids between plasma and cells. ApoE-containing lipoprotein particles are internalized into cells by low-density lipoprotein receptors (LDLRs), whereas apoA-I can interact with the ATP-binding cassette subfamily A member 1 (ABCA1) transporter to efflux cholesterol and phospholipids out of cells. ApoE and apoA-I also mediate receptor-independent effects, such as binding to and neutralizing LPS. Both apoE and apoA-I are expressed by lung cells, which allows apoE/LDLR- and apoA-I/ABCA1-dependent pathways to modulate normal lung health and the pathogenesis of respiratory diseases, including asthma, acute lung injury, cancer, emphysema, pulmonary fibrosis, and pulmonary hypertension. Data from human studies and research using experimental murine model systems have shown that both apoE and apoA-I pathways play primarily protective roles in lung biology and respiratory disease. Furthermore, apolipoprotein mimetic peptides, corresponding to the LDLR-binding domain of apoE or the class A amphipathic a-helical structure of apoA-I, have antiinflammatory and antioxidant effects that attenuate the severity of lung disease in murine models. Thus, the development of inhaled apolipoprotein mimetic peptides as a novel treatment paradigm could represent a significant advance for patients with respiratory disease who do not respond to current therapies. C1 [Yao, Xianglan; Gordon, Elizabeth M.; Figueroa, Debbie M.; Barochia, Amisha V.; Levine, Stewart J.] NHLBI, Lab Asthma & Lung Inflammat, Cardiovasc & Pulm Branch, Div Intramural Res,NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Lab Asthma & Lung Inflammat, Cardiovasc & Pulm Branch, Div Intramural Res,NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 98 TC 1 Z9 1 U1 6 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG 1 PY 2016 VL 55 IS 2 BP 159 EP 169 DI 10.1165/rcmb.2016-0060TR PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA DT7XT UT WOS:000381702300002 PM 27073971 ER PT J AU Badri, MK Zhang, HH Ohyama, Y Venkitapathi, S Kamiya, N Takeda, H Ray, M Scott, G Tsuji, T Kunieda, T Mishina, Y Mochida, Y AF Badri, Mohammed K. Zhang, Honghao Ohyama, Yoshio Venkitapathi, Sundharamani Kamiya, Nobuhiro Takeda, Haruko Ray, Manas Scott, Greg Tsuji, Takehito Kunieda, Tetsuo Mishina, Yuji Mochida, Yoshiyuki TI Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE cephalometric analysis; craniofacial bone; Ellis-van Creveld syndrome; EVC2; knockout (KO) mouse ID BOVINE CHONDRODYSPLASTIC DWARFISM; ACROFACIAL DYSOSTOSIS; GENE; GROWTH; MORPHOLOGY; MUTATIONS; CILIA; EVC2 AB Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by similar to 20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. (C) 2016 Wiley Periodicals, Inc. C1 [Badri, Mohammed K.; Ohyama, Yoshio; Venkitapathi, Sundharamani; Mochida, Yoshiyuki] Boston Univ, Henry M Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA. [Badri, Mohammed K.] Taibah Univ, Coll Dent, Dept Pediat Dent & Orthodont, Al Madinah Al Munawarah, Saudi Arabia. [Zhang, Honghao; Kamiya, Nobuhiro; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Kamiya, Nobuhiro; Ray, Manas; Scott, Greg; Mishina, Yuji] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Takeda, Haruko] Univ Liege, GIGA R, Unit Anim Genom, B-4000 Liege, Belgium. [Takeda, Haruko] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium. [Tsuji, Takehito; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama, Japan. RP Mochida, Y (reprint author), 700 Albany St,W202D, Boston, MA 02118 USA. EM mochida@bu.edu FU NIH/NIDCR [DE019527, DE020843] FX Grant sponsor: NIH/NIDCR; Grant numbers: DE019527, DE020843. NR 28 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8486 EI 1932-8494 J9 ANAT REC JI Anat. Rec. PD AUG PY 2016 VL 299 IS 8 BP 1110 EP 1120 DI 10.1002/ar.23353 PG 11 WC Anatomy & Morphology SC Anatomy & Morphology GA DT7BU UT WOS:000381641900013 PM 27090777 ER PT J AU Sah, P Nussear, KE Esque, TC Aiello, CM Hudson, PJ Bansal, S AF Sah, Pratha Nussear, Kenneth E. Esque, Todd C. Aiello, Christina M. Hudson, Peter J. Bansal, Shweta TI Inferring social structure and its drivers from refuge use in the desert tortoise, a relatively solitary species SO BEHAVIORAL ECOLOGY AND SOCIOBIOLOGY LA English DT Article DE Behavioral stress response; Bipartite networks; Gopherus agassizii; Generalized linear mixed models; Modularity; Mycoplasma agassizii ID RESPIRATORY-TRACT DISEASE; JUVENILE GOPHER TORTOISES; LIZARD TILIQUA-RUGOSA; MOJAVE DESERT; BOVINE TUBERCULOSIS; CLIMATIC VARIATION; MOVEMENT PATTERNS; 2 POPULATIONS; HOME-RANGE; AGASSIZII AB For several species, refuges (such as burrows, dens, roosts, nests) are an essential resource for protection from predators and extreme environmental conditions. Refuges also serve as focal sites for social interactions, including mating, courtship, and aggression. Knowledge of refuge use patterns can therefore provide information about social structure, mating, and foraging success, as well as the robustness and health of wildlife populations, especially for species considered to be relatively solitary. In this study, we construct networks of burrow use to infer social associations in a threatened wildlife species typically considered solitary-the desert tortoise. We show that tortoise social networks are significantly different than null networks of random associations, and have moderate spatial constraints. We next use statistical models to identify major mechanisms behind individual-level variation in tortoise burrow use, popularity of burrows in desert tortoise habitat, and test for stressor-driven changes in refuge use patterns. We show that seasonal variation has a strong impact on tortoise burrow switching behavior. On the other hand, burrow age and topographical condition influence the number of tortoises visiting a burrow in desert tortoise habitat. Of three major population stressors affecting this species (translocation, drought, disease), translocation alters tortoise burrow switching behavior, with translocated animals visiting fewer unique burrows than residents. In a species that is not social, our study highlights the importance of leveraging refuge use behavior to study the presence of and mechanisms behind non-random social structure and individual-level variation. Our analysis of the impact of stressors on refuge-based social structure further emphasizes the potential of this method to detect environmental or anthropogenic disturbances. Adaptive and social behavior that affects fitness is now being increasingly incorporated in the conservation and management of wildlife species. However, direct observations of social interactions in species considered to be solitary are difficult, and therefore integration of behavior in conservation and management decisions in such species has been infrequent. For such species, we propose quantifying refuge use behavior as it can provide insights towards their (hidden) social structure, establish relevant contact patterns of infectious disease spread, and provide early warning signals of population stressors. Our study highlights this approach in a long-lived and threatened species, the desert tortoise. We provide evidence toward the presence of and identify mechanisms behind the social structure in desert tortoises formed by their burrow use preferences. We also show how individuals burrow use behavior responds to the presence of population stressors. C1 [Sah, Pratha; Bansal, Shweta] Georgetown Univ, Dept Biol, Washington, DC 20057 USA. [Nussear, Kenneth E.] Univ Nevada, Dept Geog, Reno, NV 89557 USA. [Esque, Todd C.; Aiello, Christina M.] US Geol Survey, Western Ecol Res Ctr, Las Vegas Field Stn, Henderson, NV USA. [Aiello, Christina M.; Hudson, Peter J.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Bansal, Shweta] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RP Bansal, S (reprint author), Georgetown Univ, Dept Biol, Washington, DC 20057 USA.; Bansal, S (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM shweta.bansal@georgetown.edu OI Sah, Pratha/0000-0001-8936-5871; Aiello, Christina/0000-0002-2399-5464; Bansal, Shweta/0000-0002-1740-5421 FU National Science Foundation [1216054]; Department of Defense, Ft. Irwin National Training Center; Ecosystems Mission Area of the U.S. Geological Survey FX This work was funded by the National Science Foundation Ecology of Infections Diseases grant 1216054 Invasion and Infection: Translocation and Transmission: An Experimental Study with Mycoplasma in Desert Tortoises. This work was also partially funded by a grant from the Department of Defense, Ft. Irwin National Training Center, and by the Ecosystems Mission Area of the U.S. Geological Survey. NR 75 TC 0 Z9 0 U1 19 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-5443 EI 1432-0762 J9 BEHAV ECOL SOCIOBIOL JI Behav. Ecol. Sociobiol. PD AUG PY 2016 VL 70 IS 8 BP 1277 EP 1289 DI 10.1007/s00265-016-2136-9 PG 13 WC Behavioral Sciences; Ecology; Zoology SC Behavioral Sciences; Environmental Sciences & Ecology; Zoology GA DS0DQ UT WOS:000380266000015 ER PT J AU Detrait, ER Carr, GV Weinberger, DR Lamberty, Y AF Detrait, Eric R. Carr, Greg V. Weinberger, Daniel R. Lamberty, Yves TI Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE catechol-O-methyl transferase; cognitive enhancers; dopamine; entacapone; mouse; Novel Object Recognition; rat; tolcapone ID PREFRONTAL CORTEX; OBJECT RECOGNITION; PARKINSONS-DISEASE; COGNITIVE DEFICITS; SCHIZOPHRENIA; DOPAMINE; PERFORMANCE; RELEVANCE; MODELS AB The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase ( COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brainpenetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Detrait, Eric R.; Lamberty, Yves] UCB Biopharma Sprl, Neurosci Therapeut Area, Chemin Foriest, B-1420 Braine Lalleud, Belgium. [Carr, Greg V.; Weinberger, Daniel R.] Johns Hopkins Sch Med, Lieber Inst Brain Dev, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurosci, Inst Med Genet, Baltimore, MD USA. [Carr, Greg V.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Detrait, ER (reprint author), UCB Biopharma Sprl, Neurosci Therapeut Area, Chemin Foriest, B-1420 Braine Lalleud, Belgium. EM edetrait@yahoo.fr RI Carr, Gregory/M-8821-2016 OI Carr, Gregory/0000-0002-6091-6729 FU Lieber Institute for Brain Development; Intramural Research Program of NIMH; UCB Biopharma FX Research funds were provided by the Lieber Institute for Brain Development, the Intramural Research Program of NIMH, and UCB Biopharma. NR 31 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8810 EI 1473-5849 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 2016 VL 27 IS 5 BP 415 EP 421 DI 10.1097/FBP.0000000000000208 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA DS5GV UT WOS:000380810600002 PM 26919286 ER PT J AU Ann, J Sun, W Zhou, X Jung, A Baek, J Lee, S Kim, C Yoon, S Hong, S Choi, S Turcios, NA Herold, BKA Esch, TE Lewin, NE Abramovitz, A Pearce, LV Blumberg, PM Lee, J AF Ann, Jihyae Sun, Wei Zhou, Xing Jung, Aeran Baek, Jisoo Lee, Sunho Kim, Changhoon Yoon, Suyoung Hong, Sunhye Choi, Sun Turcios, Noe A. Herold, Brienna K. A. Esch, Timothy E. Lewin, Nancy E. Abramovitz, Adelle Pearce, Larry V. Blumberg, Peter M. Lee, Jeewoo TI Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Vanilloid receptor 1; TRPV1 antagonists; Analgesic ID PYRIDINE C-REGION; VANILLOID CAPSAICIN RECEPTORS; ANALGESIC AGENTS; AGONIST ACTIVITY; ANALOGS; 2-(3-FLUORO-4-METHYLSULFONYLAMINOPHENYL)PROPANAMIDES; MECHANISMS; DOCKING AB A series of homologous analogues of prototype antagonist 1 and its urea surrogate were investigated as hTRPV1 ligands. Through one-carbon elongation in the respective pharmacophoric regions, N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea was identified as a novel and potent TRPV1 antagonistic template. Its representative compound 27 showed a potency comparable to that of lead compound 1. Docking analysis of compound 27 in our hTRPV1 homology model indicated that its binding mode was similar with that of 1S. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Ann, Jihyae; Jung, Aeran; Baek, Jisoo; Lee, Sunho; Kim, Changhoon; Yoon, Suyoung; Lee, Jeewoo] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. [Sun, Wei] Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China. [Zhou, Xing] Hainan Inst Mat Med, Haikou 570311, Peoples R China. [Hong, Sunhye; Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 120750, South Korea. [Turcios, Noe A.; Herold, Brienna K. A.; Esch, Timothy E.; Lewin, Nancy E.; Abramovitz, Adelle; Pearce, Larry V.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU Korea Science and Engineering Foundation (KOSEF) grant - Korea government (MOST) [NRF-2014M3A9B5073755]; National Leading Research Lab (NLRL) program [2011-0028885]; National Natural Science Foundation of China [81502927]; Liaoning ST Project [2014226032, 2015020733, 2015001002]; Hainan ST Project [KYYS-2014-66]; Intramural Research Program of the NIH, Center for Cancer Research, NCI in the USA [Z1A BC 005270] FX This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (NRF-2014M3A9B5073755), National Leading Research Lab (NLRL) program (2011-0028885), National Natural Science Foundation of China (81502927), Liaoning S&T Project (2014226032, 2015020733 and 2015001002), Hainan S&T Project (KYYS-2014-66), and in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI (Project Z1A BC 005270) in the USA. NR 32 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 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2016 VL 26 IS 15 BP 3603 EP 3607 DI 10.1016/j.bmcl.2016.06.010 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA DS2FA UT WOS:000380574100042 PM 27317643 ER PT J AU Wetzler, LM Feavers, IM Gray-Owen, SD Jerse, AE Rice, PA Deal, CD AF Wetzler, Lee M. Feavers, Ian M. Gray-Owen, Scott D. Jerse, Ann E. Rice, Peter A. Deal, Carolyn D. TI Summary and Recommendations from the National Institute of Allergy and Infectious Diseases (NIAID) Workshop "Gonorrhea Vaccines: the Way Forward" SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; NEISSERIA-GONORRHOEAE; GONOCOCCAL-INFECTION; ADAPTIVE IMMUNITY; POTENTIAL IMPACT; BINDING-PROTEIN; MALE-VOLUNTEERS; VACCINATION; MODEL; IMMUNOGENICITY AB There is an urgent need for the development of an antigonococcal vaccine due to the increasing drug resistance found in this pathogen. The U.S. Centers for Disease Control (CDC) have identified multidrug-resistant gonococci (GC) as among 3 "urgent" hazard-level threats to the U.S. population. In light of this, on 29 to 30 June 2015, the National Institute for Allergy and Infectious Diseases (NIAID) sponsored a workshop entitled "Gonorrhea Vaccines: the Way Forward." The goal of the workshop was to gather leaders in the field to discuss several key questions on the current status of gonorrhea vaccine research and the path forward to a licensed gonorrhea vaccine. Representatives from academia, industry, U.S. Government agencies, and a state health department were in attendance. This review summarizes each of the 4 scientific sessions and a series of 4 breakout sessions that occurred during the one and a half days of the workshop. Topics raised as high priority for future development included (i) reinvigoration of basic research to understand gonococcal infection and immunity to allow intervention in processes essential for infection; (ii) clinical infection studies to establish parallels and distinctions between in vitro and animal infection models versus natural human genital and pharyngeal infection and to inform in silico modeling of vaccine impact; and (iii) development of an integrated pipeline for preclinical and early clinical evaluation and direct comparisons of potential vaccine antigens and adjuvants and routes of delivery. C1 [Wetzler, Lee M.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. [Feavers, Ian M.] Natl Inst Biol Stand & Controls, Ridge, Herts, England. [Gray-Owen, Scott D.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, F Edward Herbert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Rice, Peter A.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. [Deal, Carolyn D.] NIAID, Div Microbiol & Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Wetzler, LM (reprint author), Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. EM lwetzler@bu.edu FU NIAID NIH HHS [R01 AI114710] NR 36 TC 2 Z9 2 U1 5 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2016 VL 23 IS 8 BP 656 EP 663 DI 10.1128/CVI.00230-16 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DS5NJ UT WOS:000380828700001 PM 27335384 ER PT J AU Tycko, R AF Tycko, Robert TI Molecular Structure of Aggregated Amyloid-beta: Insights from Solid-State Nuclear Magnetic Resonance SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ALZHEIMERS-DISEASE BRAIN; ANGLE-SPINNING NMR; A-BETA; FIBRIL FORMATION; PRECURSOR PROTEIN; IN-REGISTER; EXPERIMENTAL CONSTRAINTS; ROTATIONAL RESONANCE; QUATERNARY STRUCTURE; ELECTRON-MICROSCOPY AB Amyloid-beta (A beta) peptides aggregate to form polymorphic amyloid fibrils and a variety of intermediate assemblies, including oligomers and protofibrils, both in vitro and in human brain tissue. Since the beginning of the 21st century, considerable progress has been made to characterize the molecular structures of A beta aggregates. Full molecular structural models based primarily on data from measurements using solid-state nuclear magnetic resonance (ssNMR) have been developed for several in vitro A beta fibrils and one metastable protofibril. Partial structural characterization of other aggregation intermediates has been achieved. One full structural model for fibrils derived frombrain tissue has also been reported. Future work is likely to focus on additional structures from brain tissue and on further clarification of non-fibrillar A beta aggregates. C1 [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX Research on A beta structures in Dr. Tycko's laboratory is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health. NR 111 TC 0 Z9 0 U1 13 U2 21 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD AUG PY 2016 VL 6 IS 8 AR a024083 DI 10.1101/cshperspect.a024083 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DT7QJ UT WOS:000381681000001 ER PT J AU Hughes, HY Henderson, DK AF Hughes, Heather Y. Henderson, David K. TI Postexposure prophylaxis after hepatitis C occupational exposure in the interferon-free era SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE bloodborne pathogens; direct acting antiviral agents; hepatitis C virus; postexposure prophylaxis ID HCV GENOTYPE 1; HEALTH-CARE WORKERS; UNITED-STATES; VIRUS-INFECTION; NEEDLESTICK; MANAGEMENT; SOFOSBUVIR; VELPATASVIR; PROTECTION; MICRORNAS AB Purpose of review Healthcare personnel are at risk for occupational exposures to bloodborne pathogens. Primary prevention remains the first line of defense, but secondary prevention measures known to be effective should be implemented when percutaneous exposures occur. Hepatitis C virus (HCV) is a major infectious cause of liver-related morbidity and mortality. Chronic HCV treatment has changed dramatically, with many all-oral directly acting anti-HCV antiviral (DAA) regimens now available. Evidence for the use of DAAs as postexposure prophylaxis (PEP) after occupational exposures to HCV is summarized here. Recent findings Little new evidence supports the use of antivirals in acute HCV infection. Several preliminary studies have examined the use of DAAs or host target agents in chronic HCV treatment. Effective HCV PEP requirements likely include pan-genotypic activity and a high barrier to resistance. One investigational DAA has shown promising results as an efficacious option for all genotypes in chronic HCV treatment and may ultimately represent a potential HCV PEP agent. Summary Insufficient supporting data exist to endorse the use of DAAs for PEP after HCV occupational exposures; additional studies examining efficacy, duration, and cost-effectiveness are needed. Development of more oral drugs possessing a high barrier of resistance and equal activity against all HCV genotypes is anticipated. C1 [Hughes, Heather Y.] Charlie Norwood VA Med Ctr, Augusta, GA USA. [Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM DHenderson@cc.nih.gov NR 41 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 0951-7375 EI 1473-6527 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 2016 VL 29 IS 4 BP 373 EP 380 DI 10.1097/QCO.0000000000000281 PG 8 WC Infectious Diseases SC Infectious Diseases GA DS3YQ UT WOS:000380719000008 PM 27306563 ER PT J AU Marongiu, M Deiana, M Marcia, L Sbardellati, A Asunis, I Meloni, A Angius, A Cusano, R Loi, A Crobu, F Fotia, G Cucca, F Schlessinger, D Crisponi, L AF Marongiu, Mara Deiana, Manila Marcia, Loredana Sbardellati, Andrea Asunis, Isadora Meloni, Alessandra Angius, Andrea Cusano, Roberto Loi, Angela Crobu, Francesca Fotia, Giorgio Cucca, Francesco Schlessinger, David Crisponi, Laura TI Novel action of FOXL2 as mediator of Col1a2 gene autoregulation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE FOXL2; COL1A2; Transcriptional regulation; Ovary; ECM ID TRANSCRIPTION FACTOR FOXL2; GRANULOSA-CELL TUMORS; EPICANTHUS INVERSUS SYNDROME; FORKHEAD TRANSCRIPTION; I COLLAGEN; EXTRACELLULAR-MATRIX; OVARY; PROPEPTIDE; FOLLICLE; INTERACTS AB FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause. (C) 2016 Elsevier Inc. All rights reserved. C1 [Marongiu, Mara; Deiana, Manila; Marcia, Loredana; Asunis, Isadora; Meloni, Alessandra; Angius, Andrea; Loi, Angela; Crobu, Francesca; Cucca, Francesco; Crisponi, Laura] CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, Italy. [Sbardellati, Andrea; Cusano, Roberto; Fotia, Giorgio] Ctr Adv Studies Res & Dev Sardinia CRS4, Pula, Italy. [Marcia, Loredana; Cucca, Francesco] Univ Sassari, I-07100 Sassari, Italy. [Schlessinger, David] NIA, Genet Lab, IRP, NIH, Baltimore, MD 21224 USA. RP Crisponi, L (reprint author), CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, Italy. EM laura.crisponi@irgb.cnr.it FU Comitato Telethon Fondazione Onlus; Telethon [GP0049Y01]; Sardinian Autonomous Region [L.R. 7/2009, cRP3-154]; CNR, Italy FX This work has been supported by Comitato Telethon Fondazione Onlus, with Telethon grant to LC no GP0049Y01 and in part by Sardinian Autonomous Region (L.R. 7/2009) grant cRP3-154 to FC and by CNR, Italy grant FaReBio2011 'Farmaci e Reti Biotecnologiche di Qualita' to FC. NR 68 TC 1 Z9 1 U1 4 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2016 VL 416 IS 1 BP 200 EP 211 DI 10.1016/j.ydbio.2016.05.022 PG 12 WC Developmental Biology SC Developmental Biology GA DS6BO UT WOS:000380866900019 PM 27212026 ER PT J AU Geva, S Cooper, JM Gadian, DG Mishkin, M Vargha-Khadem, F AF Geva, Sharon Cooper, Janine M. Gadian, David G. Mishkin, Mortimer Vargha-Khadem, Faraneh TI Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Working memory; Hippocampus ID MEDIAL TEMPORAL-LOBE; SHORT-TERM-MEMORY; PREFRONTAL CORTEX; FRONTAL-LOBE; RELATIONAL INFORMATION; PARAHIPPOCAMPAL CORTEX; DEVELOPMENTAL AMNESIA; COGNITIVE-PROCESSES; RECOGNITION MEMORY; MACAQUE MONKEYS AB One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. C1 [Geva, Sharon; Cooper, Janine M.; Mishkin, Mortimer; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, Cognit Neurosci & Neuropsychiat Sect, 30 Guilford St, London WC1N 1EH, England. [Gadian, David G.] UCL, Inst Child Hlth, Environm Imaging & Biophys Sect, 30 Guilford St, London WC1N 1EH, England. [Mishkin, Mortimer] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Cooper, Janine M.] Murdoch Childrens Res Inst, Australian Ctr Child Neuropsychol Studies, Flemington Rd, Parkville, Vic 3052, Australia. RP Geva, S (reprint author), UCL, Inst Child Hlth, Cognit Neurosci & Neuropsychiat Sect, 30 Guilford St, London WC1N 1EH, England. EM s.geva@ucl.ac.uk; janine.cooper@mcri.edu.au; d.gadian@ucl.ac.uk; mishkinm@mail.nih.gov; f.vargha-khadem@ucl.ac.uk FU Medical Research Council [G0300117-65439, G1002276-98624]; Intramural Research Program of the National Institute of Mental Health; NIH/DHHS; National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London FX This work was funded by the Medical Research Council (grants Nos. G0300117-65439 and G1002276-98624) and the Intramural Research Program of the National Institute of Mental Health, NIH/DHHS, and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. NR 67 TC 1 Z9 1 U1 7 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 EI 1878-9307 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD AUG PY 2016 VL 20 BP 12 EP 22 DI 10.1016/j.dcn.2016.06.001 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DS5UH UT WOS:000380847600003 PM 27288821 ER PT J AU Singh, N Johnstone, DB Martin, KA Tempera, I Kaplan, MJ Denny, MF AF Singh, Namrata Johnstone, Duncan B. Martin, Kayla A. Tempera, Italo Kaplan, Mariana J. Denny, Michael F. TI Alterations in nuclear structure promote lupus autoimmunity in a mouse model SO DISEASE MODELS & MECHANISMS LA English DT Article DE Nucleus; Chromatin; Histone modifications; Calreticulin; Lamina; Autoantibody ID LAMIN-B-RECEPTOR; NEUTROPHIL EXTRACELLULAR TRAPS; MYELOPROLIFERATIVE NEOPLASMS; A-TYPE; H-Y; ERYTHEMATOSUS; AUTOANTIBODIES; ENVELOPE; DISEASE; CHROMATIN AB Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger-Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbr(ic/+)), and the (NZWxB6.Lbr(ic))F-1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZWxB6.Lbr(ic))F-1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Faslpr mice, and were predominantly of the IgG2 subclasses. The antinuclear antibody staining profile of female (NZWxB6.Lbr(ic))F-1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus-prone genetic background, suggesting a mechanism for the development of lupus autoimmunity in genetically predisposed individuals that is induced by the disruption of nuclear architecture. C1 [Singh, Namrata] Univ Iowa, Internal Med, Iowa City, IA 52242 USA. [Johnstone, Duncan B.] Temple Univ, Sch Med, Sect Nephrol Internal Med, Philadelphia, PA 19140 USA. [Martin, Kayla A.; Tempera, Italo] Temple Univ, Fels Inst Canc Res, Dept Immunol Microbiol, Philadelphia, PA 19140 USA. [Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Denny, Michael F.] Temple Univ, Sch Med, Rheumatol Sect, Philadelphia, PA 19140 USA. RP Denny, MF (reprint author), Temple Univ, Sch Med, Rheumatol Sect, Philadelphia, PA 19140 USA. EM mikedenny@verizon.net FU National Institutes of Health, by a National Institute of Arthritis and Musculoskeletal and Skin Diseases New Investigator Grant [R03-AR061026]; Alliance for Lupus Research Target Identification in Lupus Grant; Department of Medicine at Temple University Faculty Research Development Award FX This work was supported by the National Institutes of Health, provided by a National Institute of Arthritis and Musculoskeletal and Skin Diseases New Investigator Grant [grant number R03-AR061026 to M.F.D.], the Alliance for Lupus Research Target Identification in Lupus Grant to M.F.D., and the Department of Medicine at Temple University Faculty Research Development Award to M.F.D. NR 91 TC 0 Z9 0 U1 1 U2 1 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 AUG 1 PY 2016 VL 9 IS 8 BP 885 EP 897 DI 10.1242/dmm.024851 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DT8PW UT WOS:000381754600006 PM 27483354 ER PT J AU Lee, WH Lisanby, SH Laine, AF Peterchev, AV AF Lee, W. H. Lisanby, S. H. Laine, A. F. Peterchev, A. V. TI Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model SO EUROPEAN PSYCHIATRY LA English DT Article DE Unipolar depression; Mania and bipolar disorder; MRI; ECT; Transcranial magnetic stimulation (TMS) ID TREATMENT-RESISTANT DEPRESSION; ULTRABRIEF STIMULUS TECHNIQUE; ES ELECTROSHOCK APPARATUS; DIPOLE ESTIMATION ERRORS; SIEMENS KONVULSATOR-III; LOW CURRENT AMPLITUDE; EEG SOURCE ANALYSIS; BRAIN-STIMULATION; ANISOTROPIC CONDUCTIVITIES; ENDOGENOUS-DEPRESSION AB Background: This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods: The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results: The standard ECT configurations and current amplitude of 800-900 mA produced the strongest overall stimulation with median of 1.8-2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions: The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. (C) 2016 Elsevier Masson SAS. All rights reserved. C1 [Lee, W. H.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Lisanby, S. H.; Peterchev, A. V.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Lisanby, S. H.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Lisanby, S. H.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Lisanby, S. H.] NIMH, NIH, Bethesda, MD 20892 USA. [Laine, A. F.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Peterchev, A. V.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. [Peterchev, A. V.] Duke Univ, Dept Elect & Comp Engn, Durham, NC 27708 USA. RP Peterchev, AV (reprint author), Duke Univ, Dept Psychiat & Behav Sci, DUMC, Box 3620, Durham, NC 27710 USA. EM angel.peterchev@duke.edu OI Peterchev, Angel/0000-0002-4385-065X FU National Institutes of Health [R01MH091083] FX This work was supported by the National Institutes of Health under grant R01MH091083 and an ANSYS Strategic Research Partnership. The authors thank Drs. Paolo Maccarini and Murali Kadiramangalam for the ANSYS license donation. NR 73 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PD AUG PY 2016 VL 36 BP 55 EP 64 DI 10.1016/j.eurpsy.2016.03.003 PG 10 WC Psychiatry SC Psychiatry GA DS2EI UT WOS:000380556000008 PM 27318858 ER PT J AU Patounakis, G Ozcan, MC Chason, RJ Norian, JM Payson, M DeCherney, AH Yauger, BJ AF Patounakis, George Ozcan, Meghan C. Chason, Rebecca J. Norian, John M. Payson, Mark DeCherney, Alan H. Yauger, Belinda J. TI Impact of a prior cesarean delivery on embryo transfer: a prospective study SO FERTILITY AND STERILITY LA English DT Article DE Embryo transfer; cesarean delivery; IVF; cesarean scar ID IN-VITRO FERTILIZATION; BODY-MASS INDEX; SUBSEQUENT FERTILITY; CLINICAL PREGNANCY; TRANSFER CATHETER; SECTION; COMPLICATIONS; METAANALYSIS; OUTCOMES; BLOOD AB Objective: To determine whether a history of prior cesarean delivery (CD) makes ET more difficult and impacts pregnancy outcomes. Design: Prospective cohort study. Setting: Tertiary care military facility. Patient(s): One hundred ninety-four patients with previous delivery undergoing IVF/intracytoplasmic sperm injection (ICSI)-ET. Intervention(s): None. Main Outcome Measure(s): Live birth (primary), positive hCG, clinical pregnancy, and time to perform ET. Result(s): There was no statistically significant difference between patients with a history of only vaginal deliveries versus those with a history of CD for live birth (39% vs. 32%), positive hCG (56% vs. 53%), or clinical pregnancy (49% vs. 41%). Embryo transfers took longer in the history of CD group (157 vs. 187 seconds) and were more likely to have mucus (27% vs. 45%) or blood (8% vs. 21%) on the catheter. Conclusion(s): Embryo transfers performed on patients with a prior CD took 30 seconds longer. They were also more likely to have blood or mucus on the catheter. Despite the apparently more difficult transfers, pregnancy outcomes were not different between the two groups. (C) 2016 by American Society for Reproductive Medicine. C1 [Patounakis, George; DeCherney, Alan H.] NICHHD, NIH, Bethesda, MD 20892 USA. [Ozcan, Meghan C.; Chason, Rebecca J.; Yauger, Belinda J.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Norian, John M.] HRC Fertil, Pasadena, CA USA. [Payson, Mark] Dominion Fertil, Arlington, VA USA. [Payson, Mark] Inova Fairfax Hosp Womens Ctr, Falls Church, VA USA. RP Yauger, BJ (reprint author), Walter Reed Natl Mil Med Ctr, Dept Obstet & Gynecol, 4494 North Palmer Rd, Bethesda, MD 20889 USA. EM belinda.j.yauger.mil@mail.mil FU Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland FX Supported, in part, by the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. NR 22 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2016 VL 106 IS 2 BP 311 EP 316 DI 10.1016/j.fertnstert.2016.03.045 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DS4PQ UT WOS:000380763400018 PM 27087400 ER PT J AU Royster, GD Krishnamoorthy, K Csokmay, JM Yauger, BJ Chason, RJ DeCherney, AH Wolff, EF Hill, MJ AF Royster, Greene Donald Krishnamoorthy, Kavitha Csokmay, John M. Yauger, Belinda J. Chason, Rebecca J. DeCherney, Alan H. Wolff, Erin F. Hill, Micah J. TI Are intracytoplasmic sperm injection and high serum estradiol compounding risk factors for adverse obstetric outcomes in assisted reproductive technology? SO FERTILITY AND STERILITY LA English DT Article DE Elevated E-2; adverse obstetric outcomes; IVF; ICSI ID IN-VITRO FERTILIZATION; SINGLETON PREGNANCIES; PERINATAL OUTCOMES; CONCEIVED PREGNANCIES; EMBRYO IMPLANTATION; PREECLAMPSIA; METAANALYSIS AB Objective: To evaluate whether intracytoplasmic sperm injection (ICSI) use and E-2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation. Design: Retrospective cohort study. Setting: Large private ART practice. Patient(s): A total of 383 women who underwent ART resulting in a singleton live birth. Intervention(s): None. Main Outcome Measure(s): Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants. Result(s): Patients with adverse placental outcomes had higher peak serum E-2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E-2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E-2 was >3,000 pg/mL and continued to increase in a linear fashion until E-2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E-2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles. Conclusion(s): ICSI and elevated E-2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E-2 and ICSI with adverse placental events is novel and warrants further investigation. (C) 2016 by American Society for Reproductive Medicine. C1 [Royster, Greene Donald; Csokmay, John M.; Yauger, Belinda J.; Chason, Rebecca J.; Hill, Micah J.] Walter Reed Natl Mil Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Bethesda, MD USA. [Royster, Greene Donald; DeCherney, Alan H.; Wolff, Erin F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Krishnamoorthy, Kavitha] Univ Miami Jackson Hlth Syst, Dept Obstet & Gynecol, Miami, FL USA. RP Royster, GD (reprint author), 10 CRC,Room 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM DonRoysterMD@gmail.com FU Intramural research program of the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland FX Supported, in part, by Intramural research program of the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. NR 28 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2016 VL 106 IS 2 BP 363 EP U181 DI 10.1016/j.fertnstert.2016.04.023 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DS4PQ UT WOS:000380763400026 PM 27172401 ER PT J AU Marsh, EE Bernardi, LA Steinberg, ML de Chavez, PJ Visser, JA Carnethon, MR Baird, DD AF Marsh, Erica E. Bernardi, Lia A. Steinberg, Marissa L. de Chavez, Peter J. Visser, Jenny A. Carnethon, Mercedes R. Baird, Donna D. TI Novel correlates between antimullerian hormone and menstrual cycle characteristics in African-American women (23-35 years-old) SO FERTILITY AND STERILITY LA English DT Article DE AMH; ovarian reserve; African-American women ID ANTI-MULLERIAN HORMONE; POLYCYSTIC-OVARY-SYNDROME; REPRODUCTIVE-AGE WOMEN; ANTRAL FOLLICLE COUNT; THYROID AUTOIMMUNITY; CAUCASIAN WOMEN; RESERVE; MENOPAUSE; CONTRACEPTIVES; RECRUITMENT AB Objective: To characterize normative antimullerian hormone (AMH) levels and ascertain which factors are associated with AMH in a large cohort of reproductive-age women. Design: Cross-sectional study. Setting: Not applicable. Patient(s): A total of 1,654 African-American women (AAW) ages 23-34 at recruitment. Intervention(s): Not applicable. Main Outcome Measure(s): Serum AMH measured using an ultrasensitive ELISA. Result(s): The median AMH was 3.18 ng/mL, and there was a significant, but nonlinear, relationship between age and AMH, with levels peaking at age 25. As AMH was not normally distributed, log transformation was performed and used for all analyses. In a multivariable age-adjusted model, body mass index, current use of hormonal contraception, and history of a thyroid condition were inversely associated with AMH, while history of abnormal menstrual bleeding and menstrual cycles longer than 35 days were positively associated with AMH. Conclusion(s): While age is correlated with AMH, it accounts for only a portion of the variation seen. This study adds valuable information to the existing literature on normative AMH levels in young reproductive-age women. While our findings fill a critical data gap for ovarian reserve in AAW, the insights gained will be of benefit for all women. (C) 2016 by American Society for Reproductive Medicine. C1 [Marsh, Erica E.; Bernardi, Lia A.; Steinberg, Marissa L.] Northwestern Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Feinberg Sch Med, Chicago, IL 60611 USA. [de Chavez, Peter J.; Carnethon, Mercedes R.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Visser, Jenny A.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Marsh, EE (reprint author), Northwestern Univ, Div Reprod Endocrinol & Infertil, 676 North St Clair St,Suite 1845, Chicago, IL 60611 USA. EM erica-marsh@northwestern.edu RI Visser, Jenny /F-8156-2011; Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU National Institutes of Health (NIH) [P01HD57877, R21 HD077479-01]; Women's Reproductive Health Research Scholar Program at Northwestern [NIH K12HD050121]; RWJ Harold Amos Medical Faculty Development Award; Friends of Prentice Women's Health Research Award; Evergreen Invitational Women's Health Grants Initiative; Woman's Board of Northwestern Memorial Hospital Grant; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX Supported by the National Institutes of Health (NIH; grant nos. P01HD57877 and R21 HD077479-01 to E.E.M.), the Women's Reproductive Health Research Scholar Program at Northwestern (grant no. NIH K12HD050121 to E.E.M.), the RWJ Harold Amos Medical Faculty Development Award (to E.E.M.), the Friends of Prentice Women's Health Research Award (to E.E.M.), the Evergreen Invitational Women's Health Grants Initiative (to E.E.M.), and the Woman's Board of Northwestern Memorial Hospital Grant (to L.A.B.). In addition, this research was supported in part (ongoing salary for D.D.B.) by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 48 TC 2 Z9 2 U1 2 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 AUG PY 2016 VL 106 IS 2 BP 443 EP U271 DI 10.1016/j.fertnstert.2016.04.008 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DS4PQ UT WOS:000380763400037 PM 27114331 ER PT J AU Doran, AG Wong, K Flint, J Adams, DJ Hunter, KW Keane, TM AF Doran, Anthony G. Wong, Kim Flint, Jonathan Adams, David J. Hunter, Kent W. Keane, Thomas M. TI Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations SO GENOME BIOLOGY LA English DT Article DE Sequencing; Mouse genomes; Laboratory mouse; Genomic variation; Disease; Cancer; arthritis; Biological pathways ID PHOSPHATIDYLCHOLINE TRANSFER PROTEIN; DNA MISMATCH-REPAIR; PHOSPHORYLASE-KINASE DEFICIENCY; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; PROMOTER POLYMORPHISMS; EXTRACELLULAR-MATRIX; STRUCTURAL VARIATION; PROSTATE-CANCER; GASTRIC-CANCER AB Background: The Mouse Genomes Project is an ongoing collaborative effort to sequence the genomes of the common laboratory mouse strains. In 2011, the initial analysis of sequence variation across 17 strains found 56.7 M unique single nucleotide polymorphisms (SNPs) and 8.8 M indels. We carry out deep sequencing of 13 additional inbred strains (BUB/BnJ, C57BL/10J, C57BR/cdJ, C58/J, DBA/1J, I/LnJ, KK/HiJ, MOLF/EiJ, NZB/B1NJ, NZW/LacJ, RF/J, SEA/GnJ and ST/bJ), cataloguing molecular variation within and across the strains. These strains include important models for immune response, leukaemia, age-related hearing loss and rheumatoid arthritis. We now have several examples of fully sequenced closely related strains that are divergent for several disease phenotypes. Results: Approximately 27.4 M unique SNPs and 5 M indels are identified across these strains compared to the C57BL/6 J reference genome (GRCm38). The amount of variation found in the inbred laboratory mouse genome has increased to 71 M SNPs and 12 M indels. We investigate the genetic basis of highly penetrant cancer susceptibility in RF/J finding private novel missense mutations in DNA damage repair and highly cancer associated genes. We use two highly related strains (DBA/1J and DBA/2J) to investigate the genetic basis of collagen-induced arthritis susceptibility. Conclusions: This paper significantly expands the catalogue of fully sequenced laboratory mouse strains and now contains several examples of highly genetically similar strains with divergent phenotypes. We show how studying private missense mutations can lead to insights into the genetic mechanism for a highly penetrant phenotype. C1 [Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Doran, Anthony G.; Wong, Kim; Adams, David J.; Keane, Thomas M.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Flint, Jonathan] Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.; Keane, TM (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. EM hunterk@mail.nih.gov; tk2@sanger.ac.uk OI Doran, Anthony/0000-0003-3061-4102; Keane, Thomas/0000-0001-7532-6898 FU Medical Research Council [MR/L007428/1]; BBSRC [BB/M000281/1]; Wellcome Trust; Cancer Research UK; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Medical Research Council (MR/L007428/1), BBSRC (BB/M000281/1) and the Wellcome Trust. DJA is supported by Cancer Research UK and the Wellcome Trust. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 100 TC 1 Z9 1 U1 5 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD AUG 1 PY 2016 VL 17 AR 167 DI 10.1186/s13059-016-1024-y PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DS5XB UT WOS:000380855200001 PM 27480531 ER PT J AU Hohenadel, MG Baier, LJ Piaggi, P Muller, YL Hanson, RL Krakoff, J Thearle, MS AF Hohenadel, M. G. Baier, L. J. Piaggi, P. Muller, Y. L. Hanson, R. L. Krakoff, J. Thearle, M. S. TI The impact of genetic variants on BMI increase during childhood versus adulthood SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID BODY-MASS INDEX; MELANOCORTIN-4 RECEPTOR GENE; PIMA-INDIANS; AMERICAN-INDIANS; ENERGY-EXPENDITURE; OBESITY; WEIGHT; RISK; ASSOCIATION; ADIPOSITY AB BACKGROUND: Genetic variants that predispose individuals to obesity may have differing influences during childhood versus adulthood, and additive effects of such variants are likely to occur. Our ongoing studies to identify genetic determinants of obesity in American Indians have identified 67 single-nucleotide polymorphisms (SNPs) that reproducibly associate with maximum lifetime non-diabetic body mass index (BMI). This study aimed to identify when, during the lifetime, these variants have their greatest impact on BMI increase. SUBJECTS/METHODS: A total of 5906 Native Americans of predominantly Pima Indian heritage with repeated measures of BMI between the ages of 5 and 45 years were included in this study. The association between each SNP with the rates of BMI increase during childhood (5-19 years) and adulthood (20-45 years) were assessed separately. The significant SNPs were used to calculate a cumulative allelic risk score (ARS) for childhood and adulthood, respectively, to assess the additive effect of these variants within each period of life. RESULTS: The majority of these SNPs (36 of 67) were associated with rate of BMI increase during childhood (P-value range: 0.00004-0.05), whereas only nine SNPs were associated with rate of BMI change during adulthood (P-value range: 0.002-0.02). These 36 SNPs associated with childhood BMI gain likely had a cumulative effect as a higher childhood-ARS associated with rate of BMI change (beta=0.032 kg m(-2) per year per risk allele, 95% confidence interval: 0.027-0.036, P<0.0001), such that at age 19 years, individuals with the highest number of risk alleles had a BMI of 10.2 kg m(-2) greater than subjects with the lowest number of risk alleles. CONCLUSIONS: Overall, our data indicates that genetic polymorphisms associated with lifetime BMI may influence the rate of BMI increase during different periods in the life course. The majority of these polymorphisms have a larger impact on BMI during childhood, providing further evidence that prevention of obesity will need to begin early in life. C1 [Hohenadel, M. G.; Baier, L. J.; Piaggi, P.; Muller, Y. L.; Hanson, R. L.; Krakoff, J.; Thearle, M. S.] NIDDKD, Phoenix Epidemiol & Clin Res Branch, 4212N 16th St, Phoenix, AZ 85016 USA. RP Hohenadel, MG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212N 16th St, Phoenix, AZ 85016 USA. EM maximilian.hohenadel@nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX We gratefully acknowledge the help of the nursing staff, physician assistants, laboratory technicians and dietary staffs of all three branches of the National Institute of Diabetes, Digestive and Kidney Disease in Phoenix, AZ, USA. Most of all, we thank the volunteers for their participation in the studies. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Study protocols are registered under ClinicalTrials.gov: NCT00339482 and NCT00340132. NR 49 TC 0 Z9 0 U1 6 U2 6 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 AUG PY 2016 VL 40 IS 8 BP 1301 EP 1309 DI 10.1038/ijo.2016.53 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DS4KG UT WOS:000380749400014 PM 27076275 ER PT J AU Coakley, M Hurt, DE AF Coakley, Meghan Hurt, Darrell E. TI 3D Printing in the Laboratory: Maximize Time and Funds with Customized and Open-Source Labware SO JALA LA English DT Article DE 3D printing; computer-assisted design; prototyping; equipment AB 3D printing, also known as additive manufacturing, is the computer-guided process of fabricating physical objects by depositing successive layers of material. It has transformed manufacturing across virtually every industry, bringing about incredible advances in research and medicine. The rapidly growing consumer market now includes convenient and affordable desktop 3D printers. These are being used in the laboratory to create custom 3D-printed equipment, and a growing community of designers are contributing open-source, cost-effective innovations that can be used by both professionals and enthusiasts. User stories from investigators at the National Institutes of Health and the biomedical research community demonstrate the power of 3D printing to save valuable time and funding. While adoption of 3D printing has been slow in the biosciences to date, the potential is vast. The market predicts that within several years, 3D printers could be commonplace within the home; with so many practical uses for 3D printing, we anticipate that the technology will also play an increasingly important role in the laboratory. ?? ?????????????3D?????????????????????????????????????????????????3D printing????????????????????????????????????????????????????????????????????????????????????????3D?????????????????????????????3D?????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????3D????????????????????????????3D??????????????????????????????????????????3D????????????????????????????????3D?????????????????????????????????????????????????????????? ?? ?? ????? ??? 3D ???? ??? ???? ?? ???? ?? ??? ???? ??? ?? ??? ???????. ? ??? ?? ?? ??? ?? ?? ??? ??? ???? ??? ?? ??? ??? ??? ??? ????. ??? ???? ??? ??? ?? ???? ??? ???? 3D ???? ???????. ??? ??? 3D ?? ??? ??? ?? ????? ???? ???, ???? ???? ????? ??? ? ??? ??? ??? ? ?? ?? ??? ?????? ??? ???? ????. ?? ???(National Institutes of Health)? ????? ?? ?????? ??? ?? ???, 3D ??? ??? ?? ??? ??? ??? ??? ? ??? ?????. ???? 3D ???? ?????? ??? ?????? ???? ?????. ??? ? ? ??? 3D ???? ?? ??? ???? ??? ?????. ??? ?? 3D ??? ?? ??? ??, ? ??? ?????? ?? ? ??? ??? ? ??? ?????. ?? 3D ??,???????,??????????????????????????????????????????????,?????????????????,???????3D ??????????????????????,????????? 3D ????,???????????????????????,???????????????,??????????????????(National Institutes of Health)??????????????????????,3D ?????????????????????,?? 3D ????????????????,?????????????????,?????,3D ??????????????? 3D ??????,????,??,????,?????????????????? ?? 3D ?????????,???????????????????????????????????????????,?????????????????,?????????3D ??????????????????????,????????? 3D ????,??????????????????????????,???????????????,?????????????????? (National Institutes of Health) ???????????????????????,3D ?????????????????????,?? 3D ????????????????,????????????,?????,3D ???????????????? 3D ??????,????,??,????,??????????????????? C1 [Coakley, Meghan] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 5601 Fishers Lane 4A33, Bethesda, MD 20852 USA. [Hurt, Darrell E.] Bioinformat & Computat Biosci Branch, Bethesda, MD USA. RP Coakley, M (reprint author), NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 5601 Fishers Lane 4A33, Bethesda, MD 20852 USA.; Hurt, DE (reprint author), NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 5601 Fishers Lane,4A50, Bethesda, MD 20852 USA. EM meghan.coakley@nih.gov; darrellh@niaid.nih.gov FU HHS Ignite initiative from the US Department of Health and Human Services; HHS Ventures initiative from the US Department of Health and Human Services FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors are founders and project leads for the NIH 3D Print Exchange. The Exchange is owned and managed by the Office of Cyber Infrastructure and Computational Biology, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The site was created in collaboration with the Eunice Kennedy Shriver National Institute for Child Health and Human Development and the National Library of Medicine. Initial funding and support for the Exchange were provided in part by HHS Ignite and HHS Ventures, initiatives from the US Department of Health and Human Services. NR 18 TC 2 Z9 2 U1 4 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2211-0682 EI 1540-2452 J9 JALA-J LAB AUTOM JI JALA PD AUG PY 2016 VL 21 IS 4 BP 489 EP 495 DI 10.1177/2211068216649578 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA DS7KS UT WOS:000380963000002 PM 27197798 ER PT J AU Zhu, HZ Zhou, P Alcauter, S Chen, YY Cao, HB Tian, M Ming, D Qi, HZ Wang, XM Zhao, X He, F Ni, HY Gao, W AF Zhu, Haoze Zhou, Peng Alcauter, Sarael Chen, Yuanyuan Cao, Hongbao Tian, Miao Ming, Dong Qi, Hongzhi Wang, Xuemin Zhao, Xin He, Feng Ni, Hongyan Gao, Wei TI Changes of intranetwork and internetwork functional connectivity in Alzheimer's disease and mild cognitive impairment SO JOURNAL OF NEURAL ENGINEERING LA English DT Article DE Alzheimer's disease; resting state functional magnetic resonance imaging; amnestic mild cognitive impairment; networks ID DEFAULT-MODE NETWORK; RESTING-STATE FMRI; WORKING-MEMORY; EXECUTIVE DYSFUNCTION; SALIENCE NETWORK; BRAIN; TASK; ATTENTION; DEMENTIA; CORTEX AB Objective. Alzheimer's disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain's key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer's disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease. C1 [Ni, Hongyan] Tianjin First Ctr Hosp, Radiol Dept, Tianjin, Peoples R China. [Zhu, Haoze; Zhou, Peng; Chen, Yuanyuan; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng] Tianjin Univ, Sch Precis Instrument & Optoelectr Engn, Tianjin, Peoples R China. [Alcauter, Sarael] Univ Nacl Autonoma Mexico, Inst Neurobiol, Mexico City 04510, DF, Mexico. [Cao, Hongbao] NIH, Dept Mental Hlth, Bldg 10, Bethesda, MD 20892 USA. [Gao, Wei] Cedars Sinai Med Ctr, Biomed Imaging Res Inst, Dept Biomed Sci & Acad Imaging, Los Angeles, CA 90048 USA. RP Ni, HY (reprint author), Tianjin First Ctr Hosp, Radiol Dept, Tianjin, Peoples R China.; Zhou, P (reprint author), Tianjin Univ, Sch Precis Instrument & Optoelectr Engn, Tianjin, Peoples R China.; Gao, W (reprint author), Cedars Sinai Med Ctr, Biomed Imaging Res Inst, Dept Biomed Sci & Acad Imaging, Los Angeles, CA 90048 USA. EM zpzp@tju.edu.cn; nihyan@sina.com; gaow@cshs.org FU National Natural Science Foundation of China [31271062, 81222021, 810171423, 61172008, 51377120, 51007063]; Natural Science Foundation of Tianjin [13JCQNJC13900]; Ministry of Science and Technology of China [2012BAI34B02]; Ministry of Education of China [NCET-10-0618] FX National Natural Science Foundation of China: 31271062, 81222021, 810171423, 61172008, 51377120, 51007063 Natural Science Foundation of Tianjin: 13JCQNJC13900; National Key Technology R&D Program of the Ministry of Science and Technology of China: 2012BAI34B02; Program for New Century Excellent Talents in University of the Ministry of Education of China: NCET-10-0618 NR 0 TC 2 Z9 2 U1 5 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD AUG PY 2016 VL 13 IS 4 AR 046008 DI 10.1088/174-2560/13/4/046008 PG 12 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA DS3FQ UT WOS:000380668900011 PM 27247279 ER PT J AU Pretegiani, E Mari, F Renieri, A Penco, S Dotti, MT AF Pretegiani, Elena Mari, Francesca Renieri, Alessandra Penco, Silvana Dotti, Maria Teresa TI Nicolaides-Baraitser syndrome: defining a phenotype SO JOURNAL OF NEUROLOGY LA English DT Letter ID INTELLECTUAL DISABILITY C1 [Pretegiani, Elena] NEI, Sensorimotor Res Lab, IRP, NIH, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA. [Pretegiani, Elena; Dotti, Maria Teresa] Univ Siena, Dept Med Surg & Neurol Sci, Neurodegenerat Dis Unit, Siena, Italy. [Mari, Francesca; Renieri, Alessandra] Univ Siena, Med Genet, Siena, Italy. [Mari, Francesca; Renieri, Alessandra] Azienda Osped Univ Senese, Genet Med, Siena, Italy. [Penco, Silvana] AO Niguarda Ca Granda, Med Genet, Milan, Italy. RP Pretegiani, E (reprint author), NEI, Sensorimotor Res Lab, IRP, NIH, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.; Pretegiani, E (reprint author), Univ Siena, Dept Med Surg & Neurol Sci, Neurodegenerat Dis Unit, Siena, Italy. EM elena.pretegiani@nih.gov NR 10 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD AUG PY 2016 VL 263 IS 8 BP 1659 EP 1660 DI 10.1007/s00415-016-8194-0 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DS3OH UT WOS:000380691900022 PM 27286846 ER PT J AU Baeksted, C Nissen, A Pappot, H Bidstrup, PE Mitchell, SA Basch, E Dalton, SO Johansen, C AF Baeksted, Christina Nissen, Aase Pappot, Helle Bidstrup, Pernille Envold Mitchell, Sandra A. Basch, Ethan Dalton, Susanne Oksbjerg Johansen, Christoffer TI Danish Translation and Linguistic Validation of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Patient-reported outcomes; PRO-CTCAE; linguistic validation; symptomatic toxicity; treatment adverse events; cancer clinical trials ID SYMPTOMS AB Context. The Common Terminology Criteria for Adverse Events (CTCAE) is the basis for standardized clinician-based grading and reporting of adverse events in cancer clinical trials. The U.S. National Cancer Institute has developed the PatientReported Outcomes version of the CTCAE (PRO-CTCAE) to incorporate patient self-reporting of symptomatic adverse events. Objectives. The aim of the study was to translate and linguistically validate a Danish language version of PRO-CTCAE. Methods. The U.S. English language PRO-CTCAE was translated into Danish using forward and backward procedures with reconciliation. The linguistic validity of the PRO-CTCAE Danish was examined in two successive rounds of semistructured cognitive interviews in a sample of 56 patients equally distributed by gender and cancer type (prostate, head and neck, lung, breast, gynecological, gastrointestinal, and hematological cancer), and who were currently undergoing cancer treatment. Results. In the first round of linguistic validation (n = 42), the phrasing of five symptomatic toxicities was adjusted, and the refined phrasing was retested in a second round of interviews (n = 14). Agreement about phrasing that was both culturally acceptable and semantically comprehensible was achieved in the second round. Statements from participants describing the meaning of the PRO-CTCAE symptomatic toxicities support conceptual equivalence to the U.S. English language version. Conclusion. Availability of the NCI PRO-CTCAE in languages beyond English will support international congruence in selfreporting of side effects of cancer treatment. A rigorous methodology was used to develop the Danish language version of PRO-CTCAE. Results provide preliminary support for the use of PRO-CTCAE in cancer clinical trials that include Danish speakers. (C) 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Baeksted, Christina; Nissen, Aase] Danish Canc Soc, Unit Documentat & Qual, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. [Bidstrup, Pernille Envold; Dalton, Susanne Oksbjerg; Johansen, Christoffer] Danish Canc Soc, Unit Survivorship, Copenhagen, Denmark. [Baeksted, Christina; Pappot, Helle; Johansen, Christoffer] Rigshosp, Finsen Ctr, Dept Oncol, Copenhagen, Denmark. [Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Rockville, MD USA. [Basch, Ethan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Canc Outcomes Res Program, Chapel Hill, NC USA. RP Baeksted, C (reprint author), Danish Canc Soc, Unit Documentat & Qual, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. EM baeksted@cancer.dk FU Danish Cancer Society [127 12 004-9102]; Department of Oncology, Rigshospitalet, Copenhagen University Hospital FX This study was supported by grants from the Danish Cancer Society (127 12 004-9102) and Department of Oncology, Rigshospitalet, Copenhagen University Hospital. The authors declare that they have no conflicts of interest. 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD AUG PY 2016 VL 52 IS 2 BP 292 EP 297 DI 10.1016/j.jpainsymman.2016.02.008 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DT7RD UT WOS:000381683000020 ER PT J AU Toprani, VM Joshi, SB Kueltzo, LA Schwartz, RM Middaugh, CR Volkin, DB AF Toprani, Vishal M. Joshi, Sangeeta B. Kueltzo, Lisa A. Schwartz, Richard M. Middaugh, C. Russell Volkin, David B. TI A Micro-Polyethylene Glycol Precipitation Assay as a Relative Solubility Screening Tool for Monoclonal Antibody Design and Formulation Development SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE solubility; monoclonal antibody; VRC01; HIV; polyethylene glycol; formulation; candidate selection; comparability; stability ID PROTEIN CONCENTRATION FORMULATIONS; BROADLY NEUTRALIZING ANTIBODIES; COMPARABILITY ASSESSMENTS; HIV-1 NEUTRALIZATION; EXCLUDED-VOLUME; SERUM-ALBUMIN; MECHANISM; VACCINE AB Adequate protein solubility is an important prerequisite for development, manufacture, and administration of biotherapeutic drug candidates, especially for high-concentration protein formulations. A previously established method for determining the relative apparent solubility (thermodynamic activity) of proteins using polyethylene glycol (PEG) precipitation is adapted for screening and comparing monoclonal antibody (mAb) candidates where only limited quantities (<= 1 mg) are available. This micro-PEG assay is used to evaluate various broadly neutralizing mAb candidates to HIV-1 viral spike (gp120 and gp41 glycoproteins). Using similar to 1 mg of VRC01-WT mAb per assay, the precision of the micro-PEG assay was established. A series of 7 different broadly neutralizing mAbs to the HIV-1 viral spike proteins were compared by curve shape (%PEG vs. protein concentration), %PEG(midpoint) determinations, and extrapolated apparent solubility values. Numerous formulation conditions were then evaluated for their relative effects on the VRC01-WT mAb. The PEG(midpt) and apparent solubility values of VRC01-WT mAb decreased as the solution pH increased and increased as NaCl and arginine were added. A final optimization of the micro-PEG assay established that amounts as low as 0.1-0.2 mg can be used. Thus, the micro-PEG assay has significant potential as a relative solubility screening tool during candidate selection and early formulation development. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. C1 [Toprani, Vishal M.; Joshi, Sangeeta B.; Middaugh, C. Russell; Volkin, David B.] Univ Kansas, Macromol & Vaccine Stabilizat Ctr, Dept Pharmaceut Chem, 2030 Becker Dr, Lawrence, KS 66047 USA. [Kueltzo, Lisa A.; Schwartz, Richard M.] NIAID, Vaccine Prod Program, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Volkin, DB (reprint author), Univ Kansas, Macromol & Vaccine Stabilizat Ctr, Dept Pharmaceut Chem, 2030 Becker Dr, Lawrence, KS 66047 USA. EM volkin@ku.edu FU Vaccine Research Center (NIAID/NIH); Gilead Sciences, Inc. FX The University of Kansas authors wish to thank and acknowledge Vaccine Research Center (NIAID/NIH) for providing the mAbs and financial support of this study. Additional financial support for V. M. Toprani was also provided by a graduate student fellowship from Gilead Sciences, Inc. 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 0022-3549 EI 1520-6017 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2016 VL 105 IS 8 BP 2319 EP 2327 DI 10.1016/j.xphs.2016.05.021 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA DT8UE UT WOS:000381770400010 PM 27368120 ER PT J AU Torain, MJ Maragh-Bass, AC Dankwa-Mullen, I Hisam, B Kodadek, LM Lilley, EJ Najjar, P Changoor, NR Rose, JA Zogg, CK Maddox, YT Britt, LD Haider, AH AF Torain, Maya J. Maragh-Bass, Allysha C. Dankwa-Mullen, Irene Hisam, Butool Kodadek, Lisa M. Lilley, Elizabeth J. Najjar, Peter Changoor, Navin R. Rose, John A., Jr. Zogg, Cheryl K. Maddox, Yvonne T. Britt, L. D. Haider, Adil H. TI Surgical Disparities: A Comprehensive Review and New Conceptual Framework SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID TRAUMATIC BRAIN-INJURY; MINIMALLY INVASIVE SURGERY; HIGH-VOLUME HOSPITALS; SOCIAL-CLASS BIAS; RACIAL DISPARITIES; SOCIOECONOMIC-STATUS; UNITED-STATES; RACIAL/ETHNIC DISPARITIES; UNCONSCIOUS RACE; CANCER-SURGERY C1 [Torain, Maya J.; Maragh-Bass, Allysha C.; Hisam, Butool; Lilley, Elizabeth J.; Najjar, Peter; Changoor, Navin R.; Rose, John A., Jr.; Zogg, Cheryl K.; Haider, Adil H.] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA USA. [Torain, Maya J.; Maragh-Bass, Allysha C.; Hisam, Butool; Lilley, Elizabeth J.; Najjar, Peter; Changoor, Navin R.; Rose, John A., Jr.; Zogg, Cheryl K.; Haider, Adil H.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Dankwa-Mullen, Irene] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA. [Maddox, Yvonne T.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hisam, Butool] Dow Univ Hlth Sci, Coll Med, Karachi, Pakistan. [Kodadek, Lisa M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Britt, L. D.] Eastern Virginia Med Sch, Dept Surg, Norfolk, VA 23501 USA. RP Haider, AH (reprint author), Ctr Surg & Publ Hlth, 1620 Tremont St,Suite 4-020, Boston, MA 02120 USA. EM ahhaider@partners.org FU National Institutes of Health (NIH); American College of Surgeons (ACS) Summit on Surgical Disparities Research FX The research was supported in its completion by the planning committee of the 2015 National Institutes of Health (NIH) and American College of Surgeons (ACS) Summit on Surgical Disparities Research. The ACS was represented by Drs LD Britt, Adil H Haider, and Beth Sutton; the NIH was represented by Drs Yvonne Maddox, Irene Dankwa-Mullen, Claudette Brooks, and Salina Waddy. The NIH guided the creation of the theoretical framework for the present research; the ACS has provided a searchable database that now contains the results of our literature review (available at: https://www.facs.org/health-care-disparities/search). We would also like to thank Anju Ranjit, MD, MPH, from the Center for Surgery and Public Health in Boston, MA, for her assistance with developing the PROSPERO listing of the review methodology. NR 86 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2016 VL 223 IS 2 BP 408 EP 418 DI 10.1016/j.jamcollsurg.2016.04.047 PG 11 WC Surgery SC Surgery GA DS4KY UT WOS:000380751200027 PM 27296524 ER PT J AU Chang, LW Grabowski, MK Ssekubugu, R Nalugoda, F Kigozi, G Nantume, B Lessler, J Moore, SM Quinn, TC Reynolds, SJ Gray, RH Serwadda, D Wawer, MJ AF Chang, Larry W. Grabowski, Mary K. Ssekubugu, Robert Nalugoda, Fred Kigozi, Godfrey Nantume, Betty Lessler, Justin Moore, Sean M. Quinn, Thomas C. Reynolds, Steven J. Gray, Ronald H. Serwadda, David Wawer, Maria J. TI Heterogeneity of the HIV epidemic in agrarian, trading, and fishing communities in Rakai, Uganda: an observational epidemiological study SO LANCET HIV LA English DT Article ID LAKE VICTORIA; RISK-FACTORS; PREVALENCE; DISEASE; PRIORITIZATION; PREVENTION; INFECTION; DISTRICT; SPREAD; MODEL AB Background Understanding the extent to which HIV burden differs across communities and the drivers of local disparities is crucial for an effective and targeted HIV response. We assessed community-level variations in HIV prevalence, risk factors, and treatment and prevention service uptake in Rakai, Uganda. Methods The Rakai Community Cohort Study (RCCS) is an open, population-based cohort of people aged 15-49 years in 40 communities. Participants are HIV tested and interviewed to obtain sociodemographic, behavioural, and health information. RCCS data from Aug 10, 2011, to May 30, 2013, were used to classify communities as agrarian (n=27), trading (n=9), or lakeside fishing sites (n=4). We mapped HIV prevalence with Bayesian methods, and characterised variability across and within community classifications. We also assessed differences in HIV risk factors and uptake of antiretroviral therapy and male circumcision between community types. Findings 17119 individuals were included, 9215 (54%) of whom were female. 9931 participants resided in agrarian, 3318 in trading, and 3870 in fishing communities. Median HIV prevalence was higher in fishing communities (42%, range 38-43) than in trading (17%, 11-21) and agrarian communities (14%, 9-26). Antiretroviral therapy use was significantly lower in both men and women in fishing communities than in trading (age-adjusted prevalence risk ratio in men 0.64, 95% CI 0.44-0.97; women 0.53, 0.42-0.66) and agrarian communities (men 0.55, 0. 42-0.72; women 0.65, 0.54-0.79), as was circumcision coverage among men (vs trading 0.48, 0.42-0.55; vs agrarian 0.64, 0.56-0.72). Self-reported risk behaviours were significantly higher in men than in women and in fishing communities than in other community types. Interpretation Substantial heterogeneity in HIV prevalence, risk factors, and service uptake in Rakai, Uganda, emphasises the need for local surveillance and the design of targeted HIV responses. High HIV burden, risk behaviours, and low use of combination HIV prevention in fishing communities make these populations a priority for intervention. C1 [Chang, Larry W.; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Sch Med, Div Infect Dis, Dept Med, Baltimore, MD USA. [Chang, Larry W.; Grabowski, Mary K.; Ssekubugu, Robert; Nalugoda, Fred; Kigozi, Godfrey; Nantume, Betty; Gray, Ronald H.; Serwadda, David; Wawer, Maria J.] Rakai Hlth Sci Program, Entebbe, Uganda. [Chang, Larry W.; Grabowski, Mary K.; Lessler, Justin; Moore, Sean M.; Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Social & Behav Intervent Program, Baltimore, MD USA. [Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. RP Chang, LW (reprint author), Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. EM lchang8@jhmi.edu FU National Institute of Mental Health [K23MH086338, R01MH107275]; National Institute of Allergy and Infectious Diseases [U01AI100031, R01AI110324, R01AI102939]; National Institute of Child Health and Development [RO1HD070769, R01HD050180]; National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; Bill & Melinda Gates Foundation [22006.02]; Johns Hopkins University Center for AIDS Research [P30AI094189] FX We thank the participants of the RH SP RCCS. This study was supported by the National Institute of Mental Health (K23MH086338, R01MH107275), the National Institute of Allergy and Infectious Diseases (R01AI110324, U01AI100031, R01AI110324, R01AI102939), the National Institute of Child Health and Development (RO1HD070769, R01HD050180), and the National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; the Bill & Melinda Gates Foundation (22006.02); and the Johns Hopkins University Center for AIDS Research (P30AI094189). NR 28 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 2352-3018 J9 LANCET HIV JI Lancet HIV PD AUG PY 2016 VL 3 IS 8 BP E388 EP E396 DI 10.1016/S2352-3018(16)30034-0 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DS5SK UT WOS:000380842400011 PM 27470029 ER PT J AU Wang, HD Wolock, TM Carter, A Nguyen, G Kyu, HH Gakidou, E Hay, SI Mills, EJ Trickey, A Msemburi, W Coates, MM Mooney, MD Fraser, MS Sligar, A Salomon, J Larson, HJ Friedman, J Abajobir, AA Abate, KH Abbas, KM Abd El Razek, MM Abd-Allah, F Abdulle, AM Abera, SF Abubakar, I Abu-Raddad, LJ Abu-Rmeileh, NME Abyu, GY Adebiyi, AO Adedeji, IA Adelekan, AL Adofo, K Adou, AK Ajala, ON Akinyemiju, TF Akseer, N Al Lami, FH Al-Aly, Z Alam, K Alam, NKM Alasfoor, D Aldhahri, SFS Aldridge, RW Alegretti, MA Aleman, AV Alemu, ZA Alfonso-Cristancho, R Ali, R Alkerwi, A Alla, F Al-Raddadi, RMS Alsharif, U Alvarez, E Alvis-Guzman, N Amare, AT Amberbir, A Amegah, AK Ammar, W Amrock, SM Antonio, CAT Anwari, P Auml;rnlov, J Al Artaman, Asayesh, H Asghar, RJ Assadi, R Atique, S Atkins, LS Avokpaho, EFGA Awasthi, A Quintanilla, BPA Bacha, U Badawi, A Barac, A Barnighausen, T Basu, A Bayou, TA Bayou, YT Bazargan-Hejazi, S Beardsley, J Bedi, N Bennett, DA Bensenor, IM Betsu, BD Beyene, AS Bhatia, E Bhutta, ZA Biadgilign, S Bikbov, B Birlik, SM Bisanzio, D Brainin, M Brazinova, A Breitborde, NJK Brown, A Burch, M Butt, ZA Campuzano, JC Cardenas, R Carrero, JJ Castaneda-Orjuela, CA Rivas, JC Catala-Lopez, F Chang, HY Chang, JC Chavan, L Chen, WQ Chiang, PPC Chibalabala, M Chisumpa, VH Choi, JYJ Christopher, DJ Ciobanu, LG Cooper, C Dahiru, T Damtew, SA Dandona, L Dandona, R das Neves, J de Jager, P De Leo, D Degenhardt, L Dellavalle, RP Deribe, K Deribew, A Jarlais, DCD Dharmaratne, SD Ding, EL Doshi, PP Driscoll, TR Dubey, M Elshrek, YM Elyazar, I Endries, AY Ermakov, SP Eshrati, B Esteghamati, A Faghmous, IDA Sofia e Sa Farinha, C Faro, A Farvid, MS Farzadfar, F Fereshtehnejad, SM Fernandes, JC Fischer, F Fitchett, JRA Foigt, N Fullman, N Furst, T Gankpe, FG Gebre, T Gebremedhin, AT Gebru, AA Geleijnse, JM Gessner, BD Gething, PW Ghiwot, TT Giroud, M Gishu, MD Glaser, E Goenka, S Goodridge, A Gopalani, SV Goto, A Gugnani, HC Guimaraes, MDC Gupta, R Gupta, R Gupta, V Haagsma, J Hafezi-Nejad, N Hagan, H Hailu, GB Hamadeh, RR Hamidi, S Hammami, M Hankey, GJ Hao, YT Harb, HL Harikrishnan, S Haro, JM Harun, KM Havmoeller, R Hedayati, MT Heredia-Pi, IB Hoek, HW Horino, M Horita, N Hosgood, HD Hoy, DG Hsairi, M Hu, GQ Huang, H Huang, JJ Iburg, KM Idrisov, BT Innos, K Iyer, VJ Jacobsen, KH Jahanmehr, N Jakovljevic, MB Javanbakht, M Jayatilleke, AU Jeemon, P Jha, V Jiang, GH Jiang, Y Jibat, T Jonas, JB Kabir, Z Kamal, R Kan, HD Karch, A Karema, CK Karletsos, D Kasaeian, A Kaul, A Kawakami, N Kayibanda, JF Keiyoro, PN Kemp, AH Kengne, AP Kesavachandran, CN Khader, YS Khalil, I Khan, AR Khan, EA Khang, YH Khubchandani, J Kim, YJ Kinfu, Y Kivipelto, M Kokubo, Y Kosen, S Koul, PA Koyanagi, A Defo, BK Bicer, BK Kulkarni, VS Kumar, GA Lal, DK Lam, H Lam, JO Langan, SM Lansingh, VC Larsson, A Leigh, J Leung, R Li, YM Lim, SS Lipshultz, SE Liu, SW Lloyd, BK Logroscino, G Lotufo, PA Lunevicius, R Abd El Razek, HM Mahdavi, M Majdan, M Majeed, A Makhlouf, C Malekzadeh, R Mapoma, CC Marcenes, W Martinez-Raga, J Marzan, MB Masiye, F Mason-Jones, AJ Mayosi, BM Mckee, M Meaney, PA Mehndiratta, MM Mekonnen, AB Melaku, YA Memiah, P Memish, ZA Mendoza, W Meretoja, A Meretoja, TJ Mhimbira, FA Miller, TR Mikesell, J Mirarefin, M Mohammad, KA Mohammed, S Mokdad, AH Monasta, L Moradi-Lakeh, M Mori, R Mueller, UO Murimira, B Murthy, GVS Naheed, A Naldi, L Nangia, V Nash, D Nawaz, H Nejjari, C Ngalesoni, FN Ngirabega, JDD Le Nguyen, Q Nisar, MI Norheim, OF Norman, RE Nyakarahuka, L Ogbo, FA Oh, IH Ojelabi, FA Olusanya, BO Olusanya, JO Opio, JN Oren, E Ota, E Padukudru, MA Park, HY Park, JH Patil, ST Patten, SB Paul, VK Pearson, K Peprah, EK Pereira, CC Perico, N Pesudovs, K Petzold, M Phillips, MR Pillay, JD Plass, D Polinder, S Pourmalek, F Prokop, DM Qorbani, M Rafay, A Rahimi, K Rahimi-Movaghar, V Rahman, M Rahman, MHU Rahman, SU Rai, RK Rajsic, S Ram, U Rana, SM Rao, PV Remuzzi, G Rojas-Rueda, D Ronfani, L Roshandel, G Roy, A Ruhago, GM Saeedi, MY Sagar, R Saleh, MM Sanabria, JR Santos, IS Sarmiento-Suarez, R Sartorius, B Sawhney, M Schutte, AE Schwebel, DC Seedat, S Sepanlou, SG Servan-Mori, EE Shaikh, MA Sharma, R She, J Sheikhbahaei, S Shen, JB Shibuya, K Shin, HH Sigfusdottir, ID Silpakit, N Silva, DAS Silveira, DGA Simard, EP Sindi, S Singh, JA Singh, OP Singh, PK Skirbekk, V Sliwa, K Soneji, S Sorensen, RJD Soriano, JB Soti, DO Sreeramareddy, CT Stathopoulou, V Steel, N Sunguya, BF Swaminathan, S Sykes, BL Tabares-Seisdedos, R Talongwa, RT Tavakkoli, M Taye, B Tedla, BA Tekle, T Shifa, GT Temesgen, AM Terkawi, AS Tesfay, FH Tessema, GA Thapa, K Thomson, AJ Thorne-Lyman, AL Tobe-Gai, R Topor-Madry, R Towbin, JA Tran, BX Dimbuene, ZT Tsilimparis, N Tura, AK Ukwaja, KN Uneke, CJ Uthman, OA Venketasubramanian, N Vladimirov, SK Vlassov, VV Vollset, SE Wang, LH Weiderpass, E Weintraub, RG Werdecker, A Westerman, R Wijeratne, T Wilkinson, JD Wiysonge, CS Wolfe, CDA Won, SH Wong, JQ Xu, GL Yadav, AK Yakob, B Yalew, AZ Yano, YC Yaseri, M Yebyo, HG Yip, P Yonemoto, N Yoon, SJ Younis, MZ Yu, CH Yu, SC Zaidi, Z Zaki, ME Zeeb, H Zhang, H Zhao, Y Zodpey, S Zoeckler, L Zuhlke, LJ Lopez, AD Murray, CJL AF Wang, Haidong Wolock, Tim M. Carter, Austin Nguyen, Grant Kyu, Hmwe Hmwe Gakidou, Emmanuela Hay, Simon I. Mills, Edward J. Trickey, Adam Msemburi, William Coates, Matthew M. Mooney, Meghan D. Fraser, Maya S. Sligar, Amber Salomon, Joshua Larson, Heidi J. Friedman, Joseph Abajobir, Amanuel Alemu Abate, Kalkidan Hassen Abbas, Kaja M. Abd El Razek, Mohamed Magdy Abd-Allah, Foad Abdulle, Abdishakur M. Abera, Semaw Ferede Abubakar, Ibrahim Abu-Raddad, Laith J. Abu-Rmeileh, Niveen M. E. Abyu, Gebre Yitayih Adebiyi, Akindele Olupelumi Adedeji, Isaac Akinkunmi Adelekan, Ademola Lukman Adofo, Koranteng Adou, Arsene Kouablan Ajala, Oluremi N. Akinyemiju, Tomi F. Akseer, Nadia Al Lami, Faris Hasan Al-Aly, Ziyad Alam, Khurshid Alam, Noore K. M. Alasfoor, Deena Aldhahri, Saleh Fahed S. Aldridge, Robert William Alegretti, Miguel Angel Aleman, Alicia V. Alemu, Zewdie Aderaw Alfonso-Cristancho, Rafael Ali, Raghib Alkerwi, Ala'a Alla, Francois Al-Raddadi, Rajaa Mohammad Salem Alsharif, Ubai Alvarez, Elena Alvis-Guzman, Nelson Amare, Azmeraw T. Amberbir, Alemayehu Amegah, Adeladza Kofi Ammar, Walid Amrock, Stephen Marc Antonio, Carl Abelardo T. Anwari, Palwasha Arnlov, Johan Al Artaman Asayesh, Hamid Asghar, Rana Jawad Assadi, Reza Atique, Suleman Atkins, Lydia S. Avokpaho, Euripide Frinel G. Arthur Awasthi, Ashish Quintanilla, Beatriz Paulina Ayala Bacha, Umar Badawi, Alaa Barac, Aleksandra Barnighausen, Till Basu, Arindam Bayou, Tigist Assefa Bayou, Yibeltal Tebekaw Bazargan-Hejazi, Shahrzad Beardsley, Justin Bedi, Neeraj Bennett, Derrick A. Bensenor, Isabela M. Betsu, Balem Demtsu Beyene, Addisu Shunu Bhatia, Eesh Bhutta, Zulfiqar A. Biadgilign, Sibhatu Bikbov, Boris Birlik, Sait Mentes Bisanzio, Donal Brainin, Michael Brazinova, Alexandra Breitborde, Nicholas J. K. Brown, Alexandria Burch, Michael Butt, Zahid A. Campuzano, Julio Cesar Cardenas, Rosario Carrero, Juan Jesus Castaneda-Orjuela, Carlos A. Rivas, Jacqueline Castillo Catala-Lopez, Ferran Chang, Hsing-Yi Chang, Jung-chen Chavan, Laxmikant Chen, Wanqing Chiang, Peggy Pei-Chia Chibalabala, Mirriam Chisumpa, Vesper Hichilombwe Choi, Jee-Young Jasmine Christopher, Devasahayam Jesudas Ciobanu, Liliana G. Cooper, Cyrus Dahiru, Tukur Damtew, Solomon Abreha Dandona, Lalit Dandona, Rakhi das Neves, Jose de Jager, Pieter De Leo, Diego Degenhardt, Louisa Dellavalle, Robert P. Deribe, Kebede Deribew, Amare Jarlais, Don C. Des Dharmaratne, Samath D. Ding, Eric L. Doshi, Pratik Pinal Driscoll, Tim R. Dubey, Manisha Elshrek, Yousef Mohamed Elyazar, Iqbal Endries, Aman Yesuf Ermakov, Sergey Petrovich Eshrati, Babak Esteghamati, Alireza Faghmous, Imad D. A. Sofia e Sa Farinha, Carla Faro, Andre Farvid, Maryam S. Farzadfar, Farshad Fereshtehnejad, Seyed-Mohammad Fernandes, Joao C. Fischer, Florian Fitchett, Joseph Robert Ander Foigt, Nataliya Fullman, Nancy Furst, Thomas Gankpe, Fortune Gbetoho Gebre, Teshome Gebremedhin, Amanuel Tesfay Gebru, Alemseged Aregay Geleijnse, Johanna M. Gessner, Bradford D. Gething, Peter W. Ghiwot, Tsegaye Tewelde Giroud, Maurice Gishu, Melkamu Dedefo Glaser, Elizabeth Goenka, Shifalika Goodridge, Amador Gopalani, Sameer Vali Goto, Atsushi Gugnani, Harish Chander Guimaraes, Mark D. C. Gupta, Rahul Gupta, Rajeev Gupta, Vipin Haagsma, Juanita Hafezi-Nejad, Nima Hagan, Holly Hailu, Gessessew Bugssa Hamadeh, Randah Ribhi Hamidi, Samer Hammami, Mouhanad Hankey, Graeme J. Hao, Yuantao Harb, Hilda L. Harikrishnan, Sivadasanpillai Haro, Josep Maria Harun, Kimani M. Havmoeller, Rasmus Hedayati, Mohammad T. Heredia-Pi, Ileana Beatriz Hoek, Hans W. Horino, Masako Horita, Nobuyuki Hosgood, H. Dean Hoy, Damian G. Hsairi, Mohamed Hu, Guoqing Huang, Hsiang Huang, John J. Iburg, Kim Moesgaard Idrisov, Bulat T. Innos, Kaire Iyer, Veena J. Jacobsen, Kathryn H. Jahanmehr, Nader Jakovljevic, Mihajlo B. Javanbakht, Mehdi Jayatilleke, Achala Upendra Jeemon, Panniyammakal Jha, Vivekanand Jiang, Guohong Jiang, Ying Jibat, Tariku Jonas, Jost B. Kabir, Zubair Kamal, Ritul Kan, Haidong Karch, Andre Karema, Corine Kakizi Karletsos, Dimitris Kasaeian, Amir Kaul, Anil Kawakami, Norito Kayibanda, Jeanne Francoise Keiyoro, Peter Njenga Kemp, Andrew Haddon Kengne, Andre Pascal Kesavachandran, Chandrasekharan Nair Khader, Yousef Saleh Khalil, Ibrahim Khan, Abdur Rahman Khan, Ejaz Ahmad Khang, Young-Ho Khubchandani, Jagdish Kim, Yun Jin Kinfu, Yohannes Kivipelto, Miia Kokubo, Yoshihiro Kosen, Soewarta Koul, Parvaiz A. Koyanagi, Ai Defo, Barthelemy Kuate Bicer, Burcu Kucuk Kulkarni, Veena S. Kumar, G. Anil Lal, Dharmesh Kumar Lam, Hilton Lam, Jennifer O. Langan, Sinead M. Lansingh, Van C. Larsson, Anders Leigh, James Leung, Ricky Li, Yongmei Lim, Stephen S. Lipshultz, Steven E. Liu, Shiwei Lloyd, Belinda K. Logroscino, Giancarlo Lotufo, Paulo A. Lunevicius, Raimundas Abd El Razek, Hassan Magdy Mahdavi, Mahdi Majdan, Marek Majeed, Azeem Makhlouf, Carla Malekzadeh, Reza Mapoma, Chabila C. Marcenes, Wagner Martinez-Raga, Jose Marzan, Melvin Barrientos Masiye, Felix Mason-Jones, Amanda J. Mayosi, Bongani M. Mckee, Martin Meaney, Peter A. Mehndiratta, Man Mohan Mekonnen, Alemayehu B. Melaku, Yohannes Adama Memiah, Peter Memish, Ziad A. Mendoza, Walter Meretoja, Atte Meretoja, Tuomo J. Mhimbira, Francis Apolinary Miller, Ted R. Mikesell, Joseph Mirarefin, Mojde Mohammad, Karzan Abdulmuhsin Mohammed, Shafiu Mokdad, Ali H. Monasta, Lorenzo Moradi-Lakeh, Maziar Mori, Rintaro Mueller, Ulrich O. Murimira, Brighton Murthy, Gudlavalleti Venkata Satyanarayana Naheed, Aliya Naldi, Luigi Nangia, Vinay Nash, Denis Nawaz, Haseeb Nejjari, Chakib Ngalesoni, Frida Namnyak Ngirabega, Jean De Dieu Quyen Le Nguyen Nisar, Muhammad Imran Norheim, Ole F. Norman, Rosana E. 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CA GBD 2015 HIV Collaborators TI Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015 SO LANCET HIV LA English DT Article ID PROJECTION PACKAGE; SYSTEMATIC ANALYSIS; UNAIDS ESTIMATION; MALE CIRCUMCISION; 188 COUNTRIES; INFECTION; PREVENTION; EPIDEMIC; MODEL; TRIAL AB Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license C1 [Wang, Haidong; Wolock, Tim M.; Carter, Austin; Nguyen, Grant; Kyu, Hmwe Hmwe; Gakidou, Emmanuela; Hay, Simon I.; Msemburi, William; Coates, Matthew M.; Mooney, Meghan D.; Fraser, Maya S.; Sligar, Amber; Larson, Heidi J.; Friedman, Joseph; Brown, Alexandria; Dandona, Lalit; Fullman, Nancy; Haagsma, Juanita; Khalil, Ibrahim; Lim, Stephen S.; Mikesell, Joseph; Mokdad, Ali H.; Moradi-Lakeh, Maziar; Pearson, Katherine; Silpakit, Naris; Sorensen, Reed J. D.; Temesgen, Awoke Misganaw; Vollset, Stein Emil; Zoeckler, Leo; Murray, Christopher J. L.] Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. 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[Gessner, Bradford D.] Agence Medecine Prevent, Paris, France. [Giroud, Maurice] Univ Hosp Dijon, Dijon, France. [Gishu, Melkamu Dedefo; Tura, Abera Kenay] Haramaya Univ, Dire Dawa, Ethiopia. [Gishu, Melkamu Dedefo] Kersa Hlth & Demog Surveillance Syst, Harar, Ethiopia. [Glaser, Elizabeth] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Goodridge, Amador] INDICASAT AIP, Inst Invest Cientif, City Of Knowledge, Panama. [Goodridge, Amador] INDICASAT AIP, Serv Alta Tecnol, City Of Knowledge, Panama. [Gopalani, Sameer Vali] Govt Federated States Micronesia, Dept Hlth & Social Aff airs, Palikir, Micronesia. [Goto, Atsushi] Tokyo Womens Med Univ, Dept Publ Hlth, Tokyo, Japan. [Gugnani, Harish Chander] St James Sch Med, Dept Microbiol, The Quarter, Anguilla. [Gugnani, Harish Chander] St James Sch Med, Dept Epidemiol & Biostat, The Quarter, Anguilla. [Guimaraes, Mark D. C.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. West Virginia Bur Publ Hlth, Charleston, WV USA. Eternal Heart Care Ctr, Jaipur, Rajasthan, India. Res Inst, Jaipur, Rajasthan, India. [Gupta, Vipin] Univ Delhi, Delhi, India. [Hagan, Holly] NYU, New York, NY USA. [Hamadeh, Randah Ribhi] Arabian Gulf Univ, Manama, Bahrain. [Hamidi, Samer] Hamdan Bin Mohammed Smart Univ, Dubai, U Arab Emirates. [Hammami, Mouhanad] Wayne Cty Dept Hlth & Human Serv, Detroit, MI USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia. [Hankey, Graeme J.] Harry Perkins Inst Med Res, Nedlands, WA, Australia. [Hankey, Graeme J.] Western Australian Neurosci Res Inst, Nedlands, WA, Australia. [Hao, Yuantao] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China. [Harikrishnan, Sivadasanpillai] Sree Chitra Tirunal Inst Med Sci & Technol, Trivandrum, Kerala, India. [Koyanagi, Ai] Res & Dev Unit, Barcelona, Spain. [Haro, Josep Maria] Parc Sanitari Sant Joan de Deu CIBERSAM, Barcelona, Spain. [Haro, Josep Maria] Univ Barcelona, Barcelona, Spain. [Harun, Kimani M.] Kenyatta Univ, Nairobi, Kenya. [Hedayati, Mohammad T.] Mazandaran Univ Med Sci, Sari, Iran. [Hoek, Hans W.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Skirbekk, Vegard] Columbia Univ, New York, NY USA. [Horino, Masako] Nevada Div Behav & Publ Hlth, Carson City, NV USA. [Horino, Masako] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Horita, Nobuyuki] Yokohama City Univ, Sch Med, Yokohama, Kanagawa, Japan. [Hosgood, H. Dean] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hoy, Damian G.] Secretariat Pacific Commun, Publ Hlth Div, Noumea, New Caledonia. [Hsairi, Mohamed] Natl Inst Publ Hlth, Tunis, Tunisia. [Hu, Guoqing] Cent S Univ, Dept Epidemiol & Hlth Stat, Sch Publ Hlth, Changsha, Hunan, Peoples R China. [Huang, Hsiang] Cambridge Hlth Alliance, Cambridge, MA USA. [Huang, John J.] Yale Univ, New Haven, CT USA. [Iburg, Kim Moesgaard] Aarhus Univ, Aarhus, Denmark. [Idrisov, Bulat T.] Bashkir State Med Univ, Ufa, Russia. [Idrisov, Bulat T.] Boston Univ, Boston Med Ctr, Boston, MA 02215 USA. Boston Univ, Boston Med Ctr, Boston, MA 02215 USA. [Innos, Kaire] Natl Inst Hlth Dev, Tallinn, Estonia. [Iyer, Veena J.] Indian Inst Publ Hlth Gandhinagar, Ahmadabad, Gujarat, India. [Jacobsen, Kathryn H.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Jah