FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fairhurst, RM AF Fairhurst, Rick M. TI High Antimalarial Efficacy of Dihydroartemisinin-Piperaquine on the China-Myanmar Border: The Calm before the Storm SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material ID UNCOMPLICATED PLASMODIUM-FALCIPARUM; RESISTANCE; CAMBODIA; MALARIA C1 NIAID, Natl Inst Hlth, Lab Malaria & Vector Res, Rockville, MD 20852 USA. RP Fairhurst, RM (reprint author), NIAID, Natl Inst Hlth, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov FU Intramural NIH HHS NR 10 TC 3 Z9 3 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2015 VL 93 IS 3 BP 436 EP 437 DI 10.4269/ajtmh.15-0349 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CR3TB UT WOS:000361254900003 PM 26283745 ER PT J AU Lindsey, S Piatt, JH Worthington, P Sonmez, C Satheye, S Schneider, JP Pochan, DJ Langhans, SA AF Lindsey, Stephan Piatt, Joseph H. Worthington, Peter Soenmez, Cem Satheye, Sameer Schneider, Joel P. Pochan, Darrin J. Langhans, Sigrid A. TI Beta Hairpin Peptide Hydrogels as an Injectable Solid Vehicle for Neurotrophic Growth Factor Delivery SO BIOMACROMOLECULES LA English DT Article ID DRUG-DELIVERY; CONTROLLED-RELEASE; PHEOCHROMOCYTOMA CELLS; DESIGNED PEPTIDE; PROTEIN DELIVERY; DIFFERENTIATION; SCAFFOLDS; BIODEGRADATION; ENCAPSULATION; CONNECTIONS AB There is intense interest in developing novel methods for the sustained delivery of low levels of clinical therapeutics. MAX8 is a peptide-based beta-hairpin hydrogel that has unique shear thinning properties that allow for immediate rehealing after the removal of shear forces, making MAX8 an excellent candidate for injectable drug delivery at a localized injury site. The current studies examined the feasibility of using MAX8 as a delivery system for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), two neurotrophic growth factors currently used in experimental treatments of spinal cord injuries. Experiments determined that encapsulation of NGF and BDNF within MAX8 did not negatively impact gel formation or rehealing and that shear thinning did not result in immediate growth factor release. ELISA, microscopy, rheology, and Western blotting experiments collectively demonstrate the functional capabilities of the therapeutic-loaded hydrogels to (i) maintain a protective environment against in vitro degradation of encapsulated therapeutics for at least 28 days; and (ii) allow for sustained release of NGF and BDGF capable of initiating neurite-like extensions of PC12 cells, most likely due to NGF/BDGF signaling pathways. Importantly, while the 21 day release profiles could be tuned by adjusting the MAX8 hydrogel concentration, the initial shear thinning of the hydrogel (e.g., during injection) does not induce significant premature loss of the encapsulated therapeutic, most likely due to effective trapping of growth factors within structurally robust domains that are maintained during the application of shear forces. Together, our data suggests that MAX8 allows for greater dosage control and sustained therapeutic growth factor delivery, potentially alleviating side effects and improving the efficacy of current therapies. C1 [Lindsey, Stephan; Worthington, Peter; Langhans, Sigrid A.] Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, Wilmington, DE 19803 USA. [Piatt, Joseph H.] Alfred I DuPont Hosp Children, Nemours Neurosci Ctr, Wilmington, DE 19803 USA. [Worthington, Peter] Univ Delaware, Biomed Engn Grad Program, Newark, DE 19716 USA. [Soenmez, Cem; Schneider, Joel P.] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Satheye, Sameer; Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA. RP Lindsey, S (reprint author), Nemours AI duPont Hosp Children, Nemours Biomed Res, 1701 Rockland Rd, Wilmington, DE 19803 USA. EM stephan.lindsey@nemours.org RI Sonmez, Cem/C-2730-2015 OI Sonmez, Cem/0000-0002-6071-641X FU National Institute of General Medical Sciences of the National Institutes of Health [NIGMS-8P20GM103464-0]; American Cancer Society [RSG-09-021-01-CNE]; Nemours Foundation; UD-NIST Center for Neutron Scattering from NIST, U.S. Department of Commerce [70NANB12H239]; Center for Cancer Research, National Cancer Institute FX This work was supported in part by Award Number NIGMS-8P20GM103464-0 (SL and SAL) from the National Institute of General Medical Sciences of the National Institutes of Health, the American Cancer Society Grant Number RSG-09-021-01-CNE (SAL), and funds from the Nemours Foundation (S.L. and S.A.L.). D.J.P. and S.S. would like to acknowledge funding from the UD-NIST Center for Neutron Scattering under cooperative agreement 70NANB12H239 from NIST, U.S. Department of Commerce. Parts of this work were supported by the Center for Cancer Research, National Cancer Institute. The statements, findings, conclusions, and recommendations are those of the author(s) and do not necessarily reflect the view of NIST or the U.S. Department of Commerce. NR 53 TC 12 Z9 12 U1 10 U2 54 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 SEP PY 2015 VL 16 IS 9 BP 2672 EP 2683 DI 10.1021/acs.biomac.5b00541 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA CR4WV UT WOS:000361341700013 PM 26225909 ER PT J AU Han, SS Rosenberg, PS Ghosh, A Landi, MT Caporaso, NE Chatterjee, N AF Han, Summer S. Rosenberg, Philip S. Ghosh, Arpita Landi, Maria Teresa Caporaso, Neil E. Chatterjee, Nilanjan TI An Exposure-Weighted Score Test for Genetic Associations Integrating Environmental Risk Factors SO BIOMETRICS LA English DT Article DE Environmental exposures; Gene-environment interaction; GWAS; Score test; SNPs ID GENOME-WIDE ASSOCIATION; CANCER SUSCEPTIBILITY LOCI; LUNG-CANCER; HAN CHINESE; MODELS; INDEPENDENCE; VARIANTS; DISEASE; 5P15.33; WOMEN AB Current methods for detecting genetic associations lack full consideration of the background effects of environmental exposures. Recently proposed methods to account for environmental exposures have focused on logistic regressions with gene-environment interactions. In this report, we developed a test for genetic association, encompassing a broad range of risk models, including linear, logistic and probit, for specifying joint effects of genetic and environmental exposures. We obtained the test statistics by maximizing over a class of score tests, each of which involves modified standard tests of genetic association through a weight function. This weight function reflects the potential heterogeneity of the genetic effects by levels of environmental exposures under a particular model. Simulation studies demonstrate the robust power of these methods for detecting genetic associations under a wide range of scenarios. Applications of these methods are further illustrated using data from genome-wide association studies of type 2 diabetes with body mass index and of lung cancer risk with smoking. C1 [Han, Summer S.] Stanford Univ, Dept Radiol, Sch Med, Palo Alto, CA 94305 USA. [Rosenberg, Philip S.; Landi, Maria Teresa; Caporaso, Neil E.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20852 USA. [Ghosh, Arpita] Publ Hlth Fdn India, New Delhi 110070, India. RP Han, SS (reprint author), Stanford Univ, Dept Radiol, Sch Med, Palo Alto, CA 94305 USA. EM chattern@mail.nih.gov FU National Institutes of Health, National Cancer Institute (Division of Cancer Epidemiology and Genetics) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (Division of Cancer Epidemiology and Genetics). We are grateful to Dr. David Siegmund for helpful advice and pointers to the literature for an extreme value theory related to calculations of p-values of the maximum test. NR 30 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2015 VL 71 IS 3 BP 596 EP 605 DI 10.1111/biom.12328 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CR7JY UT WOS:000361527000004 PM 26134142 ER PT J AU Fogarty, CB Fay, MP Flegg, JA Stepniewska, K Fairhurst, RM Small, DS AF Fogarty, Colin B. Fay, Michael P. Flegg, Jennifer A. Stepniewska, Kasia Fairhurst, Rick M. Small, Dylan S. TI Bayesian Hierarchical Regression on Clearance Rates in the Presence of "Lag" and "Tail" Phases with an Application to Malaria Parasites SO BIOMETRICS LA English DT Article DE Bayesian; Changepoint models; Clearance rate estimation; Drug resistance; Hierarchical linear models; Left censoring; Malaria; Plasmodium falciparum ID PLASMODIUM-FALCIPARUM MALARIA; ARTEMISININ RESISTANCE; MODELS; ESTIMATOR AB We present a principled technique for estimating the effect of covariates on malaria parasite clearance rates in the presence of "lag" and "tail" phases through the use of a Bayesian hierarchical linear model. The hierarchical approach enables us to appropriately incorporate the uncertainty in both estimating clearance rates in patients and assessing the potential impact of covariates on these rates into the posterior intervals generated for the parameters associated with each covariate. Furthermore, it permits us to incorporate information about individuals for whom there exists only one observation time before censoring, which alleviates a systematic bias affecting inference when these individuals are excluded. We use a changepoint model to account for both lag and tail phases, and hence base our estimation of the parasite clearance rate only on observations within the decay phase. The Bayesian approach allows us to treat the delineation between lag, decay, and tail phases within an individual's clearance profile as themselves being random variables, thus taking into account the additional uncertainty of boundaries between phases. We compare our method to existing methodology used in the antimalarial research community through a simulation study and show that it possesses desirable frequentist properties for conducting inference. We use our methodology to measure the impact of several covariates on Plasmodium falciparum clearance rate data collected in 2009 and 2010. Though our method was developed with this application in mind, it can be easily applied to any biological system exhibiting these hindrances to estimation. C1 [Fogarty, Colin B.; Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Fay, Michael P.; Fairhurst, Rick M.] NIH, Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. [Flegg, Jennifer A.; Stepniewska, Kasia] Univ Oxford, WorldWide Antimalarial Resistance Network WWARN, Oxford OX3 7LJ, England. [Flegg, Jennifer A.; Stepniewska, Kasia] Univ Oxford, Ctr Trop Med, Nuffield Dept Clin Med, Oxford OX3 7LJ, England. [Flegg, Jennifer A.] Monash Univ, Sch Math Sci, Melbourne, Vic 3004, Australia. [Flegg, Jennifer A.] Monash Univ, Monash Acad Cross & Interdisciplinary Math Applic, Melbourne, Vic 3004, Australia. RP Fogarty, CB (reprint author), Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. EM cfogarty@wharton.upenn.edu OI Fay, Michael P./0000-0002-8643-9625; Flegg, Jennifer/0000-0002-8809-726X FU NIH, NIAID FX We thank Dr. Chanaki Amaratunga for providing the data used in Section 4. This research was supported in part by the Intramural Research Program of the NIH, NIAID. NR 22 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2015 VL 71 IS 3 BP 751 EP 759 DI 10.1111/biom.12307 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CR7JY UT WOS:000361527000020 PM 25851174 ER PT J AU Zhang, M Xi, ZR Zinman, L Bruni, AC Maletta, RG Curcio, SAM Rainero, I Rubino, E Pinessi, L Nacmias, B Sorbi, S Galimberti, D Lang, AE Fox, S Surace, EI Ghani, M Guo, J Sato, C Moreno, D Liang, Y Keith, J Traynor, BJ St George-Hyslop, P Rogaeva, E AF Zhang, Ming Xi, Zhengrui Zinman, Lorne Bruni, Amalia C. Maletta, Raffaele G. Curcio, Sabrina A. M. Rainero, Innocenzo Rubino, Elisa Pinessi, Lorenzo Nacmias, Benedetta Sorbi, Sandro Galimberti, Daniela Lang, Anthony E. Fox, Susan Surace, Ezequiel I. Ghani, Mahdi Guo, Jing Sato, Christine Moreno, Danielle Liang, Yan Keith, Julia Traynor, Bryan J. St George-Hyslop, Peter Rogaeva, Ekaterina TI Mutation analysis of CHCHD10 in different neurodegenerative diseases SO BRAIN LA English DT Letter ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENE C1 [Zhang, Ming; Xi, Zhengrui; Ghani, Mahdi; Guo, Jing; Sato, Christine; Moreno, Danielle; Liang, Yan; St George-Hyslop, Peter; Rogaeva, Ekaterina] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada. [Zinman, Lorne; Keith, Julia] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Bruni, Amalia C.; Maletta, Raffaele G.; Curcio, Sabrina A. M.] Azienda Sanit Provinciale Catanzaro, Reg Neurogenet Ctr, Lamezia Terme, Italy. [Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo] Univ Turin, Rita Levi Montalcini Dept Neurosci, Neurol 1, I-10124 Turin, Italy. [Nacmias, Benedetta; Sorbi, Sandro] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, I-50121 Florence, Italy. [Galimberti, Daniela] Univ Milan, Neurol Unit, Dept Pathophysiol & Transplantat, Ctr Dino Ferrari,Fdn Ca Granda,IRCCS Osped Maggio, Milan, Italy. [Lang, Anthony E.; Fox, Susan] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON M5T 2S8, Canada. [Lang, Anthony E.; Fox, Susan; St George-Hyslop, Peter; Rogaeva, Ekaterina] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada. [Lang, Anthony E.; Fox, Susan; St George-Hyslop, Peter; Rogaeva, Ekaterina] Univ Toronto, Dept Med, Div Neurol, Toronto, ON M5S 1A8, Canada. [Surace, Ezequiel I.] Consejo Nacl Invest Cient & Tecn, Lab Biol Mol, Inst Invest Neurol Dr Raul Carrea FLENI, RA-1033 Buenos Aires, DF, Argentina. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0XY, England. RP Rogaeva, E (reprint author), Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Krembil Discovery Tower,60 Leonard St, Toronto, ON M5T 2S8, Canada. EM ekaterina.rogaeva@utoronto.ca RI Rubino, Elisa/K-3282-2016; , raffaele/K-4421-2016 OI Rubino, Elisa/0000-0002-7553-7553; galimberti, daniela/0000-0002-9284-5953; NACMIAS, Benedetta/0000-0001-9338-9040; sorbi, sandro/0000-0002-0380-6670; , raffaele/0000-0002-0758-1835 FU Wellcome Trust [081864, 089703] NR 10 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD SEP 1 PY 2015 VL 138 AR e380 DI 10.1093/brain/awv082 PN 9 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CR5PS UT WOS:000361396200006 PM 25833818 ER PT J AU Khalili, H Gong, J Brenner, H Austin, TR Hutter, CM Baba, Y Baron, JA Berndt, SI Bezieau, S Caan, B Campbell, PT Chang-Claude, J Chanock, SJ Chen, C Hsu, L Jiao, S Conti, DV Duggan, D Fuchs, CS Gala, M Gallinger, S Haile, RW Harrison, TA Hayes, R Hazra, A Henderson, B Haiman, C Hoffmeister, M Hopper, JL Jenkins, MA Kolonel, LN Kury, S LaCroix, A Le Marchand, L Lemire, M Lindor, NM Ma, J Manson, JE Morikawa, T Nan, H Ng, K Newcomb, PA Nishihara, R Potter, JD Qu, CH Schoen, RE Schumacher, FR Seminara, D Taverna, D Thibodeau, S Wactawski-Wende, J White, E Wu, K Zanke, BW Casey, G Hudson, TJ Kraft, P Peters, U Slattery, ML Ogino, S Chan, AT AF Khalili, Hamed Gong, Jian Brenner, Hermann Austin, Thomas R. Hutter, Carolyn M. Baba, Yoshifumi Baron, John A. Berndt, Sonja I. Bezieau, Stephane Caan, Bette Campbell, Peter T. Chang-Claude, Jenny Chanock, Stephen J. Chen, Constance Hsu, Li Jiao, Shuo Conti, David V. Duggan, David Fuchs, Charles S. Gala, Manish Gallinger, Steven Haile, Robert W. Harrison, Tabitha A. Hayes, Richard Hazra, Aditi Henderson, Brian Haiman, Chris Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Kolonel, Laurence N. Kuery, Sebastien LaCroix, Andrea Le Marchand, Loic Lemire, Mathieu Lindor, Noralane M. Ma, Jing Manson, Joann E. Morikawa, Teppei Nan, Hongmei Ng, Kimmie Newcomb, Polly A. Nishihara, Reiko Potter, John D. Qu, Conghui Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Taverna, Darin Thibodeau, Stephen Wactawski-Wende, Jean White, Emily Wu, Kana Zanke, Brent W. Casey, Graham Hudson, Thomas J. Kraft, Peter Peters, Ulrike Slattery, Martha L. Ogino, Shuji Chan, Andrew T. CA GECCO CGFR TI Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer SO CARCINOGENESIS LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; GENOME-WIDE ASSOCIATION; POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; ULCERATIVE-COLITIS; COLON-CANCER; SUSCEPTIBILITY LOCI; MOLECULAR-FEATURES; CROHNS-DISEASE; MAIT CELLS AB We identified the minor allele (T) in SNP rs11676348 to have pleiotropic effect on risk of UC and CRC, particularly in tumors with an inflammatory component. Our findings offer the promise of risk stratification of UC patients for developing CRC.Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11794 CRC cases and 14190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (P (heterogeneity) = 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (P (heterogeneity) = 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (P (heterogeneity) = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC. C1 [Khalili, Hamed; Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gong, Jian; Hsu, Li; Jiao, Shuo; Harrison, Tabitha A.; LaCroix, Andrea; Newcomb, Polly A.; Potter, John D.; Qu, Conghui; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Cosortium DKTK, Heidelberg, Germany. [Austin, Thomas R.] Whitman Coll, Walla Walla, WA 99362 USA. [Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Baba, Yoshifumi] Kumamoto Univ, Dept Surg Gastroenterol, Kumamoto, Japan. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Caan, Bette] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Chen, Constance; Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA USA. [Conti, David V.; Henderson, Brian; Haiman, Chris; Schumacher, Fredrick R.; Casey, Graham] Univ So Calif, Keck Sch Med, Los Angeles, CA USA. [Duggan, David; Taverna, Darin] Syst Imaginat, Computat Biol, Phoenix, AZ USA. [Fuchs, Charles S.; Ng, Kimmie; Nishihara, Reiko; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Hazra, Aditi; Ma, Jing; Nan, Hongmei; Kraft, Peter; Chan, Andrew T.] Indiana Univ, Dept Epidemiol, Sch Publ Hlth, Indianapolis, IN 46204 USA. [Gallinger, Steven] Toronto Gen Hosp, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Haile, Robert W.] Stanford Canc Inst, Palo Alto, CA USA. [Hayes, Richard; Jenkins, Mark A.] NYU, Div Epidemiol, Sch Med, New York, NY USA. [Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Australia. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Epidemiol Program, Ctr Canc, Honolulu, HI 96822 USA. [Lemire, Mathieu; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Serv, Scottsdale, AZ USA. [Manson, Joann E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Nishihara, Reiko; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Potter, John D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Med Ctr, Pittsburgh, PA USA. [Thibodeau, Stephen] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Zanke, Brent W.] Ottawa Hosp, Clin Epidemiol Program, Res Inst, Ottawa, OK USA. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, OK USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM shuji_ogino@dfci.harvard.edu; achan@mgh.harvard.edu RI Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; KURY, Sebastien/0000-0001-5497-0465; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X; Hoffmeister, Michael/0000-0002-8307-3197 FU Crohn's and Colitis Foundation of America (CCFA); American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Institutes of Health [R01 CA60987, UM1 CA167551, R01 CA48998, CA61757, U01 CA074783, CA42182, R01 CA076366, K05 CA154337]; National Cancer Institute, National Institutes of Health [U01 CA122839, R01 CA143237]; National Institutes of Health: Australasian Colorectal Cancer Family Registry [U01/U24 CA097735]; National Institutes of Health: Familial Colorectal Neoplasia Collaborative Group [U01/U24 CA074799]; National Institutes of Health: Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24 CA074800]; National Institutes of Health: Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]; National Institutes of Health: Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; National Institutes of Health: University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Institutes of Health; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research; Ontario Ministry of Research and Innovation; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; NIH [U01 HG004446]; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; [R01 CA137178]; [R01 CA050385]; [R01 CA151993]; [P01 CA87969]; [P30 DK043351]; [P50 CA127003]; [UM1 CA 167552]; [UM1 CA186107]; [K24 [DK]098311]; [K07 CA190673]; [K07 CA148894] FX Funded by R01 CA137178, R01 CA050385, R01 CA151993, P01 CA87969, P30 DK043351, P50 CA127003, UM1 CA 167552, UM1 CA186107, K23 DK099681, K24 [DK]098311, K07 CA190673 and K07 CA148894. Senior investigator grant from the Crohn's and Colitis Foundation of America (CCFA) to A.T.C. A career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681 to H.K.).; GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; COLO2&3: National Institutes of Health (R01 CA60987).; CCFR: National Institutes of Health (UM1 CA167551) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839 and R01 CA143237 to G.C. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CFR. The following CFR centers contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794) and the University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806).; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 and CA61757 to M.L.S.);; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager,M. et al. (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet., 39, 645-649), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. (2009) Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat. Genet., 41, 986-990, and Petersen, G.M. et al. (2010) A genome-wide association study identifies pancreatic cancer susceptibility locion chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet., 42, 224-228), and the Lung Cancer and Smoking study (Landi,M.T. et al. (2009) A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am. J. Hum. Genet., 85, 679-691). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207v.1p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093 v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446 and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping.; PHS: National Institutes of Health (CA42182).; PMH: National Institutes of Health (R01 CA076366 to P.A.N.).; VITAL: National Institutes of Health (K05 CA154337).; WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. NR 50 TC 4 Z9 4 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2015 VL 36 IS 9 BP 999 EP 1007 DI 10.1093/carcin/bgv086 PG 9 WC Oncology SC Oncology GA CR5QA UT WOS:000361397000008 PM 26071399 ER PT J AU Soekadar, SR Witkowski, M Birbaumer, N Cohen, LG AF Soekadar, Surjo R. Witkowski, Matthias Birbaumer, Niels Cohen, Leonardo G. TI Enhancing Hebbian Learning to Control Brain Oscillatory Activity SO CEREBRAL CORTEX LA English DT Article DE brain stimulation; Hebbian learning; motor cortex; sensorimotor rhythms ID DIRECT-CURRENT STIMULATION; INTERFACE BCI SYSTEM; HUMAN MOTOR CORTEX; COMPUTER INTERFACE; CHRONIC STROKE; EXCITABILITY; MODULATION; MOVEMENT; IMAGERY; HUMANS AB Sensorimotor rhythms (SMR, 8-15 Hz) are brain oscillations associated with successful motor performance, imagery, and imitation. Voluntary modulation of SMR can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill are unknown. Here, we provide evidence for a causal link between function of the primary motor cortex (M1), active during motor skill learning and retention, and successful acquisition of abstract skills such as control over SMR. Thirty healthy participants were trained on 5 consecutive days to control SMR oscillations. Each participant was randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the other 2. Cathodal tDCS blocked the beneficial effects of training, as evidenced with sham tDCS. One month later, the newly acquired skill remained superior in the anodal tDCS group. Thus, application of weak electric currents of opposite polarities over M1 differentially modulates learning SMR control, pointing to this primary cortical region as a common substrate for acquisition of physical motor skills and learning to control brain oscillatory activity. C1 [Soekadar, Surjo R.; Witkowski, Matthias; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sect, NIH, Bethesda, MD 20892 USA. [Soekadar, Surjo R.; Witkowski, Matthias] Univ Tubingen Hosp, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, Tubingen, Germany. [Soekadar, Surjo R.; Witkowski, Matthias; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Birbaumer, Niels] IRCCS, Osped San Camillo, Venice, Italy. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sect, NIH, Bldg 10,Room 7D54, Bethesda, MD 20892 USA. EM CohenL@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD, USA; Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of Health Sciences, Bethesda, MD, USA; German Federal Ministry of Education and Research (BMBF) [01GQ0831, 16SV5838K]; European Commission [288551]; Deutsche Forschungsgemeinschaft (DFG) [SO932-1]; Deutsche Forschungsgemeinschaft (Reinhart Koselleck Project); Volkswagenstiftung (VW); Baden-Wurttemberg Stiftung FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD, USA; the Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of Health Sciences, Bethesda, MD, USA; the German Federal Ministry of Education and Research (BMBF, grant number 01GQ0831, 16SV5838K to S.R.S. and N.B.); the European Commission under the project WAY (grant number 288551 to S.R.S. and N.B.); the Deutsche Forschungsgemeinschaft (DFG, grant number SO932-1 to S.R.S. and Reinhart Koselleck Project support to N.B.); Volkswagenstiftung (VW) and the Baden-Wurttemberg Stiftung. NR 54 TC 10 Z9 10 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 2409 EP 2415 DI 10.1093/cercor/bhu043 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000007 PM 24626608 ER PT J AU Sannino, S Gozzi, A Cerasa, A Piras, F Scheggia, D Manago, F Damiano, M Galbusera, A Erickson, LC Tonelli, DD Bifone, A Tsaftaris, SA Caltagirone, C Weinberger, DR Spalletta, G Papaleo, F AF Sannino, Sara Gozzi, Alessandro Cerasa, Antonio Piras, Fabrizio Scheggia, Diego Manago, Francesca Damiano, Mario Galbusera, Alberto Erickson, Lucy C. Tonelli, Davide De Pietri Bifone, Angelo Tsaftaris, Sotirios A. Caltagirone, Carlo Weinberger, Daniel R. Spalletta, Gianfranco Papaleo, Francesco TI COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans SO CEREBRAL CORTEX LA English DT Article DE cognition; cortical thickness; dopamine; postero-parietal cortex; prefrontal cortex ID CATECHOL-O-METHYLTRANSFERASE; POSTERIOR PARIETAL CORTEX; VAL(108/158) MET GENOTYPE; 22Q11.2 DELETION SYNDROME; CARDIO-FACIAL SYNDROME; GRAY-MATTER VOLUME; PREFRONTAL CORTEX; CEREBRAL-CORTEX; HUMAN BRAIN; NEUROTOXIC LESIONS AB Genetic variations in catechol-O-methyltransferase (COMT) that modulate cortical dopamine have been associated with pleiotropic behavioral effects in humans and mice. Recent data suggest that some of these effects may vary among sexes. However, the specific brain substrates underlying COMT sexual dimorphisms remain unknown. Here, we report that genetically driven reduction in COMT enzyme activity increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice and humans. Dichotomous changes in PFC cytoarchitecture were also observed: reduced COMT increased a measure of neuronal density in males, while reducing it in female mice. Consistent with the neuroanatomical findings, COMT-dependent sex-specific morphological brain changes were paralleled by divergent effects on PFC-dependent working memory in both mice and humans. These findings emphasize a specific sex-gene interaction that can modulate brain morphological substrates with influence on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric populations. C1 [Sannino, Sara; Scheggia, Diego; Manago, Francesca; Tonelli, Davide De Pietri; Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy. [Gozzi, Alessandro; Damiano, Mario; Galbusera, Alberto; Bifone, Angelo] Ctr Neurosci & Cognit Sci UNITN, Ist Italiano Tecnol, I-38068 Rovereto, Italy. [Cerasa, Antonio] Natl Res Council CNR, IBFM Inst Bioimaging & Mol Physiol, I-88100 Germaneto, CZ, Italy. [Piras, Fabrizio; Caltagirone, Carlo; Spalletta, Gianfranco] IRCCS Santa Lucia Fdn, I-00142 Rome, Italy. [Erickson, Lucy C.] NIMH, NIH, Bethesda, MD 20892 USA. [Tsaftaris, Sotirios A.] IMT Inst Adv Studies, I-55100 Lucca, Italy. [Weinberger, Daniel R.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Papaleo, Francesco] Univ Padua, Dipartimento Sci Farmaco, I-35131 Padua, Italy. RP Papaleo, F (reprint author), Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy. EM francesco.papaleo@iit.it RI piras, fabrizio/M-7902-2016; Galbusera, Alberto/N-5531-2016; cerasa, antonio/E-8614-2011; De Pietri Tonelli, Davide/E-2102-2011; OI piras, fabrizio/0000-0003-3566-5494; Galbusera, Alberto/0000-0001-7213-0013; cerasa, antonio/0000-0002-8022-4770; De Pietri Tonelli, Davide/0000-0001-9537-8900; Gozzi, Alessandro/0000-0002-5731-4137; Papaleo, Francesco/0000-0002-6326-0657 FU Istituto Italiano di Tecnologia; Marie Curie Reintegration-Grant [FP7-268247]; Italian Ministry of Health Grants for Young Researcher [GR-2010-2315883] FX This research was supported by the Istituto Italiano di Tecnologia, the Marie Curie Reintegration-Grant (FP7-268247), and by the Italian Ministry of Health Grants for Young Researcher (GR-2010-2315883). NR 73 TC 7 Z9 7 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 2529 EP 2541 DI 10.1093/cercor/bhu053 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000017 PM 24658585 ER PT J AU Liu, X Yanagawa, T Leopold, DA Fujii, N Duyn, JH AF Liu, Xiao Yanagawa, Toru Leopold, David A. Fujii, Naotaka Duyn, Jeff H. TI Robust Long-Range Coordination of Spontaneous Neural Activity in Waking, Sleep and Anesthesia SO CEREBRAL CORTEX LA English DT Article DE anesthesia; electrocorticography; resting-state networks; sleep; spontaneous activity ID RESTING STATE NETWORKS; FUNCTIONAL CONNECTIVITY; BRAIN ACTIVITY; NEURONAL AVALANCHES; BOLD CONNECTIVITY; CLUSTER-ANALYSIS; AROUSAL SYSTEMS; MOTOR CORTEX; DEFAULT MODE; TOP-DOWN AB Although the emerging field of functional connectomics relies increasingly on the analysis of spontaneous fMRI signal covariation to infer the spatial fingerprint of the brain's large-scale functional networks, the nature of the underlying neuro-electrical activity remains incompletely understood. In part, this lack in understanding owes to the invasiveness of electrophysiological acquisition, the difficulty in their simultaneous recording over large cortical areas, and the absence of fully established methods for unbiased extraction of network information from these data. Here, we demonstrate a novel, data-driven approach to analyze spontaneous signal variations in electrocorticographic (ECoG) recordings from nearly entire hemispheres of macaque monkeys. Based on both broadband analysis and analysis of specific frequency bands, the ECoG signals were found to co-vary in patterns that resembled the fMRI networks reported in previous studies. The extracted patterns were robust against changes in consciousness associated with sleep and anesthesia, despite profound changes in intrinsic characteristics of the raw signals, including their spectral signatures. These results suggest that the spatial organization of large-scale brain networks results from neural activity with a broadband spectral feature and is a core aspect of the brain's physiology that does not depend on the state of consciousness. C1 [Liu, Xiao; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Yanagawa, Toru; Fujii, Naotaka] RIKEN, Brain Sci Inst, Lab Adapt Intelligence, Saitama, Japan. [Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Liu, X (reprint author), 10 Ctr Dr,Bldg 10,Rm B1D-723A-MSC 1065, Bethesda, MD 20892 USA. EM liux15@ninds.nih.gov RI Liu, Xiao/C-5943-2016 FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This research was supported (in part) by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 56 TC 5 Z9 5 U1 4 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 2929 EP 2938 DI 10.1093/cercor/bhu089 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000052 PM 24812083 ER PT J AU Morin, EL Hadj-Bouziane, F Stokes, M Ungerleider, LG Bell, AH AF Morin, Elyse L. Hadj-Bouziane, Fadila Stokes, Mark Ungerleider, Leslie G. Bell, Andrew H. TI Hierarchical Encoding of Social Cues in Primate Inferior Temporal Cortex SO CEREBRAL CORTEX LA English DT Article DE face processing; facial expression; identity; gaze direction; monkey ID HUMAN NEURAL SYSTEM; FACIAL-EXPRESSION; GAZE-DIRECTION; INFEROTEMPORAL CORTEX; EMOTIONAL EXPRESSION; FACE PERCEPTION; DISTINCT REPRESENTATIONS; SELECTIVE RESPONSES; MONKEY AMYGDALA; SINGLE NEURONS AB Faces convey information about identity and emotional state, both of which are important for our social interactions. Models of face processing propose that changeable versus invariant aspects of a face, specifically facial expression/gaze direction versus facial identity, are coded by distinct neural pathways and yet neurophysiological data supporting this separation are incomplete. We recorded activity from neurons along the inferior bank of the superior temporal sulcus (STS), while monkeys viewed images of conspecific faces and nonface control stimuli. Eight monkey identities were used, each presented with 3 different facial expressions (neutral, fear grin, and threat). All facial expressions were displayed with both a direct and averted gaze. In the posterior STS, we found that about one-quarter of face-responsive neurons are sensitive to social cues, the majority of which being sensitive to only one of these cues. In contrast, in anterior STS, not only did the proportion of neurons sensitive to social cues increase, but so too did the proportion of neurons sensitive to conjunctions of identity with either gaze direction or expression. These data support a convergence of signals related to faces as one moves anteriorly along the inferior bank of the STS, which forms a fundamental part of the face-processing network. C1 [Morin, Elyse L.; Hadj-Bouziane, Fadila; Ungerleider, Leslie G.; Bell, Andrew H.] NIMH, NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Stokes, Mark] Univ Oxford, Oxford Ctr Human Brain Act, Oxford, England. [Stokes, Mark] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Bell, AH (reprint author), MRC Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England. EM andrew.bell@mrc-cbu.cam.ac.uk FU National Institute of Mental Health Intramural Research Program FX This work was supported by the National Institute of Mental Health Intramural Research Program (E.L.M., F.H.B., L.G.U., and A.H.B.). NR 56 TC 2 Z9 3 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2015 VL 25 IS 9 BP 3036 EP 3045 DI 10.1093/cercor/bhu099 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CR6NK UT WOS:000361464000062 PM 24836688 ER PT J AU Landon, AL Muniandy, PA Houng, S Shetty, A Becker, K Borden, K Gartenhaus, RB AF Landon, Ari L. Muniandy, Parameswary A. Houng, Simone Shetty, Amol Becker, Kevin Borden, Katherine Gartenhaus, Ronald B. TI eIF4E3 forms a novel cap-binding complex for mRNA translation initiation. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Landon, Ari L.; Muniandy, Parameswary A.; Houng, Simone; Shetty, Amol; Gartenhaus, Ronald B.] Univ Maryland, Baltimore, MD 21201 USA. [Becker, Kevin] NIA, Baltimore, MD 21224 USA. [Borden, Katherine] Univ Montreal, Montreal, PQ H3C 3J7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA B08 DI 10.1158/1557-3265.HEMMAL14-B08 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200046 ER PT J AU Rosean, TR Tompkins, VS Sompallae, R Norian, LA Morse, HC Waldschmidt, TJ Janz, S AF Rosean, Timothy R. Tompkins, Van S. Sompallae, Ramakrishna Norian, Lyse A. Morse, Herbert C., III Waldschmidt, Thomas J. Janz, Siegfried TI The tumor microenvironment is the main source of IL-6 for plasmacytoma development in mice. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Rosean, Timothy R.; Tompkins, Van S.; Sompallae, Ramakrishna; Norian, Lyse A.; Waldschmidt, Thomas J.; Janz, Siegfried] Univ Iowa, Iowa City, IA USA. [Morse, Herbert C., III] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A04 DI 10.1158/1557-3265.HEMMAL14-A04 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200004 ER PT J AU Triplett, TA Cardenas, KT Jones, JN Selden, HJ Jasso, GJ Balasubramanyam, S Hu, ZC Li, LQ Love, PE Ehrlich, LIR AF Triplett, Todd A. Cardenas, Kim T. Jones, Jessica N. Selden, Hilary J. Jasso, Guadalupe J. Balasubramanyam, Sadhana Hu, Zicheng Li Liqi Love, Paul E. Ehrlich, Lauren I. R. TI Altered myeloid cells in the tumor microenvironment promote growth of T cell acute lymphoblastic leukemia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Triplett, Todd A.; Cardenas, Kim T.; Jones, Jessica N.; Selden, Hilary J.; Jasso, Guadalupe J.; Balasubramanyam, Sadhana; Hu, Zicheng; Ehrlich, Lauren I. R.] Univ Texas Austin, Austin, TX 78712 USA. [Li Liqi; Love, Paul E.] NIH, Bethesda, MD 20892 USA. NR 0 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A02 DI 10.1158/1557-3265.HEMMAL14-A02 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200002 ER PT J AU Varmus, H AF Varmus, Harold TI Initial characterization of genetically engineered mice carrying a conditional allele of a splicing factor gene (U2AF1) commonly mutated in myeloid disorders. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Hematologic Malignancies - Translating Discoveries to Novel Therapies CY SEP 20-23, 2014 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Varmus, Harold] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2015 VL 21 SU 17 MA A39 DI 10.1158/1557-3265.HEMMAL14-A39 PG 1 WC Oncology SC Oncology GA CR5ME UT WOS:000361386200032 ER PT J AU Evans, SR Rubin, D Follmann, D Pennello, G Huskins, WC Powers, JH Schoenfeld, D Chuang-Stein, C Cosgrove, SE Fowler, VG Lautenbach, E Chambers, HF AF Evans, Scott R. Rubin, Daniel Follmann, Dean Pennello, Gene Huskins, W. Charles Powers, John H. Schoenfeld, David Chuang-Stein, Christy Cosgrove, Sara E. Fowler, Vance G., Jr. Lautenbach, Ebbing Chambers, Henry F. TI Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE DOOR; RADAR; antibiotic use strategies ID EQUIVALENCE TRIALS; ANTIMICROBIAL USE; NON-INFERIORITY; SAMPLE-SIZE AB Clinical trials that compare strategies to optimize antibiotic use are of critical importance but are limited by competing risks that distort outcome interpretation, complexities of noninferiority trials, large sample sizes, and inadequate evaluation of benefits and harms at the patient level. The Antibacterial Resistance Leadership Group strives to overcome these challenges through innovative trial design. Response adjusted for duration of antibiotic risk (RADAR) is a novel methodology utilizing a superiority design and a 2-step process: (1) categorizing patients into an overall clinical outcome (based on benefits and harms), and (2) ranking patients with respect to a desirability of outcome ranking (DOOR). DOORs are constructed by assigning higher ranks to patients with (1) better overall clinical outcomes and (2) shorter durations of antibiotic use for similar overall clinical outcomes. DOOR distributions are compared between antibiotic use strategies. The probability that a randomly selected patient will have a better DOOR if assigned to the new strategy is estimated. DOOR/RADAR represents a new paradigm in assessing the risks and benefits of new strategies to optimize antibiotic use. C1 [Evans, Scott R.] Harvard Univ, Boston, MA 02115 USA. [Rubin, Daniel] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Follmann, Dean] NIAID, NIH, Bethesda, MD 20892 USA. [Pennello, Gene] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Huskins, W. Charles] Mayo Clin, Div Pediat Infect Dis, Rochester, MN USA. [Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA. [Powers, John H.] NIH, Leidos Biomed Res, Div Clin Res, Bethesda, MD 20892 USA. [Schoenfeld, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chuang-Stein, Christy] Pfizer Inc, Groton, CT 06340 USA. [Cosgrove, Sara E.] Johns Hopkins Univ, Baltimore, MD USA. [Fowler, Vance G., Jr.] Duke Univ, Durham, NC USA. [Lautenbach, Ebbing] Univ Penn, Philadelphia, PA 19104 USA. [Chambers, Henry F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Evans, SR (reprint author), Harvard Univ, Sch Publ Hlth, CBAR Biostat, FXB 513,651 Huntington Ave, Boston, MA 02115 USA. EM evans@sdac.harvard.edu FU National Institute of Allergy and Infectious Diseases of the NIH [UM1AI104681]; National Cancer Institute, NIH [HHSN261200800001E] FX This work was supported by the National Institute of Allergy and Infectious Diseases of the NIH (award number UM1AI104681) and in part with federal funds from the National Cancer Institute, NIH (contract number HHSN261200800001E). NR 14 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2015 VL 61 IS 5 BP 800 EP 806 DI 10.1093/cid/civ495 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR6PD UT WOS:000361468700021 PM 26113652 ER PT J AU Inker, LA Tighiouart, H Aspelund, T Gudnason, V Harris, T Indridason, OS Palsson, R Shastri, S Levey, AS Sarnak, MJ AF Inker, Lesley A. Tighiouart, Hocine Aspelund, Thor Gudnason, Vilmundur Harris, Tamara Indridason, Olafur S. Palsson, Runolfur Shastri, Shani Levey, Andrew S. Sarnak, Mark J. TI Lifetime Risk of Stage 3-5 CKD in a Community-Based Sample in Iceland SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CLINICAL-PRACTICE GUIDELINE; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; UNITED-STATES; HIGHER ALBUMINURIA; RENAL-DISEASE; REFERENCE VALUES; ESTIMATED GFR AB Background and objectives Lifetime risk estimates of CKD can be used effectively in public education campaigns. This study sought to estimate lifetime risk of incident CKD stage 3 and higher in Iceland for people without CKD by the age of 45 years. Design, setting, participants, & measurements This was a prospective cohort study with longitudinal creatinine measurements of residents in Reykjavik, Iceland, from 1967 to 2005. CKD was ascertained by two consecutive eGFR measurements <60 ml/min per 1.73 m(2), development of treated kidney failure, one eGFR <60ml/min per 1.73 m(2) if the participant died before the next evaluation, or one eGFR, <45 ml/min per 1.73 m(2) if it was the last eGFR. Results Mean follow-up was 25 (SD10) years. Of the study participants, 727 (19%) developed the outcome and 942 (24%) died first. By age 85 years, the lifetime risks for 45-year-old women and men without prevalent CKD were 35.8% (95% confidence interval [95% CI], 32.7 to 38.9) and 21.3% (95% CI, 18.7 to 23.8), respectively. Risk was higher in individuals with a lower eGFR, hypertension, and a higher body mass index. Lifetime risk for higher stages of CKD 3b and 4 were less common than stage 3a; by age 85 years, the lifetime risks for CKD stages 3a, 3b, and 4 in women were 38.5% (95% CI, 25.8 to 51.1), 19.4% (95% CI, 8.9 to 29.9), and 3.6% (95% CI, 2.2 to 5.0), respectively. Conclusions The lifetime risk of developing CKD stage 3 or higher is substantial, emphasizing the importance of strategies to prevent development of CKD throughout the course of life. Estimates are lower than reported using single estimates of GFR, emphasizing the importance of confirming estimates of reduced GFR in studies of CKD. C1 [Inker, Lesley A.; Levey, Andrew S.; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Tighiouart, Hocine] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Tighiouart, Hocine] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur; Palsson, Runolfur] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Harris, Tamara] NIA, Bethesda, MD 20892 USA. [Indridason, Olafur S.; Palsson, Runolfur] Landspitali Natl Univ Hosp, Div Nephrol, Reykjavik, Iceland. [Shastri, Shani] Univ Texas SW Med Ctr Dallas, Div Nephrol, Dallas, TX 75390 USA. RP Inker, LA (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM linker@tuftsmedicalcenter.org RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institutes of Health [R01-DK082447]; National Institute on Aging [N01AG12100]; Icelandic Heart Association (Hjartavernd); Icelandic Parliament (Althingi) FX This study was supported by the National Institutes of Health (Grant R01-DK082447), the National Institute on Aging (Contract N01AG12100), the Icelandic Heart Association (Hjartavernd), and the Icelandic Parliament (Althingi). The funding sources were not required to approve publication of the finished manuscript. NR 33 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2015 VL 10 IS 9 BP 1575 EP 1584 DI 10.2215/CJN.00180115 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CR2HM UT WOS:000361148200012 PM 26286924 ER PT J AU Korczyn, AD Schachter, SC Amlerova, J Bialer, M Boas, WV Brazdil, M Brodtkorb, E Engel, J Gotman, J Komarek, V Leppik, IE Marusic, P Meletti, S Metternich, B Moulin, CJA Muhlert, N Mula, M Nakken, KO Picard, F Schulze-Bonhage, A Theodore, W Wolf, P Zeman, A Rektor, I AF Korczyn, Amos D. Schachter, Steven C. Amlerova, Jana Bialer, Meir Boas, Walter van Emde Brazdil, Milan Brodtkorb, Eylert Engel, Jerome, Jr. Gotman, Jean Komarek, Vladmir Leppik, Ilo E. Marusic, Petr Meletti, Stefano Metternich, Birgitta Moulin, Chris J. A. Muhlert, Nils Mula, Marco Nakken, Karl O. Picard, Fabienne Schulze-Bonhage, Andreas Theodore, William Wolf, Peter Zeman, Adam Rektor, Ivan TI Third International Congress on Epilepsy, Brain and Mind: Part 1 SO EPILEPSY & BEHAVIOR LA English DT Review DE Epilepsy; Cognition; Social cognition; Religion; Music; Handedness; Accelerated forgetting; Networks ID TEMPORAL-LOBE EPILEPSY; FACIAL EMOTION RECOGNITION; AUTOBIOGRAPHICAL MEMORY; DEJA-VU; RETROGRADE-AMNESIA; BASAL GANGLIA; NEURAL BASIS; EEG-FMRI; CEREBRAL ORGANIZATION; SOCIAL COGNITION AB Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks. (C) 2015 Elsevier Inc. All rights reserved. C1 [Korczyn, Amos D.] Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel. [Schachter, Steven C.] Harvard Univ, Sch Med, Consortia Improving Med Innovat & Technol, Boston, MA 02163 USA. [Amlerova, Jana; Marusic, Petr] Charles Univ Prague, Dept Neurol, Motol Univ Hosp, Fac Med 2, Prague, Czech Republic. [Bialer, Meir] Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Inst Drug Res, Jerusalem, Israel. [Boas, Walter van Emde] Dutch Epilepsy Clin Fdn SEIM, Dept EEG, Heemstede, Netherlands. Masaryk Univ, Brno Epilepsy Ctr, St Annes Hosp, Brno, Czech Republic. [Brazdil, Milan; Rektor, Ivan] Masaryk Univ, Sch Med, Brno, Czech Republic. [Brodtkorb, Eylert] Univ Trondheim Hosp, St Olavs Hosp, Dept Neurol & Clin Neurophysiol, Trondheim, Norway. [Brodtkorb, Eylert] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Engel, Jerome, Jr.] UCLA Neurol, Los Angeles, CA USA. [Gotman, Jean] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Komarek, Vladmir] Charles Univ Prague, Dept Paediat Neurol, Fac Med 2, Motol Univ Hosp, Prague, Czech Republic. [Leppik, Ilo E.] Univ Minnesota, MINCEP Epilepsy Care, Minneapolis, MN USA. [Meletti, Stefano] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neural Sci, Modena, Italy. [Metternich, Birgitta; Schulze-Bonhage, Andreas] Univ Hosp, Epilepsy Ctr, Freiburg, Germany. [Moulin, Chris J. A.] Univ Bourgogne, Lab Study Learning & Dev, Dijon, France. [Muhlert, Nils] Cardiff Univ, Sch Psychol, Cardiff CF10 3AX, S Glam, Wales. [Muhlert, Nils] Cardiff Univ, Brain Res Imaging Ctr, Cardiff CF10 3AX, S Glam, Wales. [Mula, Marco] St George Hosp, Atkinson Morley Reg Neurosci Ctr, Epilepsy Grp, London, England. [Nakken, Karl O.] Oslo Univ Hosp, Natl Ctr Epilepsy, Oslo, Norway. [Picard, Fabienne] Univ Hosp Geneva, Dept Neurol, Geneva, Switzerland. [Picard, Fabienne] Med Sch Geneva, Geneva, Switzerland. [Theodore, William] NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Wolf, Peter] Danish Epilepsy Ctr Filadelfia, Dianalund, Denmark. [Wolf, Peter] Univ Fed Santa Catarina, Neurol Serv, Dept Clin Med, Florianopolis, SC, Brazil. [Zeman, Adam] Univ Exeter, Sch Med, Exeter, Devon, England. [Boas, Walter van Emde] Dutch Epilepsy Clin Fdn SEIN, Epilepsy Monitoring Unit, Heemstede, Netherlands. [Brazdil, Milan; Rektor, Ivan] CEITEC, Brno, Czech Republic. [Leppik, Ilo E.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [Mula, Marco] St Georges Univ London, Inst Med & Biomed Sci, London, England. RP Schachter, SC (reprint author), Harvard Univ, Sch Med, Consortia Improving Med Innovat & Technol, Boston, MA 02163 USA. EM sschacht@bidmc.harvard.edu RI Muhlert, Nils/A-7907-2013; Meletti, Stefano/O-3622-2015; Korczyn, Amos/C-3461-2017; OI Muhlert, Nils/0000-0002-6414-5589; Meletti, Stefano/0000-0003-0334-539X; Korczyn, Amos/0000-0003-0125-2579; Moulin, Chris/0000-0001-9784-4362; Mula, Marco/0000-0002-9415-3395; Fortier, Jonathan/0000-0002-6335-9614 FU project "CEITEC - Central European Institute of Technology" from European Regional Development Fund [CZ.1.05/1.1.00/02.0068] FX The study was supported by the project "CEITEC - Central European Institute of Technology" (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund. NR 159 TC 3 Z9 3 U1 1 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD SEP PY 2015 VL 50 BP 116 EP 137 DI 10.1016/j.yebeh.2015.06.044 PG 22 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CR2UN UT WOS:000361186300026 PM 26276417 ER PT J AU Mani, R Chiang, CL Frissora, FW Yan, RB Mo, XK Baskar, S Rader, C Klisovic, R Phelps, MA Chen, CS Lee, RJ Byrd, JC Baiocchi, R Lee, LJ Muthusamy, N AF Mani, Rajeswaran Chiang, Chi-Ling Frissora, Frank W. Yan, Ribai Mo, Xiaokui Baskar, Sivasubramanian Rader, Christoph Klisovic, Rebecca Phelps, Mitch A. Chen, Ching-Shih Lee, Robert J. Byrd, John C. Baiocchi, Robert Lee, L. James Muthusamy, Natarajan TI ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ROR1; ESTABLISHMENT; EXPRESSION; ANTIGEN; LINE AB Mantle-cell lymphoma (MCL) remains incurable despite numerous therapeutic advances. OSU-2S, a novel nonimmunosuppressive FTY720 (Fingolimod) derivative, exhibits potent cytotoxicity in MCL cell lines and primary cells. OSU-2S increased the surface expression of CD74, a therapeutic antibody target in MCL cells. OSU-2S, in combination with anti-CD74 antibody milatuzumab, enhanced cytotoxicity in MCL. Moreover, MCL tumor antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeted immunonanoparticle-carrying OSU-2S (2A2-OSU-2S-ILP)-mediated selective cytotoxicity of MCL in vitro, as well as activity in a xenografted mouse model of MCL in vivo. The newly developed OSU-2S delivery using ROR1-directed immunonanoparticles provide selective targeting of OSU-2S to MCL and other ROR1(+) malignancies, sparing normal B cells. Published by Elsevier Inc. on behalf of ISEH - International Society for Experimental Hematology. C1 [Mani, Rajeswaran; Chiang, Chi-Ling; Frissora, Frank W.; Klisovic, Rebecca; Byrd, John C.; Baiocchi, Robert; Muthusamy, Natarajan] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Mani, Rajeswaran; Chiang, Chi-Ling; Frissora, Frank W.; Phelps, Mitch A.; Chen, Ching-Shih; Lee, Robert J.; Byrd, John C.; Baiocchi, Robert; Muthusamy, Natarajan] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Mani, Rajeswaran; Chen, Ching-Shih; Byrd, John C.; Baiocchi, Robert; Muthusamy, Natarajan] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. [Chiang, Chi-Ling; Lee, Robert J.; Lee, L. James] Ohio State Univ, Ctr Affordable Nanoengn Polymer Biomed Devices, Columbus, OH 43210 USA. [Yan, Ribai; Chen, Ching-Shih; Byrd, John C.] Ohio State Univ, Coll Pharm, Div Med Chem, Columbus, OH 43210 USA. [Mo, Xiaokui] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Baskar, Sivasubramanian] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rader, Christoph] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Rader, Christoph] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. [Phelps, Mitch A.; Lee, Robert J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Lee, L. James] Ohio State Univ, Dept Biomol & Chem Engn, Columbus, OH 43210 USA. RP Muthusamy, N (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Hematol, Dept Internal Med Mol Virol Immunol & Med Genet &, 455E,410 West 12th Ave, Columbus, OH 43210 USA. EM raj.muthusamy@osumc.edu RI Mani, Rajeswaran/Q-2762-2015; Chiang, Chi-Ling/O-3038-2016 OI Chiang, Chi-Ling/0000-0002-0275-9673 FU Leukemia and Lymphoma Society [7004-11]; Harry Mangurian Foundation; D. Warren Brown Foundation; Robert I Anthony Leukemia Fund; National Science Foundation [NSEC EEC-0914790] FX We thank the patients who supported this research. This work was supported by The Leukemia and Lymphoma Society (grant no. 7004-11) and by grants from the Harry Mangurian Foundation, the D. Warren Brown Foundation, the Robert I Anthony Leukemia Fund, and the National Science Foundation (grant no. NSEC EEC-0914790). NR 13 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 BP 770 EP 774 DI 10.1016/j.exphem.2015.04.008 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XH UT WOS:000361417200004 PM 25937048 ER PT J AU Hoetscher, N Feuermann, Y Wingert, S Rehage, M Thalheimer, FB Bohnenberger, H Mohr, S Schroeder, T Serve, H Oellerich, T Hennighausen, L Rieger, MA AF Hoetscher, Nadine Feuermann, Yonatan Wingert, Susanne Rehage, Maike Thalheimer, Frederic B. Bohnenberger, Hanibal Mohr, Sebastian Schroeder, Timm Serve, Hubert Oellerich, Thomas Hennighausen, Lothar Rieger, Michael A. TI STAT5-REGULATED MICRORNA-193B CONTROLS HEMATOPOIETIC STEM CELL EXPANSION AND LEUICEMOGENESIS BY MODULATING CYTOKINE RECEPTOR SIGNALING SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Hoetscher, Nadine; Feuermann, Yonatan; Wingert, Susanne; Rehage, Maike; Thalheimer, Frederic B.; Mohr, Sebastian; Serve, Hubert; Oellerich, Thomas; Rieger, Michael A.] Goethe Univ Frankfurt, D-60054 Frankfurt, Main, Germany. [Bohnenberger, Hanibal] Univ Gottingen, D-37073 Gottingen, Germany. [Schroeder, Timm] Swiss Fed Inst Technol, Zurich, Switzerland. [Hennighausen, Lothar] NIH, 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3161 BP S91 EP S91 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400218 ER PT J AU Kurotaki, D Nakabayashi, J Nishiyama, A Sasaki, H Kaneko, N Koizumi, S Ozato, K Suzuki, Y Tamura, T AF Kurotaki, Daisuke Nakabayashi, Jun Nishiyama, Akira Sasaki, Haruka Kaneko, Naofumi Koizumi, Shin-ichi Ozato, Keiko Suzuki, Yutaka Tamura, Tomohiko TI ENHANCER LANDSCAPE DYNAMICS DURING MONOCYTE AND DENDRITIC CELL DEVELOPMENT AND THE ROLE OF THE TRANSCRIPTION FACTOR IRF8 SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Kurotaki, Daisuke; Nishiyama, Akira; Sasaki, Haruka; Kaneko, Naofumi; Koizumi, Shin-ichi; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan. [Ozato, Keiko] NICHD, NIH, Bethesda, MD USA. [Suzuki, Yutaka] Univ Tokyo, Grad Sch Frontier Sci, Dept Comp Biol, Tokyo, Japan. [Nakabayashi, Jun; Tamura, Tomohiko] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 232, Japan. 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3189 BP S98 EP S98 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400245 ER PT J AU Kurotaki, D Yamamoto, M Nishiyama, A Uno, K Ban, T Ichino, M Sasaki, H Matsunaga, S Yoshinari, M Ryo, A Nakazawa, M Ozato, K Tamura, T AF Kurotaki, Daisuke Yamamoto, Michio Nishiyama, Akira Uno, Kazuhiro Ban, Tatsuma Ichino, Motohide Sasaki, Haruka Matsunaga, Satoko Yoshinari, Masahiro Ryo, Akihide Nakazawa, Masatoshi Ozato, Keiko Tamura, Tomohiko TI IRF8 INHIBITS THE ACTIVITY OF C/EBP alpha TO RESTRAIN MONONUCLEAR PHAGOCYTE PROGENITORS FROM DIFFERENTIATING INTO NEUTROPHILS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Kurotaki, Daisuke; Yamamoto, Michio; Nishiyama, Akira; Uno, Kazuhiro; Ban, Tatsuma; Ichino, Motohide; Sasaki, Haruka; Yoshinari, Masahiro; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan. [Matsunaga, Satoko; Ryo, Akihide] Yokohama City Univ, Grad Sch Med, Dept Microbiol, Yokohama, Kanagawa 232, Japan. [Nakazawa, Masatoshi] Yokohama City Univ, Grad Sch Med, Dept Expt Anim Sci, Yokohama, Kanagawa 232, Japan. [Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3097 BP S75 EP S75 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400154 ER PT J AU Sasaki, H Kurotaki, D Osato, N Sato, H Sasaki, I Koizumi, S Wang, HS Kaneda, C Nishiyama, A Kaisho, T Aburatani, H Morse, HC Ozato, K Tamura, T AF Sasaki, Haruka Kurotaki, Daisuke Osato, Naoki Sato, Hideaki Sasaki, Izumi Koizumi, Shin-ichi Wang, Hongsheng Kaneda, Chika Nishiyama, Akira Kaisho, Tsuneyasu Aburatani, Hiroyuki Morse, Herbert C., III Ozato, Keiko Tamura, Tomohiko TI A ROLE OF THE TRANSCRIPTION FACTOR IRF8 IN BASOPHIL AND MAST CELL DEVELOPMENT SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH) CY SEP 17-19, 2015 CL Kyoto, JAPAN SP Int Soc Expt Hematol C1 [Sasaki, Haruka; Kurotaki, Daisuke; Sato, Hideaki; Koizumi, Shin-ichi; Kaneda, Chika; Nishiyama, Akira; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan. [Osato, Naoki; Aburatani, Hiroyuki] Univ Tokyo, Res Ctr Adv Sci & Technol, Div Genome Sci, Tokyo, Japan. [Sasaki, Izumi; Kaisho, Tsuneyasu] Osaka Univ, IFReC, Lab Immune Reg, Osaka, Japan. [Wang, Hongsheng; Morse, Herbert C., III] NIAID, NIH, Rockville, MD USA. [Ozato, Keiko] NICHD, NIH, Bethesda, MD USA. NR 0 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 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2015 VL 43 IS 9 SU 1 MA 3170 BP S93 EP S93 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CR5XJ UT WOS:000361417400227 ER PT J AU Schiffman, M Vaughan, LM Raine-Bennett, TR Castle, PE Katki, HA Gage, JC Fetterman, B Befano, B Wentzensen, N AF Schiffman, Mark Vaughan, Laurence M. Raine-Bennett, Tina R. Castle, Philip E. Katki, Hormuzd A. Gage, Julia C. Fetterman, Barbara Befano, Brian Wentzensen, Nicolas TI A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ASC-US; HPV testing; Cervical screening; Triage ID HUMAN-PAPILLOMAVIRUS; CANCER; GUIDELINES; PERFORMANCE; SPECIMENS; COHORT; TESTS; DNA AB Background. In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity (TM) (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. Methods. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0 years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3 +, 563 with CIN2, and 1187 with 100 mu M, respectively. Three-dimensional modeling suggests how these tyrosine kinase inhibitors bind and inhibit filarial protein activity. Conclusions. Given the safety of imatinib in humans, plans are underway for pilot clinical trials to assess its efficacy in patients with filarial infections. C1 [O'Connell, Elise M.; Bennuru, Sasisekhar; Steel, Cathy; Nutman, Thomas B.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. RP O'Connell, EM (reprint author), NIAID, Parasit Dis Lab, 4 Ctr Dr,Bldg 4,Rm B1-05, Bethesda, MD 20892 USA. EM oconnellem@mail.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. NR 35 TC 3 Z9 3 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 SEP 1 PY 2015 VL 212 IS 5 BP 684 EP 693 DI 10.1093/infdis/jiv065 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800003 PM 25657255 ER PT J AU Kirkpatrick, BD Durbin, AP Pierce, KK Carmolli, MP Tibery, CM Grier, PL Hynes, N Diehl, SA Elwood, D Jarvis, AP Sabundayo, BP Lyon, CE Larsson, CJ Jo, M Lovchik, JM Luke, CJ Walsh, MC Fraser, EA Subbarao, K Whitehead, SS AF Kirkpatrick, Beth D. Durbin, Anna P. Pierce, Kristen K. Carmolli, Marya P. Tibery, Cecilia M. Grier, Palmtama L. Hynes, Noreen Diehl, Sean A. Elwood, Dan Jarvis, Adrienne P. Sabundayo, Beulah P. Lyon, Caroline E. Larsson, Catherine J. Jo, Matthew Lovchik, Janece M. Luke, Catherine J. Walsh, Mary C. Fraser, Ellen A. Subbarao, Kanta Whitehead, Steven S. TI Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE dengue vaccine; live attenuated tetravalent vaccine; clinical trial ID CLINICAL-EVALUATION; CANDIDATE; VOLUNTEERS; SAFE; TRIAL; IMMUNOGENICITY; RDEN1-DELTA-30; TRANSMISSION; PHASE-1; HUMANS AB Background. The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic. C1 [Kirkpatrick, Beth D.; Pierce, Kristen K.; Carmolli, Marya P.; Diehl, Sean A.; Jarvis, Adrienne P.; Lyon, Caroline E.; Larsson, Catherine J.; Walsh, Mary C.; Fraser, Ellen A.] Univ Vermont, Coll Med, Vaccine Testing Ctr, Dept Med, Burlington, VT 05405 USA. [Durbin, Anna P.; Tibery, Cecilia M.; Grier, Palmtama L.; Hynes, Noreen; Elwood, Dan; Sabundayo, Beulah P.; Jo, Matthew; Lovchik, Janece M.] Johns Hopkins Univ, Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Luke, Catherine J.; Subbarao, Kanta; Whitehead, Steven S.] NIAID, Bethesda, MD 20892 USA. RP Kirkpatrick, BD (reprint author), Univ Vermont, Coll Med, Vaccine Testing Ctr, Dept Med, 89 Beaumont Ave, Burlington, VT 05405 USA. EM beth.kirkpatrick@uvm.edu FU National Institute of Allergy and Infectious Diseases Intramural Research Program, National Institutes of Health [HHSN272200900010C] FX This work was supported by the National Institute of Allergy and Infectious Diseases Intramural Research Program, National Institutes of Health (contract HHSN272200900010C). NR 27 TC 25 Z9 26 U1 0 U2 6 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 SEP 1 PY 2015 VL 212 IS 5 BP 702 EP 710 DI 10.1093/infdis/jiv082 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800005 PM 25801652 ER PT J AU Laeyendecker, O Redd, AD Nason, M Longosz, AF Karim, QA Naranbhai, V Garrett, N Eshleman, SH Karim, SSA Quinn, TC AF Laeyendecker, Oliver Redd, Andrew D. Nason, Martha Longosz, Andrew F. Karim, Quarraisha Abdool Naranbhai, Vivek Garrett, Nigel Eshleman, Susan H. Karim, Salim S. Abdool Quinn, Thomas C. TI Antibody Maturation in Women Who Acquire HIV Infection While Using Antiretroviral Preexposure Prophylaxis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; preexposure prophylaxis; antibody maturation; incidence assay ID ENZYME-IMMUNOASSAY; TENOFOVIR GEL; THERAPY; ASSAY; SEROCONVERSION; TRANSMISSION; PREVENTION; AVIDITY; TRIAL AB The CAPRISA 004 preexposure prophylaxis (PrEP) randomized trial demonstrated that women who used a vaginal gel containing the antiretroviral drug tenofovir (TFV) had a 39% lower risk of acquiring human immunodeficiency virus (HIV). It is not known whether topical TFV alters the antibody response to breakthrough HIV infection. In this study, antibody maturation was evaluated using 3 serologic assays: the BED capture enzyme immunoassay (CEIA), the Bio-Plex (Luminex) assay, and the Bio-Rad avidity assay. Tests were performed using serum samples collected 3, 6, 9, 12, 24, 36, 48, and >48 months after seroconversion from 95 women in the CAPRISA 004 trial (35 in the TFV gel arm and 60 in the placebo arm). For the BED CEIA and Luminex assay, linear mixed effects models were used to examine test results by study arm. Cox proportional hazard analysis was used to examine time to avidity cutoff. Anti-HIV antibody titers did not differ between study arms. Women assigned to TFV gel demonstrated slower antibody avidity maturation, as determined by the Bio-Rad (P = .04) and gp120 Bio-Plex (P = .028) assays. Women who were assigned to receive topical TFV but became infected had slower antibody avidity maturation, with potential implications for diagnosis and antibody-based incidence assays as access to antiretroviral therapy-based PrEP is increased. C1 [Laeyendecker, Oliver; Redd, Andrew D.; Longosz, Andrew F.; Quinn, Thomas C.] Johns Hopkins Univ, NIAID, Lab Immunoregulat, Div Intramural Res,NIH, Baltimore, MD 21205 USA. [Nason, Martha] Johns Hopkins Univ, NIAID, Biostat Res Branch, NIH, Baltimore, MD 21205 USA. [Laeyendecker, Oliver; Redd, Andrew D.; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. [Karim, Quarraisha Abdool; Eshleman, Susan H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Karim, Salim S. Abdool] Columbia Univ, Dept Clin Epidemiol, New York, NY USA. [Karim, Salim S. Abdool] Columbia Univ, Dept Med, New York, NY USA. [Karim, Salim S. Abdool] Ragon Inst, Boston, MA USA. [Karim, Quarraisha Abdool; Naranbhai, Vivek; Garrett, Nigel; Karim, Salim S. Abdool] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, Durban, South Africa. RP Laeyendecker, O (reprint author), Johns Hopkins Univ, Sch Med, 855 North Wolfe St,Rangos Bldg,Room 538A, Baltimore, MD 21205 USA. EM olaeyen1@jhmi.edu OI Naranbhai, Vivek/0000-0003-4281-8882; Laeyendecker, Oliver/0000-0002-6429-4760; Abdool Karim, Salim/0000-0002-4986-2133 FU NIAID, National Institutes of Health (NIH) [AI51794]; National Research Foundation [67385]; Columbia University-Southern African Fogarty AIDS International Training and Research Programme - Fogarty International Center, NIH [D43TW00231]; LifeLab, a biotechnology centre of the South African Government Department of Science and Technology; US Agency for International Development (USAID); FHI360 (USAID) [GPO-A-00-05-00022-00, 132119]; Technology Innovation Agency (LifeLab); CONRAD, Eastern Virginia Medical School (USAID) [GP00-08-00005-00, PPA-09-046]; HIV Prevention Trials Network; NIAID; National Institute on Drug Abuse; National Institute of Mental Health; Office of AIDS Research, NIH [UM1AI068613]; NIAID [R01 AI095068]; Division of Intramural Research, NIAID, NIH FX This work was supported by the NIAID, National Institutes of Health (NIH; grant AI51794); the National Research Foundation (grant 67385), the Columbia University-Southern African Fogarty AIDS International Training and Research Programme, funded by the Fogarty International Center, NIH (grant D43TW00231); and a training grant from LifeLab, a biotechnology centre of the South African Government Department of Science and Technology. The parent trial (CAPRISA 004) was supported by the US Agency for International Development (USAID), FHI360 (USAID cooperative agreement GPO-A-00-05-00022-00; contract 132119), and the Technology Innovation Agency (LifeLab). Tenofovir was provided by Gilead Sciences and the gel was manufactured and supplied for the CAPRISA 004 trial by CONRAD. The current studies are part of the CAPRISA TRAPS (Tenofovir Gel Research for AIDS Prevention Science) Program, which is funded by CONRAD, Eastern Virginia Medical School (USAID cooperative grant GP00-08-00005-00; subproject agreement PPA-09-046). The research was also supported by the HIV Prevention Trials Network, sponsored by NIAID, the National Institute on Drug Abuse, the National Institute of Mental Health, and the Office of AIDS Research, NIH (UM1AI068613); and by the NIAID (R01 AI095068). Additional support was provided in part by the Division of Intramural Research, NIAID, NIH. NR 18 TC 7 Z9 7 U1 0 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 SEP 1 PY 2015 VL 212 IS 5 BP 754 EP 759 DI 10.1093/infdis/jiv110 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800011 PM 25712973 ER PT J AU Ivers, LC Charles, RC Hilaire, IJ Mayo-Smith, LM Teng, JE Jerome, JG Rychert, J LaRocque, RC Xu, P Kovac, P Ryan, ET Qadri, F Almazor, CP Franke, MF Harris, JB AF Ivers, Louise C. Charles, Richelle C. Hilaire, Isabelle J. Mayo-Smith, Leslie M. Teng, Jessica E. Jerome, J. Gregory Rychert, Jenna LaRocque, Regina C. Xu, Peng Kovac, Pavol Ryan, Edward T. Qadri, Firdausi Almazor, Charles P. Franke, Molly F. Harris, Jason B. TI Immunogenicity of the Bivalent Oral Cholera Vaccine Shanchol in Haitian Adults With HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Cholera vaccine; HIV; Shanchol (BivWC); immunogenicity ID PNEUMOCOCCAL DISEASE; MOZAMBIQUE; CHILDREN; O1 AB We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4(+) T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera. C1 [Ivers, Louise C.; Teng, Jessica E.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Ivers, Louise C.; Franke, Molly F.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Charles, Richelle C.; LaRocque, Regina C.; Ryan, Edward T.; Harris, Jason B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ivers, Louise C.; Hilaire, Isabelle J.; Teng, Jessica E.; Jerome, J. Gregory; Almazor, Charles P.; Franke, Molly F.] Massachusetts Gen Hosp, Partners Hlth, Boston, MA 02114 USA. [Charles, Richelle C.; Mayo-Smith, Leslie M.; Rychert, Jenna; LaRocque, Regina C.; Ryan, Edward T.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Xu, Peng; Kovac, Pavol] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM jbharris@mgh.harvard.edu RI Xu, Peng/K-7036-2012 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [R01 AI099243, R01 AI106878, U01 AI AI058935, R01 AI10355]; NIH [K08 AI089721]; Massachusetts General Hospital FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; R01 AI099243 to J. B. H. and L. C. I.; R01 AI106878 to E. T. R., P. K., and F. Q.; U01 AI AI058935 to E. T. R. and F. Q.; and R01 AI10355); an NIH Career Development Award (K08 AI089721 to R. C. C.); and Massachusetts General Hospital (Massachusetts General Hospital physician scientist development award to R. C. C.). NR 12 TC 1 Z9 1 U1 1 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 SEP 1 PY 2015 VL 212 IS 5 BP 779 EP 783 DI 10.1093/infdis/jiv108 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800014 PM 25722294 ER PT J AU Wilson, EMP Hullsiek, KH Sereti, I Baker, JV AF Wilson, Eleanor M. P. Hullsiek, Katherine Huppler Sereti, Irini Baker, Jason V. TI Characterization of Immune Failure by Monocyte Activation Phenotypes in HIV-Infected Patients Receiving Antiretroviral Therapy Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Wilson, Eleanor M. P.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA. [Hullsiek, Katherine Huppler] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA. [Baker, Jason V.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Baker, Jason V.] Hennepin Cty Med Ctr, Div Infect Dis, Minneapolis, MN 55415 USA. RP Wilson, EMP (reprint author), NIAID, 9000 Rockville Pike,Bldg 10,Rm 8C-434,MSC 1756, Bethesda, MD 20892 USA. EM wilsonele@mail.nih.gov OI Wilson, Eleanor/0000-0002-4855-514X FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; NCRR NIH HHS [KL2 RR033182] NR 1 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2015 VL 212 IS 5 BP 841 EP 842 DI 10.1093/infdis/jiv165 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR4EO UT WOS:000361284800022 PM 25791115 ER PT J AU Yaniv, Y Ganesan, A Yang, DM Ziman, BD Lyashkov, AE Levchenko, A Zhang, J Lakatta, EG AF Yaniv, Yael Ganesan, Ambhighainath Yang, Dongmei Ziman, Bruce D. Lyashkov, Alexey E. Levchenko, Andre Zhang, Jin Lakatta, Edward G. TI Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells Kinetics of PKA activation in heart pacemaker cells SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Computational modeling; Coupled-clock system; Pacemaker; Phosphorylation ID DEPENDENT PROTEIN-KINASE; SINOATRIAL NODE CELLS; CARDIAC MYOCYTES; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTOR; PHOSPHORYLATION; CAMP; MECHANISMS; DOMAINS; CARDIOMYOCYTES AB cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PICA activity match the increase in AP firing rate in response to beta-adrenergic receptor (beta-AR) stimulation or phosphodiesterase (PDE) inhibition, that alters the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirus expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of beta-AR stimulation (by Isoproterenol) the magnitude of the increases in PICA activity and the spontaneous AP firing rate were similar (0.4 +/- 0.1 nM vs. 0.6 +/- 0.15 nM, respectively). Moreover, the kinetics (t(1/2)) of the increases in PICA activity and spontaneous AP firing rate in response to beta-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into a mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PICA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (beta-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca2+-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Yaniv, Yael] Technion Israel Inst Technol, Biomed Engn Fac, IL-3200003 Haifa, Israel. [Ganesan, Ambhighainath] Johns Hopkins Univ Med, Dept Biomed Engn, Baltimore, MD USA. [Yang, Dongmei; Ziman, Bruce D.; Lyashkov, Alexey E.; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Biomed Res Ctr, Intramural Res Program,NIA, Baltimore, MD 21224 USA. [Levchenko, Andre] Yale Univ, Syst Biol Inst, New Haven, CT USA. [Zhang, Jin] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Zhang, Jin] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Zhang, Jin] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Yaniv, Y (reprint author), Technion Israel Inst Technol, Biomed Engn Fac, IL-3200003 Haifa, Israel. EM yaely@bm.technion.ac.il; lakattae@grc.nia.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health, Public Health Service [NIH R01-DK073368, GM07024]; AHA Predoctoral Fellowship; Technion V.P.R. Fund-Mallat Family Research Fund; Technion E.V.P.R. Fund-Elias Fund for Medical research; NSFC-ISF [398/14] FX The work was supported partially by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Public Health Service Grants NIH R01-DK073368 (J.Z., A.L.) and GM07024 (A.L.), AHA Predoctoral Fellowship (A.G.) as well as Technion V.P.R. Fund-Mallat Family Research Fund, Technion E.V.P.R. Fund-Elias Fund for Medical research, and by the NSFC-ISF joint research program, no. 398/14 (Y.Y.). NR 40 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2015 VL 86 BP 168 EP 178 DI 10.1016/j.yjmcc.2015.07.024 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CR5YA UT WOS:000361419100020 PM 26241846 ER PT J AU Payne, TH Corley, S Cullen, TA Gandhi, TK Harrington, L Kuperman, GJ Mattison, JE McCallie, DP McDonald, CJ Tang, PC Tierney, WM Weaver, C Weir, CR Zaroukian, MH AF Payne, Thomas H. Corley, Sarah Cullen, Theresa A. Gandhi, Tejal K. Harrington, Linda Kuperman, Gilad J. Mattison, John E. McCallie, David P. McDonald, Clement J. Tang, Paul C. Tierney, William M. Weaver, Charlotte Weir, Charlene R. Zaroukian, Michael H. TI Report of the AMIA EHR-2020 Task Force on the status and future direction of EHRs SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ELECTRONIC HEALTH RECORD; CLINICAL DECISION-SUPPORT; PROVIDER ORDER ENTRY; QUALITY-OF-CARE; PATIENT SAFETY; MEDICATION RECONCILIATION; INFORMATION-TECHNOLOGY; HOSPITAL DISCHARGE; AMBULATORY-CARE; SYSTEMS C1 [Payne, Thomas H.] Univ Washington, UW Med Informat Technol Serv, Dept Med, Seattle, WA 98195 USA. [Corley, Sarah] NextGen Healthcare, Mclean, VA USA. [Cullen, Theresa A.] Vet Hlth Adm, Washington, DC USA. [Gandhi, Tejal K.] Natl Patient Safety Fdn, Boston, MA USA. [Kuperman, Gilad J.] New York Presbyterian Hosp, New York, NY USA. [Mattison, John E.] Kaiser Permanente, Pasadena, CA USA. [McCallie, David P.] Cerner Corp, Kansas City, MO USA. [McDonald, Clement J.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Tang, Paul C.] Palo Alto Med Fdn, Palo Alto, CA USA. [Tierney, William M.] Indiana Univ Sch Med, Regenstrief Inst Inc, Indianapolis, IN 46202 USA. [Weir, Charlene R.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Zaroukian, Michael H.] Sparrow Hlth Syst, Lansing, MI USA. [Zaroukian, Michael H.] Michigan State Univ, Dept Med, Coll Human Med, E Lansing, MI 48824 USA. RP Payne, TH (reprint author), UW Med Informat Technol Serv, Box 359968,325 Ninth Ave, Seattle, WA 98104 USA. EM tpayne@u.washington.edu NR 89 TC 14 Z9 14 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2015 VL 22 IS 5 BP 1102 EP 1110 DI 10.1093/jamia/ocv066 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CR4DS UT WOS:000361282600021 PM 26024883 ER PT J AU Johnson, RA Wendler, D AF Johnson, Rebecca A. Wendler, David TI Challenging the Sanctity of Donorism: Patient Tissue Providers as Payment-Worthy Contributors SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID STORED BIOLOGICAL SAMPLES; RESEARCH PARTICIPANTS; GENETICS RESEARCH; BIOBANKS; CONSENT; CANCER; MONEY; WANT AB Many research projects rely on human biological materials and some of these projects generate revenue. Recently, it has been argued that investigators have a moral claim to share in the revenue generated by these projects, whereas persons who provide the biological material have no such claim (Truog, Kesselheim, and Joffe 2012). In this paper, we critically analyze this view and offer a positive proposal for why tissue providers have a moral claim to benefit. Focusing on payment as a form of benefit, we argue that research is a joint project and propose a contribution principle for paying participants in those joint projects. We distinguish between contributions that shape a project's revenue generating properties, grounding a claim to payment, and contributions that fail to ground such a claim. We conclude, contrary to existing arguments and practices, that some tissue providers have a moral claim to payment beyond compensation for risk and burden. This conclusion suggests that investigators, institutions, and sponsors should reconsider the fairness of their current practices. C1 [Johnson, Rebecca A.] NIH, Dept Bioeth, Bethesda, MD USA. [Wendler, David] NIH, Sect Res Eth, Dept Bioeth, Clin Ctr, Bethesda, MD USA. NR 55 TC 1 Z9 1 U1 0 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 EI 1086-3249 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD SEP PY 2015 VL 25 IS 3 BP 291 EP 333 PG 43 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA CR5WE UT WOS:000361414300004 PM 26412739 ER PT J AU Bishop, LR Lionakis, MS Sassi, M Murphy, PM Hu, XJ Huang, DW Sherman, B Qiu, J Yang, J Lempicki, RA Kovacs, JA AF Bishop, Lisa R. Lionakis, Michail S. Sassi, Monica Murphy, Philip M. Hu, Xiaojun Huang, Da Wei Sherman, Brad Qiu, Ju Yang, Jun Lempicki, Richard A. Kovacs, Joseph A. TI Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice SO MICROBES AND INFECTION LA English DT Article DE Pneumocystis; PCP; Chemokines; Chemokine receptor; Knock-out mice ID ALVEOLAR EPITHELIAL-CELLS; LARGE GENE LISTS; CARINII-PNEUMONIA; VIRUS-INFECTION; LUNG TISSUES; RESPONSES; MURINA; INTERFERON; IMMUNITY; MONOCYTE AB We examined gene expression levels of multiple chemokines and chemokine receptors during Pneumocystis murina infection in wild-type and immunosuppressed mice, using microarrays and qPCR. In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, Cxcr6, and Cxcr2 increased at days 32-41 post-infection, with a return to baseline by day 75-150. Concomitant increases were seen in Ccr2, Cxcr3, and Cxcr6, but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2, Cxcr3, and Cxcr6 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [Bishop, Lisa R.; Sassi, Monica; Kovacs, Joseph A.] Natl Inst Hlth, Dept Crit Care Med, NIH Clin Ctr, Bethesda, MD 20892 USA. [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. [Murphy, Philip M.] NIAID, Lab Mol Immunol, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hu, Xiaojun; Huang, Da Wei; Sherman, Brad; Qiu, Ju; Yang, Jun; Lempicki, Richard A.] Leidos Biomed Res Inc, Lab Immunopathogenesis & Bioinformat, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Kovacs, JA (reprint author), Bldg 10,Room 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@mail.nih.gov RI Leidos, LHRI/C-2876-2017 FU Intramural Research Programs of the NIH Clinical Center; National Cancer Institute, National Institutes of Health; National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN261200800001E] FX This research was supported in part by the Intramural Research Programs of the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases, National Institutes of Health. This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health, and the National Institute of Allergy and Infectious Diseases, National Institutes of Health under Contract No. HHSN261200800001E. NR 46 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD SEP PY 2015 VL 17 IS 9 BP 638 EP 650 DI 10.1016/j.micinf.2015.05.008 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CR3WT UT WOS:000361264500005 PM 26052064 ER PT J AU Strauss, KA Ferreira, C Bottiglieri, T Zhao, X Arning, E Zhang, S Zeisel, SH Escolar, ML Presnick, N Puffenberger, EG Vugrek, O Kovacevic, L Wagner, C Mazariegos, GV Mudd, SH Soltys, K AF Strauss, Kevin A. Ferreira, Carlos Bottiglieri, Teodoro Zhao, Xueqing Arning, Erland Zhang, Shucha Zeisel, Steven H. Escolar, Maria L. Presnick, Nancy Puffenberger, Erik G. Vugrek, Oliver Kovacevic, Lucija Wagner, Conrad Mazariegos, George V. Mudd, S. Harvey Soltys, Kyle TI Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Transsulfuration; Methyltransferases; S-adenosylhomocysteine; Liver transplantation ID SYRUP-URINE-DISEASE; METHIONINE METABOLISM; PLASMA HOMOCYSTEINE; MASS-SPECTROMETRY; BRAIN METHIONINE; ADENOSYLMETHIONINE; METHYLATION; TISSUES; UREMIA; METHYLTRANSFERASES AB A child with severe S-adenosylhomocysteine hydrolase (AHCY) deficiency (AHCY c.428A > G, p.Tyr143Cys; c.982 T > G, p.Tyr328Asp) presented at 8 months of age with growth failure, microcephaly, global developmental delay, myopathy, hepatopathy, and factor VII deficiency. Plasma methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) were markedly elevated and the molar concentration ratio of AdoMet:AdoHcy, believed to regulate a myriad of methyltransferase reactions, was 15% of the control mean. Dietary therapy failed to normalize biochemical markers or alter the AdoMet to AdoHcy molar concentration ratio. At 40 months of age, the proband received a liver segment from a healthy, unrelated living donor. Mean AdoHcy decreased 96% and the AdoMet:AdoHcy concentration ratio improved from 0.52 +/- 0.19 to 1.48 +/- 0.79 mol:mol (control 4.10 +/- 2.11 mol:mol). Blood methionine and AdoMet were normal and stable during 6 months of follow-up on an unrestricted diet. Average calculated tissue methyltransferase activity increased from 43 +/- 26% to 60 +/- 22%, accompanied by signs of increased transmethylation in vivo. Factor VII activity increased from 12% to 100%. During 6 postoperative months, head growth accelerated 4-fold and the patient made promising gains in gross motor, language, and social skills. (C) 2015 Elsevier Inc. All rights reserved. C1 [Strauss, Kevin A.; Presnick, Nancy; Puffenberger, Erik G.] Clin Special Children, Strasburg, PA 17579 USA. [Strauss, Kevin A.; Puffenberger, Erik G.] Franklin & Marshall Coll, Lancaster, PA 17604 USA. [Strauss, Kevin A.] Lancaster Gen Hosp, Lancaster, PA USA. [Ferreira, Carlos] NHGRI, NIH, Bethesda, MD 20892 USA. [Bottiglieri, Teodoro] Baylor Res Inst, Inst Metab Dis, Ctr Metabol, Dallas, TX USA. [Zhao, Xueqing; Zhang, Shucha; Zeisel, Steven H.] Univ North Carolina Chapel Hill, Inst Nutr Res, Kannapolis, NC USA. [Escolar, Maria L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Program Study Neurodev Rare Disorders, Pittsburgh, PA 15213 USA. [Escolar, Maria L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Ctr Rare Dis Therapy, Pittsburgh, PA 15213 USA. [Vugrek, Oliver; Kovacevic, Lucija] Rudjer Boskovic Inst, Translat Med Grp, Zagreb, Croatia. [Wagner, Conrad] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. [Mazariegos, George V.; Soltys, Kyle] UPMC, Childrens Hosp Pittsburgh, Hillman Ctr Pediat Transplantat, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. [Mazariegos, George V.; Soltys, Kyle] UPMC, Childrens Hosp Pittsburgh, Ctr Rare Dis Therapy, Pittsburgh, PA USA. [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Strauss, KA (reprint author), Clin Special Children, 535 Bunker Hill Rd, Strasburg, PA 17579 USA. EM kstrauss@clinicforspecialchildren.org RI Escolar, Maria/J-3721-2016 FU European Union [316289-InnoMol]; Amish and Mennonite communities of the Northeastern United States FX Research at the Clinic for Special Children is supported in part by charitable donations from Amish and Mennonite communities of the Northeastern United States. Dr. Vugrek was supported by funds received from the European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration under grant agreement No. 316289-InnoMol, FP7-REGPOT-2012-2013-1. NR 42 TC 3 Z9 3 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2015 VL 116 IS 1-2 SI SI BP 44 EP 52 DI 10.1016/j.ymgme.2015.06.005 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CR5ZT UT WOS:000361423600007 PM 26095522 ER PT J AU Maarup, TJ Chen, AH Porter, FD Farhat, NY Ory, DS Sidhu, R Jiang, XN Dickson, PI AF Maarup, Timothy J. Chen, Agnes H. Porter, Forbes D. Farhat, Nicole Y. Ory, Daniel S. Sidhu, Rohini Jiang, Xuntian Dickson, Patricia I. TI Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann Pick C1 SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Niemann Pick C; Cyclodextrin; Therapeutic; Ototoxicity ID DISEASE TYPE-C; CYCLODEXTRIN OVERCOMES; LUNG TOXICITY; HUMAN PLASMA; CHOLESTEROL; QUANTIFICATION; PROGRESSION; TRANSPORT; MIGLUSTAT; INFUSION AB Niemann-Pick C, type 1 (NPC1) is a progressive autosomal recessive neurologic disease caused by defective intracellular cholesterol and lipid trafficking. There are currently no United States Food and Drug Administration approved treatments for NPC1. We undertook a study evaluating the safety, efficacy, and biomarker response of intrathecal 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200 mg intrathecal HP-beta-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-beta-CD injections. Intrathecal HP-beta-CD has been generally safe and well tolerated in this subject. There has been an improvement in vertical gaze. The subject has developed subclinical hearing loss at high frequency that is likely HP-beta-CD related. Plasma 24-(S)-hydroxycholesterol, a pharmacodynamic biomarker for cholesterol redistribution in the central nervous system, was significantly increased in response to each of the first 5 drug administrations. Further dosing as well as dose escalations are needed to more completely ascertain the safety and efficacy of intrathecal HP-beta-CD. (C) 2015 Elsevier Inc. All rights reserved. C1 [Maarup, Timothy J.; Dickson, Patricia I.] Harbor UCLA Med Ctr, Dept Pediat, Div Med Genet, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Chen, Agnes H.] Harbor UCLA Med Ctr, Dept Pediat, Div Neurol, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Porter, Forbes D.; Farhat, Nicole Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, DHHS, Bethesda, MD USA. [Ory, Daniel S.; Sidhu, Rohini; Jiang, Xuntian] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO USA. RP Maarup, TJ (reprint author), Child Hlth Res Ctr, 1124 W Carson St,Box 465, Torrance, CA 90502 USA. EM tmaarup@labiomed.org RI Sidhu, Rohini/G-3547-2012 FU National Center for Advancing Translational Sciences through UCLA CTSI Grant [UL1TR000124] FX The project described was supported by the National Center for Advancing Translational Sciences through UCLA CTSI Grant UL1TR000124. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 27 TC 9 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2015 VL 116 IS 1-2 SI SI BP 75 EP 79 DI 10.1016/j.ymgme.2015.07.001 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CR5ZT UT WOS:000361423600011 PM 26189084 ER PT J AU Yao, YG Kajigaya, S Young, NS AF Yao, Yong-Gang Kajigaya, Sachiko Young, Neal S. TI Mitochondrial DNA mutations in single human blood cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE mtDNA; Single cell analysis; Mutation; Hematopoietic stem cells ID SUBSTANTIA-NIGRA NEURONS; MTDNA CONTROL REGION; STEM-CELLS; SEQUENCE HETEROGENEITY; POINT MUTATIONS; CD34(+) CELLS; ANCIENT DNA; CLONAL EXPANSION; INDIVIDUAL CELLS; BONE-MARROW AB Determination mitochondrial DNA (mtDNA) sequences from extremely small amounts of DNA extracted from tissue of limited amounts and/or degraded samples is frequently employed in medical, forensic, and anthropologic studies. Polymerase chain reaction (PCR) amplification followed by DNA cloning is a routine method, especially to examine heteroplasmy of mtDNA mutations. In this review, we compare the mtDNA mutation patterns detected by three different sequencing strategies. Cloning and sequencing methods that are based on PCR amplification of DNA extracted from either single cells or pooled cells yield a high frequency of mutations, partly due to the artifacts introduced by PCR and/or the DNA cloning process. Direct sequencing of PCR product which has been amplified from DNA in individual cells is able to detect the low levels of mtDNA mutations present within a cell. We further summarize the findings in our recent studies that utilized this single cell method to assay mtDNA mutation patterns in different human blood cells. Our data show that many somatic mutations observed in the end-stage differentiated cells are found in hematopoietic stem cells (HSCs) and progenitors within the CD34(+) cell compartment. Accumulation of mtDNA variations in the individual CD34(+) cells is affected by both aging and family genetic background. Granulocytes harbor higher numbers of mutations compared with the other cells, such as CD34(+) cells and lymphocytes. Serial assessment of mtDNA mutations in a population of single CD34(+) cells obtained from the same donor over time suggests stability of some somatic mutations. CD34(+) cell clones from a donor marked by specific mtDNA somatic mutations can be found in the recipient after transplantation. The significance of these findings is discussed in terms of the lineage tracing of HSCs, aging effect on accumulation of mtDNA mutations and the usage of mtDNA sequence in forensic identification. (C) 2015 Elsevier B.V. All rights reserved. C1 [Yao, Yong-Gang] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China. [Yao, Yong-Gang] Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China. [Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Yao, YG (reprint author), Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China. EM yaoyg@mail.kiz.ac.cn FU MOST of China [2011CB910902]; National Natural Science Foundation of China [31171225, 30925021] FX We thank the two anonymous reviewers for their critical comments on the early version of the manuscript. Y.-G.Y. was supported by the MOST of China (2011CB910902) and the National Natural Science Foundation of China (31171225 and 30925021). NR 82 TC 3 Z9 3 U1 7 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP PY 2015 VL 779 BP 68 EP 77 DI 10.1016/j.mrfmmm.2015.06.009 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA CR3RT UT WOS:000361251500007 PM 26149767 ER PT J AU Mehta, R Ying, GS Houston, S Isakova, T Nessel, L Ojo, A Go, A Lash, J Kusek, J Grunwald, J Wolf, M Invest, CS AF Mehta, Rupal Ying, Gui Shuang Houston, Samuel Isakova, Tamara Nessel, Lisa Ojo, Akinlolu Go, Alan Lash, Jim Kusek, John Grunwald, Juan Wolf, Myles Invest, C. R. I. C. Study TI Phosphate, fibroblast growth factor 23 and retinopathy in chronic kidney disease: the Chronic Renal Insufficiency Cohort Study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE CKD; FGF-23; phosphate; retinopathy; vascular disease ID RETINAL MICROVASCULAR ABNORMALITIES; LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; SERUM PHOSPHORUS; ARTERIAL CALCIFICATION; ATHEROSCLEROSIS RISK; DIABETIC-RETINOPATHY; HEART-FAILURE; ALL-CAUSE; MORTALITY AB Elevated circulating concentrations of phosphate and fibroblast growth factor 23 (FGF23) contribute to the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Retinopathy is a common manifestation of microvascular disease in CKD, but its associations with phosphate and FGF23 have not been studied. We tested the hypothesis that higher serum phosphate is associated with more severe retinopathy in individuals with CKD, independent of FGF23 and known risk factors for retinopathy. We tested the associations of serum phosphate and plasma FGF23 with retinopathy in a cross-sectional analysis of 1800 participants in the Chronic Renal Insufficiency Cohort Study who underwent fundus photography. Retinopathy severity was graded according to the Early Treatment of Diabetic Retinopathy Severity score, and retinal venous and arterial diameters were measured. Mean estimated glomerular filtration rate (eGFR) was 46.5 +/- 15.4 mL/min/1.73 m(2), mean serum phosphate was 3.7 +/- 0.6 mg/dl and median plasma C-terminal FGF23 was 133 RU/mL (interquartile range 87.2, 217.8 RU/mL). In multivariable ordinal logistic regression models, higher serum phosphate was associated with greater retinopathy severity independent of hypertension, diabetes, CKD severity and FGF23 [adjusted odds ratio of being in one higher category of retinopathy severity: 1.19 per 1 standard deviation increase; 95% confidence interval (CI) 1.05, 1.36; P = 0.007]. Presence of diabetes or hypertension did not modify the results. Higher serum phosphate was also independently associated with greater retinal venous diameter (multivariable-adjusted 1.70 A mu m increase per 1 standard deviation increase in phosphate; 95% CI 0.46, 2.93; P = 0.007). FGF23 levels were not independently associated with retinopathy severity or retinal venous diameter, and neither FGF23 nor phosphate was associated with retinal arterial diameter. Among individuals with moderate-to-severe CKD, higher serum phosphate but not FGF23 was independently associated with more severe retinopathy and microvascular retinal venous dilatation. C1 [Mehta, Rupal; Isakova, Tamara; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Nephrol & Hypertens, Chicago, IL 60611 USA. [Mehta, Rupal; Isakova, Tamara; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Ctr Translat Metab & Hlth, Chicago, IL 60611 USA. [Ying, Gui Shuang; Nessel, Lisa; Grunwald, Juan] Univ Penn, Philadelphia, PA 19104 USA. [Houston, Samuel] Wills Eye Hosp & Res Inst, Philadelphia, PA USA. [Ojo, Akinlolu] Univ Michigan, Ann Arbor, MI 48109 USA. [Go, Alan] Kaiser Permanente, Oakland, CA USA. [Lash, Jim] Univ Illinois, Chicago, IL USA. [Kusek, John] NIDDK, Bethesda, MD 20892 USA. RP Mehta, R (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, Div Nephrol & Hypertens, Chicago, IL 60611 USA. EM rupal.mehta@northwestern.edu FU NCATS NIH HHS [UL1 TR000424, UL1 TR000433, UL1 TR000439, UL1 TR000003, UL1TR-000424, UL1TR000003, UL1TR000439, UL1TR000433]; NCRR NIH HHS [M01 RR-16500, UL1 RR024131, UL1 RR029879, UL1RR029879, UL1 RR-024131, M01 RR016500]; NIDDK NIH HHS [U01DK061021, U01DK060990, U01DK060963, U01 DK061021, U01 DK060990, U01 DK060963, R01DK081374, R01 DK081374, K23 DK087858, DK074151, K23 DK081673, K23DK081673, K24 DK093723, K24DK093723, R01 DK074151, U01 DK060902, U01 DK060980, U01 DK060984, U01 DK061022, U01 DK061028, U01DK060902, U01DK060980, U01DK060984, U01DK061022, U01DK061028]; NIGMS NIH HHS [P30 GM103337, P30GM103337] NR 51 TC 2 Z9 2 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 2015 VL 30 IS 9 BP 1534 EP 1541 DI 10.1093/ndt/gfv123 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA CR4LL UT WOS:000361303800020 PM 25910495 ER PT J AU Ellingson, BM Bendszus, M Boxerman, J Barboriak, D Erickson, BJ Smits, M Nelson, SJ Gerstner, E Alexander, B Goldmacher, G Wick, W Vogelbaum, M Weller, M Galanis, E Kalpathy-Cramer, J Shankar, L Jacobs, P Pope, WB Yang, DW Chung, C Knopp, MV Cha, S van den Bent, MJ Chang, S Al Yung, WK Cloughesy, TF Wen, PY Gilbert, MR AF Ellingson, Benjamin M. Bendszus, Martin Boxerman, Jerrold Barboriak, Daniel Erickson, Bradley J. Smits, Marion Nelson, Sarah J. Gerstner, Elizabeth Alexander, Brian Goldmacher, Gregory Wick, Wolfgang Vogelbaum, Michael Weller, Michael Galanis, Evanthia Kalpathy-Cramer, Jayashree Shankar, Lalitha Jacobs, Paula Pope, Whitney B. Yang, Dewen Chung, Caroline Knopp, Michael V. Cha, Soonme van den Bent, Martin J. Chang, Susan Al Yung, W. K. Cloughesy, Timothy F. Wen, Patrick Y. Gilbert, Mark R. CA Jumpstarting Brain Tumor Drug Dev TI Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials SO NEURO-ONCOLOGY LA English DT Review DE Brain Tumor Imaging Protocol; clinical trials; glioblastoma; MRI ID NEWLY-DIAGNOSED GLIOBLASTOMA; NUCLEAR MAGNETIC-RESONANCE; RANDOMIZED PHASE-III; HIGH-GRADE GLIOMAS; MP-RAGE; RESPONSE ASSESSMENT; INTEROBSERVER VARIABILITY; GADODIAMIDE INJECTION; ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMAS AB A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems. C1 [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Neuro Oncol Program, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Tumor Imaging Lab, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Pope, Whitney B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Bendszus, Martin] Univ Heidelberg Hosp, Dept Neuroradiol, Heidelberg, Germany. [Boxerman, Jerrold] Brown Univ, Warrne Alpert Med Sch, Dept Diagnost Imaging, Providence, RI 02912 USA. [Barboriak, Daniel] Duke Univ, Sch Med, Dept Neuroradiol, Durham, NC USA. [Erickson, Bradley J.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Smits, Marion] Erasmus MC Univ, Dept Radiol, Rotterdam, Netherlands. [Nelson, Sarah J.; Cha, Soonme] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Gerstner, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Alexander, Brian; Wen, Patrick Y.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Goldmacher, Gregory; Wick, Wolfgang] ICON Med Imaging, Med & Sci Affairs, Warrington, PA USA. [Wick, Wolfgang] Univ Clin Heidelberg, Dept Neurooncol, Natl Ctr Tumor Dis, Heidelberg, Germany. [Vogelbaum, Michael] Cleveland Clin, Dept Neurol Surg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Galanis, Evanthia] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [Shankar, Lalitha; Jacobs, Paula] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Chung, Caroline] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Chung, Caroline] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Knopp, Michael V.] Ohio State Univ, Wright Ctr Innovat Biomed Imaging, Div Imaging Sci, Wexner Med Ctr, Columbus, OH 43210 USA. [van den Bent, Martin J.] Erasmus MC Canc Inst, Dept Neurooncol, Rotterdam, Netherlands. [Cha, Soonme; Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Al Yung, W. K.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Neurooncol, Houston, TX 77030 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Gilbert, Mark R.] NCI, Neurooncol Branch, Bethesda, MD USA. [Ellingson, Benjamin M.; Gerstner, Elizabeth; Wen, Patrick Y.] ABTC, Baltimore, MD USA. [Ellingson, Benjamin M.; Nelson, Sarah J.] Ivy Consortium Early Phase Clin Trials, Garden City, NY USA. [Ellingson, Benjamin M.; Boxerman, Jerrold; Barboriak, Daniel] ACRIN, Philadelphia, PA USA. [Bendszus, Martin; Smits, Marion; Wick, Wolfgang; van den Bent, Martin J.] EORTC, Brussels, Belgium. [Erickson, Bradley J.; Gerstner, Elizabeth] Alliance Clin Trials Oncol, Duarte, CA USA. [Ellingson, Benjamin M.; Barboriak, Daniel; Erickson, Bradley J.; Goldmacher, Gregory; Knopp, Michael V.] RSNA Quantitat Imaging Biomarker Alliance QIBA, Arlington, VA USA. [Ellingson, Benjamin M.; Boxerman, Jerrold; Barboriak, Daniel; Erickson, Bradley J.; Pope, Whitney B.] Amer Soc Neuroradiol ASNR, Oak Brook, IL USA. [Boxerman, Jerrold] Amer Soc Funct Neuroradiol ASFNR, Austin, TX USA. [Vogelbaum, Michael; Gilbert, Mark R.] RTOG, Atlanta, GA USA. RP Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Radiol Sci, 924 Westwood Blvd,Suite 650, Los Angeles, CA 90095 USA. EM bellingson@mednet.ucla.edu RI Gilbert, Mark/J-7494-2016; Smits, Marion/E-4795-2011; OI Gilbert, Mark/0000-0003-2556-9722; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU Roche/Genentech Research Grant; Siemens Healthcare Research Grant; National Brain Tumor Society Research Grant FX Roche/Genentech Research Grant (B.M.E.), Siemens Healthcare Research Grant (B.M.E.), National Brain Tumor Society Research Grant (B.M.E.). NR 62 TC 31 Z9 31 U1 3 U2 11 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 SEP PY 2015 VL 17 IS 9 BP 1188 EP 1198 DI 10.1093/neuonc/nov095 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MH UT WOS:000361306400004 PM 26250565 ER PT J AU Miller, LR Miller, FG AF Miller, Lisa R. Miller, Franklin G. TI Understanding placebo effects: Implications for nursing practice SO NURSING OUTLOOK LA English DT Article DE Placebo; Nursing; Clinician-patient relationship ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; EXPECTATIONS; ACUPUNCTURE AB Placebo effects permeate many aspects of the clinical environment. However, little attention has been devoted, to placebo effects in the nursing literature. Recent research shows that the promotion of placebo responses can enhance certain pat-lent outcomes. Nurses are situated in an ideal position to take on this task. This article suggests ways for nurses to ethically promote placebo responses in daily practice. C1 [Miller, Lisa R.] LAC USC Med Ctr, Dept Emergency Med, Los Angeles, CA USA. [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 36 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 2015 VL 63 IS 5 BP 601 EP 606 DI 10.1016/j.outlook.2015.03.002 PG 6 WC Nursing SC Nursing GA CR3YH UT WOS:000361268500008 PM 26211845 ER PT J AU Williams, JK Cashion, AK AF Williams, Janet K. Cashion, Ann K. TI Using clinical genomics in health care: Strategies to create a prepared workforce SO NURSING OUTLOOK LA English DT Article DE Genomics; Nursing; Education ID EDUCATION C1 [Williams, Janet K.] Univ Iowa, Iowa City, IA 52242 USA. [Cashion, Ann K.] NINR, NIH, Bethesda, MD 20892 USA. RP Williams, JK (reprint author), Univ Iowa, 50 Newton Rd, Iowa City, IA 52242 USA. EM janet-williams@uiowa.edu NR 15 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 2015 VL 63 IS 5 BP 607 EP 609 DI 10.1016/j.outlook.2015.04.001 PG 3 WC Nursing SC Nursing GA CR3YH UT WOS:000361268500009 PM 26211844 ER PT J AU Girardi, T Salafia, C Shah, R Merz, G Misra, D Miller, R Katzmann, P Moye, J AF Girardi, Theresa Salafia, Carolyn Shah, Ruchit Merz, George Misra, Dawn Miller, Richard Katzmann, Philip Moye, John TI ANGLES IN NORMAL PLACENTAL CHORIONIC SURFACE VESSEL NETWORKS FOLLOW HYDRODYNAMIC BIFURCATION RULES SO PLACENTA LA English DT Meeting Abstract C1 [Girardi, Theresa; Salafia, Carolyn; Shah, Ruchit] Placental Analyt, Larchmont, NY USA. [Girardi, Theresa; Salafia, Carolyn; Merz, George] New York State Off Mental Retardat & Dev Disabil, Inst Basic Res, Placental Modulat, Staten Isl, NY USA. [Misra, Dawn] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Miller, Richard; Katzmann, Philip] Univ Rochester, Sch Med, Obstet & Gynecol & Pathol, Rochester, NY USA. [Miller, Richard; Katzmann, Philip; Moye, John] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD SEP PY 2015 VL 36 IS 9 MA P1.59 BP A30 EP A31 PG 2 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CR3UV UT WOS:000361259500105 ER PT J AU Masoumi, Z Familari, M Magnusson, M Mezey, E Hansson, S AF Masoumi, Zahra Familari, Mary Magnusson, Mattias Mezey, Eva Hansson, Stefan TI CHARACTERIZING THE HEMATOPOIETIC STEM/PROGENITOR CELLS IN THE PLACENTA AND UMBILICAL CORD BLOOD FROM NORMAL AND PREECLAMPTIC SUBJECTS SO PLACENTA LA English DT Meeting Abstract C1 [Masoumi, Zahra; Hansson, Stefan] Lund Univ, Univ Lund Hosp, Dept Clin Sci, Div Obstet & Gynecol, Lund, Sweden. [Familari, Mary] Univ Melbourne, Dept Zool, Melbourne, Vic, Australia. [Magnusson, Mattias] Lund Univ, Lund Stem Cell Ctr, Mol Med & Gene Therapy, Lund, Sweden. [Mezey, Eva] NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD SEP PY 2015 VL 36 IS 9 MA P2.65 BP A57 EP A57 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CR3UV UT WOS:000361259500189 ER PT J AU Salafia, C Girardi, T Schwartz, N Shah, R Merz, G Misra, D Miller, R Katzmann, P Moye, J AF Salafia, Carolyn Girardi, Theresa Schwartz, Nadav Shah, Ruchit Merz, George Misra, Dawn Miller, Richard Katzmann, Philip Moye, John TI TERM PCSVN FEATURES ARE PREDICTED BY ULTRASOUND MEASURES AT 11-14 WEEKS SO PLACENTA LA English DT Meeting Abstract C1 [Salafia, Carolyn; Girardi, Theresa; Shah, Ruchit] Placental Analyt, Larchmont, NY USA. [Salafia, Carolyn; Girardi, Theresa; Merz, George] New York State Off Mental Retardat & Dev Disabil, Inst Basic Res, Placental Modulat, Staten Isl, NY USA. [Schwartz, Nadav] Hosp Univ Penn, Div Maternal Fetal Med, Philadelphia, PA 19104 USA. [Misra, Dawn] WayneState Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Miller, Richard; Katzmann, Philip; Moye, John] Univ Rochester, Sch Med, Obstet & Gynecol & Pathol, Rochester, NY USA. [Miller, Richard; Katzmann, Philip] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD SEP PY 2015 VL 36 IS 9 MA P1.02 BP A11 EP A12 PG 2 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CR3UV UT WOS:000361259500049 ER PT J AU Shah, R Salafia, C Girardi, T Merz, G Misra, D Newschaffer, C Miller, R Moye, J AF Shah, Ruchit Salafia, Carolyn Girardi, Theresa Merz, George Misra, Dawn Newschaffer, Craig Miller, Richard Moye, John TI CHORIONIC SURFACE VASCULAR NETWORKS (CSVN) IN HIGH AND LOW ASD RISK PLACENTAS: CALIBER, VESSEL COUNT AND MURRAY'S LAW SO PLACENTA LA English DT Meeting Abstract C1 [Salafia, Carolyn; Girardi, Theresa; Merz, George] New York State Off Mental Retardat & Dev Disabil, Inst Basic Res, Placental Modulat, Staten Isl, NY USA. [Shah, Ruchit; Salafia, Carolyn; Girardi, Theresa] Placental Analyt, Larchmont, NY USA. [Misra, Dawn] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Newschaffer, Craig] Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. [Miller, Richard] Univ Rochester, Sch Med, Obstet & Gynecol & Pathol, Rochester, NY USA. [Miller, Richard; Moye, John] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD SEP PY 2015 VL 36 IS 9 MA P1.08 BP A14 EP A14 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CR3UV UT WOS:000361259500055 ER PT J AU Salem, NM Lin, YH Moriguchi, T Lim, SY Salem, N Hibbeln, JR AF Salem, N. M. Lin, Y. H. Moriguchi, T. Lim, S. Y. Salem, N., Jr. Hibbeln, J. R. TI Distribution of omega-6 and omega-3 polyunsaturated fatty acids in the whole rat body and 25 compartments SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Alpha-linolenic acid; Linoleic acid; Docosahaexenoic acid; Arachidonic acid; n-3; n-6 ID ALPHA-LINOLENIC-ACID; DOCOSAHEXAENOIC ACID; LIPID-COMPOSITION; ARACHIDONIC-ACID; BRAIN; METABOLISM; DIET; DEFICIENCY; LIVER AB The steady state compositions of omega-6 and omega-3 polyunsaturated fatty acids (PUFA) throughout the various viscera and tissues within the whole body of rats have not previously been described in a comprehensive manner. Dams consumed diets containing 10 wt% fat (15% linoleate and 3% alpha-linolenate). Male offspring (n=9) at 7-week of age were euthanized and dissected into 25 compartments. Total lipid fatty acids for each compartment were quantified by GC/FID and summed for the rat whole body; total n-6 PUFA was 12 wt% and total n-3 PUFA was 2.1% of total fatty acids. 18:2n-6 accounted for 84% of the total n-6 PUFA, 20:4n-6 was 12%, 18:3n-3 was 59% of the total n-3 PUFA, 20:5n-3 was 2.1%, and 22:6n-3 was 32%. The white adipose tissue contained the greatest amounts of 18:2n-6 (1.5 g) and 18:3n-3 (0.2 g). 20:4n-6 was highest in muscle (60 mg) and liver (57 mg), while 22:6n-3 was greatest in muscle (46 mg), followed by liver (27 mg) and carcass (20 mg). In terms of fatty acid composition expressed as a percentage, 18:2n-6 was the highest in the heart (13 wt%), while 18:3n-3 was about 13 wt% for skin, white adipose tissue and fur. 20:4n-6 was highest (21-25 wt%) in the circulation, kidney, and spleen, while 22:6n-3 was highest in the brain (12 wt%), followed by the heart (7.9 wt%), liver (5.9 wt%), and spinal cord (5.1 wt%). Selectivity was greatest when comparing 22:6n-3 in brain (12%) to white adipose (0.08%) (68-fold) and 22:5n-6 in testes (15.6%) compared to white adipose (0.02%), 780-fold. Published by Elsevier Ltd. C1 [Salem, N. M.; Lin, Y. H.; Hibbeln, J. R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Moriguchi, T.] Azabu Univ, Dept Food & Life Sci, Sagamihara, Kanagawa, Japan. [Lim, S. Y.] Korea Maritime & Ocean Univ, Div Marine Environm & Biosci, Busan, South Korea. [Salem, N., Jr.] DSM Nutr Prod Inc, Nutr Lipids, Columbia, MD USA. RP Lin, YH (reprint author), NIAAA, NIH, Lab Membrane Biochem & Biophys, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA. EM yuhong.lin@nih.gov FU Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism; National Institutes of Health FX This project was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 29 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD SEP PY 2015 VL 100 BP 13 EP 20 DI 10.1016/j.plefa.2015.06.002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA CR5TD UT WOS:000361406100003 PM 26120061 ER PT J AU Pavletic, AJ Pao, M Wright, ME AF Pavletic, Adriana J. Pao, Maryland Wright, Mary E. TI Exercise-induced Elevation of Liver Enzymes in a Healthy Female Research Volunteer SO PSYCHOSOMATICS LA English DT Letter C1 [Pavletic, Adriana J.; Pao, Maryland] NIMH, Off Clin Director, Bethesda, MD 20892 USA. [Wright, Mary E.] NIAID, Div Clin Res, Bethesda, MD 20892 USA. RP Pavletic, AJ (reprint author), NIMH, Off Clin Director, Bethesda, MD 20892 USA. EM pavletia@mail.nih.gov FU Intramural NIH HHS [, Z99 MH999999] NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2015 VL 56 IS 5 BP 604 EP 606 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CR0KD UT WOS:000361006500025 PM 26362917 ER PT J AU Witte, S O'Shea, JJ Vahedi, G AF Witte, Steven O'Shea, John J. Vahedi, Golnaz TI Super-enhancers: Asset management in immune cell genomes SO TRENDS IN IMMUNOLOGY LA English DT Review ID BETA-GLOBIN LOCUS; MASTER TRANSCRIPTION FACTORS; PROTEIN-DNA INTERACTIONS; T-HELPER-CELLS; GENE-EXPRESSION; CHROMATIN ARCHITECTURE; REGULATORY ELEMENTS; IDENTITY GENES; IN-VIVO; DIFFERENTIATION AB Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. C1 [Witte, Steven; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Vahedi, Golnaz] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Vahedi, Golnaz] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Vahedi, G (reprint author), Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. EM vahedi@mail.med.upenn.edu FU NIAID NIH HHS [K22 AI112570] NR 86 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD SEP PY 2015 VL 36 IS 9 BP 519 EP 526 DI 10.1016/j.it.2015.07.005 PG 8 WC Immunology SC Immunology GA CR5TI UT WOS:000361406600004 PM 26277449 ER PT J AU Birger, RB Kouyos, RD Cohen, T Griffiths, EC Huijben, S Mina, M Volkova, V Grenfell, B Metcalf, CJE AF Birger, Ruthie B. Kouyos, Roger D. Cohen, Ted Griffiths, Emily C. Huijben, Silvie Mina, Michael Volkova, Victoriya Grenfell, Bryan Metcalf, C. Jessica E. TI The potential impact of coinfection on antimicrobial chemotherapy and drug resistance SO TRENDS IN MICROBIOLOGY LA English DT Review DE drug resistance; coinfection; immune modulation; resource competition; parasite interactions ID PLASMODIUM-FALCIPARUM MALARIA; MEDIATED APPARENT COMPETITION; HORIZONTAL GENE-TRANSFER; HOST-RANGE PLASMIDS; MYCOBACTERIUM-TUBERCULOSIS; ANTIBIOTIC-RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; PREVENTIVE TREATMENT; NASAL COLONIZATION AB Across a range of pathogens, resistance to chemotherapy is a growing problem in both public health and animal health. Despite the ubiquity of coinfection, and its potential effects on within-host biology, the role played by coinfecting pathogens on the evolution of resistance and efficacy of antimicrobial chemotherapy is rarely considered. In this review, we provide an overview of the mechanisms of interaction of coinfecting pathogens, ranging from immune modulation and resource modulation, to drug interactions. We discuss their potential implications for the evolution of resistance, providing evidence in the rare cases where it is available. Overall, our review indicates that the impact of coinfection has the potential to be considerable, suggesting that this should be taken into account when designing antimicrobial drug treatments. C1 [Birger, Ruthie B.; Mina, Michael; Grenfell, Bryan; Metcalf, C. Jessica E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Kouyos, Roger D.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland. [Kouyos, Roger D.] Univ Zurich, Inst Med Virol, Zurich, Switzerland. [Cohen, Ted] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Griffiths, Emily C.] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Huijben, Silvie] Univ Barcelona, Hosp Clin Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain. [Mina, Michael] Emory Univ, Sch Med, Med Scientist Training Program, Atlanta, GA USA. [Volkova, Victoriya] Kansas State Univ, Coll Vet Med, Inst Computat Comparat Med, Dept Diagnost Med Pathobiol, Manhattan, KS 66506 USA. [Grenfell, Bryan; Metcalf, C. Jessica E.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Birger, RB (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. EM rbirger@princeton.edu RI Infektiologie, USZ/A-6921-2011; Kouyos, Roger/G-6226-2014; Birger, Ruthie/F-2416-2014 OI Kouyos, Roger/0000-0002-9220-8348; Birger, Ruthie/0000-0002-2960-5084 FU RAPIDD program of the Science & Technology Directorate; Department of Ecology and Evolutionary Biology at Princeton University; Swiss National Science foundation (SNSF) [PZ00P3_142411]; NIH from the National Institute of General Medical Sciences [U54GM088558]; Society in Science - Branco Weiss Fellowship; Marie Curie ILF Fellowship; Institute of Computational Comparative Medicine at the College of Veterinary Medicine of Kansas State University; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health; Bill and Melinda Gates Foundation; [HSHQDC-12-C-00058] FX This work emerged from a meeting funded by the RAPIDD program of the Science & Technology Directorate. RAPIDD is administered by the Department of Homeland Security and the Fogarty International Center, National Institutes of Health; Science and Technology Directorate, Department of Homeland Security; contract HSHQDC-12-C-00058. We would like to thank the other attendees at the meeting not represented in the author list for their valuable contributions to discussions. EBB is supported by the Department of Ecology and Evolutionary Biology at Princeton University. RDK is funded by the Swiss National Science foundation (SNSF #PZ00P3_142411). TC is supported by NIH U54GM088558 from the National Institute of General Medical Sciences; the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences of the National Institutes of Health. SH was funded by the Society in Science - Branco Weiss Fellowship and Marie Curie ILF Fellowship. VVV is supported through the Institute of Computational Comparative Medicine at the College of Veterinary Medicine of Kansas State University. BTG is supported by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health. CJEM is funded by the Bill and Melinda Gates Foundation. NR 100 TC 8 Z9 8 U1 10 U2 32 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 2015 VL 23 IS 9 BP 537 EP 544 DI 10.1016/j.tim.2015.05.002 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA CR5WA UT WOS:000361413900006 PM 26028590 ER PT J AU Romling, U Galperin, MY AF Romling, Ute Galperin, Michael Y. TI Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions SO TRENDS IN MICROBIOLOGY LA English DT Review DE bacterial genomes; bacterial-host interaction; biofilm structure; environmental bacteria; polysaccharide export; nanocellulose ID CYCLIC-DI-GMP; PSEUDOMONAS-FLUORESCENS SBW25; ENTERICA SEROVAR TYPHIMURIUM; COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI; BIOFILM FORMATION; AGROBACTERIUM-TUMEFACIENS; ACETOBACTER-XYLINUM; GLUCONACETOBACTER-HANSENII; SALMONELLA-ENTERICA AB Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits - which differ among various taxa - affect the enzymatic activity and product yield in vivo by modulating (i) the expression of the biosynthesis apparatus, (ii) the export of the nascent beta-D-glucan polymer to the cell surface, and (iii) the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of resulting biofilms, which is particularly important for the interactions of bacteria with higher organisms - leading to rhizosphere colonization and modulating the virulence of cellulose-producing bacterial pathogens inside and outside of host cells. We review the organization of four principal types of cellulose synthase operon found in various bacterial genomes, identify additional bcs genes that encode components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms and in the choice between acute infection and persistence in the host. C1 [Romling, Ute] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden. [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Romling, U (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden. EM Ute.Romling@ki.se; galperin@ncbi.nlm.nih.gov OI Romling, Ute/0000-0003-3812-6621 FU Swedish Research Council Natural Sciences and Engineering; Karolinska Institutet; Petrus and Augusta Hedlund Foundation; NIH Intramural Research Program at the U.S. National Library of Medicine FX We thank the members of the Romling laboratory for comments on this manuscript. This work was supported by the Swedish Research Council Natural Sciences and Engineering, the Karolinska Institutet and Petrus and Augusta Hedlund Foundation (to U.R.), and the NIH Intramural Research Program at the U.S. National Library of Medicine (M.Y.G.). NR 98 TC 15 Z9 15 U1 17 U2 91 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 2015 VL 23 IS 9 BP 545 EP 557 DI 10.1016/j.tim.2015.05.005 PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA CR5WA UT WOS:000361413900007 PM 26077867 ER PT J AU Payne, RO Milne, KH Elias, SC Edwards, NJ Douglas, AD Brown, RE Silk, SE Biswas, S Miura, K Roberts, R Rampling, TW Venkatraman, N Hodgson, SH Labbe, GM Halstead, FD Ockenhouse, CF Kathcart, AK Qabar, AN Waters, NC Soisson, LA Woods, C Birkett, AJ Long, CA Vekemans, J Diggs, CL Hill, AVS Lawrie, AM Dutta, S Draper, SJ AF Payne, R. O. Milne, K. H. Elias, S. C. Edwards, N. J. Douglas, A. D. Brown, R. E. Silk, S. E. Biswas, S. Miura, K. Roberts, R. Rampling, T. W. Venkatraman, N. Hodgson, S. H. Labbe, G. M. Halstead, F. D. Ockenhouse, C. F. Kathcart, A. K. Qabar, A. N. Waters, N. C. Soisson, L. A. Woods, C. Birkett, A. J. Long, C. A. Vekemans, J. Diggs, C. L. Hill, A. V. S. Lawrie, A. M. Dutta, S. Draper, S. J. TI Assessment of FMP2.1/AS01B, an asexual blood-stage malaria vaccine, in a phase I/II a clinical trial using blood-stage controlled human malaria infection SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Payne, R. O.; Milne, K. H.; Elias, S. C.; Edwards, N. J.; Douglas, A. D.; Brown, R. E.; Silk, S. E.; Biswas, S.; Roberts, R.; Rampling, T. W.; Venkatraman, N.; Hodgson, S. H.; Labbe, G. M.; Halstead, F. D.; Hill, A. V. S.; Lawrie, A. M.; Draper, S. J.] Univ Oxford, Jenner Inst, Oxford, England. [Miura, K.; Long, C. A.] NIH, Lab Malaria & Vector Res, Washington, DC USA. [Ockenhouse, C. F.; Kathcart, A. K.; Qabar, A. N.; Waters, N. C.; Dutta, S.] Walter Reed Army Inst Res, Mil Malaria Res Program, Silver Spring, MD USA. [Soisson, L. A.; Diggs, C. L.] US Agcy Int Dev, Washington, DC 20523 USA. [Woods, C.; Birkett, A. J.] PATH Malaria Vaccine Initiat, Washington, DC USA. [Vekemans, J.] GSK, Rixensart, Belgium. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI BP 22 EP 22 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758800052 ER PT J AU Paul, R Duong, V Lambrechts, L Ly, S Lay, SR Long, K Ngan, C Tarantola, A Scott, T Sakuntabhai, A Buchy, P AF Paul, R. Duong, V. Lambrechts, L. Ly, S. Lay, S. R. Long, K. Ngan, C. Tarantola, A. Scott, T. Sakuntabhai, A. Buchy, P. TI Dengue transmission dynamics: the role of asymptomatic infections SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Paul, R.; Lambrechts, L.; Sakuntabhai, A.] Inst Pasteur, Paris, France. [Paul, R.; Lambrechts, L.; Sakuntabhai, A.] CNRS, Paris, France. [Duong, V.; Ly, S.; Lay, S. R.; Tarantola, A.; Buchy, P.] Inst Pasteur Cambodia, Phnom Penh, Cambodia. [Long, K.; Scott, T.] Univ Calif Davis, Davis, CA 95616 USA. [Long, K.; Scott, T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ngan, C.] Minist Hlth, Natl Ctr Malariol, Phnom Penh, Cambodia. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI BP 37 EP 37 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758800089 ER PT J AU Deribe, K Cano, J Newport, MJ Golding, N Pullan, RL Sime, H Gebretsadik, A Assefa, A Kebede, A Hailu, A Rebollo, MP Shafi, O Bockarie, MJ Aseffa, A Hay, SI Reithinger, R Enquselassie, F Davey, G Brooker, SJ AF Deribe, K. Cano, J. Newport, M. J. Golding, N. Pullan, R. L. Sime, H. Gebretsadik, A. Assefa, A. Kebede, A. Hailu, A. Rebollo, M. P. Shafi, O. Bockarie, M. J. Aseffa, A. Hay, S. I. Reithinger, R. Enquselassie, F. Davey, G. Brooker, S. J. TI Mapping and modelling the geographical distribution and environmental limits of podoconiosis in Ethiopia SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Deribe, K.; Newport, M. J.; Davey, G.] Brighton & Sussex Med Sch, Brighton, E Sussex, England. [Deribe, K.; Enquselassie, F.] Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia. [Cano, J.; Pullan, R. L.; Reithinger, R.; Brooker, S. J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England. [Golding, N.; Hay, S. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Sime, H.; Gebretsadik, A.; Assefa, A.; Kebede, A.] Ethiopian Publ Hlth Inst, Addis Ababa, Ethiopia. [Hailu, A.] Univ Addis Ababa, Sch Med, Addis Ababa, Ethiopia. [Rebollo, M. P.; Bockarie, M. J.] Univ Liverpool, Liverpool Sch Trop Med, Ctr Neglected Trop Dis, Liverpool L3 5QA, Merseyside, England. [Shafi, O.] Fed Minist Hlth, Addis Ababa, Ethiopia. [Aseffa, A.] Armauer Hansen Res Inst ALERT, Addis Ababa, Ethiopia. [Hay, S. I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Hay, S. I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Reithinger, R.] RTI Int, Washington, DC USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI BP 39 EP 40 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758800096 ER PT J AU De Santis, O Audran, R Pothin, E Warpelin-Decrausaz, L Vallotton, L Wuerzner, G Cochet, C Estoppey, D Steiner-Monard, V Lonchampt, S Thierry, AC Mayor, C Bailer, RT Mbaya, OT Zhou, Y Ploquin, A Sullivan, NJ Graham, BS Roman, F De Ryck, I Ballou, R Kieny, MP Moorthy, V Spertini, F Genton, B AF De Santis, O. Audran, R. Pothin, E. Warpelin-Decrausaz, L. Vallotton, L. Wuerzner, G. Cochet, C. Estoppey, D. Steiner-Monard, V. Lonchampt, S. Thierry, A. -C. Mayor, C. Bailer, R. T. Mbaya, O. Tshiani Zhou, Y. Ploquin, A. Sullivan, N. J. Graham, B. S. Roman, F. De Ryck, I. Ballou, R. Kieny, M. P. Moorthy, V. Spertini, F. Genton, B. TI Safety and immunogenicity of the Chimpanzee-Adenovirus vectored Ebola vaccine: the Lausanne phase I/IIa clinical trial SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [De Santis, O.; Cochet, C.; Estoppey, D.; Lonchampt, S.; Genton, B.] Policlin Med Univ, Lausanne, Switzerland. [Audran, R.; Steiner-Monard, V.; Thierry, A. -C.; Mayor, C.; Spertini, F.] Univ Lausanne Hosp, Div Immunol & Allergy, Lausanne, Switzerland. [Pothin, E.; Genton, B.] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Warpelin-Decrausaz, L.; Vallotton, L.; Wuerzner, G.] Univ Lausanne Hosp, Clin Trial Unit, Lausanne, Switzerland. [Bailer, R. T.; Mbaya, O. Tshiani; Zhou, Y.; Ploquin, A.; Sullivan, N. J.; Graham, B. S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Roman, F.; De Ryck, I.; Ballou, R.] GSK Vaccines, Rixensart, Belgium. [Kieny, M. P.; Moorthy, V.] WHO, CH-1211 Geneva, Switzerland. [Genton, B.] Univ Lausanne Hosp, Infect Dis Serv, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI BP 43 EP 43 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758800104 ER PT J AU Franca, C Hostetler, J He, W Robinson, LJ Lin, E Li, CSN Suen, W Sharma, S Gruszczyk, J Malhotra, I Frato, G Siba, P Galinski, M Kazura, J Schofield, L Wright, G Tham, WH Takashima, E Tsuboi, T Fairhurst, RM Rayner, J King, CL Mueller, I AF Franca, C. Hostetler, J. He, W. Robinson, L. J. Lin, E. Li, C. S. N. Suen, Wai Sharma, S. Gruszczyk, J. Malhotra, I. Frato, G. Siba, P. Galinski, M. Kazura, J. Schofield, L. Wright, G. Tham, W. H. Takashima, E. Tsuboi, T. Fairhurst, R. M. Rayner, J. King, C. L. Mueller, I. TI Identification of potential novel P. vivax vaccine candidates: naturally-acquired immune responses to a panel of P. vivax blood-stage antigens are associated with reduced risk of clinical malaria episodes in Papua New Guinean children SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Franca, C.; Robinson, L. J.; Li, C. S. N.; Schofield, L.; Mueller, I.] Univ Melbourne, Walter & Eliza Hall Inst, Div Populat Hlth & Immun, Melbourne, Vic, Australia. [Franca, C.; He, W.; Robinson, L. J.; Li, C. S. N.; Gruszczyk, J.; Schofield, L.; Tham, W. H.; Mueller, I.] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia. [Hostetler, J.; Sharma, S.; Wright, G.; Rayner, J.] Wellcome Trust Sanger Inst, Malaria Programme, Hinxton, Cambs, England. [Hostetler, J.; Fairhurst, R. M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [He, W.; Gruszczyk, J.; Tham, W. H.] Walter & Eliza Hall Inst Med Res, Div Infect & Immun, Melbourne, Vic, Australia. [Robinson, L. J.; Lin, E.; Siba, P.] PNG Inst Med Res, Malaria Immunoepidemiol Unit, Madang, Papua N Guinea. [Malhotra, I.; Frato, G.; Kazura, J.; King, C. L.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Galinski, M.] Emory Univ, Div Infect Dis, Atlanta, GA 30322 USA. [Schofield, L.] James Cook Univ, Australian Inst Trop Hlth & Med, Townsville, Qld 4811, Australia. [Takashima, E.; Tsuboi, T.] Ehime Univ, Proteosci Ctr, Matsuyama, Ehime, Japan. [Mueller, I.] Inst Global Hlth ISGLOBAL, Barcelona, Spain. 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 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI BP 105 EP 105 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758800255 ER PT J AU Kleine, C Chertow, DS Edwards, JK Sprecher, A Scaini, R Guilliani, R AF Kleine, C. Chertow, D. S. Edwards, J. K. Sprecher, A. Scaini, R. Guilliani, R. TI Ebola virus disease - clinical manifestations and management SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Kleine, C.] Univ Hosp Frankfurt, Frankfurt, Germany. [Kleine, C.; Chertow, D. S.; Edwards, J. K.; Sprecher, A.; Scaini, R.; Guilliani, R.] Medecins Sans Frontieres, Brussels, Belgium. [Chertow, D. S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2015 VL 20 SU 1 SI SI MA PS1.085 BP 204 EP 204 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CQ7BW UT WOS:000360758801085 ER PT J AU Broach, JR Bharatula, V Chereji, R Elfvin, N Bjorklund, S Morozov, A AF Broach, James R. Bharatula, Vasudha Chereji, Razvan Elfvin, Nils Bjorklund, Stefan Morozov, Alexandre TI The Msn2 mediated stress response: Survival based on "hedging your bet" and a dynamic interplay of transcription factor binding and nucleosome occupancy SO YEAST LA English DT Meeting Abstract CT 27th International Conference on Yeast Genetics and Molecular Biology (ICYGMB) CY SEP 06-12, 2015 CL Fondazione Edmund Mach, Levico Terme, ITALY SP Inst Cell Biol Nas Ukraine, Roche, Singer Instruments, Tema Ric, EMBO, Wiley Blackwell, Federat European Microbiol Soc, Assoc Genetica Italiana, Stanford Univ, DSB, Athesina Studiorum Univ, Soc Italiana Microbiologia Generale & Biotecnologie Microbiche, Saccharomyces Genome Database, Fondazione Bruno Kessler, Prov Autonoma Trento HO Fondazione Edmund Mach C1 [Broach, James R.; Bharatula, Vasudha] Penn State Coll Med, Dept Biochem & Mol Biol, Hershey, PA USA. [Chereji, Razvan] Natl Inst Child Hlth & Dev, Bethesda, MD USA. [Elfvin, Nils; Bjorklund, Stefan] Umea Univ, Dept Biochem, S-90187 Umea, Sweden. [Morozov, Alexandre] Rutgers State Univ, Dept Phys, New Brunswick, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP PY 2015 VL 32 SU 1 MA PS12-5 BP S221 EP S222 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA CR6OF UT WOS:000361466200377 ER PT J AU Kunkel, T AF Kunkel, Thomas TI Studies of leding and lagging strand DNA replication fidelity in yeast SO YEAST LA English DT Meeting Abstract CT 27th International Conference on Yeast Genetics and Molecular Biology (ICYGMB) CY SEP 06-12, 2015 CL Fondazione Edmund Mach, Levico Terme, ITALY SP Inst Cell Biol Nas Ukraine, Roche, Singer Instruments, Tema Ric, EMBO, Wiley Blackwell, Federat European Microbiol Soc, Assoc Genetica Italiana, Stanford Univ, DSB, Athesina Studiorum Univ, Soc Italiana Microbiologia Generale & Biotecnologie Microbiche, Saccharomyces Genome Database, Fondazione Bruno Kessler, Prov Autonoma Trento HO Fondazione Edmund Mach C1 [Kunkel, Thomas] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP PY 2015 VL 32 SU 1 MA PL1-1 BP S29 EP S29 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA CR6OF UT WOS:000361466200003 ER PT J AU Reidy, M Masison, D AF Reidy, Michael Masison, Daniel TI Deciphering molecular chaperone networks using yeast prions SO YEAST LA English DT Meeting Abstract CT 27th International Conference on Yeast Genetics and Molecular Biology (ICYGMB) CY SEP 06-12, 2015 CL Fondazione Edmund Mach, Levico Terme, ITALY SP Inst Cell Biol Nas Ukraine, Roche, Singer Instruments, Tema Ric, EMBO, Wiley Blackwell, Federat European Microbiol Soc, Assoc Genetica Italiana, Stanford Univ, DSB, Athesina Studiorum Univ, Soc Italiana Microbiologia Generale & Biotecnologie Microbiche, Saccharomyces Genome Database, Fondazione Bruno Kessler, Prov Autonoma Trento HO Fondazione Edmund Mach C1 [Reidy, Michael; Masison, Daniel] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP PY 2015 VL 32 SU 1 MA W6-3 BP S71 EP S72 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA CR6OF UT WOS:000361466200085 ER PT J AU Resnick, MA Nguyen, TA Menendez, D AF Resnick, Michael A. Thuy-Ai Nguyen Menendez, Daniel TI The yeast road to human p53 and associated inflammatory responses SO YEAST LA English DT Meeting Abstract CT 27th International Conference on Yeast Genetics and Molecular Biology (ICYGMB) CY SEP 06-12, 2015 CL Fondazione Edmund Mach, Levico Terme, ITALY SP Inst Cell Biol Nas Ukraine, Roche, Singer Instruments, Tema Ric, EMBO, Wiley Blackwell, Federat European Microbiol Soc, Assoc Genetica Italiana, Stanford Univ, DSB, Athesina Studiorum Univ, Soc Italiana Microbiologia Generale & Biotecnologie Microbiche, Saccharomyces Genome Database, Fondazione Bruno Kessler, Prov Autonoma Trento HO Fondazione Edmund Mach C1 [Resnick, Michael A.; Thuy-Ai Nguyen; Menendez, Daniel] NIEHS, Chromosome Stabil Grp, Genome Instabil Struct Biol Dept, NIH, Res Triangle Pk, NC 27517 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP PY 2015 VL 32 SU 1 MA PL7-1 BP S42 EP S42 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA CR6OF UT WOS:000361466200027 ER PT J AU Lee, MR Schwandt, ML Bollinger, JW Dias, AA Oot, EN Goldman, D Hodgkinson, CA Leggio, L AF Lee, Mary R. Schwandt, Melanie L. Bollinger, Jared W. Dias, Alexandra A. Oot, Emily N. Goldman, David Hodgkinson, Colin A. Leggio, Lorenzo TI Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on Drinking Behavior in Alcohol Dependence: An Exploratory Investigation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Thyroid Hormone; Deiodinases; Alcohol Dependence; Genetics; Single Nucleotide Polymorphisms; Hypothalamic-Pituitary-Thyroid Axis ID PITUITARY-THYROID AXIS; TYPE-2 DEIODINASE; INSULIN-RESISTANCE; GENE POLYMORPHISM; HORMONE TRH; RECEPTOR; TRIIODOTHYRONINE; THR92ALA; FEEDBACK; ETHANOL AB BackgroundAbnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism; however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence. The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes: D1, D2, and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNPs) of these deiodinase genes may play a role in HPT dysfunction. MethodsThis study explored the effect of three functionally significant SNPs (D1: rs2235544, D2: rs225014, and rs12885300) of deiodinase genes on drinking behavior and thyroid-stimulating hormone (TSH) levels in alcohol-dependent (N=521) and control subjects (N=288). ResultsRs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by Timeline Follow Back. Alcohol-dependent subjects had significantly higher TSH levels compared to controls; however, there was no effect of genotype on TSH levels for either group. ConclusionsThese findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol-drinking behavior. C1 [Lee, Mary R.; Bollinger, Jared W.; Dias, Alexandra A.; Oot, Emily N.; Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD 20892 USA. [Lee, Mary R.; Bollinger, Jared W.; Dias, Alexandra A.; Oot, Emily N.; Leggio, Lorenzo] NIDA, NIH, Bethesda, MD 20892 USA. [Schwandt, Melanie L.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Goldman, David; Hodgkinson, Colin A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA. RP Lee, MR (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD 20892 USA. EM leemary@mail.nih.gov; lorenzo.leg-gio@nih.gov RI Goldman, David/F-9772-2010; Schwandt, Melanie/L-9866-2016; Leggio, Lorenzo/M-2972-2016 OI Goldman, David/0000-0002-1724-5405; FU NIH [ZIA-AA000218]; Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Research Program of the National Institute on Drug Abuse (NIDA) FX This study was supported by NIH intramural funding ZIA-AA000218 (PI: Leggio) jointly supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Intramural Research Program of the National Institute on Drug Abuse (NIDA). NR 31 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2015 VL 39 IS 9 BP 1665 EP 1670 DI 10.1111/acer.12814 PG 6 WC Substance Abuse SC Substance Abuse GA CQ7ZB UT WOS:000360824300011 PM 26207529 ER PT J AU White, A Castle, IJP Chen, CM Shirley, M Roach, D Hingson, R AF White, Aaron Castle, I-Jen P. Chen, Chiung M. Shirley, Mariela Roach, Deidra Hingson, Ralph TI Converging Patterns of Alcohol Use and Related Outcomes Among Females and Males in the United States, 2002 to 2012 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Binge Drinking; Gender Gap; Sex Differences; Age of Onset; College Drinking; Drinking and Driving; Trend; Marijuana ID GENDER-DIFFERENCES; BINGE DRINKING; BRAIN-DAMAGE; YOUNG-ADULTS; WOMEN; CONSEQUENCES; CONSUMPTION; PREVALENCE; EPIDEMIOLOGY; TRENDS AB BackgroundFemales in the United States consume less alcohol and cause and experience fewer alcohol-related harms than males. However, recent research suggests such gaps might be narrowing. The purpose of this study was to explore changes in alcohol use and associated outcomes among females and males in the United States between 2002 and 2012. MethodsData from the National Survey on Drug Use and Health were used to assess the prevalence and trends for females and males aged 12+ in lifetime abstinence, age of onset, current drinking, binge drinking, drinking and driving, reaching DSM-IV criteria for an alcohol use disorder, combining alcohol with other drugs such as marijuana, and other variables. Of particular interest was whether differences between females and males narrowed during the decade under study. ResultsDifferences in the drinking patterns of females and males aged 12+ narrowed between 2002 and 2012 for current drinking, number of drinking days per month, past year DSM-IV alcohol abuse, and past-year driving under the influence of alcohol. In addition, convergence was noted in 1 or more age subgroups for the prevalence of binge drinking and DSM-IV alcohol dependence and mean age at drinking onset. Divergence in drinking habits did not occur for any measure in any age subgroups with the exception of a greater increase in the prevalence of combining alcohol with marijuana among young adult male drinkers than female drinkers aged 18 to 25. ConclusionsBetween 2002 and 2012, differences in alcohol consumption and related outcomes narrowed for females and males. Reasons for converging patterns of alcohol use are unclear and do not appear to be easily explainable by recent trends in employment status, pregnancy status, or marital status. More research is needed to identify the psychosocial and environmental contributors to these changes and to assess implications for prevention and treatment efforts. C1 [White, Aaron; Shirley, Mariela; Roach, Deidra; Hingson, Ralph] NIAAA, NIH, Bethesda, MD 20892 USA. [Castle, I-Jen P.; Chen, Chiung M.] CSR Inc, Arlington, VA USA. RP White, A (reprint author), NIAAA, NIH, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM whitea4@mail.nih.gov FU Alcohol Epidemiologic Data System project - National Institute on Alcohol Abuse and Alcoholism [HHSN275201300016C] FX This study was supported in part by the Alcohol Epidemiologic Data System project funded by the National Institute on Alcohol Abuse and Alcoholism through contract HHSN275201300016C to CSR, Incorporated. NR 43 TC 12 Z9 12 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2015 VL 39 IS 9 BP 1712 EP 1726 DI 10.1111/acer.12815 PG 15 WC Substance Abuse SC Substance Abuse GA CQ7ZB UT WOS:000360824300017 PM 26331879 ER PT J AU Kant, AK Graubard, BI AF Kant, Ashima K. Graubard, Barry I. TI Within-person comparison of eating behaviors, time of eating, and dietary intake on days with and without breakfast: NHANES 2005-2010 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE breakfast; chrononutrition; eating behaviors; eating frequency; energy density; food pattern equivalents; main meals; NHANES; obesity; time of eating ID BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; ADULTS NATIONAL-HEALTH; ENERGY-INTAKE; AMERICAN ADULTS; NUTRIENT INTAKE; FOOD-INTAKE; CONSUMPTION; CHRONOTYPE; TRENDS AB Background: Breakfast omission is known to be associated with lower 24-h energy intake. However, little is known about downstream eating behaviors subsequent to skipping breakfast in free-living individuals. Objective: We replicated the traditional crossover design of nutrition studies in a naturalistic setting to compare within-person differences in self-reported eating behaviors, energy intake, and other dietary characteristics of individuals on a day that included breakfast with a day that omitted breakfast. Design: We used cross-sectional dietary data for 2132 adult respondents who reported breakfast in only one of 2 dietary recalls in the NHANES 2005-2010. Dietary outcomes examined included meal-and snack-eating behaviors, clock time of eating episodes, and intakes of energy, macronutrients, and food groups. Regression methods accounted for replicate diet measurements, covariates, and survey-design characteristics. Results: The breakfast meal provided a mean of 508 kcal in men and 374 kcal in women, but differences in 24-h energy intakes between the breakfast and no-breakfast day were 247 and 187 kcal, respectively. Energy intakes at the lunch meal were higher on the no-breakfast day (202 kcal in men and 121 kcal in women), and the reported time of lunch was similar to 35 min earlier. The energy contribution of dinner or its reported time did not differ. A higher number of energy-adjusted servings of fruit and whole grains were reported on the breakfast day, but the energy and macronutrient density of reported foods were not different. Conclusions: In free-living American adults, the eating time for lunch was earlier, and the lunch meal provided more energy on the no-breakfast day than on the breakfast day. Although the quality of dietary selections reflected in the energy and macronutrient density of a day's intake did not differ between the breakfast and the no-breakfast day, breakfast skippers may need encouragement to consume fruit and whole grains at other eating episodes. C1 [Kant, Ashima K.] CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. EM ashima.kant@qc.cuny.edu FU Department of Health and Human Services, National Cancer Institute, NIH FX Supported in part by the intramural research program of the Department of Health and Human Services, National Cancer Institute, NIH (to BIG). NR 37 TC 7 Z9 7 U1 9 U2 38 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 SEP PY 2015 VL 102 IS 3 BP 661 EP 670 DI 10.3945/ajcn.115.110262 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR2II UT WOS:000361150900018 PM 26178722 ER PT J AU Anderson, CAM Cobb, LK Miller, ER Woodward, M Hottenstein, A Chang, AR Mongraw-Chaffin, M White, K Charleston, J Tanaka, T Thomas, L Appel, LJ AF Anderson, Cheryl A. M. Cobb, Laura K. Miller, Edgar R., III Woodward, Mark Hottenstein, Annette Chang, Alex R. Mongraw-Chaffin, Morgana White, Karen Charleston, Jeanne Tanaka, Toshiko Thomas, Letitia Appel, Lawrence J. TI Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE adherence; behavioral intervention; clinical trial; diet; sodium ID MODEST SALT REDUCTION; BLOOD-PRESSURE; DIETARY-SODIUM; CARDIOVASCULAR-DISEASE; POTASSIUM INTAKE; URINARY SODIUM; NONPHARMACOLOGIC INTERVENTIONS; PUBLIC-HEALTH; UNITED-STATES; EXCRETION AB Background: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. Objective: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. Design: We conducted a 2-phase study that included adults >= 18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. Results: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: 2956.8 mg/d; 95% CI: 21538.7, 2374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: 21090 mg/d (P = 0.001); Joosens' equation mean difference: 2796 mg/d (P = 0.04)]. Conclusions: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. C1 [Anderson, Cheryl A. M.; Mongraw-Chaffin, Morgana] Univ Calif San Diego, Sch Med, Div Prevent Med, San Diego, CA 92103 USA. [Anderson, Cheryl A. M.; Cobb, Laura K.; Miller, Edgar R., III; Charleston, Jeanne; Appel, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Miller, Edgar R., III; Appel, Lawrence J.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, George Inst Global Hlth, Oxford, England. [Hottenstein, Annette] Sensational Sustenance Inc, Baltimore, MD USA. [Chang, Alex R.] Geisinger Hlth Syst, Div Nephrol, Danville, PA USA. [Miller, Edgar R., III; White, Karen; Charleston, Jeanne; Thomas, Letitia; Appel, Lawrence J.] Johns Hopkins Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. RP Anderson, CAM (reprint author), Univ Calif San Diego, Sch Med, Div Prevent Med, San Diego, CA 92103 USA. EM c1anderson@ucsd.edu RI Woodward, Mark/D-8492-2015 FU McCormick Science Institute; National Heart, Lung, and Blood Institute [K01 HL092595] FX Supported by a grant from the McCormick Science Institute and in part by a grant from the National Heart, Lung, and Blood Institute (K01 HL092595; to CAMA). NR 56 TC 1 Z9 1 U1 3 U2 13 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 SEP PY 2015 VL 102 IS 3 BP 671 EP 679 DI 10.3945/ajcn.114.100750 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR2II UT WOS:000361150900019 PM 26269371 ER PT J AU Yu, DX Shu, XO Li, HL Yang, G Cai, QY Xiang, YB Ji, BT Franke, AA Gao, YT Zheng, W Zhang, XL AF Yu, Danxia Shu, Xiao-Ou Li, Honglan Yang, Gong Cai, Qiuyin Xiang, Yong-Bing Ji, Bu-Tian Franke, Adrian A. Gao, Yu-Tang Zheng, Wei Zhang, Xianglan TI Dietary isoflavones, urinary isoflavonoids, and risk of ischemic stroke in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ischemic stroke; phytoestrogen; prospective cohort study; soy isoflavone; women ID CARDIOVASCULAR-DISEASE MORTALITY; AMERICAN-HEART-ASSOCIATION; POSTMENOPAUSAL WOMEN; FLAVONOID INTAKE; BREAST-CANCER; SOY PROTEIN; HEALTH; PHYTOESTROGENS; METAANALYSIS; PROFESSIONALS AB Background: Hormone therapy has been shown to increase risk of ischemic stroke in women. Plant-derived estrogens, particularly soy isoflavones, are known to have some estrogenic effects and have been marketed as natural alternatives to hormone therapy. Concerns have been raised about whether high isoflavone exposure may be related to ischemic stroke risk as well. Objective: We examined the dietary intake of isoflavones and the urinary excretion of isoflavonoids in relation to risk of ischemic stroke in women. Design: A prospective cohort study was conducted in 66,832 Chinese women (aged 40-70 y) who had no cardiovascular disease or cancer at baseline. Usual dietary intakes were assessed via in-person interviews with the use of a validated food-frequency questionnaire. Incident strokes were ascertained during follow-up home visits and confirmed by medical records. We also conducted a nested case-control study in postmenopausal women who had never used hormone therapy, including 1422 incident ischemic stroke cases and 1422 controls individually matched by age, date and time of urine sample collection, time since last meal, and use of antibiotics. Urinary isoflavonoids were measured with the use of high-performance liquid chromatography coupled with mass spectrometry. Results: During a mean follow-up of 10 y, 3110 incident ischemic strokes were verified. Dietary isoflavone intake was associated with increased risk of ischemic stroke; multivariable-adjusted HRs from lowest to highest quintiles were 1.00, 1.05, 1.10, 1.11, and 1.24, respectively (95% CI: 1.08, 1.42; P-trend = 0.002). In the case-control study, a similar positive association was observed for dietary isoflavones, but no significant associations were shown for the urinary isoflavonoid concentration [OR: 1.01 (95% CI: 0.77, 1.32) for comparison of extreme quintiles]. Conclusions: A habitually high intake of soy isoflavones may be associated with a modest but significant increase in risk of ischemic stroke in women. However, no association was shown for the urinary excretion of isoflavonoids. C1 [Yu, Danxia; Shu, Xiao-Ou; Yang, Gong; Cai, Qiuyin; Zheng, Wei; Zhang, Xianglan] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. [Li, Honglan; Gao, Yu-Tang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Franke, Adrian A.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. RP Zhang, XL (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. EM xianglan218@gmail.com FU NIH [R01HL095931, R37CA070867, UM1-CA182910, P30CA71789]; Vanderbilt-Ingram Cancer Center [P30CA068485] FX Supported by the NIH (grants R01HL095931, R37CA070867, UM1-CA182910, and P30CA71789). The sample preparation was performed at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485). NR 30 TC 2 Z9 2 U1 3 U2 13 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 SEP PY 2015 VL 102 IS 3 BP 680 EP 686 DI 10.3945/ajcn.115.111591 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR2II UT WOS:000361150900020 PM 26245809 ER PT J AU Bailey, RL Looker, AC Lu, ZH Fan, RZ Eicher-Miller, HA Fakhouri, TH Gahche, JJ Weaver, CM Mills, JL AF Bailey, Regan L. Looker, Anne C. Lu, Zhaohui Fan, Ruzong Eicher-Miller, Heather A. Fakhouri, Tala H. Gahche, Jaime J. Weaver, Connie M. Mills, James L. TI B-vitamin status and bone mineral density and risk of lumbar osteoporosis in older females in the United States SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE DXA; NHANES; bone turnover markers; homocysteine; osteoporosis ID RANDOMIZED CONTROLLED-TRIAL; METHYLMALONIC ACID CONCENTRATIONS; NUTRITION EXAMINATION SURVEYS; FOLIC-ACID; POSTMENOPAUSAL WOMEN; TURNOVER MARKERS; TOTAL HOMOCYSTEINE; NATIONAL-HEALTH; FRACTURE RISK; COBALAMIN DEFICIENCY AB Background: Previous data suggest that elevated serum total homocysteine (tHcy) may be a risk factor for bone fracture and osteoporosis. Nutritional causes of elevated tHcy are suboptimal B-vitamin status. To our knowledge, this is the first nationally representative report on the relation of B vitamins and bone health from a population with folic acid fortification. Objective: The purpose of this analysis was to examine the relation between B-vitamin status biomarkers and bone mineral density (BMD), risk of osteoporosis, and biomarkers of bone turnover. Design: We examined the relation of tHcy, methylmalonic acid (MMA), and serum/red blood cell folate and total-body and lumbar spine BMD in women aged >= 50 y participating in the NHANES 1999-2004 (n = 2806), a nationally representative cross-sectional survey. These are the only years with concurrent measurement of tHcy and whole-body dual-energy X-ray absorptiometry. We also examined B-vitamin biomarkers relative to bone turnover markers, bone alkaline phosphatase, and urinary N-terminal cross-linked telopeptide of type I collagen in a 1999-2002 subset with available data (n = 1813). Results: In comparison with optimal concentrations, women with elevated tHcy were older with lower serum vitamin B-12, red blood cell folate, and dietary micronutrient intakes and had significantly higher mean +/- SE markers of bone turnover (bone alkaline phosphatase: 15.8 +/- 0.59 compared with 14.0 +/- 0.25 mu g/L; urinary N-terminal crosslinked telopeptide of type I collagen: 48.2 +/- 2.9 compared with 38.9 +/- 0.90 nmol bone collagen equivalents per mmol creatinine/L). Elevated MMA (OR: 1.88; 95% CI: 1.10, 3.18) and tHcy (OR: 2.17; 95% CI: 1.14, 4.15) were related to increased risk of lumbar osteoporosis. When examined as a continuous variable, tHcy was negatively associated, serum folates were positively associated, and MMA and vitamin B-12 were not significantly associated with lumbar and total-body BMD. Conclusion: In this nationally representative population of older US women with high exposure to B vitamins through food fortification and dietary supplements, only elevated tHcy and MMA were independently associated with risk of lumbar spine osteoporosis. C1 [Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Lu, Zhaohui; Fan, Ruzong; Mills, James L.] NIH, Eunice Kennedy Shriver Natl Inst Child & Human De, Bethesda, MD 20892 USA. [Looker, Anne C.; Gahche, Jaime J.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Bailey, Regan L.; Eicher-Miller, Heather A.; Weaver, Connie M.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Fakhouri, Tala H.] ICF Int, Rockville, MD USA. RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. EM baileyr@mail.nih.gov FU Intramural Research Program, Eunice Kennedy Shriver National Institute of Child and Human Development; Office of Dietary Supplements, NIH FX Supported in part by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child and Human Development and the Office of Dietary Supplements, NIH. NR 80 TC 3 Z9 3 U1 4 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2015 VL 102 IS 3 BP 687 EP 694 DI 10.3945/ajcn.115.108787 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CR2II UT WOS:000361150900021 PM 26224297 ER PT J AU Besharat, S Poustchi, H Mohamadkhani, A Roshandel, G Freedman, ND Merat, S Sotoudelunanesh, R Malekzadeh, R AF Besharat, Sima Poustchi, Hossein Mohamadkhani, Ashraf Roshandel, Gholamreza Freedman, Neal D. Merat, Shahin Sotoudelunanesh, Rasoul Malekzadeh, Reza TI Central Obesity and Advanced Liver Stiffness in Hepatitis B: Result from Golestan Hepatitis B Cohort Study SO ARCHIVES OF IRANIAN MEDICINE LA English DT Article DE Central obesity; chronic Hepatitis B; liver fibrosis; liver stiffness; waist circumference ID METABOLIC SYNDROME; FATTY LIVER; TRANSIENT ELASTOGRAPHY; FIBROSIS PROGRESSION; VIRUS INFECTION; STEATOSIS; ASSOCIATION; DISEASE; RISK; CARRIERS AB Background: Chronic infection with the hepatitis B virus and obesity may both contribute synergistically to liver disease, although relatively few studies have investigated this hypothesis. Therefore, in this study, we evaluated the relationship between central obesity and the liver stiffness in the Golestan Hepatitis B cohort study (GHBCS). Methods: Our study included 304 chronic hepatitis B (CHB) patients enrolled from GHBCS. Liver stiffness measurement (LSM) and laboratory tests were performed after a follow-up of 4 years (2012). The hepatitis B viral load was measured at the baseline and follow-up using the real-time PCR method. Waist circumference >= 102 cm in men and 89 cm in women (central obesity) was considered to be abnormal. Advanced liver stiffness (ALS) was defined as LSM >= 8 KPa. Statistical analysis was performed using SPSS-V17. Logistic regression was used to test predictors of advanced liver stiffness (LSM 8 KPa). Linear regression was used to test the predictive value of variables in ALT (as a continuous variable). P-value of less than 0.05 was considered statistically significant. Results: Among these CHB patients, 19 (7.4%) cases with a mean (+/- SD) age of 49.5 (+/- 6.3) developed ALS after 4 years of follow-up. Multivariate analysis showed a significant predictive role of central obesity and viral load in ALS. Conclusions: Central obesity is related to the liver stiffness in chronic hepatitis B patients. Conclusions: Central obesity is related to the liver stiffness in chronic hepatitis B patients. C1 [Besharat, Sima; Poustchi, Hossein; Mohamadkhani, Ashraf; Merat, Shahin; Sotoudelunanesh, Rasoul] Univ Tehran Med Sci, Digest Dis Res Inst, Liver & Pancreatobiliary Dis Res Ctr, Tehran, Iran. [Besharat, Sima; Roshandel, Gholamreza] Golestan Univ Med Sci, Golestan Res Ctr Gastroentrol & Hepatol, Gorgan, Iran. [Roshandel, Gholamreza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran. [Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Poustchi, H (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Inst, Deputy Educ, N Kargar St,POB 14117, Tehran, Iran. EM h.poustchi@gmail.com RI Freedman, Neal/B-9741-2015; Besharat, Sima/L-7351-2016; Roshandel, gholamreza/N-2260-2016 OI Freedman, Neal/0000-0003-0074-1098; Besharat, Sima/0000-0002-0540-6056; Roshandel, gholamreza/0000-0002-5494-0722 FU Tehran University of Medical Sciences (TUMS) FX This paper is in partial fulfillment of a doctoral thesis in cellular and molecular research. Authors give thanks for the financial support of Tehran University of Medical Sciences (TUMS), Research Deputy. Special thanks are given to the staff of Digestive Diseases Research Institute (DDRI), laboratory division. NR 25 TC 1 Z9 1 U1 0 U2 3 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 EI 1735-3947 J9 ARCH IRAN MED JI Arch. Iran. Med. PD SEP PY 2015 VL 18 IS 9 BP 562 EP 566 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CR3II UT WOS:000361225200001 PM 26317595 ER PT J AU Sodt, AJ Pastor, RW Lyman, E AF Sodt, Alexander J. Pastor, Richard W. Lyman, Edward TI Hexagonal Substructure and Hydrogen Bonding in Liquid-Ordered Phases Containing Palmitoyl Sphingomyelin SO BIOPHYSICAL JOURNAL LA English DT Article ID ADDITIVE FORCE-FIELD; LIPID-BILAYERS; CONDENSED COMPLEXES; PLASMA-MEMBRANE; MODEL MEMBRANES; MOLECULAR-LEVEL; CELL-MEMBRANES; CHOLESTEROL; MIXTURES; DYNAMICS AB All-atom simulation data are presented for ternary mixtures of palmitoyl sphingomyelin (PSM), cholesterol, and either palmitoyl oleoyl phosphatidyl choline or dioleoyl phosphatidyl choline (DOPC). For comparison, data for a mixture of dipalmitoyl phosphatidyl choline (DPPC), cholesterol, and DOPC are also presented. Compositions corresponding to the liquid-ordered phase, the liquid-disordered phase, and coexistence of the two phases are simulated for each mixture. Within the liquid-ordered phase, cholesterol is preferentially solvated by DOPC if it is available, but if DOPC is replaced by POPC, cholesterol is preferentially solvated by PSM. In the DPPC mixtures, cholesterol interacts preferentially with the saturated chains via its smooth face, whereas in the PSM mixtures, cholesterol interacts preferentially with PSM via its rough face. Interactions between cholesterol and PSM have a very particular character: hydrogen bonding between cholesterol and the amide of PSM rotates the tilt of the amide plane, which primes it for more robust hydrogen bonding with other PSM. Cholesterol-PSM hydrogen bonding also locally modifies the hexagonal packing of hydrocarbon chains in the liquid-ordered phase of PSM mixtures. C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA. [Lyman, Edward] Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA. [Lyman, Edward] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. RP Lyman, E (reprint author), Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA. EM elyman@udel.edu FU Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI); National Institutes of Health [P41GM103712-S1]; NHLBI LoBoS cluster FX This research was supported in part by the Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, and utilized the NHLBI LoBoS cluster. Anton computer time was provided by the National Resource for Biomedical Supercomputing (NRBSC), the Pittsburgh Supercomputing Center (PSC), and the Biomedical Technology Research Center for Multiscale Modeling of Biological Systems through grant P41GM103712-S1 from the National Institutes of Health. The Anton machine at NRBSC/PSC was generously made available by D.E. Shaw Research. NR 59 TC 13 Z9 13 U1 3 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD SEP 1 PY 2015 VL 109 IS 5 BP 948 EP 955 DI 10.1016/j.bpj.2015.07.036 PG 8 WC Biophysics SC Biophysics GA CQ9UK UT WOS:000360960500012 PM 26331252 ER PT J AU Nagle, CM Dixon, SC Jensen, A Kjaer, SK Modugno, F deFazio, A Fereday, S Hung, J Johnatty, SE Fasching, PA Beckmann, MW Lambrechts, D Vergote, I Van Nieuwenhuysen, E Lambrechts, S Risch, HA Rossing, MA Doherty, JA Wicklund, KG Chang-Claude, J Goodman, MT Ness, RB Moysich, K Heitz, F du Bois, A Harter, P Schwaab, I Matsuo, K Hosono, S Goode, EL Vierkant, RA Larson, MC Fridley, BL Hogdall, C Schildkraut, JM Weber, RP Cramer, DW Terry, KL Bandera, EV Paddock, L Rodriguez-Rodriguez, L Wentzensen, N Yang, HP Brinton, LA Lissowska, J Hogdall, E Lundvall, L Whittemore, A McGuire, V Sieh, W Rothstein, J Sutphen, R Anton-Culver, H Ziogas, A Pearce, CL Wu, AH Webb, PM AF Nagle, C. M. Dixon, S. C. Jensen, A. Kjaer, S. K. Modugno, F. deFazio, A. Fereday, S. Hung, J. Johnatty, S. E. Fasching, P. A. Beckmann, M. W. Lambrechts, D. Vergote, I. Van Nieuwenhuysen, E. Lambrechts, S. Risch, H. A. Rossing, M. A. Doherty, J. A. Wicklund, K. G. Chang-Claude, J. Goodman, M. T. Ness, R. B. Moysich, K. Heitz, F. du Bois, A. Harter, P. Schwaab, I. Matsuo, K. Hosono, S. Goode, E. L. Vierkant, R. A. Larson, M. C. Fridley, B. L. Hogdall, C. Schildkraut, J. M. Weber, R. P. Cramer, D. W. Terry, K. L. Bandera, E. V. Paddock, L. Rodriguez-Rodriguez, L. Wentzensen, N. Yang, H. P. Brinton, L. A. Lissowska, J. Hogdall, E. Lundvall, L. Whittemore, A. McGuire, V. Sieh, W. Rothstein, J. Sutphen, R. Anton-Culver, H. Ziogas, A. Pearce, C. L. Wu, A. H. Webb, P. M. CA Australian Ovarian Canc Study Grp Ovarian Canc Assoc Consortium TI Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; obesity; overall survival; progression-free survival; ovarian cancer-specific survival ID PROTEIN EXPRESSION; HORMONE-THERAPY; CELL-GROWTH; IN-VITRO; RISK; ESTROGEN; IMPACT; MORTALITY; GENE; TIME AB Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: >= 35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer. C1 [Nagle, C. M.; Dixon, S. C.; Webb, P. M.] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia. [Dixon, S. C.; Webb, P. M.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia. [Jensen, A.; Kjaer, S. K.; Hogdall, E.] Danish Canc Soc Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark. [Kjaer, S. K.; Hogdall, C.; Lundvall, L.] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark. [Modugno, F.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Modugno, F.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Modugno, F.] Magee Womens Res Inst, Womens Canc Res Program, Philadelphia, PA USA. [Modugno, F.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [deFazio, A.; Hung, J.] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. [deFazio, A.; Hung, J.] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Westmead, NSW 2145, Australia. [Fereday, S.; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Johnatty, S. E.] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia. [Fasching, P. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fasching, P. A.; Beckmann, M. W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Lambrechts, D.] VIB, Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, D.] Univ Leuven, Dept Oncol, Leuven, Belgium. [Vergote, I.; Van Nieuwenhuysen, E.; Lambrechts, S.] Univ Hosp Leuven, Leuven Canc Inst, Dept Obstet & Gynecol, Leuven, Belgium. [Risch, H. A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Rossing, M. A.; Wicklund, K. G.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Doherty, J. A.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH USA. [Chang-Claude, J.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Goodman, M. T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Ness, R. B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Moysich, K.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Heitz, F.; du Bois, A.; Harter, P.] Knappschaft GmbH, Evang Huyssens Stiftung, Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany. [Heitz, F.; du Bois, A.; Harter, P.] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [Schwaab, I.] Inst Humangenet Wiesbaden, Wiesbaden, Germany. [Matsuo, K.] Kyushu Univ, Dept Prevent Med, Fac Med Sci, Nagoya, Aichi, Japan. [Hosono, S.] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Goode, E. L.; Vierkant, R. A.; Larson, M. C.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA. [Fridley, B. L.] Univ Kansas, Dept Biostat, Kansas City, KS USA. [Schildkraut, J. M.; Weber, R. P.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Cramer, D. W.; Terry, K. L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Bandera, E. V.; Rodriguez-Rodriguez, L.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Paddock, L.] New Jersey State Canc Registry, Trenton, NJ USA. [Wentzensen, N.; Yang, H. P.; Brinton, L. A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Lissowska, J.] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Hogdall, E.] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark. [Whittemore, A.; McGuire, V.; Sieh, W.; Rothstein, J.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Sutphen, R.] Univ S Florida, Coll Med, Epidemiol Ctr, Tampa, FL USA. [Anton-Culver, H.; Ziogas, A.] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Pearce, C. L.; Wu, A. H.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Nagle, CM (reprint author), QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia. EM christina.nagle@qimrberghofer.edu.au RI Bowtell, David/H-1007-2016; Johnatty, Sharon/R-8890-2016; OI Bowtell, David/0000-0001-9089-7525; Johnatty, Sharon/0000-0002-7888-1966; Kjaer, Susanne/0000-0002-8347-1398 FU Ovarian Cancer Association Consortium; Ovarian Cancer Research Fund; National Institutes of Health [R01-CA61107, R01-CA95023, R01-CA126841, P01-CA17054, NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720, R01-CA074850, R01-CA080742, R01-CA112523, R01-CA087538, R01-CA058598, N01-CN-55424, N01-PC-67001, R01-CA122443, P50-CA136393, P30-CA15083, R01-CA076016, R01-CA054419, P50-CA105009, U01-CA71966, R01-CA016056, K07-CA143047, R01-CA106414, R01CA058860, R01CA092044, PSA042205]; Department of Defense [DAMD17-02-1-0666, W81XWH-10-1-02802, DAMD17-02-1-0669, DAMD17-01-1-0729, DAMD17-98-1-8659]; National Cancer Institute [K07-CA80668]; NIH/National Center for Research Resources/General Clinical Research Center [MO1-RR000056, P50-CA159981]; National Health and Medical Research Council of Australia; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Queensland; Cancer Council of South Australia; Cancer Council of Tasmania; Cancer Foundation of Western Australia; National Health and Medical Research Council of Australia [199600, 400281]; Danish Cancer Society, Copenhagen, Denmark [94 222 52]; Mermaid I project; California Cancer Research Program [00-01389V-20170, R03-CA113148, R03-CA115195, N01-CN25403, 2II0200]; ELAN Funds of the University of Erlangen-Nuremberg; Nationaal Kankerplan; German Federal Ministry of Education and Research; Programme of Clinical Biomedical Research [01 GB 9401]; Ministry of Education, Science, Sports, Culture and Technology of Japan; Ministry Health, Labour and Welfare of Japan; Takeda Science Foundation; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Cancer Institute of New Jersey; Intramural Research Program of the National Cancer Institute; Cancer Prevention Institute of California [U01-CA69417]; American Cancer Society [CRTG-00-196-01-CCE]; Celma Mastry Ovarian Cancer Foundation; Lon V Smith Foundation [LVS-39420]; NHMRC; NHMRC Program [552429]; University of Sydney Cancer Research Fund; Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre; [K07-CA080668] FX We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. The Australian Ovarian Cancer Study Management Group (D Bowtell, G Chenevix-Trench, A deFazio, D Gertig, A Green and PM Webb) and ACS Investigators (A Green, P Parsons, N Hayward, PM Webb and D Whiteman) thank all the clinical and scientific collaborators (see http://www.aocstudy.org/) and the women who participated in these studies for their contribution. We thank Gilian Peuteman, Thomas Van Brussel and Dominiek Smeets for technical assistance (for BEL). The cooperation of the 32 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. We assume full responsibility for analyses and interpretation of these data (for CON). The German Ovarian Cancer Study (GER) thank Ursula Eilber for competent technical assistance (for GER). Funding: The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund. This work was supported by the following: National Institutes of Health (R01-CA61107 (for MAL); R01-CA95023 and R01-CA126841 (for HOP); P01-CA17054 (for USC); NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563 and P30-CA072720 (for NJO); (R01-CA074850 and R01-CA080742 (for CON); R01-CA112523 and R01-CA087538 (for DOV); R01-CA058598, N01-CN-55424 and N01-PC-67001 (for HAW); R01-CA122443, P50-CA136393 and P30-CA15083 (for MAC and MAY); R01-CA076016 (for NCO); R01-CA054419 and P50-CA105009 (for NEC); U01-CA71966, R01-CA016056 and K07-CA143047 (for STA); R01-CA106414 (for TBO); R01CA058860, R01CA092044 and PSA042205 (for UCI); Department of Defense (DAMD17-02-1-0666 (for NCO); W81XWH-10-1-02802 (for NEC); DAMD17-02-1-0669 (for HOP); DAMD17-01-1-0729 (for AUS); DAMD17-98-1-8659 (for TBO); National Cancer Institute K07-CA80668 (for HOP); NIH/National Center for Research Resources/General Clinical Research Center grant MO1-RR000056 and P50-CA159981 (for HOP); National Health and Medical Research Council of Australia, Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, Cancer Foundation of Western Australia; National Health and Medical Research Council of Australia (199600 and 400281) (for AUS); Danish Cancer Society, Copenhagen, Denmark (94 222 52) and the Mermaid I project (for MAL); FM supported by funding from K07-CA080668 (for HOP); California Cancer Research Program (00-01389V-20170, R03-CA113148, R03-CA115195, N01-CN25403 and 2II0200) (for USC); ELAN Funds of the University of Erlangen-Nuremberg (for BAV); Nationaal Kankerplan (for BEL); German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and data management by the German Cancer Research Center (for GER); Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, and by a grant from Takeda Science Foundation (for JPN); Mayo Foundation, Minnesota Ovarian Cancer Alliance, Fred C. and Katherine B.; Andersen Foundation (for MAC and MAY); Cancer Institute of New Jersey (for NJO); Intramural Research Program of the National Cancer Institute (for POL); Cancer Prevention Institute of California (U01-CA69417) (for STA); American Cancer Society (CRTG-00-196-01-CCE), Celma Mastry Ovarian Cancer Foundation (for TBO); and Lon V Smith Foundation grant LVS-39420 (for UCI). PW is supported by a Fellowship from NHMRC and CN is supported by NHMRC Program grant 552429 (for AUS). AdF is supported by the University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre (for AUS). NR 66 TC 14 Z9 15 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 1 PY 2015 VL 113 IS 5 BP 817 EP 826 DI 10.1038/bjc.2015.245 PG 10 WC Oncology SC Oncology GA CQ6PU UT WOS:000360727200016 PM 26151456 ER PT J AU Gardner, K Hoppe, C Mijovic, A Thein, SL AF Gardner, Kate Hoppe, Carolyn Mijovic, Aleksandar Thein, Swee L. TI How we treat delayed haemolytic transfusion reactions in patients with sickle cell disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE delayed haemolytic transfusion reactions; hyperhaemolysis; vaso-occlusive crisis; alloantibodies; sickle cell disease ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; BLOOD-TRANSFUSION; RENAL-FAILURE; INTRAVENOUS IMMUNOGLOBULIN; CLINICAL-SIGNIFICANCE; UNITED-KINGDOM; RED-CELLS; ANEMIA; ALLOIMMUNIZATION; ALLOANTIBODIES AB Transfusion therapy is effective in the prevention and treatment of many complications of sickle cell disease (SCD). However, its benefits must be balanced against its risks, including delayed haemolytic transfusion reactions (DHTR). Not only is the relative rate of alloimmunization higher in patients with SCD than in other patient populations, but attendant risks associated with DHTR are even greater in SCD. Clinicians' awareness of DHTR events is poor because symptoms of DHTR mimic acute vaso-occlusive pain and immunohaematology findings are often negative. Transfusions delivered in the acute rather than elective setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends on the clinical severity, ranging from supportive care to immunosuppression, and optimization of erythropoiesis. DHTR must be considered in any recently transfused patient presenting with acute sickle cell pain. Meticulous documentation of transfusion and immunohaematology history is key. We anticipate an increase in DHTR events in SCD patients with the increasing use of red blood cell transfusion therapy. C1 [Gardner, Kate; Thein, Swee L.] Kings Coll London, Fac Life Sci & Med, Mol Haematol, London WC2R 2LS, England. [Gardner, Kate; Mijovic, Aleksandar; Thein, Swee L.] Kings Coll Hosp NHS Fdn Trust, Dept Haematol Med, London, England. [Hoppe, Carolyn] Childrens Hosp & Res Ctr Oakland, Div Hematol Oncol, Oakland, CA USA. [Thein, Swee L.] NHLBI, NIH, Sickle Cell Branch, Bethesda, MD 20892 USA. RP Thein, SL (reprint author), NHLBI, NIH, Bldg 10-CRC-5E-5142,10 Ctr Dr, Bethesda, MD 20892 USA. EM sl.thein@nih.gov NR 71 TC 8 Z9 8 U1 0 U2 7 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 SEP PY 2015 VL 170 IS 6 BP 745 EP 756 DI 10.1111/bjh.13494 PG 12 WC Hematology SC Hematology GA CQ7BG UT WOS:000360757200003 PM 25967919 ER PT J AU Steinberg, MH Rodgers, GP AF Steinberg, Martin H. Rodgers, Griffin P. TI HbA(2): biology, clinical relevance and a possible target for ameliorating sickle cell disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE HbS polymer; haemoglobin switching; foetal haemoglobin; delta-globin gene; sickle haemoglobin ID DELTA-GLOBIN GENE; BETA-THALASSEMIA MUTATIONS; FETAL-HEMOGLOBIN; HEREDITARY PERSISTENCE; CAPILLARY-ELECTROPHORESIS; HEMATOLOGICAL PARAMETERS; IRON-DEFICIENCY; HB A(2); IN-VIVO; EXPRESSION AB HbA(2), a tetramer of - and -globin chains, provides a diagnostic clue to the presence of -thalassaemia trait. This minor haemoglobin, which forms about 2-3% of the total, has no known physiological role, but has the interesting property of preventing polymerization of deoxy-sickle haemoglobin. If it were possible to increase the level of HbA(2) sufficiently it could have a benefit in sickle cell disease similar to that of foetal haemoglobin. Moreover, HbA(2) is present in all erythrocytes, an advantage not found with foetal haemoglobin, which is heterocellularly expressed. The molecular basis of HbA(2) gene (HBD) expression is partially understood, and with new molecular tools, it might be possible to induce levels of HbA(2) that could be clinically important. However, high concentrations of this positively charged haemoglobin might damage the erythrocyte membrane; also, the reciprocal relationship of - and -globin gene (HBD and HBG1/2, respectively) expression might negate any benefit of increasing transcription of the former. C1 [Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Rodgers, Griffin P.] NIDDK, NIH, Bethesda, MD USA. RP Steinberg, MH (reprint author), Boston Univ, Sch Med, Dept Med, 72 E Concord St, Boston, MA 02118 USA. EM mhsteinb@bu.edu FU [R01 HL107443]; [R01 HL 87681] FX Supported in part by: R01 HL107443 and R01 HL 87681 (MHS) NR 68 TC 1 Z9 1 U1 3 U2 11 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 SEP PY 2015 VL 170 IS 6 BP 781 EP 787 DI 10.1111/bjh.13570 PG 7 WC Hematology SC Hematology GA CQ7BG UT WOS:000360757200006 PM 26104837 ER PT J AU Maresso, KC Tsai, KY Brown, PH Szabo, E Lippman, S Hawk, ET AF Maresso, Karen Colbert Tsai, Kenneth Y. Brown, Powel H. Szabo, Eva Lippman, Scott Hawk, Ernest T. TI Molecular Cancer Prevention: Current Status and Future Directions SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE molecular prevention; chemoprevention; prevention; randomized controlled trial ID RANDOMIZED CONTROLLED-TRIAL; SQUAMOUS-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; FAMILIAL ADENOMATOUS POLYPOSIS; SERVICES TASK-FORCE; 2ND PRIMARY TUMORS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HELICOBACTER-PYLORI ERADICATION; INFLAMMATORY-BOWEL-DISEASE; INVASIVE BREAST-CANCER AB The heterogeneity and complexity of advanced cancers strongly support the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (eg, aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the US Food and Drug Administration for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet it has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, several challenges to the field must be addressed. Here, the authors provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results from major randomized controlled trials. (c) 2015 American Cancer Society. C1 [Maresso, Karen Colbert] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Tsai, Kenneth Y.] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Dermatol, Houston, TX 77030 USA. [Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Lippman, Scott] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Hawk, Ernest T.] Univ Texas MD Anderson Canc Ctr, Early Prevent Canc, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. RP Hawk, ET (reprint author), Div Canc Prevent & Populat Sci, Early Prevent Canc, Dan L Duncan Bldg CPB8-3088,1515 Holcombe Blvd, Houston, TX 77030 USA. EM ehawk@mdanderson.org FU MD Anderson Cancer Center [5P30CA016672-37]; American Association for Cancer Research Landon Foundation Innovator Award for Cancer Prevention Research; University of California San Diego Moores Cancer Center from the National Institutes of Health [3P30CA023100-28]; National Institutes of Health [N01, R01] FX This work was supported in part by the Boone Pickens Distinguished Chair for Early Prevention of Cancer to Ernest T. Hawk; by an American Association for Cancer Research Landon Foundation Innovator Award for Cancer Prevention Research, the Duncan Family Institute Seed funding program, and the T. Boone Pickens Endowment to Kenneth Y. Tsai; and by the MD Anderson Cancer Center Support Grant 5P30CA016672-37 and the University of California San Diego Moores Cancer Center Support Grant 3P30CA023100-28 from the National Institutes of Health. Powel H. Brown reports grants from the National Institutes of Health (N01, R01) during the conduct of the study; personal fees and grants ( Promise, Scientific Advisory Board) from the Susan G. Komen Foundation, and grants from the Breast Cancer Research Foundation outside the submitted work. Ernest T. Hawk reports consultant/advisor fees from PLx Pharma Inc and Pozen Inc; consultant/advisor fees as well as grant/research funding from Cancer Prevention Pharmaceuticals; royalties from John Wiley & Sons Ltd; nonfinancial support from the National Cancer Institute, the American Association of Cancer Research, Huntsman Cancer Institute, the University of Kansas Cancer Center, Mayo Clinic Cancer Center, Roswell Park Cancer Institute, Ohio State University Comprehensive Cancer Center, Simmons Cancer Center, and the American Cancer Society; and grants from the National Institutes of Health/National Cancer Institute and the Cancer Prevention Research Institute of Texas outside the submitted work. Karen Colbert Maresso, Eva Szabo, and Scott Lippman report no conflicts of interest. NR 319 TC 10 Z9 10 U1 5 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 2015 VL 65 IS 5 BP 345 EP 383 DI 10.3322/caac.21287 PG 39 WC Oncology SC Oncology GA CR0EH UT WOS:000360990600004 PM 26284997 ER PT J AU Mirabello, L Koster, R Moriarity, BS Spector, LG Meltzer, PS Gary, J Machiela, MJ Pankratz, N Panagiotou, OA Largaespada, D Wang, ZM Gastier-Foster, JM Gorlick, R Khanna, C de Toledo, SRC Petrilli, AS Patino-Garcia, A Sierrasesumaga, L Lecanda, F Andrulis, IL Wunder, JS Gokgoz, N Serra, M Hattinger, C Picci, P Scotlandi, K Flanagan, AM Tirabosco, R Amary, MF Halai, D Ballinger, ML Thomas, DM Davis, S Barkauskas, DA Marina, N Helman, L Otto, GM Becklin, KL Wolf, NK Weg, MT Tucker, M Wacholder, S Fraumeni, JF Caporaso, NE Boland, JF Hicks, BD Vogt, A Burdett, L Yeager, M Hoover, RN Chanock, SJ Savage, SA AF Mirabello, Lisa Koster, Roelof Moriarity, Branden S. Spector, Logan G. Meltzer, Paul S. Gary, Joy Machiela, Mitchell J. Pankratz, Nathan Panagiotou, Orestis A. Largaespada, David Wang, Zhaoming Gastier-Foster, Julie M. Gorlick, Richard Khanna, Chand de Toledo, Silvia Regina Caminada Petrilli, Antonio S. Patino-Garcia, Ana Sierrasesumaga, Luis Lecanda, Fernando Andrulis, Irene L. Wunder, Jay S. Gokgoz, Nalan Serra, Massimo Hattinger, Claudia Picci, Piero Scotlandi, Katia Flanagan, Adrienne M. Tirabosco, Roberto Amary, Maria Fernanda Halai, Dina Ballinger, Mandy L. Thomas, David M. Davis, Sean Barkauskas, Donald A. Marina, Neyssa Helman, Lee Otto, George M. Becklin, Kelsie L. Wolf, Natalie K. Weg, Madison T. Tucker, Margaret Wacholder, Sholom Fraumeni, Joseph F., Jr. Caporaso, Neil E. Boland, Joseph F. Hicks, Belynda D. Vogt, Aurelie Burdett, Laurie Yeager, Meredith Hoover, Robert N. Chanock, Stephen J. Savage, Sharon A. TI A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma SO CANCER DISCOVERY LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-5; HIGH-GRADE OSTEOSARCOMA; STUDY-GROUP PROTOCOLS; PROGNOSTIC-FACTORS; POTENTIAL TARGET; GENETIC SCREEN; TUMOR-GROWTH; RECEPTOR; CELLS AB Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 x 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene. SIGNIFICANCE: Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma. (C) 2015 AACR. C1 [Mirabello, Lisa; Koster, Roelof; Machiela, Mitchell J.; Panagiotou, Orestis A.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F., Jr.; Caporaso, Neil E.; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20850 USA. [Moriarity, Branden S.; Spector, Logan G.; Largaespada, David] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Moriarity, Branden S.; Largaespada, David; Otto, George M.; Weg, Madison T.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Moriarity, Branden S.; Largaespada, David; Becklin, Kelsie L.; Wolf, Natalie K.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Moriarity, Branden S.; Largaespada, David] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA. [Meltzer, Paul S.; Khanna, Chand; Davis, Sean; Helman, Lee] NCI, Ctr Canc Res, NIH, Bethesda, MD 20850 USA. [Gary, Joy] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20850 USA. [Gary, Joy] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. [Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Wang, Zhaoming; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith] Frederick Natl Lab Canc Res, Canc Genom Res Lab, Leidos Biomed Res, Frederick, MD USA. [Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Columbus, OH USA. [Gastier-Foster, Julie M.] Ohio State Univ, Dept Pathol & Pediat, Columbus, OH 43210 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA. [de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.] Univ Fed Sao Paulo, Pediat Oncol Inst, GRAACC, Sao Paulo, SP, Brazil. [Patino-Garcia, Ana; Sierrasesumaga, Luis; Lecanda, Fernando] Univ Navarra, Dept Pediat, Univ Navarra Clin, E-31080 Pamplona, Spain. [Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia] Ist Ortoped Rizzoli, Expt Oncol Lab, Bologna, Italy. [Flanagan, Adrienne M.] UCL, Inst Canc, London, England. [Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina] Royal Natl Orthopaed Hosp Natl Hlth Serv Trust, Stanmore, Middx, England. [Ballinger, Mandy L.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Thomas, David M.] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia. [Barkauskas, Donald A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Marina, Neyssa] Stanford Univ, Palo Alto, CA 94304 USA. [Marina, Neyssa] Lucile Packard Childrens Hosp, Palo Alto, CA USA. RP Mirabello, L (reprint author), NCI, NIH, 9609 Med Ctr Dr,Room 6E422, Bethesda, MD 20850 USA. EM mirabellol@mail.nih.gov RI Koster, Roelof/E-2158-2016; Savage, Sharon/B-9747-2015; Andrulis, Irene/E-7267-2013; Serra, Massimo/J-4878-2016; Hattinger, Claudia/Q-1212-2016; Panagiotou, Orestis/I-5934-2015; Picci, Piero/J-5979-2016 OI Koster, Roelof/0000-0003-1424-8579; Ballinger, Mandy/0000-0002-9706-0514; Machiela, Mitchell/0000-0001-6538-9705; Spector, Logan/0000-0003-2516-0222; Savage, Sharon/0000-0001-6006-0740; Serra, Massimo/0000-0003-0742-1177; Hattinger, Claudia/0000-0002-9316-5095; Panagiotou, Orestis/0000-0001-9604-8380; Picci, Piero/0000-0002-8519-4101 FU intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; Bone Cancer Research Trust UK; NIH [U01CA122371]; Zach Sobiech Osteosarcoma Fund of Children's Cancer Research Fund; Human Specimen Banking Grant of the Children's Oncology Group from the National Cancer Institute, NIH [U24 CA114766]; WWWW (QuadW) Foundation, Inc.; Ontario Research Fund; Canadian Foundation for Innovation; Regione Emilia-Romagna; Royal National Orthopaedic Hospital Musculoskeletal Research Programme; Biobank; National Institute for Health Research UCLH Biomedical Research Centre; UCL Experimental Cancer Centre; FIS [PI13/01476]; ISCIII; La Fundacion Bancaria "La Caixa," Fundacion Caja Navarra; Rainbows for Kate Foundation; Liddy Shriver Sarcoma Initiative; Victorian Cancer Agency; Australian National Health and Medical Research Council [APP1004017]; Cancer Australia [APP1067094]; [U10 CA98543] FX This study was funded by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. This work was supported by the Bone Cancer Research Trust UK (to A.M. Flanagan), and grants (to L.G. Spector) from the NIH U01CA122371 and from The Zach Sobiech Osteosarcoma Fund of Children's Cancer Research Fund. Research is supported by the Chair's Grant U10 CA98543 and Human Specimen Banking Grant U24 CA114766 of the Children's Oncology Group from the National Cancer Institute, NIH. Additional support for research is provided by a grant from the WWWW (QuadW) Foundation, Inc. to the Children's Oncology Group. This work was supported by grants to I.L. Andrulis and J.S. Wunder from the Ontario Research Fund and the Canadian Foundation for Innovation. This study was also supported by biobank grants from the Regione Emilia-Romagna, and by the infrastructure and personnel of the Royal National Orthopaedic Hospital Musculoskeletal Research Programme and Biobank. Support was also provided to A.M. Flanagan [University College London (UCL)] by the National Institute for Health Research UCLH Biomedical Research Centre, and the UCL Experimental Cancer Centre, funding from PI13/01476, FIS, ISCIII, and La Fundacion Bancaria "La Caixa," Fundacion Caja Navarra to A. Patino-Garcia and L. Sierrasesumaga, and the AECC project to F. Lecanda. The International Sarcoma Kindred Study was supported by the Rainbows for Kate Foundation, the Liddy Shriver Sarcoma Initiative, the Victorian Cancer Agency, the Australian National Health and Medical Research Council (APP1004017), and Cancer Australia (APP1067094). NR 60 TC 11 Z9 12 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2015 VL 5 IS 9 BP 920 EP 931 DI 10.1158/2159-8290.CD-15-0125 PG 12 WC Oncology SC Oncology GA CQ8DA UT WOS:000360835200023 PM 26084801 ER PT J AU Yanik, EL Siddiqui, K Engels, EA AF Yanik, Elizabeth L. Siddiqui, Kulsoom Engels, Eric A. TI Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis SO CANCER MEDICINE LA English DT Article DE Immunosuppressants; kidney cancer; kidney transplantation; prostate cancer; rapamycin; sirolimus; skin cancer ID NONMELANOMA SKIN-CANCER; RANDOMIZED CONTROLLED-TRIAL; RENAL-ALLOGRAFT RECIPIENTS; SQUAMOUS-CELL CARCINOMAS; MAMMALIAN TARGET; CALCINEURIN INHIBITORS; MYCOPHENOLATE-MOFETIL; RAPAMYCIN INHIBITORS; CYCLOSPORINE-A; IMMUNOSUPPRESSION AB Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR]=0.71, 95% CI=0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR=0.49, 95% CI=0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR=0.19, 95% CI=0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR=1.06, 95% CI=0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR=0.40, 95% CI=0.20-0.81), and higher prostate cancer incidence (IRR=1.85, 95% CI=1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk. C1 [Yanik, Elizabeth L.; Siddiqui, Kulsoom; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Siddiqui, Kulsoom] Washington Univ, Brown Sch Social Work, St Louis, MO USA. RP Yanik, EL (reprint author), NCI, 9609 Med Canc Dr,Rm 6E-216, Bethesda, MD 20892 USA. EM elizabeth.yanik@nih.gov OI Yanik, Elizabeth/0000-0002-5835-0201 FU National Cancer Institute FX This research was supported by the Intramural Research Program of the National Cancer Institute. NR 50 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD SEP PY 2015 VL 4 IS 9 BP 1448 EP 1459 DI 10.1002/cam4.487 PG 12 WC Oncology SC Oncology GA CR0KM UT WOS:000361007400015 PM 26108799 ER PT J AU Bornstein, MH Putnick, DL Lansford, JE Deater-Deckard, K Bradley, RH AF Bornstein, Marc H. Putnick, Diane L. Lansford, Jennifer E. Deater-Deckard, Kirby Bradley, Robert H. TI A Developmental Analysis of Caregiving Modalities Across Infancy in 38 Low- and Middle-Income Countries SO CHILD DEVELOPMENT LA English DT Article ID CHILD-DEVELOPMENT; YOUNG-CHILDREN; GENDER SIMILARITIES; PARENTS; RESPONSIVENESS; METAANALYSIS; LIFE AB Caregiving is requisite to wholesome child development from the beginning of life. A cross-sectional microgenetic analysis of six caregiving practices across the child's 1st year (0-12months) in 42,539 families from nationally representative samples in 38 low- and middle-income countries is reported. Rates of caregiving varied tremendously within and across countries. However, caregiving practices followed one of two developmental trajectories: (a) greater proportions of caregivers read, told stories, and named, counted, and drew with each additional month of infant age, and (b) proportions of caregivers who played, sang songs, and took their infants outside increased each month from birth but reached an asymptote at 4-5months. Rates and growth functions of caregiving have implications for infant care and development. C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Lansford, Jennifer E.] Duke Univ, Durham, NC 27706 USA. [Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [Bradley, Robert H.] Arizona State Univ, Tempe, AZ 85287 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Suite 8030 6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov OI Deater-Deckard, Kirby/0000-0003-4151-2152; Putnick, Diane/0000-0002-6323-749X FU Intramural Research Program of the NIH, NICHD FX We thank A. Hancioglu, Y. Ota, O. Petrovic, and N. Ulkuer. This research was supported by the Intramural Research Program of the NIH, NICHD. NR 79 TC 1 Z9 1 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-3920 EI 1467-8624 J9 CHILD DEV JI Child Dev. PD SEP-OCT PY 2015 VL 86 IS 5 BP 1571 EP 1587 DI 10.1111/cdev.12402 PG 17 WC Psychology, Educational; Psychology, Developmental SC Psychology GA CR2UI UT WOS:000361185700018 PM 26280672 ER PT J AU Mammen, A AF Mammen, Andrew TI A 62-Year-Old Woman with Muscle Weakness Comment SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Mammen, Andrew] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Mammen, A (reprint author), NIAMS, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Regulat, NIH, Bldg 50,Room 1146, Bethesda, MD 20892 USA. EM andrew.mammen@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2015 VL 61 IS 9 BP 1136 EP 1136 DI 10.1373/clinchem.2014.236869 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CR1TD UT WOS:000361107000005 PM 26319450 ER PT J AU Yu, JXA Castranova, D Pham, VN Weinstein, BM AF Yu, Jianxin A. Castranova, Daniel Pham, Van N. Weinstein, Brant M. TI Single-cell analysis of endothelial morphogenesis in vivo SO DEVELOPMENT LA English DT Article DE Endothelial morphogenesis; Single-cell analysis; Plexin D1; Morphodynamics; Lumenization; Tight junction; Claudin 5 ID VASCULAR LUMEN FORMATION; 3-DIMENSIONAL EXTRACELLULAR MATRICES; MOLECULAR-MECHANISMS; PHENOTYPIC HETEROGENEITY; TRANSGENIC ZEBRAFISH; AXONAL REPULSION; BLOOD-VESSELS; ANGIOGENESIS; TIP; TUBULOGENESIS AB Vessel formation has been extensively studied at the tissue level, but the difficulty in imaging the endothelium with cellular resolution has hampered study of the morphogenesis and behavior of endothelial cells (ECs) in vivo. We are using endothelial-specific transgenes and high-resolution imaging to examine single ECs in zebrafish. By generating mosaics with transgenes that simultaneously mark endothelial nuclei and membranes we are able to definitively identify and study the morphology and behavior of individual ECs during vessel sprouting and lumen formation. Using these methods, we show that developing trunk vessels are composed of ECs of varying morphology, and that single-cell analysis can be used to quantitate alterations in morphology and dynamics in ECs that are defective in proper guidance and patterning. Finally, we use single-cell analysis of intersegmental vessels undergoing lumen formation to demonstrate the coexistence of seamless transcellular lumens and single or multicellular enclosed lumens with autocellular or intercellular junctions, suggesting that heterogeneous mechanisms contribute to vascular lumen formation in vivo. The tools that we have developed for single EC analysis should facilitate further rigorous qualitative and quantitative analysis of EC morphology and behavior in vivo. C1 [Yu, Jianxin A.; Castranova, Daniel; Pham, Van N.; Weinstein, Brant M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM weinsteb@mail.nih.gov FU intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [ZIA-HD001011]; Leducq Foundation FX This study was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [ZIA-HD001011], and by the Leducq Foundation. Deposited in PMC for release after 12 months. NR 60 TC 9 Z9 9 U1 2 U2 13 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD SEP PY 2015 VL 142 IS 17 BP 2951 EP + DI 10.1242/dev.123174 PG 24 WC Developmental Biology SC Developmental Biology GA CQ7DO UT WOS:000360763300010 PM 26253401 ER PT J AU Zhang, CP Li, Y Wang, LS Sun, SR Liu, GS Leng, JH Guo, J Lv, L Li, WD Zhang, CL Hu, G Yu, ZJ Yang, XL AF Zhang, Cuiping Li, Yi Wang, Leishen Sun, Shurong Liu, Gongshu Leng, Junhong Guo, Jia Lv, Li Li, Weidong Zhang, Cuilin Hu, Gang Yu, Zhijie Yang, Xilin TI Blood group AB is protective factor for gestational diabetes mellitus: a prospective population-based study in Tianjin, China SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE gestational diabetes mellitus; Tianjin; Chinese; ABO blood type ID GENETIC-VARIANTS; RISK; ASSOCIATION; CANCER; CLASSIFICATION; SUSCEPTIBILITY; HYPERGLYCEMIA; METAANALYSIS; PREGNANCY; DIAGNOSIS AB BackgroundThe ABO blood types are associated with cancers, cardiovascular diseases and type 2 diabetes mellitus but whether they are also associated with gestational diabetes mellitus (GDM) is unknown. We examined the relationship between the ABO blood types and the risk of GDM in a prospective population-based Chinese cohort. MethodsFrom 2010 to 2012, we recruited 14198 pregnant women within the first 12weeks of gestation in Tianjin, China. All women had a glucose challenge test (GCT) at 24-28 gestational weeks, followed by a 75-g 2-h oral glucose tolerance test if the results from GCT were 7.8mmol/L. GDM was diagnosed based on the glucose cut-points of the International Association of Diabetes and Pregnancy Study Group criteria. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for traditional risk factors. Stratified analysis was performed by family history of diabetes (yes versus no). Sensitivity analyses were also performed by using the World Health Organization (WHO) criteria for GDM. ResultsWomen with blood groups A, B or O (i.e. non-AB) were associated with increased risk of GDM as compared with those with blood group AB (adjusted OR: 1.44, 95% CI: 1.13-1.83). Sensitivity analyses showed that the result was consistent using WHO criteria. The adjusted OR of blood group non-AB versus AB for GDM was enhanced among women with a family history of diabetes (2.69, 1.21-5.96) and attenuated among those without (1.33, 1.03-1.71). ConclusionsBlood group AB was a protective factor against GDM in pregnant Chinese women. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Leng, Junhong; Yang, Xilin] Tianjin Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Tianjin 300070, Peoples R China. [Zhang, Cuiping; Li, Yi; Wang, Leishen; Sun, Shurong; Liu, Gongshu; Leng, Junhong; Guo, Jia; Lv, Li] Tianjin Women & Childrens Hlth Ctr, Tianjin, Peoples R China. [Li, Weidong] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. [Hu, Gang] Pennington Biomed Res Ctr, Chron Dis Epidemiol Lab, Baton Rouge, LA 70808 USA. [Yu, Zhijie] Dalhousie Univ, Populat Canc Res Program, Halifax, NS, Canada. [Yu, Zhijie] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. RP Yang, XL (reprint author), Tianjin Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Tianjin 300070, Peoples R China. EM yxl@hotmail.com FU BRIDGES [LT09-227]; Lilly Diabetes FX The authors thank all doctors, nurses and research staffs at the 65 community hospitals, six district-level women and children's health centres, Tianjin Women and Children's Health Center (TWCHC) and other secondary obstetric or tertiary hospitals in Tianjin, for their participation in this study. All authors contributed to the analysis and preparation of the manuscript. All authors, except WL, ZY, GH, CZH and XY, contributed to the collection of the data. XY (the corresponding author) and CZH (the first author) will take full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript. This project was supported by BRIDGES (Grant number: LT09-227). BRIDGES is an International Diabetes Federation programme supported by an educational grant from Lilly Diabetes. NR 40 TC 5 Z9 5 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD SEP PY 2015 VL 31 IS 6 BP 627 EP 637 DI 10.1002/dmrr.2650 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CR2UD UT WOS:000361185200011 PM 25820620 ER PT J AU Zhao, L Zabel, MK Wang, X Ma, WX Shah, P Fariss, RN Qian, HH Parkhurst, CN Gan, WB Wong, WT AF Zhao, Lian Zabel, Matthew K. Wang, Xu Ma, Wenxin Shah, Parth Fariss, Robert N. Qian, Haohua Parkhurst, Christopher N. Gan, Wen-Biao Wong, Wai T. TI Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration SO EMBO MOLECULAR MEDICINE LA English DT Article DE apoptosis; microglia; phagocytosis; retinal degeneration; retinitis pigmentosa ID CHRONIC INFLAMMATORY REACTION; HUMAN RETINITIS-PIGMENTOSA; CELL-DEATH; NEURONAL DEATH; PHOSPHATIDYLSERINE EXTERNALIZATION; FRACTALKINE RECEPTOR; AMYLOID-BETA; MOUSE MODEL; T-CELLS; ACTIVATION AB Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod degeneration is accompanied by early infiltration of microglia, upregulation of phagocytic molecules in microglia, and presentation of eat-me signals on mutated rods. On live-cell imaging, infiltrating microglia interact dynamically with photoreceptors via motile processes and engage in rapid phagocytic engulfment of non-apoptotic rods. Microglial contribution to rod demise is evidenced by morphological and functional amelioration of photoreceptor degeneration following genetic ablation of retinal microglia. Molecular inhibition of microglial phagocytosis using the vitronectin receptor antagonist cRGD also improved morphological and functional parameters of degeneration. Our findings highlight primary microglial phagocytosis as a contributing mechanism underlying cell death in retinitis pigmentosa and implicate microglia as a potential cellular target for therapy. C1 [Zhao, Lian; Zabel, Matthew K.; Wang, Xu; Ma, Wenxin; Shah, Parth; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. [Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. [Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. [Parkhurst, Christopher N.; Gan, Wen-Biao] NYU, Sch Med, Skirball Inst, Dept Neurosci & Physiol, New York, NY USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017; OI Wong, Wai/0000-0003-0681-4016; Zabel, Matthew/0000-0003-2591-7379 FU National Eye Institute Intramural Research Program; US National Institutes of Health [1R01NS087198] FX The authors gratefully acknowledge Drs. Joe Hollyfield and Vera Bonilha for providing access to the Foundation Fighting Blindness human RP eye collection, and Dr Tiansen Li for ocular tissues from rd16 and RPGRIP-/- mice. This study is supported by funds from the National Eye Institute Intramural Research Program (to W.T.W, R.N.F., H.Q.) and by US National Institutes of Health grants 1R01NS087198 (to W-B.G.). NR 61 TC 25 Z9 26 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD SEP PY 2015 VL 7 IS 9 BP 1179 EP 1197 DI 10.15252/emmm.201505298 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CQ9VS UT WOS:000360963900008 PM 26139610 ER PT J AU Bibby, K Fischer, RJ Casson, LW Stachler, E Haas, CN Munster, VJ AF Bibby, Kyle Fischer, Robert J. Casson, Leonard W. Stachler, Elyse Haas, Charles N. Munster, Vincent J. TI Persistence of Ebola Virus in Sterilized Wastewater SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS LA English DT Article ID HEMORRHAGIC-FEVER; ENVIRONMENT STATE; RESEARCH NEEDS; WEST-AFRICA; STABILITY; DISEASE; CONGO; ENTEROVIRUSES; DISINFECTANTS; TRANSMISSION AB In the wake of the ongoing 2014/2015 Ebola virus outbreak, significant questions regarding the appropriate handling of Ebola virus-contaminated liquid waste remain, including the persistence of Ebola virus in wastewater. To address these uncertainties, we evaluated the persistence of Ebola virus spiked in sterilized domestic sewage. The viral titer decreased approximately 99% within the first test day from an initial viral titer of 10(6) TCID50 mL(-1); however, it could not be determined if this initial rapid decrease was due to aggregation or inactivation of the viral particles. The subsequent viral titer decrease was less rapid, and infectious Ebola virus particles persisted for all 8 days of the test. The inactivation constant (k) was determined to be -1.08 (2.1 days for a 90% viral titer decrease). Due to experimental conditions, we believe these results to be an upper bound for Ebola virus persistence in wastewater. Wastewater composition is inherently heterogeneous; subsequently, we caution that interpretation of these results should be made within a holistic assessment, including the effects of wastewater composition, dilution, and potential exposure routes within wastewater infrastructure. While it remains unknown if Ebola virus may be transmitted via wastewater, these data demonstrate a potential exposure route to infectious Ebola virus via wastewater and emphasize the value of a precautionary approach to wastewater handling in an epidemic response. C1 [Bibby, Kyle; Casson, Leonard W.; Stachler, Elyse] Univ Pittsburgh, Dept Civil & Environm Engn, Pittsburgh, PA 15261 USA. [Bibby, Kyle] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA. [Fischer, Robert J.; Munster, Vincent J.] NIAID, NIH, Virol Lab, Div Intramural Res, Hamilton, MT 59840 USA. [Haas, Charles N.] Drexel Univ, Dept Civil Architectural & Environm Engn, Philadelphia, PA 19104 USA. RP Bibby, K (reprint author), Univ Pittsburgh, Dept Civil & Environm Engn, Pittsburgh, PA 15261 USA. EM BibbyKJ@Pitt.edu; munstervj@niaid.nih.gov OI Stachler, Elyse/0000-0002-4961-1983; Munster, Vincent/0000-0002-2288-3196; Bibby, Kyle/0000-0003-3142-6090 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Science Foundation [1508415, 1507285] FX This study was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Science Foundation Grants 1508415 (K.B. and L.W.C.) and 1507285 (C.N.H.). We acknowledge the anonymous wastewater sampling site for assistance. NR 42 TC 8 Z9 8 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2328-8930 J9 ENVIRON SCI TECH LET JI Environ. Sci. Technol. Lett. PD SEP PY 2015 VL 2 IS 9 BP 245 EP 249 DI 10.1021/acs.estlett.5b00193 PG 5 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA CR1MW UT WOS:000361090000003 ER PT J AU Birger, R Kouyos, R Dushoff, J Grenfell, B AF Birger, Ruthie Kouyos, Roger Dushoff, Jonathan Grenfell, Bryan TI Modeling the effect of HIV coinfection on clearance and sustained virologic response during treatment for hepatitis C virus SO EPIDEMICS LA English DT Article DE Mathematical model; HCV-HIV; Antiviral therapy; Immune response; Coinfection ID HUMAN-IMMUNODEFICIENCY-VIRUS; DYNAMICS IN-VIVO; CELL-PROLIFERATION; INFECTED PATIENTS; IMMUNE-RESPONSES; VIRAL DYNAMICS; DRUG-USERS; INTERFERON; SOFOSBUVIR; RIBAVIRIN AB Background: HIV/hepatitis C (HCV) coinfection is a major concern in global health today. Each pathogen can exacerbate the effects of the other and affect treatment outcomes. Understanding the within-host dynamics of these coinfecting pathogens is crucial, particularly in light of new, direct-acting antiviral agents (DAAs) for HCV treatment that are becoming available. Methods and findings: In this study, we construct a within-host mathematical model of HCV/HIV coinfection by adapting a previously published model of HCV monoinfection to include an immune system component in infection clearance. We explore the effect of HIV-coinfection on spontaneous HCV clearance and sustained virologic response (SVR) by building in decreased immune function with increased HIV viral load. Treatment is modeled by modifying HCV burst-size, and we use clinically-relevant parameter estimates. Our model replicates real-world patient outcomes; it outputs infected and uninfected target cell counts, and HCV viral load for varying treatment and coinfection scenarios. Increased HIV viral load and reduced CD4(+) count correlate with decreased spontaneous clearance and SVR chances. Treatment efficacy/duration combinations resulting in SVR are calculated for HIV-positive and negative patients, and crucially, we replicate the new findings that highly efficacious DAAs reduce treatment differences between HIV-positive and negative patients. However, we also find that if drug efficacy decays sufficiently over treatment course, SVR differences between HIV-positive and negative patients reappear. Conclusions: Our model shows theoretical evidence of the differing outcomes of HCV infection in cases where the immune system is compromised by HIV. Understanding what controls these outcomes is especially important with the advent of efficacious but often prohibitively expensive DAAs. Using a model to predict patient response can lend insight into optimal treatment design, both in helping to identify patients who might respond well to treatment and in helping to identify treatment pathways and pitfalls. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Birger, Ruthie; Grenfell, Bryan] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Kouyos, Roger] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. [Kouyos, Roger] Univ Zurich, Inst Med Virol, Zurich, Switzerland. [Dushoff, Jonathan] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. [Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Birger, R (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 106a Guyot Hall, Princeton, NJ 08544 USA. EM rbirger@princeton.edu RI Infektiologie, USZ/A-6921-2011; Kouyos, Roger/G-6226-2014; Birger, Ruthie/F-2416-2014 OI Kouyos, Roger/0000-0002-9220-8348; Birger, Ruthie/0000-0002-2960-5084 FU Princeton University, Department of Ecology and Evolutionary Biology; Swiss National Science Foundation [PZOOP3-142411]; Bill and Melinda Gates Foundation; RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security; Fogarty International Center, NIH FX We thank Professors Andrea Graham and Simon Levin, Department of Ecology and Evolutionary Biology, Princeton University for their helpful comments and insights. R.B. was supported by the Princeton University, Department of Ecology and Evolutionary Biology. R.D.K. was supported by the Swiss National Science Foundation # PZOOP3-142411. B.G. was supported by the Bill and Melinda Gates Foundation and the RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center, NIH. NR 54 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1755-4365 J9 EPIDEMICS-NETH JI Epidemics PD SEP PY 2015 VL 12 BP 1 EP 10 DI 10.1016/j.epidem.2015.04.001 PG 10 WC Infectious Diseases SC Infectious Diseases GA CQ9MD UT WOS:000360938100001 PM 26342237 ER PT J AU Londono, JEC Tian, QH Hammer, K Schroder, L Londono, JC Reil, JC He, T Oberhofer, M Mannebach, S Mathar, I Philipp, SE Tabellion, W Schweda, F Dietrich, A Kaestner, L Laufs, U Birnbaumer, L Flockerzi, V Freichel, M Lipp, P AF Londono, Juan E. Camacho Tian, Qinghai Hammer, Karin Schroeder, Laura Londono, Julia Camacho Reil, Jan C. He, Tao Oberhofer, Martin Mannebach, Stefanie Mathar, Ilka Philipp, Stephan E. Tabellion, Wiebke Schweda, Frank Dietrich, Alexander Kaestner, Lars Laufs, Ulrich Birnbaumer, Lutz Flockerzi, Veit Freichel, Marc Lipp, Peter TI A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling SO EUROPEAN HEART JOURNAL LA English DT Article DE Calcium; Ion channels; Cardiac remodelling; Background Ca2+ entry; TRPC1/TRPC4 ID RECEPTOR POTENTIAL CHANNELS; HEART-FAILURE; MOUSE HEART; HYPERTROPHY; MICE; ACTIVATION; TRPC; EXPRESSION; MYOCYTES; PROTEIN AB Aims Pathological cardiac hypertrophy is a major predictor for the development of cardiac diseases. Neuroendocrine factors such as norepinephrine and angiotensin II trigger Ca2+-dependent processes leading to cell growth and cardiac hypertrophy. Here, we report the identification of a constitutively active background Ca2+ entry (BGCE) pathway that is not affected by inhibition of voltage-gated Ca2+ channels but critically depends on the presence of TRPC1 and TRPC4 proteins, members of the TRP family of cation channels. It fine-tunes Ca2+ cycling in beating cardiomyocytes under basal conditions and during neurohumoral stimulation. Suppression of BGCE protects against development of maladaptive cardiac remodelling without evidence for alterations in cardiac or extra-cardiac functions and may represent a potential new therapeutic strategy to attenuate the pathogenesis of associated diseases.Pathological cardiac hypertrophy is a major predictor for the development of cardiac diseases. It is associated with chronic neurohumoral stimulation and with altered cardiac Ca2+ signalling in cardiomyocytes. TRPC proteins form agonist-induced cation channels, but their functional role for Ca2+ homeostasis in cardiomyocytes during fast cytosolic Ca2+ cycling and neurohumoral stimulation leading to hypertrophy is unknown. Methods and results In a systematic analysis of multiple knockout mice using fluorescence imaging of electrically paced adult ventricular cardiomyocytes and Mn2+-quench microfluorimetry, we identified a background Ca2+ entry (BGCE) pathway that critically depends on TRPC1/C4 proteins but not others such as TRPC3/C6. Reduction of BGCE in TRPC1/C4-deficient cardiomyocytes lowers diastolic and systolic Ca2+ concentrations both, under basal conditions and under neurohumoral stimulation without affecting cardiac contractility measured in isolated hearts and in vivo. Neurohumoral-induced cardiac hypertrophy as well as the expression of foetal genes (ANP, BNP) and genes regulated by Ca2+-dependent signalling (RCAN1-4, myomaxin) was reduced in TRPC1/C4 knockout (DKO), but not in TRPC1- or TRPC4-single knockout mice. Pressure overload-induced hypertrophy and interstitial fibrosis were both ameliorated in TRPC1/C4-DKO mice, whereas they did not show alterations in other cardiovascular parameters contributing to systemic neurohumoral-induced hypertrophy such as renin secretion and blood pressure. Conclusions The constitutively active TRPC1/C4-dependent BGCE fine-tunes Ca2+ cycling in beating adult cardiomyocytes. TRPC1/C4-gene inactivation protects against development of maladaptive cardiac remodelling without altering cardiac or extracardiac functions contributing to this pathogenesis. C1 [Londono, Juan E. Camacho; Mathar, Ilka; Freichel, Marc] Heidelberg Univ, Inst Pharmakol, D-69120 Heidelberg, Germany. [Londono, Juan E. Camacho; Londono, Julia Camacho; Mannebach, Stefanie; Mathar, Ilka; Philipp, Stephan E.; Flockerzi, Veit; Freichel, Marc] Expt & Klin Pharmakol & Toxikol, D-66421 Homburg, Germany. [Londono, Juan E. Camacho; He, Tao; Freichel, Marc] DZHK German Ctr Cardiovasc Res, Heidelberg, Germany. [Tian, Qinghai; Hammer, Karin; Schroeder, Laura; Oberhofer, Martin; Tabellion, Wiebke; Kaestner, Lars; Lipp, Peter] Inst Mol Zellbiol, D-66421 Homburg, Germany. [Reil, Jan C.; Laufs, Ulrich] Innere Med III Univ Saarlandes, D-66421 Homburg, Germany. [He, Tao] Heidelberg Univ, Dept Cardiol, Res Unit Cardiac Epigenet, D-69120 Heidelberg, Germany. [He, Tao] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Schweda, Frank] Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany. [Dietrich, Alexander] LMU, Walther Straub Inst Pharmakol & Toxikol, D-80336 Munich, Germany. [Birnbaumer, Lutz] NIEHS, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA. RP Freichel, M (reprint author), INF 366, D-69120 Heidelberg, Germany. EM marc.freichel@pharma.uni-heidelberg.de; peter.lipp@uniklinikum-saarland.de RI Kaestner, Lars/P-6988-2016 FU KFO [196]; HOMFOR Program; DZHK (German Centre for Cardiovascular Research); BMBF (German Ministry of Education and Research); NIH [Z01-ES-101684]; [GK-1326]; [SFB-530] FX This work was supported by the KFO 196 (M.F., P.L., V.F., L.K., and U.L.), GK-1326 (M.F., P.L., V.F., L.K., and S.P.), SFB-530 (M.F., V.F., P.L., and S.E.P.), the HOMFOR Program (P.L., L.K., V.F., and M.F.), the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research) (M.F., P.L., and L.K.), and the Intramural Research Program NIH project Z01-ES-101684 (L.B.). NR 31 TC 9 Z9 9 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP 1 PY 2015 VL 36 IS 33 BP 2257 EP 2266 DI 10.1093/eurheartj/ehv250 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BR UT WOS:000361205800017 ER PT J AU Torchia, MLG Munitic, I Castro, E Herz, J McGavern, DB Ashwell, JD AF Torchia, Maria Letizia Giardino Munitic, Ivana Castro, Ehydel Herz, Jasmin McGavern, Dorian B. Ashwell, Jonathan D. TI c-IAP ubiquitin protein ligase activity is required for 4-1BB signaling and CD8(+) memory T-cell survival SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE 4-1BB; CD8(+) memory T cell; lymphocytic choriomeningitis virus; Signal transduction; T-cell memory; Ubiquitination ID KAPPA-B ACTIVATION; FAMILY-MEMBERS; IMMUNE-SYSTEM; TNFR FAMILY; COSTIMULATION; APOPTOSIS; INHIBITORS; EXPRESSION; RESPONSES; EFFECTOR AB Cellular inhibitor of apoptosis proteins (c-IAP) 1 and 2 are widely expressed ubiquitin protein ligases that regulate a variety of cellular functions, including the sensitivity of T cells to costimulation. 4-1BB is a TNF receptor family member that signals via a complex that includes TRAF family members and the c-IAPs to upregulate NF-kappa B and ERK, and has been implicated in memory T-cell survival. Here, we show that effector and memory T cells from mice expressing a dominant negative E3-inactive c-IAP2 (c-IAP2(H570A)) have impaired signaling downstream of 4-1BB. When infected with lymphocytic choriomeningitis virus, unlike mice in which c-IAPs were acutely downregulated by c-IAP antagonists, the primary response of c-IAP2(H570A) mice was normal. However, the number of antigen-specific CD8(+) but not CD4(+) T cells declined more rapidly and to a greater extent in c-IAP2(H570A) mice than in WT controls. Studies with T-cell adoptive transfer demonstrated that the enhanced decay of memory cells was T-cell intrinsic. Thus, c-IAP E3 activity is required for 4-1BB coreceptor signaling and maintenance of CD8(+) T-cell memory. C1 [Torchia, Maria Letizia Giardino; Munitic, Ivana; Castro, Ehydel; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Herz, Jasmin; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Room 3002,Bldg 37, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX We are grateful to the National Institutes of Health Tetramer Core Facility at Emory University for supplying tetramers. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 43 TC 1 Z9 1 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2015 VL 45 IS 9 BP 2672 EP 2682 DI 10.1002/eji.201445342 PG 11 WC Immunology SC Immunology GA CQ9GK UT WOS:000360921200022 ER PT J AU Zheng, C Baum, BJ Liu, X Goldsmith, CM Perez, P Jang, SI Cotrim, AP McCullagh, L Ambudkar, IS Alevizos, I AF Zheng, C. Baum, B. J. Liu, X. Goldsmith, C. M. Perez, P. Jang, S-I Cotrim, A. P. McCullagh, L. Ambudkar, I. S. Alevizos, I. TI Persistence of hAQP1 expression in human salivary gland cells following AdhAQP1 transduction is associated with a lack of methylation of hCMV promoter SO GENE THERAPY LA English DT Article ID ADENOVIRAL-MEDIATED TRANSFER; INCREASED FLUID SECRETION; IMMEDIATE-EARLY PROMOTER; RAT SUBMANDIBULAR-GLAND; TRANSGENE EXPRESSION; AQUAPORIN-1 CDNA; GENE DELIVERY; CYTOMEGALOVIRUS-INFECTION; CMV PROMOTER; IN-VITRO AB In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector encoding human aquaporin-1 (hAQP1). This vector uses the human cytomegalovirus enhancer/promoter (hCMVp). As subject peak responses were at times much longer (7-42 days) than expected, we hypothesized that the hCMVp may not be methylated in human salivary gland cells to the extent previously observed in rodent salivary gland cells. This hypothesis was supported in human salivary gland primary cultures and human salivary gland cell lines after transduction with AdhAQP1. Importantly, hAQP1 maintained its function in those cells. Conversely, when we transduced mouse and rat cell lines in vitro and submandibular glands in vivo with AdhAQP1, the hCMVp was gradually methylated over time and associated with decreased hAQP1 expression and function in vitro and decreased hAQP1 expression in vivo. These data suggest that the hCMVp in AdhAQP1 was probably not methylated in transduced human salivary gland cells of responding subjects, resulting in an unexpectedly longer functional expression of hAQP1. C1 [Zheng, C.; Baum, B. J.; Liu, X.; Goldsmith, C. M.; Perez, P.; Jang, S-I; Cotrim, A. P.; McCullagh, L.; Ambudkar, I. S.; Alevizos, I.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Alevizos, I (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM iambudkar@nidcr.nih.gov; alevizosi@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health FX We thank Cindy Clark, NIH Library Editing Service, for reviewing the manuscript. The Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, provided all support for this research. NR 48 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD SEP PY 2015 VL 22 IS 9 BP 758 EP 766 DI 10.1038/gt.2015.55 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CQ8XY UT WOS:000360895200008 PM 26177970 ER PT J AU Parikh, S Goldstein, A Koenig, MK Scaglia, F Enns, GM Saneto, R Anselm, I Cohen, BH Falk, MJ Greene, C Gropman, AL Haas, R Hirano, M Morgan, P Sims, K Tarnopolsky, M Van Hove, JLK Wolfe, L DiMauro, S AF Parikh, Sumit Goldstein, Amy Koenig, Mary Kay Scaglia, Fernando Enns, Gregory M. Saneto, Russell Anselm, Irina Cohen, Bruce H. Falk, Marni J. Greene, Carol Gropman, Andrea L. Haas, Richard Hirano, Michio Morgan, Phil Sims, Katherine Tarnopolsky, Mark Van Hove, Johan L. K. Wolfe, Lynne DiMauro, Salvatore TI Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society SO GENETICS IN MEDICINE LA English DT Review DE consensus criteria; Delphi method; mitochondrial disease; mitochondrial medicine; Mitochondrial Medicine Society ID KEARNS-SAYRE-SYNDROME; CEREBRAL FOLATE-DEFICIENCY; EXOME SEQUENCING REVEALS; DNA DEPLETION SYNDROME; COMPLEX-I DEFICIENCY; COMPARATIVE GENOMIC HYBRIDIZATION; RESPIRATORY-CHAIN DEFICIENCIES; CLINICAL-PRACTICE PROTOCOL; BRAIN-STEM INVOLVEMENT; RAT-LIVER MITOCHONDRIA AB Purpose: The purpose of this statement is to review the literature regarding mitochondrial disease and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are engaged in diagnosing and treating these patients. Methods: The Writing Group members were appointed by the Mitochondrial Medicine Society. The panel included members with expertise in several different areas. The panel members utilized a comprehensive review of the literature, surveys, and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Results: Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease. Conclusion: The Delphi process enabled the formation of consensus-based recommendations. We hope that these recommendations will help standardize the evaluation, diagnosis, and care of patients with suspected or demonstrated mitochondrial C1 [Parikh, Sumit] Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Dept Neurol, Cleveland, OH 44106 USA. [Goldstein, Amy] Childrens Hosp Pittsburgh, Dept Pediat, Div Child Neurol, Pittsburgh, PA 15213 USA. [Koenig, Mary Kay] Univ Texas Med Sch Houston, Div Child & Adolescent Neurol, Dept Pediat, Houston, TX USA. [Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Scaglia, Fernando] Texas Childrens Hosp, Houston, TX 77030 USA. [Enns, Gregory M.] Stanford Univ, Lucile Packard Childrens Hosp, Div Med Genet, Dept Pediat, Palo Alto, CA 94304 USA. [Saneto, Russell] Univ Washington, Seattle Childrens Hosp, Dept Neurol, Seattle, WA 98195 USA. [Saneto, Russell] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Anselm, Irina] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Cohen, Bruce H.] Childrens Hosp Med Ctr Akron, Dept Pediat, NeuroDev Sci Ctr, Akron, OH USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Greene, Carol] Univ Maryland, Med Ctr, Dept Pediat, Baltimore, MD 21201 USA. [Gropman, Andrea L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gropman, Andrea L.] George Washington Univ Hlth Sci, Washington, DC USA. [Haas, Richard] UCSD Med Ctr, Dept Neurosci & Pediat, La Jolla, CA USA. [Haas, Richard] Rady Childrens Hosp, La Jolla, CA USA. [Hirano, Michio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Morgan, Phil] Seattle Childrens Hosp, Dept Anesthesiol, Seattle, WA USA. [Sims, Katherine] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarnopolsky, Mark] McMaster Univ, Dept Pediat & Med, Hamilton, ON, Canada. [Van Hove, Johan L. K.] Childrens Hosp Colorado, Dept Pediat Clin Genet & Metab, Denver, CO USA. [Wolfe, Lynne] NIH, Bethesda, MD 20892 USA. [DiMauro, Salvatore] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. RP Parikh, S (reprint author), Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Dept Neurol, Cleveland, OH 44106 USA. EM parikhs@ccf.org FU RAPTOR Pharmaceuticals FX G.M.E. has received unrestricted research gift funds from Edison Pharmaceuticals. M.J.F. is a consultant for Mitokyne, research collaborator for Cardero, and a research grant awardee of RAPTOR Pharmaceuticals, and is on the Scientific and Medical Advisory Board for the United Mitochondrial Disease Foundation. A.G. is a consultant for Stealth Peptides. A.L.G. is a consultant for GeneDx. S.P. conducts research for Edison Pharmaceuticals and the North American Mitochondrial Disease Consortium (NAMDC), and is on the Scientific and Medical Advisory Board for the United Mitochondrial Disease Foundation. R.S. conducts research studies for Edison Pharmaceuticals and is part of the NAMDC. F.S. works for a medical college department that owns a Mitochondrial Diagnostic Laboratory and conducts research studies for Edison and Raptor Pharmaceuticals. M.T. is president and CEO of Exerkine, which develops mitochondrial therapies, and receives speaker honoraria from Prevention Genetics and Genzyme. NR 164 TC 23 Z9 24 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD SEP PY 2015 VL 17 IS 9 BP 689 EP 701 DI 10.1038/gim.2014.177 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CQ8YY UT WOS:000360898500002 PM 25503498 ER PT J AU Feero, WG Facio, FM Glogowski, EA Hampel, HL Stopfer, JE Eidem, H Pizzino, AM Barton, DK Biesecker, LG AF Feero, W. Gregory Facio, Flavia M. Glogowski, Emily A. Hampel, Heather L. Stopfer, Jill E. Eidem, Haley Pizzino, Amy M. Barton, David K. Biesecker, Leslie G. TI Preliminary validation of a consumer-oriented colorectal cancer risk assessment tool compatible with the US Surgeon General's My Family Health Portrait SO GENETICS IN MEDICINE LA English DT Article DE colorectal cancer; family history; My Family Health Portrait; risk assessment tools ID COMMON CHRONIC DISEASES; PRIMARY-CARE; CLINICAL-USE; HISTORY; INFORMATION; PREVENTION; PROMOTION; UTILITY AB Purpose: This study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer based on personal health and family history information. The software is compatible with the US Surgeon General's My Family Health Portrait (MFHP). Methods: An algorithm for risk assessment was created using accepted colorectal risk assessment guidelines and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared with "gold standard" risk assessments developed by three expert cancer genetic counselors. Results: Genetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for colorectal cancer yielded a sensitivity for colorectal cancer risk of 81% (95% confidence interval: 54-96%) and specificity of 90% (95% confidence interval: 83-94%), as compared with genetic counselor pedigree review. The positive predictive value for risk for MFHP was 48% (95% confidence interval: 29-68%), whereas the negative predictive value was 98% (95% confidence interval: 93-99%). Agreement between MFHP and genetic counselor pedigree review was moderate (kappa = 0.54). Conclusion: The analytic validity of the MFHP colorectal cancer risk assessment software is similar to those of other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups. C1 [Feero, W. Gregory] Maine Dartmouth Family Med Residency, Fairfield, ME 04937 USA. [Facio, Flavia M.] Inova Translat Med Inst, Falls Church, VA USA. [Glogowski, Emily A.] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Hampel, Heather L.] Ohio State Univ, Div Human Genet, Columbus, OH 43210 USA. [Stopfer, Jill E.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Eidem, Haley] Vanderbilt Univ, Dept Genet, Nashville, TN 37235 USA. [Pizzino, Amy M.] Childrens Natl Hlth Syst, White Matter Dis Program, Washington, DC USA. [Barton, David K.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. RP Feero, WG (reprint author), Maine Dartmouth Family Med Residency, Fairfield, ME 04937 USA. EM wfeero@mainegeneral.org FU Genetic Disease Research Branch; Genomic Healthcare Branch, National Human Genome Research Institute, National Institutes of Health FX This project was supported by the Genetic Disease Research Branch and the Genomic Healthcare Branch, National Human Genome Research Institute, National Institutes of Health. The authors thank the following individuals for contributions made to developing the risk assessment algorithm and for their thoughtful comments on the manuscript: Andrew Freedman, Mitchell Gail, Donald Hadley, David Lanier, Colleen McBride, Gurvaneet Randhawa, Maren Scheuner, Rodolfo Valdez, and Daniel Wattendorf. Some of the data in this manuscript were presented in abstract form at the 2011 meeting of the American Society of Human Genetics in Montreal, Canada. NR 18 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD SEP PY 2015 VL 17 IS 9 BP 753 EP 756 DI 10.1038/gim.2014.179 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA CQ8YY UT WOS:000360898500011 PM 25521335 ER PT J AU Neumann, S Place, RF Krieger, CC Gershengorn, MC AF Neumann, S. Place, R. F. Krieger, C. C. Gershengorn, M. C. TI Future Prospects for the Treatment of Graves' Hyperthyroidism and Eye Disease SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE Graves' hyperthyroidism; Graves' orbitopathy; TSH receptor (TSHR); IGF-1 receptor (IGF-1R) ID GROWTH-FACTOR-I; THYROID-STIMULATING HORMONE; ADVANCED SOLID TUMORS; THYROTROPIN-RECEPTOR; TSH-RECEPTOR; ORBITAL FIBROBLASTS; INSULIN-RECEPTORS; BLOCKING ACTIVITY; HUMAN THYROCYTES; INVERSE AGONIST AB Although there are adequate therapies for Graves' hyperthyroidism, mild to moderate Graves' orbitopathy (GO) is usually treated symptomatically whereas definitive therapy is reserved for severe, vision-threatening GO. Importantly, none of the treatment regimens for Graves' disease used today are directed at the pathogenesis of the disease. Herein, we review some aspects of what is known about the pathogenesis of these 2 major components of Graves' disease, specifically the apparent important roles of the TSH and IGF-1 receptors, and thereafter describe future therapeutic approaches directed at these receptors. We propose that targeting these receptors will yield effective and better tolerated treatments for Graves' disease, especially for GO. C1 [Neumann, S.; Krieger, C. C.; Gershengorn, M. C.] NIDDK, NIH, Lab Endocrinol & Receptor Biol, Bethesda, MD 20892 USA. [Place, R. F.] Nova Therapeut LLC, Pasadena, CA USA. RP Neumann, S (reprint author), NIDDK, NIH, Lab Endocrinol & Receptor Biol, 50 South Dr, Bethesda, MD 20892 USA. EM susannen@intra.niddk.nih.gov OI Krieger, Christine/0000-0002-1856-415X FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [Z01 DK011006, Z01 DK047044] FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Z01 DK011006, Z01 DK047044). NR 67 TC 6 Z9 6 U1 1 U2 7 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 SEP PY 2015 VL 47 IS 10 BP 789 EP 796 DI 10.1055/s-0035-1555901 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CR2GV UT WOS:000361145500012 PM 26197854 ER PT J AU Roy, S He, Q Sweeney, E Carass, A Reich, DS Prince, JL Pham, DL AF Roy, Snehashis He, Qing Sweeney, Elizabeth Carass, Aaron Reich, Daniel S. Prince, Jerry L. Pham, Dzung L. TI Subject-Specific Sparse Dictionary Learning for Atlas-Based Brain MRI Segmentation SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Brain; dictionary; histogram matching; magnetic resonance imaging (MRI); patches; segmentation; sparsity ID FUZZY C-MEANS; IMAGE SEGMENTATION; LABEL FUSION; LESION SEGMENTATION; MULTIPLE-SCLEROSIS; ALGORITHM; HIPPOCAMPUS; MODEL; REGISTRATION AB Quantitative measurements from segmentations of human brain magnetic resonance (MR) images provide important biomarkers for normal aging and disease progression. In this paper, we propose a patch-based tissue classification method from MR images that uses a sparse dictionary learning approach and atlas priors. Training data for the method consists of an atlas MR image, prior information maps depicting where different tissues are expected to be located, and a hard segmentation. Unlike most atlas-based classification methods that require deformable registration of the atlas priors to the subject, only affine registration is required between the subject and training atlas. A subject-specific patch dictionary is created by learning relevant patches from the atlas. Then the subject patches are modeled as sparse combinations of learned atlas patches leading to tissue memberships at each voxel. The combination of prior information in an example-based framework enables us to distinguish tissues having similar intensities but different spatial locations. We demonstrate the efficacy of the approach on the application of whole-brain tissue segmentation in subjects with healthy anatomy and normal pressure hydrocephalus, as well as lesion segmentation in multiple sclerosis patients. For each application, quantitative comparisons are made against publicly available state-of-the art approaches. C1 [Roy, Snehashis; He, Qing; Pham, Dzung L.] Henry M Jackson Fdn Adv MilitaryMed, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. [Sweeney, Elizabeth] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. [Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, Bethesda, MD 20824 USA. RP Roy, S (reprint author), Henry M Jackson Fdn Adv MilitaryMed, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. EM snehashis.roy@nih.gov; qing.he@nih.gov; elizabethmargaretsweeney@gmail.com; aaron_carass@jhu.edu; daniel.reich@nih.gov; prince@jhu.edu; dzung.pham@nih.gov RI Reich, Daniel/E-5701-2010; OI Reich, Daniel/0000-0002-2628-4334; Roy, Snehashis/0000-0002-7997-3993; Carass, Aaron/0000-0003-4939-5085 FU Department of Defense at the Center for Neuroscience and Regenerative Medicine; Intramural Research Program of the NINDS/NIH [NIH/NINDS R01NS070906, NIH/NIBIB R21EB012765, NIH/NIBIB 1R01EB017743, NIH/NIA T32AG021334, NIH/NINDS R01NS085211, NIH/NINDS R01NS060910] FX This work was supported by the Department of Defense at the Center for Neuroscience and Regenerative Medicine, and in part by the Intramural Research Program of the NINDS/NIH, and under Grant NIH/NINDS R01NS070906, Grant NIH/NIBIB R21EB012765, Grant NIH/NIBIB 1R01EB017743, Grant NIH/NIA T32AG021334, Grant NIH/NINDS R01NS085211, and Grant NIH/NINDS R01NS060910. NR 57 TC 7 Z9 7 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD SEP PY 2015 VL 19 IS 5 BP 1598 EP 1609 DI 10.1109/JBHI.2015.2439242 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA CQ7NP UT WOS:000360791200009 PM 26340685 ER PT J AU Siegel, RL Jacobs, EJ Newton, CC Feskanich, D Freedman, ND Prentice, RL Jemal, A AF Siegel, Rebecca L. Jacobs, Eric J. Newton, Christina C. Feskanich, Diane Freedman, Neal D. Prentice, Ross L. Jemal, Ahmedin TI Deaths Due to Cigarette Smoking for 12 Smoking-Related Cancers in the United States SO JAMA INTERNAL MEDICINE LA English DT Letter ID MORTALITY C1 [Siegel, Rebecca L.; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Intramural Res Dept, Atlanta, GA 30303 USA. [Jacobs, Eric J.; Newton, Christina C.] Amer Canc Soc, Epidemiol Res Program, Intramural Res Dept, Atlanta, GA 30303 USA. [Feskanich, Diane] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Freedman, Neal D.] NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. [Prentice, Ross L.] Fred Hutchison Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. RP Siegel, RL (reprint author), Amer Canc Soc, Surveillance & Hlth Serv Res Program, Intramural Res Dept, 250 Williams St NW, Atlanta, GA 30303 USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU Intramural NIH HHS; NCI NIH HHS [P01 CA87969, UM1 CA167552]; WHI NIH HHS [N01WH42124, N01WH22110, N01WH24152, N01WH32100-32102, N01WH32105, N01WH32106, N01WH32108, N01WH32109, N01WH32111, N01WH32112, N01WH32113, N01WH32115, N01WH32118, N01WH32119, N01WH32122, N01WH42107, N01WH42108, N01WH42109, N01WH42110, N01WH42111, N01WH42112, N01WH42113, N01WH42114, N01WH42115, N01WH42116, N01WH42117, N01WH42118, N01WH42119, N01WH42120, N01WH42121, N01WH42122, N01WH42123, N01WH42125, N01WH42126, N01WH42129, N01WH42130, N01WH42131, N01WH42132, N01WH44221] NR 6 TC 11 Z9 11 U1 0 U2 4 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 SEP PY 2015 VL 175 IS 9 BP 1574 EP 1576 DI 10.1001/jamainternmed.2015.2398 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CR1CH UT WOS:000361059900042 PM 26076120 ER PT J AU Olfson, M King, M Schoenbaum, M AF Olfson, Mark King, Marissa Schoenbaum, Michael TI Treatment of Young People With Antipsychotic Medications in the United States SO JAMA PSYCHIATRY LA English DT Article ID PSYCHOSOCIAL TREATMENTS; DOUBLE-BLIND; 2ND-GENERATION ANTIPSYCHOTICS; ATYPICAL ANTIPSYCHOTICS; DISRUPTIVE BEHAVIORS; ANTISOCIAL-BEHAVIOR; MENTAL-DISORDERS; NATIONAL TRENDS; CHILDREN; ADOLESCENTS AB IMPORTANCE Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States. OBJECTIVE To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex. DESIGN, SETTING, AND PARTICIPANTS A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765 829), 2008 (n = 858 216), and 2010 (n = 851 874), including a subset from calendar year 2009 with service claims data (n = 53 896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. MAIN OUTCOMES AND MEASURES The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. RESULTS The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of younger children treated with antipsychotics in 2010 received 1 or more antipsychotic prescriptions from a child and adolescent psychiatrist. Among young people with claims for mental disorders in 2009 who were treated with antipsychotics, the most common diagnoses were attention-deficit/hyperactivity disorder in younger children (52.5%), older children (60.1%), and adolescents (34.9%) and depression in young adults (34.5%). CONCLUSIONS AND RELEVANCE Antipsychotic use increased from 2006 to 2010 for adolescents and young adults but not for children aged 12 years or younger. Peak antipsychotic use in adolescence, especially among boys, and clinical diagnosis patterns are consistent with management of developmentally limited impulsive and aggressive behaviors rather than psychotic symptoms. C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA. [King, Marissa] Yale Univ, 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, Dept Psychiat, 1051 Riverside Dr, New York, NY 10027 USA. EM mo49@cumc.columbia.edu FU National Institutes of Health; Columbia University; New York State Psychiatric Institute FX This work was funded by contracts from the National Institutes of Health to Yale University (Dr King) and Columbia University (Dr Olfson). Dr Olfson is also supported by the New York State Psychiatric Institute. NR 50 TC 26 Z9 26 U1 8 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2015 VL 72 IS 9 BP 867 EP 874 DI 10.1001/jamapsychiatry.2015.0500 PG 8 WC Psychiatry SC Psychiatry GA CR0DE UT WOS:000360987600005 PM 26132724 ER PT J AU Anticevic, A Haut, K Murray, JD Repovs, G Yang, GJ Diehl, C McEwen, SC Bearden, CE Addington, J Goodyear, B Cadenhead, KS Mirzakhanian, H Cornblatt, BA Olvet, D Mathalon, DH McGlashan, TH Perkins, DO Belger, A Seidman, LJ Tsuang, MT van Erp, TGM Walker, EF Hamann, S Woods, SW Qiu, ML Cannon, TD AF Anticevic, Alan Haut, Kristen Murray, John D. Repovs, Grega Yang, Genevieve J. Diehl, Caroline McEwen, Sarah C. Bearden, Carrie E. Addington, Jean Goodyear, Bradley Cadenhead, Kristin S. Mirzakhanian, Heline Cornblatt, Barbara A. Olvet, Doreen Mathalon, Daniel H. McGlashan, Thomas H. Perkins, Diana O. Belger, Aysenil Seidman, Larry J. Tsuang, Ming T. van Erp, Theo G. M. Walker, Elaine F. Hamann, Stephan Woods, Scott W. Qiu, Maolin Cannon, Tyrone D. TI Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk SO JAMA PSYCHIATRY LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; WORKING-MEMORY; COGNITIVE DYSFUNCTION; BIPOLAR DISORDER; TWINS DISCORDANT; HUMAN BRAIN; SCHIZOPHRENIA; CONNECTIVITY; CORTEX; SEGMENTATION AB IMPORTANCE Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. MAIN OUTCOMES AND MEASURES Whole-brain thalamic functional connectivity maps were generated using individuals' anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. RESULTS Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t(173) = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t(173) = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 x 10(-8), Spearman rho = 0.27, P < 4.75 x 10(-5), 2-tailed). CONCLUSIONS AND RELEVANCE Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness. C1 [Anticevic, Alan; Yang, Genevieve J.; Diehl, Caroline; McGlashan, Thomas H.; Woods, Scott W.; Cannon, Tyrone D.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06519 USA. [Anticevic, Alan] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT USA. [Anticevic, Alan; Yang, Genevieve J.] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [Anticevic, Alan; Haut, Kristen; Diehl, Caroline; Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06519 USA. [Anticevic, Alan; Yang, Genevieve J.] Yale Univ, Interdept Neurosci Program, New Haven, CT 06519 USA. [Murray, John D.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Repovs, Grega] Univ Ljubljana, Dept Psychol, Ljubljana, Slovenia. [McEwen, Sarah C.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [McEwen, Sarah C.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Biobehav Sci & Psychol, Los Angeles, CA USA. [Addington, Jean; Goodyear, Bradley] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin S.; Mirzakhanian, Heline; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Cornblatt, Barbara A.; Olvet, Doreen] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Perkins, Diana O.; Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Walker, Elaine F.; Hamann, Stephan] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.; Hamann, Stephan] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Qiu, Maolin] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06519 USA. [Qiu, Maolin] Yale Univ, Magnet Resonance Res Ctr, New Haven, CT 06519 USA. RP Anticevic, A (reprint author), Yale Univ, Dept Psychiat, 34 Pk St, New Haven, CT 06519 USA. EM alan.anticevic@yale.edu RI Murray, John/B-2835-2009 OI Murray, John/0000-0003-4115-8181 FU National Institute of Mental Health [MH081902, MH081857, MH081988, MH081928, MH082004, MH082022, MH081984, MH066160]; National Institutes of Health [DP5OD012109-02, T32GM 007205]; Brain and Behavior Research Foundation; Commonwealth Research Center [SCDMH82101008006] FX This study was supported by grants MH081902 (Dr Cannon), MH081857 (Dr Cornblatt), MH081988 (Dr Walker), MH081928 (Dr Seidman), MH082004 (Dr Perkins), MH082022 (Dr Cadenhead), MH081984 (Dr Addington), and MH066160 (Dr Woods) from the National Institute of Mental Health, grants DP5OD012109-02 (principal investigator: Dr Anticevic) and T32GM 007205 (Ms Yang) from the National Institutes of Health, a Brain and Behavior Research Foundation Young Investigator Award (principal investigator: Dr Anticevic), and grant SCDMH82101008006 from the Commonwealth Research Center (principal investigator: Dr Seidman). NR 65 TC 22 Z9 23 U1 3 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2015 VL 72 IS 9 BP 882 EP 891 DI 10.1001/jamapsychiatry.2015.0566 PG 10 WC Psychiatry SC Psychiatry GA CR0DE UT WOS:000360987600007 PM 26267151 ER PT J AU Zalesky, A Pantelis, C Cropley, V Fornito, A Cocchi, L McAdams, H Clasen, L Greenstein, D Rapoport, JL Gogtay, N AF Zalesky, Andrew Pantelis, Christos Cropley, Vanessa Fornito, Alex Cocchi, Luca McAdams, Harrison Clasen, Liv Greenstein, Deanna Rapoport, Judith L. Gogtay, Nitin TI Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings SO JAMA PSYCHIATRY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; INFERIOR LONGITUDINAL FASCICULUS; AUTOMATED 3-D EXTRACTION; HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; NEURODEVELOPMENTAL HYPOTHESIS; STRUCTURAL COVARIANCE; NONPSYCHOTIC SIBLINGS; NEURAL SYNCHRONY; MRI DATA AB IMPORTANCE Abnormalities in structural brain connectivity have been observed in patients with schizophrenia. Mapping these abnormalities longitudinally and understanding their genetic risk via sibship studies will provide crucial insight into progressive developmental changes associated with schizophrenia. OBJECTIVES To identify corticocortical connections exhibiting an altered developmental trajectory in adolescents with childhood-onset schizophrenia (COS) and to determine whether similar alterations are found in patients' unaffected siblings. DESIGN, SETTING, AND PARTICIPANTS Using prospective structural brain magnetic resonance imaging, large-scale corticocortical connectivity was mapped from ages 12 to 24 years in 109 patients with COS (272 images), 86 of their unaffected siblings (184 images), and 102 healthy controls (262 images) over a 20-year period beginning January 1, 1991, through April 30, 2011, as part of the ongoing COS study at the National Institute of Mental Health. MAIN OUTCOMES AND MEASURES Structural connectivity between pairs of cortical regions was estimated using a validated technique based on across-subject covariation in magnetic resonance imaging-derived cortical thickness measurements. RESULTS Compared with normally developing controls, significant left-hemisphere occipitotemporal deficits in cortical thickness correlations were found in patients with COS as well as their healthy siblings (P<.05). Deficits in siblings normalized by mid-adolescence, whereas patients with COS showed significantly longer maturational delays, with cortical thickness correlations between the left temporal lobe and left occipital cortex not showing evidence of development until early adulthood. The normalization of deficits with age in patients with COS correlated with improvement in symptoms. Compared with controls, left-hemisphere occipitotemporal thickness correlations in a subgroup of patients with high positive symptoms were significantly reduced from age 14 to 18 years (P<.05); however, other patients with low positive symptoms showed no significant deficits. CONCLUSIONS AND RELEVANCE Delayed maturation of occipitotemporal connectivity appears to be a trait marker in patients with COS, with a milder endophenotype in unaffected siblings associated with resilience to developing schizophrenia. These findings indicate genetically influenced and connection-specific developmental abnormalities in the schizophrenia connectome, and lead to the hypothesis that visual hallucinations in patients with COS may be because of delayed development of the inferior longitudinal fasciculus, a prominent occipitotemporal fiber. C1 [Zalesky, Andrew; Pantelis, Christos; Cropley, Vanessa; Fornito, Alex] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic 3010, Australia. [Zalesky, Andrew; Pantelis, Christos; Cropley, Vanessa; Fornito, Alex] Melbourne Hlth, Melbourne, Vic, Australia. [Fornito, Alex] Monash Univ, Sch Psychol & Psychiat, Monash Clin & Imaging Neurosci, Melbourne, Vic 3004, Australia. [Fornito, Alex] Monash Univ, Monash Biomed Imaging, Melbourne, Vic 3004, Australia. [Cocchi, Luca] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [McAdams, Harrison; Clasen, Liv; Greenstein, Deanna; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Zalesky, A (reprint author), Univ Melbourne, Melbourne Neuropsychiat Ctr, Level 3,Alan Gilbert Bldg, Melbourne, Vic 3010, Australia. EM azalesky@unimelb.edu.au RI Pantelis, Christos/H-7722-2014; Alex, Fornito/N-8214-2013; OI Pantelis, Christos/0000-0002-9565-0238; Alex, Fornito/0000-0001-9134-480X; ZALESKY, ANDREW/0000-0003-2298-9908; Cocchi, Luca/0000-0003-3651-2676 FU Australian National Health and Medical Research Council [GNT1047648, GNT1066779, GNT1050504, 628386]; Australian Research Council [FT130100589]; National Institute of Mental Health FX This work was supported by the National Institute of Mental Health, Australian National Health and Medical Research Council (Career Development Fellowship GNT1047648 to Dr Zalesky; GNT1066779 and GNT1050504 to Dr Fornito), and the Australian Research Council (Fellowship FT130100589 to Dr Fornito). Dr Pantelis was supported by Australian National Health and Medical Research Council Senior Principal Research Fellowship 628386. NR 51 TC 5 Z9 5 U1 5 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2015 VL 72 IS 9 BP 900 EP 908 DI 10.1001/jamapsychiatry.2015.0226 PG 9 WC Psychiatry SC Psychiatry GA CR0DE UT WOS:000360987600009 PM 26176706 ER PT J AU Ursano, RJ Kessler, RC Stein, MB Naifeh, JA Aliaga, PA Fullerton, CS Sampson, NA Kao, TC Colpe, LJ Schoenbaum, M Cox, KL Heeringa, SG AF Ursano, Robert J. Kessler, Ronald C. Stein, Murray B. Naifeh, James A. Aliaga, Pablo A. Fullerton, Carol S. Sampson, Nancy A. Kao, Tzu-Cheg Colpe, Lisa J. Schoenbaum, Michael Cox, Kenneth L. Heeringa, Steven G. CA Army Study Assess Risk Resilience TI Suicide Attempts in the US Army During the Wars in Afghanistan and Iraq, 2004 to 2009 SO JAMA PSYCHIATRY LA English DT Article ID ACTIVE-DUTY PERSONNEL; ASSESS RISK; MENTAL-DISORDERS; POSTTRAUMATIC-STRESS; COMBAT DEPLOYMENT; MAJOR DEPRESSION; SUBSTANCE USE; MILITARY; SOLDIERS; RESILIENCE AB IMPORTANCE The rate of suicide attempts in the US Army increased sharply during the wars in Afghanistan and Iraq. Research on this important health outcome has been hampered by the lack of integration among Army administrative data systems. OBJECTIVE To identify risk factors for suicide attempts among active-duty members of the regular Army from January 1, 2004, through December 31, 2009. DESIGN, SETTING, AND PARTICIPANTS This longitudinal, retrospective cohort study, as part of the Army Study to Assess Risk and Resilience in Service members (STARRS), used individual-level person-month records from Army and Department of Defense administrative data systems to examine sociodemographic, service-related, and mental health predictors of medically documented suicide attempts among active-duty regular Army soldiers from January 1, 2004, through December 31, 2009. We analyzed data from 9791 suicide attempters and an equal-probability sample of 183 826 control person-months using a discrete-time survival framework. Data analysis was performed from February 3 through November 12, 2014. MAIN OUTCOMES AND MEASURES Suicide attempts identified using Department of Defense Suicide Event Report records and diagnostic codes E950 through E958 from the International Classification of Diseases, Ninth Revision, Clinical Modification. Standardized estimates of suicide attempt risk for sociodemographic, service-related, and mental health predictor variables were constructed from Army personnel and medical records. RESULTS Enlisted soldiers accounted for 98.6% of all suicide attempts (9650 attempters; overall rate, 377.0 [95% CI, 369.7-384.7] per 100 000 person-years). In multivariate models, suicide attempts among enlisted soldiers were predicted (data reported as odds ratio [95% CI]) by female sex (2.4 [2.3-2.5]), entering Army service at 25 years or older (1.6 [1.5-1.8]), current age of 29 years or younger (<21 years, 5.6 [5.1-6.2]; 21-24 years, 2.9 [2.6-3.2]; 25-29 years, 1.6 [1.5-1.8]), white race (black, 0.7 [0.6-0.7]; Hispanic, 0.7 [0.7-0.8]; Asian, 0.7 [0.6-0.8]), an educational level of less than high school (2.0 [2.0-2.1]), being in the first 4 years of service (1-2 years, 2.4 [2.2-2.6]; 3-4 years, 1.5 [1.4-1.6]), having never (2.8 [2.6-3.0]) or previously (2.6 [2.4-2.8]) been deployed, and a mental health diagnosis during the previous month (18.2 [17.4-19.1]). Attempts among officers (overall rate, 27.9 per 100 000 person-years) were predicted by female sex (2.8 [2.0-4.1]), entering Army service at 25 years or older (2.0 [1.3-3.1]), current age of 40 years or older (0.5 [0.3-0.8]), and a mental health diagnosis during the previous month (90.2 [59.5-136.7]). Discrete-time hazard models indicated risk among enlisted soldiers was highest in the second month of service (102.7 per 100000 person-months) and declined substantially as length of service increased (mean during the second year of service, 56.0 per 100000 person-years; after 4 years of service, 29.4 per 100000 person-months), whereas risk among officers remained stable (overall mean, 6.1 per 100000 person-months). CONCLUSIONS AND RELEVANCE Our results represent, to our knowledge, the most comprehensive accounting to date of suicide attempts in the Army. The findings reveal unique risk profiles for enlisted soldiers and officers and highlight the importance of research and prevention focused on enlisted soldiers in their first Army tour. C1 [Ursano, Robert J.; Naifeh, James A.; Aliaga, Pablo A.; Fullerton, Carol S.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Kessler, Ronald C.; Sampson, Nancy A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Stein, Murray B.] Vet Affairs San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA. [Kao, Tzu-Cheg] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA. [Cox, Kenneth L.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA. [Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. RP Ursano, RJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM robert.ursano@usuhs.edu RI Wessely, Simon/A-8713-2008 FU US Department of the Army; US Department of Health and Human Services, National Institutes of Health, NIMH [U01MH087981] FX Army STARRS was sponsored by the US Department of the Army and funded by cooperative agreement U01MH087981 with the US Department of Health and Human Services, National Institutes of Health, NIMH. NR 40 TC 9 Z9 9 U1 5 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2015 VL 72 IS 9 BP 917 EP 926 DI 10.1001/jamapsychiatry.2015.0987 PG 10 WC Psychiatry SC Psychiatry GA CR0DE UT WOS:000360987600011 PM 26154106 ER PT J AU Buchbinder, D Stinson, JR Nugent, DJ Heurtier, L Suarez, F Sukumar, G Dalgard, CL Masson, C Parisot, M Zhang, Y Matthews, HF Su, HC Durandy, A Fischer, A Kracker, S Snow, AL AF Buchbinder, David Stinson, Jeffrey R. Nugent, Diane J. Heurtier, Lucie Suarez, Felipe Sukumar, Gauthaman Dalgard, Clifton L. Masson, Cecile Parisot, Melanie Zhang, Yu Matthews, Helen F. Su, Helen C. Durandy, Anne Fischer, Alain Kracker, Sven Snow, Andrew L. TI Mild B-cell lymphocytosis in patients with a CARD11 C49Y mutation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID NF-KAPPA-B; LYMPHOMA C1 [Buchbinder, David; Nugent, Diane J.] Childrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USA. [Buchbinder, David; Nugent, Diane J.] Univ Calif Irvine, Dept Pediat, Orange, CA 92668 USA. [Stinson, Jeffrey R.; Snow, Andrew L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Heurtier, Lucie; Suarez, Felipe; Durandy, Anne; Fischer, Alain; Kracker, Sven] Univ Paris 05, Sorbonne Paris Cite, Imagine Inst, Paris, France. [Heurtier, Lucie; Durandy, Anne; Fischer, Alain; Kracker, Sven] INSERM, UMR 1163, Human Lymphohematopoiesis Lab, Paris, France. [Suarez, Felipe] Hop Necker Enfants Malad, Serv Hematol Adultes, Paris, France. [Sukumar, Gauthaman; Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Masson, Cecile] Univ Paris 05, Sorbonne Paris Cite, Imagine Inst, Bioinformat Platform, Paris, France. [Parisot, Melanie] Univ Paris 05, Sorbonne Paris Cite, Imagine Inst, Genom Core Facil, Paris, France. [Zhang, Yu; Matthews, Helen F.; Su, Helen C.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA. [Fischer, Alain] Hop Necker Enfants Malad, Dept Pediat Immunol Hematol & Rheumatol, Paris, France. [Fischer, Alain] Coll France, F-75231 Paris, France. RP Buchbinder, D (reprint author), Childrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USA. EM sven.kracker@inserm.fr; andrew.snow@usuhs.edu OI Heurtier, Lucie/0000-0002-2284-6774; Snow, Andrew/0000-0002-8728-6691 FU European Research Council [249816]; Intramural NIH HHS [Z01 AI001059-01, Z99 AI999999, ZIA AI001058-03]; NIAID NIH HHS [R21 AI109187] NR 10 TC 7 Z9 7 U1 1 U2 3 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 SEP PY 2015 VL 136 IS 3 BP 819 EP + DI 10.1016/j.jaci.2015.03.008 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA CQ9EA UT WOS:000360913300042 PM 25930198 ER PT J AU Oh, H Smith-Warner, SA Tamimi, RM Wang, ML Xu, X Hankinson, SE Fuhrman, BJ Ziegler, RG Eliassen, AH AF Oh, Hannah Smith-Warner, Stephanie A. Tamimi, Rulla M. Wang, Molin Xu, Xia Hankinson, Susan E. Fuhrman, Barbara J. Ziegler, Regina G. Eliassen, A. Heather TI Dietary Fat and Fiber Intakes Are Not Associated with Patterns of Urinary Estrogen Metabolites in Premenopausal Women SO JOURNAL OF NUTRITION LA English DT Article DE diet; fiber; fat; estrogen; estrogen metabolites; premenopausal ID BREAST-CANCER RISK; CHROMATOGRAPHY-MASS SPECTROMETRY; POSTMENOPAUSAL WOMEN; STEROID-HORMONES; SEX-HORMONES; CARCINOGENESIS; MECHANISMS; REPRODUCIBILITY; EXCRETION AB Background: Interindividual differences in the bioavailability of potentially carcinogenic estrogen and estrogen metabolites (EMs) may play a role in the risk of breast cancer. Objective: We examined whether dietary intakes of fiber and fat influence premenopausal EM profiles through effects on estrogen synthesis, metabolism, or excretion. Methods: We conducted a cross-sectional analysis of 598 premenopausal women who participated in a reproducibility study (n = 109) or served as controls in a nested case-control study of breast cancer (n = 489) within the Nurses' Health Study II. Dietary intakes of fiber and fat were assessed via semiquantitative food frequency questionnaires in 1995 and 1999. Midluteal urine samples were collected between 1996 and 1999 and EMs were quantified with the use of HPLC-tandem mass spectrometry. Linear mixed models were used to estimate creatinine-adjusted geometric means for individual EMs and their pathway groups across categories of dietary intake while controlling for total energy intake and potential confounders. Results: Higher total dietary fiber intake (>25 g/d vs. <= 15 g/d) was associated with significantly higher concentrations of 4-methoxyestradiol (50% difference, P-difference = 0.01, P-trend = 0.004) and lower concentrations of 17-epiestriol (-27% difference, P-difference = 0.03, P-trend = 0.03), but was not associated with any other EMs. The associations did not vary by fiber intake from different sources. Total fat intake (>35% energy vs. <= 25% energy) was suggestively positively associated with 17-epiestriol (22.6% difference, P-difference = 0.14, P-trend = 0.06); the association was significant for polyunsaturated fatty acid (37% difference, P-difference = 0.01, P-trend = 0.01) and trans fat (36.1% difference, P-difference = 0.01, P-trend = 0.01) intakes. Conclusion: Fiber and fat intakes were not strongly associated with patterns of estrogen metabolism in premenopausal women. Our data suggest estrogen metabolism is not a major mechanism through which dietary fiber and fat may affect breast or other hormone-related cancer risks. C1 [Oh, Hannah; Smith-Warner, Stephanie A.; Tamimi, Rulla M.; Wang, Molin; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Oh, Hannah; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wang, Molin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Oh, Hannah; Tamimi, Rulla M.; Wang, Molin; Hankinson, Susan E.; Eliassen, A. Heather] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Oh, Hannah; Tamimi, Rulla M.; Wang, Molin; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xu, Xia] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Fuhrman, Barbara J.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fuhrman, Barbara J.] Univ Arkansas Med Sci, Dept Epidemiol, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. RP Oh, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM hao383@mail.harvard.edu FU National Cancer Institute [UM1 CA176726, CA67262, CA50385, HHSN261200800001E, T32 CA09001]; Division of Cancer Epidemiology and Genetics of the National Cancer Institute FX This study was supported by infrastructure grant UM1 CA176726 and research grants CA67262 and CA50385 from the National Cancer Institute and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, and with federal funds of the National Cancer Institute awarded under contract HHSN261200800001E to Science Applications International Corporation-Frederick. H Oh was funded by the National Cancer Institute T32 CA09001. NR 46 TC 2 Z9 2 U1 1 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD SEP PY 2015 VL 145 IS 9 BP 2109 EP 2116 DI 10.3945/jn.115.212779 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CQ9EO UT WOS:000360915100018 PM 26180245 ER PT J AU Brillante, B Guthrie, L Van Ryzin, C AF Brillante, Beth Guthrie, Lori Van Ryzin, Carol TI McCune-Albright Syndrome: An Overview of Clinical Features SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Editorial Material ID FIBROUS DYSPLASIA; MANAGEMENT C1 [Brillante, Beth; Guthrie, Lori] NIDCR, NIH, Skeletal Clin Studies Unit, Bethesda, MD USA. [Van Ryzin, Carol] NHGRI, NIH, Bethesda, MD 20892 USA. RP Van Ryzin, C (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM cvanryzin@mail.nih.gov NR 9 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0882-5963 J9 J PEDIATR NURS JI J. Pediatr. Nurs. PD SEP-OCT PY 2015 VL 30 IS 5 SI SI BP 815 EP 817 DI 10.1016/j.pedn.2015.06.009 PG 3 WC Nursing; Pediatrics SC Nursing; Pediatrics GA CR0AR UT WOS:000360980800047 PM 26209174 ER PT J AU Cairns, TM Huang, ZY Gallagher, JR Lin, YX Lou, H Whitbeck, C Wald, A Cohen, GH Eisenberg, RJ AF Cairns, Tina M. Huang, Zhen-Yu Gallagher, John R. Lin, Yixin Lou, Huan Whitbeck, Charles Wald, Anna Cohen, Gary H. Eisenberg, Roselyn J. TI Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific SO JOURNAL OF VIROLOGY LA English DT Article ID HSV-2 GLYCOPROTEIN C; CD8(+) T-CELLS; CRYSTAL-STRUCTURE; PSEUDORABIES VIRUS; FUNCTIONAL REGIONS; RECEPTOR-BINDING; HEPARAN-SULFATE; PROTECTS MICE; FUSION LOOPS; GUINEA-PIGS AB Herpes simplex virus 1 (HSV-1) and HSV-2 infect many humans and establish a latent infection in sensory ganglia. Although some infected people suffer periodic recurrences, others do not. Infected people mount both cell-mediated and humoral responses, including the production of virus-neutralizing antibodies (Abs) directed at viral entry glycoproteins. Previously, we examined IgGs from 10 HSV-seropositive individuals; all neutralized virus and were directed primarily against gD or gD+gB. Here, we expand our studies and examine 32 additional sera from HSV-infected individuals, 23 of whom had no recurrent disease. Using an Octet RED96 system, we screened all 32 serum samples directly for both glycoprotein binding and competition with known neutralizing anti-gD and -gB monoclonal Abs (MAbs). On average, the recurrent cohort exhibited higher binding to gD and gB and had higher neutralization titers. There were similar trends in the blocking of MAbs to critical gD and gB epitopes. When we depleted six sera of Abs to specific glycoproteins, we found different types of responses, but always directed primarily at gD and/or gB. Interestingly, in one dual-infected person, the neutralizing response to HSV-2 was due to gD2 and gB2, whereas HSV-1 neutralization was due to gD1 and gB1. In another case, virus neutralization was HSV-1 specific, with the Ab response directed entirely at gB1, despite this serum blocking type-common anti-gD and -gB neutralizing MAbs. These data are pertinent in the design of future HSV vaccines since they demonstrate the importance of both serotypes of gD and gB as immunogens. IMPORTANCE We previously showed that people infected with HSV produce neutralizing Abs directed against gD or a combination of gD+gB (and in one case, gD+gB+gC, which was HSV-1 specific). In this more extensive study, we again found that gD or gD+gB can account for the virus neutralizing response and critical epitopes of one or both of these proteins are represented in sera of naturally infected humans. However, we also found that some individuals produced a strong response against gB alone. In addition, we identified type-specific contributions to HSV neutralization from both gD and gB. Contributions from the other entry glycoproteins, gC and gH/gL, were minimal and limited to HSV-1 neutralization. Knowing the variations in how humans see and mount a response to HSV will be important to vaccine development. C1 [Cairns, Tina M.; Huang, Zhen-Yu; Lou, Huan; Whitbeck, Charles; Cohen, Gary H.] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Eisenberg, Roselyn J.] Univ Penn, Sch Dent Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Gallagher, John R.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Lin, Yixin] Pall ForteBio LLC, Menlo Pk, CA USA. [Wald, Anna] Univ Washington, Dept Med, Seattle, WA USA. RP Cairns, TM (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. EM tmcairns@dental.upenn.edu RI Wald, Anna/B-6272-2012; OI Wald, Anna/0000-0003-3486-6438; Gallagher, John/0000-0002-1954-8872 FU National Institutes of Health [AI-18289, AI-076231, AI-056045] FX This research was supported by National Institutes of Health grants AI-18289 (to G.H.C.), and AI-076231 and AI-056045 (to R.J.E). NR 63 TC 4 Z9 5 U1 1 U2 5 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 SEP PY 2015 VL 89 IS 18 BP 9213 EP 9231 DI 10.1128/JVI.01213-15 PG 19 WC Virology SC Virology GA CQ6HE UT WOS:000360704400008 PM 26109729 ER PT J AU Gjessing, MC Yutin, N Tengs, T Senkevich, T Koonin, E Ronning, HP Alarcon, M Ylving, S Lie, KI Saure, B Tran, L Moss, B Dale, OB AF Gjessing, Mona C. Yutin, Natalya Tengs, Torstein Senkevich, Tania Koonin, Eugene Ronning, Hans Petter Alarcon, Marta Ylving, Sonja Lie, Kai-Inge Saure, Britt Tran, Linh Moss, Bernard Dale, Ole Bendik TI Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOCYTOPLASMIC DNA VIRUSES; FARMED ATLANTIC SALMON; VIRION MORPHOGENESIS; BINDING-PROTEIN; SLEEPY DISEASE; CELL ENTRY; VACCINIA; GENOME; SEQUENCES; EVOLUTION AB Poxviruses are large DNA viruses of vertebrates and insects causing disease in many animal species, including reptiles, birds, and mammals. Although poxvirus-like particles were detected in diseased farmed koi carp, ayu, and Atlantic salmon, their genetic relationships to poxviruses were not established. Here, we provide the first genome sequence of a fish poxvirus, which was isolated from farmed Atlantic salmon. In the present study, we used quantitative PCR and immunohistochemistry to determine aspects of salmon gill poxvirus disease, which are described here. The gill was the main target organ where immature and mature poxvirus particles were detected. The particles were detected in detaching, apoptotic respiratory epithelial cells preceding clinical disease in the form of lethargy, respiratory distress, and mortality. In moribund salmon, blocking of gas exchange would likely be caused by the adherence of respiratory lamellae and epithelial proliferation obstructing respiratory surfaces. The virus was not found in healthy salmon or in control fish with gill disease without apoptotic cells, although transmission remains to be demonstrated. PCR of archival tissue confirmed virus infection in 14 cases with gill apoptosis in Norway starting from 1995. Phylogenomic analyses showed that the fish poxvirus is the deepest available branch of chordopoxviruses. The virus genome encompasses most key chordopoxvirus genes that are required for genome replication and expression, although the gene order is substantially different from that in other chordopoxviruses. Nevertheless, many highly conserved chordopoxvirus genes involved in viral membrane biogenesis or virus-host interactions are missing. Instead, the salmon poxvirus carries numerous genes encoding unknown proteins, many of which have low sequence complexity and contain simple repeats suggestive of intrinsic disorder or distinct protein structures. IMPORTANCE Aquaculture is an increasingly important global source of high-quality food. To sustain the growth in aquaculture, disease control in fish farming is essential. Moreover, the spread of disease from farmed fish to wildlife is a concern. Serious poxviral diseases are emerging in aquaculture, but very little is known about the viruses and the diseases that they cause. There is a possibility that viruses with enhanced virulence may spread to new species, as has occurred with the myxoma poxvirus in rabbits. Provision of the first fish poxvirus genome sequence and specific diagnostics for the salmon gill poxvirus in Atlantic salmon may help curb this disease and provide comparative knowledge. Furthermore, because salmon gill poxvirus represents the deepest branch of chordopoxvirus so far discovered, the genome analysis provided substantial insight into the evolution of different functional modules in this important group of viruses. C1 [Gjessing, Mona C.; Tengs, Torstein; Alarcon, Marta; Ylving, Sonja; Lie, Kai-Inge; Saure, Britt; Tran, Linh; Dale, Ole Bendik] Norwegian Vet Inst, Oslo, Norway. [Yutin, Natalya; Koonin, Eugene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Senkevich, Tania; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Ronning, Hans Petter] Sisomar AS, Trollbukta, Straumen, Norway. RP Gjessing, MC (reprint author), Norwegian Vet Inst, Oslo, Norway. EM mona.gjessing@vetinst.no; bmoss@nih.gov FU Research Council of Norway grant [234037]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by The Research Council of Norway grant 234037 and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 72 TC 3 Z9 3 U1 5 U2 19 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 SEP PY 2015 VL 89 IS 18 BP 9348 EP 9367 DI 10.1128/JVI.01174-15 PG 20 WC Virology SC Virology GA CQ6HE UT WOS:000360704400019 PM 26136578 ER PT J AU Pinto, AK Williams, GD Szretter, KJ White, JP Proenca-Modena, JL Liu, G Olejnik, J Brien, JD Ebihara, H Muhlberger, E Amarasinghe, G Diamond, MS Boon, ACM AF Pinto, Amelia K. Williams, Graham D. Szretter, Kristy J. White, James P. Proenca-Modena, Jose Luiz Liu, Gai Olejnik, Judith Brien, James D. Ebihara, Hideki Muehlberger, Elke Amarasinghe, Gaya Diamond, Michael S. Boon, Adrianus C. M. TI Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; EUKARYOTIC INITIATION-FACTOR-3; INDUCIBLE PROTEIN; 2'-O METHYLATION; DNA-REPLICATION; CELLS; P56; TRANSLATION; POLYMERASE; METHYLTRANSFERASE AB Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses. C1 [Pinto, Amelia K.; Williams, Graham D.; Szretter, Kristy J.; White, James P.; Proenca-Modena, Jose Luiz; Brien, James D.; Diamond, Michael S.; Boon, Adrianus C. M.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.; Boon, Adrianus C. M.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Liu, Gai; Olejnik, Judith; Amarasinghe, Gaya; Diamond, Michael S.; Boon, Adrianus C. M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Olejnik, Judith; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Olejnik, Judith; Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Labs, Boston, MA 02118 USA. [Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. [Proenca-Modena, Jose Luiz] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP, Brazil. RP Boon, ACM (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. EM jboon@dom.wustl.edu RI Proenca-Modena, Jose/C-8231-2014; OI Szretter, Kristy/0000-0003-0391-2307 FU Division of Intramural Research, NIAID, NIH; NIH grant [F32 AI112274]; [U54 AI057160]; [R01 AI104972]; [R01 AI104002]; [GM: 007067] FX This work was supported in part by grant U54 AI057160 to A.C.M.B., by grants R01 AI104972 and R01 AI104002 to M.S.D., and by the Division of Intramural Research, NIAID, NIH, to H.E.G.D.W. is supported by training grant GM: 007067. J.P.W. is supported by an F32 AI112274 NIH grant. NR 44 TC 3 Z9 3 U1 1 U2 7 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 SEP PY 2015 VL 89 IS 18 BP 9465 EP 9476 DI 10.1128/JVI.00996-15 PG 12 WC Virology SC Virology GA CQ6HE UT WOS:000360704400028 PM 26157117 ER PT J AU Liang, B Surman, S Amaro-Carambot, E Kabatova, B Mackow, N Lingemann, M Yang, LJ McLellan, JS Graham, BS Kwong, PD Schaap-Nutt, A Collins, PL Munir, S AF Liang, Bo Surman, Sonja Amaro-Carambot, Emerito Kabatova, Barbora Mackow, Natalie Lingemann, Matthias Yang, Lijuan McLellan, Jason S. Graham, Barney S. Kwong, Peter D. Schaap-Nutt, Anne Collins, Peter L. Munir, Shirin TI Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate SO JOURNAL OF VIROLOGY LA English DT Article ID FUSION PROTEIN; RSV F; PULMONARY PATHOLOGY; RHESUS-MONKEYS; COTTON RATS; GLYCOPROTEIN; LIVE; REPLICATION; INFECTION; IMMUNIZATION AB Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. IMPORTANCE Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation. C1 [Liang, Bo; Surman, Sonja; Amaro-Carambot, Emerito; Kabatova, Barbora; Mackow, Natalie; Lingemann, Matthias; Yang, Lijuan; Schaap-Nutt, Anne; Collins, Peter L.; Munir, Shirin] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [McLellan, Jason S.; Graham, Barney S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Munir, S (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM munirs@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. NR 41 TC 14 Z9 14 U1 4 U2 14 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 SEP PY 2015 VL 89 IS 18 BP 9499 EP 9510 DI 10.1128/JVI.01373-15 PG 12 WC Virology SC Virology GA CQ6HE UT WOS:000360704400031 PM 26157122 ER PT J AU Prasad, V Berger, VW AF Prasad, Vinay Berger, Vance W. TI Hard-Wired Bias: How Even Double-Blind, Randomized Controlled Trials Can Be Skewed From the Start SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID RENAL-CELL CARCINOMA; MULTIPLE-MYELOMA; CLINICAL-TRIALS; CROSSOVER; SURVIVAL; TRANSPLANTATION; MAINTENANCE; EVEROLIMUS; EFFICACY; THERAPY C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Berger, Vance W.] Univ Maryland Baltimore Cty, Biometry Res Grp, Canc Prevent Div, NCI,NIH, Rockville, MD USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov; vinayak.k.prasad@gmail.com FU Intramural NIH HHS [Z99 CA999999] NR 29 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2015 VL 90 IS 9 BP 1171 EP 1175 DI 10.1016/j.mayocp.2015.05.006 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CQ9WQ UT WOS:000360966300003 PM 26277702 ER PT J AU Abbatiello, SE Schilling, B Mani, DR Zimmerman, LJ Hall, SC Maclean, B Albertolle, M Allen, S Burgess, M Cusack, MP Gosh, M Hedrick, V Held, JM Inerowicz, HD Jackson, A Keshishian, H Kinsinger, CR Lyssand, J Makowski, L Mesri, M Rodriguez, H Rudnick, P Sadowski, P Sedransk, N Shaddox, K Skates, SJ Kuhn, E Smith, D Whiteaker, JR Whitwell, C Zhang, S Borchers, CH Fisher, SJ Gibson, BW Liebler, DC MacCoss, MJ Neubert, TA Paulovich, AG Regnier, FE Tempst, P Carr, SA AF Abbatiello, Susan E. Schilling, Birgit Mani, D. R. Zimmerman, Lisa J. Hall, Steven C. Maclean, Brendan Albertolle, Matthew Allen, Simon Burgess, Michael Cusack, Michael P. Gosh, Mousumi Hedrick, Victoria Held, Jason M. Inerowicz, H. Dorota Jackson, Angela Keshishian, Hasmik Kinsinger, Christopher R. Lyssand, John Makowski, Lee Mesri, Mehdi Rodriguez, Henry Rudnick, Paul Sadowski, Pawel Sedransk, Nell Shaddox, Kent Skates, Stephen J. Kuhn, Eric Smith, Derek Whiteaker, Jeffery R. Whitwell, Corbin Zhang, Shucha Borchers, Christoph H. Fisher, Susan J. Gibson, Bradford W. Liebler, Daniel C. MacCoss, Michael J. Neubert, Thomas A. Paulovich, Amanda G. Regnier, Fred E. Tempst, Paul Carr, Steven A. TI Large-Scale Interlaboratory Study to Develop, Analytically Validate and Apply Highly Multiplexed, Quantitative Peptide Assays to Measure Cancer-Relevant Proteins in Plasma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MONITORING MASS-SPECTROMETRY; LOW-ABUNDANCE PROTEINS; ABSOLUTE QUANTIFICATION; BIOMARKER DISCOVERY; TARGETED PROTEOMICS; ISOTOPE-DILUTION; STANDARDS; MS; PROTEOLYSIS; PERFORMANCE AB There is an increasing need in biology and clinical medicine to robustly and reliably measure tens to hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility, and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here, we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and seven control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data, we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to sub-nanogram/ml sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and interlaboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy-isotope-labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an interlaboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality control measures, enables sensitive, specific, reproducible, and quantitative measurements of proteins and peptides in complex biological matrices such as plasma. C1 [Abbatiello, Susan E.; Mani, D. R.; Burgess, Michael; Keshishian, Hasmik; Kuhn, Eric; Carr, Steven A.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Schilling, Birgit; Cusack, Michael P.; Held, Jason M.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. [Zimmerman, Lisa J.; Shaddox, Kent; Whitwell, Corbin; Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Zimmerman, Lisa J.; Shaddox, Kent; Whitwell, Corbin; Liebler, Daniel C.] Vanderbilt Ingram Canc Ctr, Jim Ayers Inst Precancer Detect & Diag, Nashville, TN 37232 USA. [Hall, Steven C.; Albertolle, Matthew; Allen, Simon; Fisher, Susan J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Maclean, Brendan; MacCoss, Michael J.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Gosh, Mousumi; Tempst, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Hedrick, Victoria; Inerowicz, H. Dorota; Regnier, Fred E.] Purdue Univ, W Lafayette, IN 47907 USA. [Jackson, Angela; Smith, Derek; Borchers, Christoph H.] Univ Victoria, Genome BC Prote Ctr, Victoria, BC V8Z 7X8, Canada. [Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Neubert, Thomas A.] NCI, NIH, Bethesda, MD 20892 USA. [Lyssand, John; Sadowski, Pawel; Neubert, Thomas A.] NYU, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Rudnick, Paul] NIST, Gaithersburg, MD 20899 USA. [Sedransk, Nell] Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. [Skates, Stephen J.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Whiteaker, Jeffery R.; Zhang, Shucha; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Carr, SA (reprint author), Broad Inst & Harvard, Cambridge, MA 02142 USA. EM scarr@broad.mit.edu OI Tempst, Paul/0000-0002-6680-3987; Held, Jason/0000-0001-8024-2736 FU National Cancer Institute, NCI Clinical Proteomic Technologies for Cancer initiative [U24 CA126476, U24 126477, U24 126480, U24 CA126485, U24 126479]; NCI [U24CA160034]; Vanderbilt University Center via NCI [U24CA159988]; National Institute of Standards and Technology [70NANB9H9001]; NCRR Shared Instrumentation program [S10 RR027953, S10 RR024604]; National Institute of Statistical Sciences; Canary Foundation FX This work was supported by grants from the National Cancer Institute (U24 CA126476, U24 126477, U24 126480, U24 CA126485, and U24 126479), part of NCI Clinical Proteomic Technologies for Cancer (http://proteomics.cancer.gov) initiative. A component of this initiative is the Clinical Proteomic Technology Assessment for Cancer (CPTAC) Network and teams, which include the Broad Institute of MIT and Harvard (with the Fred Hutchinson Cancer Research Center, Massachusetts General Hospital, the University of North Carolina at Chapel Hill, the University of Victoria, and the Plasma Proteome Institute), Memorial Sloan-Kettering Cancer Center (with the Skirball Institute at New York University), Purdue University (with Monarch Life Sciences, Indiana University, Indiana University-Purdue University Indianapolis, and the Hoosier Oncology Group), University of California, San Francisco (with the Buck Institute for Research on Aging, Lawrence Berkeley National Laboratory, and the University of Texas M.D. Anderson Cancer Center), and Vanderbilt University School of Medicine (with the University of Texas M.D. Anderson Cancer Center, the University of Washington, and the University of Arizona). The Broad Institute and Fred Hutchinson Cancer Research Center also acknowledge CPTAC phase 2 support from NCI U24CA160034, as does the Vanderbilt University Center via NCI U24CA159988. The UCSF CPTAC team gratefully acknowledges the support of the Canary Foundation for providing funds to purchase a 4000 QTRAP mass spectrometer. The Vanderbilt CPTAC team was additionally supported by Cooperative Agreement No. 70NANB9H9001 from the National Institute of Standards and Technology. B.W.G. and T.A.N. acknowledge support from the NCRR Shared Instrumentation program for instrumentation (grants S10 RR027953 and S10 RR024604, respectively). The NCI CPTAC also supported the work by the National Institute of Statistical Sciences. NR 59 TC 42 Z9 42 U1 8 U2 35 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2015 VL 14 IS 9 BP 2357 EP 2374 DI 10.1074/mcp.M114.047050 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ7YO UT WOS:000360823000006 PM 25693799 ER PT J AU Sato, K Nagaya, T Nakamura, Y Harada, T Nani, RR Shaum, JB Gorka, AP Kim, I Paik, CH Choyke, PL Schnermann, MJ Kobayashi, H AF Sato, Kazuhide Nagaya, Tadanobu Nakamura, Yuko Harada, Toshiko Nani, Roger R. Shaum, James B. Gorka, Alexander P. Kim, Insook Paik, Chang H. Choyke, Peter L. Schnermann, Martin J. Kobayashi, Hisataka TI Impact of C4'-O-Alkyl Linker on in Vivo Pharmacokinetics of Near-Infrared Cyanine/Monoclonal Antibody Conjugates SO MOLECULAR PHARMACEUTICS LA English DT Article DE cyanine; in vivo imaging; near-infrared (NIR) fluorophores; monoclonal antibody (mAb) conjugates ID MONOCLONAL-ANTIBODIES; CANCER; FLUORESCENCE; DYES AB Near-infrared (NIR) fluorophores have several advantages over visible-light fluorophores, including superior tissue penetration and lower autofluorescence. We recently accessed a new class of readily synthesized NIR cyanines containing a novel C4'-O-alkyl linker, which provides both high chemical stability and excellent optical properties. In this study, we provide the first in vivo analysis of this new class of compounds, represented by the tetrasulfonate FNIR-774 (Frederick NIR 774). Monoclonal antibody (mAb) conjugates of FNIR-774 were compared to conjugates of the commercially available dye (IRDye800CW (IR800)), one of the most widely used NIR fluorophores for clinical translation. Both dyes were conjugated to panitumumab (pan) or cetuximab (cet) with ratios of 1:2 or 1:5. Conjugates of both dyes demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. In contrast, in vivo imaging in mice showed different pharmacokinetics between pan-FNIR-774 (1:5) and pan-IR800 (1:5), or cet-FNIR-774 (1:5) and cet-IR800 (1:5). Particularly at the higher labeling density, mAb-FNIR-774 conjugates showed superior specific accumulation in tumors compared with mAb-IR800 conjugates. Thus, FNIR-774 conjugates showed superior in vivo pharmacokinetics compared with IR800 conjugates, independent of the mAb. These results suggest that FNIR-774 is a promising fluorescent probe for NIB. optical imaging. C1 [Sato, Kazuhide; Nagaya, Tadanobu; Nakamura, Yuko; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Nani, Roger R.; Shaum, James B.; Gorka, Alexander P.; Schnermann, Martin J.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. [Kim, Insook] Leidos Biomedical Res Inc, Appl Dev Res Directorate, Frederick Natl Lab, Frederick, MD 21702 USA. [Paik, Chang H.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr Radiol & Imaging S, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Schnermann, MJ (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,M5C1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov; martin.schnermann@nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 22 TC 2 Z9 2 U1 5 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP PY 2015 VL 12 IS 9 BP 3303 EP 3311 DI 10.1021/acs.molpharmaceut.5b00472 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CR1LR UT WOS:000361086800020 PM 26261913 ER PT J AU Eduati, F Mangravite, LM Wang, T Tang, H Bare, JC Huang, RL Norman, T Kellen, M Menden, MP Yang, JC Zhan, XW Zhong, R Xiao, GH Xia, MH Abdo, N Kosyk, O Friend, S Dearry, A Simeonov, A Tice, RR Rusyn, I Wright, FA Stolovitzky, G Xie, Y Saez-Rodriguez, J AF Eduati, Federica Mangravite, Lara M. Wang, Tao Tang, Hao Bare, J. Christopher Huang, Ruili Norman, Thea Kellen, Mike Menden, Michael P. Yang, Jichen Zhan, Xiaowei Zhong, Rui Xiao, Guanghua Xia, Menghang Abdo, Nour Kosyk, Oksana Friend, Stephen Dearry, Allen Simeonov, Anton Tice, Raymond R. Rusyn, Ivan Wright, Fred A. Stolovitzky, Gustavo Xie, Yang Saez-Rodriguez, Julio CA NIEHS-NCATS-UNC DREAM TI Prediction of human population responses to toxic compounds by a collaborative competition SO NATURE BIOTECHNOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; EXPRESSION; SENSITIVITY; PRINCIPLE; KNOWLEDGE; CHEMICALS; PROFILES; DATABASE; LIBRARY; MODEL AB The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal. C1 [Eduati, Federica; Menden, Michael P.; Saez-Rodriguez, Julio] European Bioinformat Inst, European Mol Biol Lab, Cambridge, England. [Mangravite, Lara M.; Bare, J. Christopher; Norman, Thea; Kellen, Mike; Friend, Stephen] Sage Bionetworks, Seattle, WA USA. [Wang, Tao; Tang, Hao; Yang, Jichen; Zhong, Rui; Xiao, Guanghua; Xie, Yang] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA. [Tang, Hao; Xie, Yang] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Huang, Ruili; Xia, Menghang; Simeonov, Anton] NIH, Div Preclin Innovat, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Zhan, Xiaowei] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Abdo, Nour; Kosyk, Oksana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Abdo, Nour] Jordan Univ Sci & Technol, Fac Med, Dept Publ Hlth, Irbid, Jordan. [Dearry, Allen; Tice, Raymond R.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Wright, Fred A.] N Carolina State Univ, Bioinformat Res Ctr, Dept Stat & Biol Sci, Raleigh, NC 27695 USA. [Stolovitzky, Gustavo] IBM Corp, IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. RP Saez-Rodriguez, J (reprint author), Rhein Westfal TH Aachen, Joint Res Ctr Computat Biomed JRC COMBINE, Aachen, Germany. EM Yang.Xie@utsouthwestern.edu; saezrodriguez@combine.rwth-aachen.de RI Falcao, Andre/A-3545-2010; Clement-Ziza, Mathieu/J-4146-2012; Amadoz, Alicia/A-9598-2014; Tang, Jing/H-4084-2012; Wang, Tao/K-3518-2016; Ruderfer, Douglas/M-5795-2016; Rusyn, Ivan/S-2426-2016; OI Bare, J. Christopher/0000-0003-1006-1491; Bacardit, Jaume/0000-0002-2692-7205; Michoel, Tom/0000-0003-4749-4725; Moore, Jonathan/0000-0002-5486-0407; Saez-Rodriguez, Julio/0000-0002-8552-8976; Falcao, Andre/0000-0002-3588-8746; Clement-Ziza, Mathieu/0000-0003-2763-249X; Amadoz, Alicia/0000-0003-3915-0404; Tang, Jing/0000-0001-7480-7710; Ruderfer, Douglas/0000-0002-2365-386X; Eduati, Federica/0000-0002-7822-3867 FU US National Institutes of Health (NIH); National Institute of Environmental Health Sciences (NIEHS) [Y2-ES-7020-01]; US Environmental Protection Agency [STAR RD83516601, RD83382501]; NIH [R01CA161608, R01HG006292, 5R01CA152301, 1R01CA172211]; European Molecular Biology Laboratory Interdisciplinary Post-Docs (EMBL EIPOD); Marie Curie Actions (COFUND) FX This research was supported in part by the US National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). This work was made possible by US Environmental Protection Agency grants STAR RD83516601 and RD83382501, NIH grants R01CA161608 and R01HG006292, and through an interagency agreement (IAG #Y2-ES-7020-01) from NIEHS to NCATS. F.E. thanks European Molecular Biology Laboratory Interdisciplinary Post-Docs (EMBL EIPOD) and Marie Curie Actions (COFUND) for funding. Best performing team was funded by NIH grants 5R01CA152301 and 1R01CA172211. NR 38 TC 11 Z9 11 U1 1 U2 11 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 SEP PY 2015 VL 33 IS 9 BP 933 EP U172 DI 10.1038/nbt.3299 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CR0EK UT WOS:000360990900021 PM 26258538 ER PT J AU Yassine, HM Boyington, JC McTamney, PM Wei, CJ Kanekiyo, M Kong, WP Gallagher, JR Wang, LS Zhang, Y Joyce, MG Lingwood, D Moin, SM Andersen, H Okuno, Y Rao, SS Harris, AK Kwong, PD Mascola, JR Nabel, GJ Graham, BS AF Yassine, Hadi M. Boyington, Jeffrey C. McTamney, Patrick M. Wei, Chih-Jen Kanekiyo, Masaru Kong, Wing-Pui Gallagher, John R. Wang, Lingshu Zhang, Yi Joyce, M. Gordon Lingwood, Daniel Moin, Syed M. Andersen, Hanne Okuno, Yoshinobu Rao, Srinivas S. Harris, Audray K. Kwong, Peter D. Mascola, John R. Nabel, Gary J. Graham, Barney S. TI Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection SO NATURE MEDICINE LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; STALK-SPECIFIC ANTIBODIES; VIRUS HEMAGGLUTININ; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; LETHAL CHALLENGE; IN-VIVO; VACCINATION; EPITOPE; DESIGN AB The antibody response to influenza is primarily focused on the head region of the hemagglutinin (HA) glycoprotein, which in turn undergoes antigenic drift, thus necessitating annual updates of influenza vaccines. In contrast, the immunogenically subdominant stem region of HA is highly conserved and recognized by antibodies capable of binding multiple HA subtypes(1-6). Here we report the structure-based development of an H1 HA stem-only immunogen that confers heterosubtypic protection in mice and ferrets. Six iterative cycles of structure-based design (Gen1-Gen6) yielded successive H1 HA stabilized-stem (HA-SS) immunogens that lack the immunodominant head domain. Antigenic characterization, determination of two HA-SS crystal structures in complex with stem-specific monoclonal antibodies and cryo-electron microscopy analysis of HA-SS on ferritin nanoparticles (H1-SS-np) confirmed the preservation of key structural elements. Vaccination of mice and ferrets with H1-SS-np elicited broadly cross-reactive antibodies that completely protected mice and partially protected ferrets against lethal heterosubtypic H5N1 influenza virus challenge despite the absence of detectable H5N1 neutralizing activity in vitro. Passive transfer of immunoglobulin from H1-SS-np-immunized mice to naive mice conferred protection against H5N1 challenge, indicating that vaccine-elicited HA stem-specific antibodies can protect against diverse group 1 influenza strains. C1 [Yassine, Hadi M.; Boyington, Jeffrey C.; McTamney, Patrick M.; Wei, Chih-Jen; Kanekiyo, Masaru; Kong, Wing-Pui; Wang, Lingshu; Zhang, Yi; Joyce, M. Gordon; Lingwood, Daniel; Moin, Syed M.; Rao, Srinivas S.; Kwong, Peter D.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gallagher, John R.; Harris, Audray K.] NIAID, Struct Informat Unit, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Andersen, Hanne] BIOQUAL Inc, Rockville, MD USA. [Okuno, Yoshinobu] Osaka Univ, Res Fdn Microbial Dis, Kanonji Inst, Kanonji, Japan. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gary.nabel@sanofi.com; bgraham@nih.gov OI Gallagher, John/0000-0002-1954-8872 FU Vaccine Research Center; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank A. Taylor, H. Bao, J.P. Todd and C. Chiedi for help with the animal studies, U. Baxa for EM studies, K. Dai and X. Chen for technical support and B. Hartman for manuscript preparation. We thank M.C. Nason for excellent statistical advice and support. We also thank K. Modjarrad and laboratory members for helpful discussions. This work was supported by the Intramural Research Program of the Vaccine Research Center and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. X-ray data were collected at the SER-CAT 22-BM beamline at the Advanced Photon Source (APS), Argonne National Laboratory. Use of APS was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under contract no. W-31-109-Eng-38. NR 48 TC 58 Z9 58 U1 7 U2 44 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 SEP PY 2015 VL 21 IS 9 BP 1065 EP + DI 10.1038/nm.3927 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CQ9US UT WOS:000360961300020 PM 26301691 ER PT J AU Jones, CP Ferre-D'Amare, AR AF Jones, Christopher P. Ferre-D'Amare, Adrian R. TI Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID X-RAY-SCATTERING; C-DI-AMP; STRUCTURAL BASIS; LIGAND-BINDING; RIBOSWITCH REVEALS; SENSING RIBOSWITCH; CRYSTAL-STRUCTURES; GENE-EXPRESSION; MACROMOLECULAR STRUCTURES; S-ADENOSYLMETHIONINE AB The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. We report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg2+ ion. We show that the affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. The ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression. C1 [Jones, Christopher P.; Ferre-D'Amare, Adrian R.] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Ferre-D'Amare, AR (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM adrian.ferre@nih.gov FU NIH; US Department of Energy; intramural program of the NHLBI, NIH; Lenfant Biomedical Fellowship FX We thank the staff at beamlines 5.0.1 and 5.0.2 of the Advanced Light Source at Lawrence Berkeley National Laboratory for crystallographic data collection; R. Trachman for SAXS data collection; G. Piszczek (US National Heart, Lung, and Blood Institute, NHLBI, National Institutes of Health (NIH)) for isothermal titration calorimetry support; and L. Fang, S. Seifert and X. Zuo at beamline 12-ID-C of the Advanced Photon Source, Argonne National Laboratory (ANL) for SAXS support. SAXS data were collected in a core facility of the Center for Cancer Research, US National Cancer Institute (NCI) allocated under agreement between NCI and ANL (PUP-24152). We also thank S. Bachas, M. Chen, C. Fagan, M. Lau, R. Trachman, K. Warner and J. Zhang for discussions. This work was partly conducted at the ALS, on the Berkeley Center for Structural Biology beamlines, which are supported by the NIH. Use of ALS and APS was supported by the US Department of Energy. This work was supported in part by the intramural program of the NHLBI, NIH, and by a Lenfant Biomedical Fellowship to C.P.J. NR 65 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2015 VL 22 IS 9 BP 679 EP U53 DI 10.1038/nsmb.3073 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CQ9KK UT WOS:000360933200010 PM 26280533 ER PT J AU Balmer, J Stanzel, BV Fischer, MD AF Balmer, J. Stanzel, B. V. Fischer, M. D. TI Stem cell therapy for retinal diseases SO OPHTHALMOLOGE LA German DT Article DE Stem cells; Retina; Retinal pigment epithelium; Age-related macular degeneration; Clinical trials ID PIGMENT EPITHELIAL-CELLS; PHOTORECEPTOR PRECURSORS; MACULAR DEGENERATION; TRANSPLANTATION; GENERATION; RPE; INTEGRATE; SHEETS; MATURE AB Background Due to an ageing population the incidence and prevalence of retinal diseases and visual disabilities will continue to grow. A great number of patients would principally be able to benefit from a stem cell-based therapy. Objectives To introduce readers to the terminology and current concepts associated with stem cell therapy in ocular research and to provide an overview of the current status of preclinical and clinical research. Materials and Methods We performed a systematic review of relevant entries on ocular stem cell therapy for retinal diseases in PubMed and ClinicalTrials.gov. Differences between various stem cell types are displayed systematically, followed by a discussion of preclinical studies. Translational aspects are highlighted leading to the first clinical trials, including surgical and ethical facets. Results In preclinical studies, photoreceptor cell precursors and retinal pigment epithelium (RPE) cells were differentiated and subretinally transplanted into animal models. Besides exclusion of a teratoma formation, some functional improvements were also observed. Intraocular transplantation of stem cell-derived RPE cells was the first successful clinical application of pluripotent stem cells in man. Conclusions Promising results of preclinical and clinical studies have identified important challenges and confirmed the potential of stem cell therapy for ophthalmology. C1 [Balmer, J.; Fischer, M. D.] Univ Oxford, Nuffield Lab Ophthalmol, Nuffield Dept Clin Neurosci, Oxford OX2 6AW, England. [Stanzel, B. V.] Univ Bonn, Univ Augenklin Bonn, Bonn, Germany. [Stanzel, B. V.] NEI, NIH, Bethesda, MD 20892 USA. [Fischer, M. D.] Univ Klinikum Tubingen, Dept Augenheilkunde, Univ Augenklin, D-72076 Tubingen, Germany. RP Fischer, MD (reprint author), Univ Klinikum Tubingen, Dept Augenheilkunde, Univ Augenklin, Tubingen Schleichstr 12-16, D-72076 Tubingen, Germany. EM dominik.fischer@med.uni-tuebingen.de NR 31 TC 1 Z9 1 U1 4 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-293X EI 1433-0423 J9 OPHTHALMOLOGE JI Ophthalmologe PD SEP PY 2015 VL 112 IS 9 BP 728 EP 737 DI 10.1007/s00347-015-0119-2 PG 10 WC Ophthalmology SC Ophthalmology GA CR0FU UT WOS:000360994700004 PM 26271739 ER PT J AU Takahashi, TT Vendruscolo, LF Takahashi, RN AF Takahashi, Tatiane T. Vendruscolo, Leandro F. Takahashi, Reinaldo N. TI Binge-like ingestion of a combination of an energy drink and alcohol leads to cognitive deficits and motivational changes SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Addiction; Alcoholism; Ethanol; Energy drink; Binge drinking; Memory; Reward ID NUCLEUS-ACCUMBENS MICRODIALYSATE; SPONTANEOUSLY HYPERTENSIVE-RATS; ADENOSINE RECEPTOR ANTAGONISTS; CENTRAL-NERVOUS-SYSTEM; PREFRONTAL CORTEX; HYPERACTIVITY DISORDER; OBJECT-RECOGNITION; DEPENDENT RATS; BRAIN-DAMAGE; WISTAR RATS AB The combination of alcohol with an energy drink (ED) is believed to contribute to risky alcohol-drinking behaviors, such as binge drinking. However, the long-term effects on cognition and reward function that are caused by the repeated binge-like ingestion of alcohol and EDs are still poorly known. The present study examined the effects of a history of repeated exposure to alcohol and/or an ED on short-term memory and alcohol-seeking behavior. Male Wistar rats were given daily intragastric administration of alcohol (3.4 g/kg) combined or not with an ED (10.71 ml/kg) for 6 consecutive days. The rats were tested for locomotion 15 min after the first intragastric treatment. Short-term memory was assessed in the novel object recognition and social discrimination tests 2-3 days after the last intragastric administration. The rewarding effect of alcohol was tested 1-3 weeks following the last intragastric administration in a conditioned place preference paradigm. The acute binge-like ingestion of alcohol decreased locomotor activity, whereas the combination of alcohol and an ED increased locomotion in the first minutes of assessment. Alcohol exposure produced cognitive deficits in both the object recognition and social discrimination tests, and adding the ED to, the alcohol solution did not modify these effects. The combination of alcohol and the ED increased alcohol-induced conditioned place preference. Thus, a history of binge-like alcohol exposure combined with the ED caused subsequent cognitive deficits and increased alcohol seeking behavior, and such behavioral effects might contribute to the progression to alcohol abuse disorders. (C) 2015 Elsevier Inc. All rights reserved. C1 [Takahashi, Tatiane T.; Takahashi, Reinaldo N.] Univ Fed Santa Catarina, Dept Pharmacol, CCB, BR-88040900 Florianopolis, SC, Brazil. [Vendruscolo, Leandro F.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Takahashi, TT (reprint author), Zent Inst Seel Gesundheit, J5, D-68159 Mannheim, Germany. EM tati.pharmacy@gmail.com OI Takahashi, Tatiane/0000-0002-7344-5487 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES); Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina (FAPESC); National Institute on Drug Abuse, Intramural Research Program (LFV) FX This study was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES), and Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina (FAPESC). Preparation of this article was supported by the National Institute on Drug Abuse, Intramural Research Program (LFV). The authors would like to thank Michael Arends for editorial assistance and Dr. Cristiane R. De Carvalho and Dr. Filipe Matheus for their scientific support. NR 34 TC 0 Z9 0 U1 3 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 2015 VL 136 BP 82 EP 86 DI 10.1016/j.pbb.2015.07.007 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA CQ9PX UT WOS:000360948300011 PM 26187003 ER PT J AU Patel, NJ Manivannan, E Joshi, P Ohulchanskyy, TJ Nani, RR Schnermann, MJ Pandey, RK AF Patel, Nayan J. Manivannan, Ethirajan Joshi, Penny Ohulchanskyy, Tymish J. Nani, Roger R. Schnermann, Martin J. Pandey, Ravindra K. TI Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDOCYANINE GREEN; PHOTODYNAMIC THERAPY; CONTRAST AGENTS; CANCER; PROBES; MICROSCOPY; LINKERS; PEG AB This report presents a simple strategy to introduce various functionalities in a cyanine dye (bis-indole-N-butylsulfonate-polymethine bearing a fused cyclic chloro-cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino-phenyl thioether group attached to a cyclohexene ring system and the two N-butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor-avid CD provides an opportunity to create multi-imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed. C1 [Patel, Nayan J.; Pandey, Ravindra K.] Cell Stress Biol Roswell Pk Canc Inst, Dept Mol Pharmacol & Canc Therapeut, Buffalo, NY 14263 USA. [Patel, Nayan J.; Manivannan, Ethirajan; Joshi, Penny; Pandey, Ravindra K.] Cell Stress Biol Roswell Pk Canc Inst, PDT Ctr, Buffalo, NY USA. [Ohulchanskyy, Tymish J.] SUNY Buffalo, Inst Lasers Photon & Biophoton, Buffalo, NY 14260 USA. [Nani, Roger R.; Schnermann, Martin J.] NCI, Chem Biol Lab, NIH, Frederick, MD 21701 USA. RP Pandey, RK (reprint author), Cell Stress Biol Roswell Pk Canc Inst, Dept Mol Pharmacol & Canc Therapeut, Buffalo, NY 14263 USA. EM ravindra.pandey@roswellpark.org RI Ohulchanskyy, Tymish/A-8221-2009 OI Ohulchanskyy, Tymish/0000-0002-7051-6534 FU NIH [CA55791, CA127369]; Photolitec, LLC; RPCI support grant [P30CA16056]; Intramural Research Program of the National Cancer Institute, National Institutes of Health; Department of Molecular Pharmacology and Cancer Therapeutics from the NIH FX The financial support from the NIH (CA55791, CA127369 and Photolitec, LLC is gratefully acknowledged. A partial support from the shared resources of the RPCI support grant (P30CA16056) is also appreciated. This work was also supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. Nayan Patel is thankful to the Department of Molecular Pharmacology and Cancer Therapeutics for providing fellowship from the NIH funded graduate students research training grant. NR 33 TC 1 Z9 1 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2015 VL 91 IS 5 BP 1219 EP 1230 DI 10.1111/php.12482 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CQ7CX UT WOS:000360761600026 PM 26108696 ER PT J AU Han, XS Yabroff, KR Guy, GP Zheng, ZY Jemal, A AF Han, Xuesong Yabroff, K. Robin Guy, Gery P., Jr. Zheng, Zhiyuan Jemal, Ahrnedin TI Has recommended preventive service use increased after elimination of cost-sharing as part of the Affordable Care Act in the United States? SO PREVENTIVE MEDICINE LA English DT Article DE Affordable Care Act; Preventive services; Cancer screening; Cost-sharing; Insurance ID SOCIOECONOMIC-STATUS; CERVICAL-CANCER; HEALTH REFORM; COVERAGE; ADULTS; DISPARITIES; GUIDELINES; BENEFITS; ACCESS AB Background. An early provision of the Affordable Care Act (ACA) eliminated cost-sharing for a range of recommended preventive services. This provision took effect in September 2010, but little is known about its effect on preventive service use. Methods. We evaluated changes in the use of recommended preventive services from 2009 (before the implementation of ACA cost-sharing provision) to 2011/2012 (after the implementation) in the Medical Expenditure Panel Survey, a nationally representative household interview survey in the US. Specifically, we examined: blood pressure check, cholesterol check, flu vaccination, and cervical, breast, and colorectal cancer screening, controlling for demographic characteristics and stratifying by insurance type. Results. There were 64,280 (21,310 before and 42,970 after the implementation of ACA cost-sharing provision) adults included in the analyses. Receipt of recent blood pressure check, cholesterol check and flu vaccination increased significantly from 2009 to 2011/2012, primarily in the privately insured population aged 18-64 years, with adjusted prevalence ratios (95% confidence intervals) 1.03 (1.01-1.05) for blood pressure check, 1.13 (1.09-1.18) for cholesterol check and 1.04 (1.00-1.08) for flu vaccination (all p-values < 0.05). However, few changes were observed for cancer screening. We observed little change in the uninsured population. Conclusions. These early observations suggest positive benefits from the ACA policy of eliminating cost-sharing for some preventive services. Future research is warranted to monitor and evaluate longer term effects of the ACA on access to care and health outcomes. (C) 2015 Elsevier Inc All rights reserved. C1 [Han, Xuesong; Zheng, Zhiyuan; Jemal, Ahrnedin] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30303 USA. [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Rockville, MD USA. [Guy, Gery P., Jr.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Han, XS (reprint author), Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA. EM xuesong.han@cancer.org FU Intramural CDC HHS [CC999999] NR 35 TC 9 Z9 9 U1 3 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 2015 VL 78 BP 85 EP 91 DI 10.1016/j.ypmed.2015.07.012 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CQ7IQ UT WOS:000360776600015 PM 26209914 ER PT J AU DeRouen, M Smith, AW Tao, L Bellizzi, KM Lynch, CF Parsons, HM Kent, EE Keegan, THM AF DeRouen, Mindy Smith, Ashley Wilder Tao, Li Bellizzi, Keith M. Lynch, Charles F. Parsons, Helen M. Kent, Erin E. Keegan, Theresa H. M. CA AYA HOPE Study Collaborative Grp TI Cancer-related information needs and cancer's impact on control over life influence health-related quality of life among adolescents and young adults with cancer SO PSYCHO-ONCOLOGY LA English DT Article DE adolescent and young adult (AYA); health-related quality of life (HRQOL); cancer survivor; information need; control; oncology ID POPULATION-BASED COHORT; CHILDHOOD-CANCER; BREAST-CANCER; SELF-EFFICACY; PSYCHOLOGICAL RESPONSE; SURVIVORS; INTERVENTION; LOCUS; EXPERIENCE; EDUCATION AB Objective Adolescents and young adults (AYAs) diagnosed with cancer between 15 and 39years of age often report need for greater amounts of cancer-related information and perceive that cancer has had a negative impact on control over their life. We examined whether unmet information need and perceived control over life are associated with health-related quality of life (HRQOL). Methods We examined data from 484 AYA cancer survivors recruited from population-based cancer registries in 2007-2008. Participants completed surveys a median of 11 months after diagnosis. Multivariable linear regression analyses estimated associations of unmet cancer-related information needs and impact of cancer on control over life on HRQOL (SF-12). Results Two-thirds of AYAs reported an intermediate or high level of unmet information need, and half (47%) reported a negative impact of cancer on control. Greater unmet information need was associated with lower overall mental and physical HRQOL and lower levels of all HRQOL subscales except vitality. A negative impact on control over life was associated with lower overall mental HRQOL as well as lower HRQOL across all subscales except general health perceptions (all p <0.05). In multivariable analyses, perceived control and unmet information need were independently associated with HRQOL (p-values for interaction >0.1). Conclusions Adolescent and young adult patients with cancer have high levels of unmet cancer-related information needs and perceived negative impact of cancer on control over life; both were independently associated with lower HRQOL. Addressing unmet information needs among AYA cancer survivors and finding ways to increase their sense of control may help improve HRQOL in this understudied population. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [DeRouen, Mindy; Tao, Li; Keegan, Theresa H. M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Smith, Ashley Wilder] NCI, Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Tao, Li] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Bellizzi, Keith M.] Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Parsons, Helen M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Kent, Erin E.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Keegan, Theresa H. M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Keegan, THM (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA. EM theresa.keegan@cpic.org OI DeRouen, Mindy/0000-0002-7198-7629 FU [N01-PC-54402]; [N01-PC-54404]; [N01-PC-35136]; [N01-PC-35139]; [N01-PC-35142]; [N01-PC-35143]; [N01-PC-35145] FX Supported by contracts N01-PC-54402, N01-PC-54404, N01-PC-35136, N01-PC-35139, N01-PC-35142, N01-PC- 35143, N01-PC-35145. NR 41 TC 7 Z9 7 U1 6 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2015 VL 24 IS 9 BP 1104 EP 1115 DI 10.1002/pon.3730 PG 12 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CR0FD UT WOS:000360992900016 PM 25611943 ER PT J AU McKinnon, RA Wiedt, T Hoffnagle, E Shrimplin, S AF McKinnon, Robin A. Wiedt, Tracy Hoffnagle, Elena Shrimplin, Sarah TI LET'S MOVE! CITIES, TOWNS AND COUNTIES: WORKING WITH LOCAL ELECTED OFFICIALS TO IMPROVE COMMUNITY FOOD AND PHYSICAL ACTIVITY ENVIRONMENTS SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID BUILT ENVIRONMENT; PUBLIC-HEALTH; PREVALENCE; OVERWEIGHT C1 [McKinnon, Robin A.] NCI, US Dept HHS, Off Assistant Secretary Hlth, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Wiedt, Tracy] Natl League Cities, Hlth & Community Wellness, Washington, DC USA. Natl League Cities, Washington, DC USA. [Shrimplin, Sarah] US Dept HHS, OASH, Region Off 3, Philadelphia, PA USA. RP McKinnon, RA (reprint author), NCI, US Dept HHS, Off Assistant Secretary Hlth, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM robin.mckinnon@nih.gov FU Robert Wood Johnson Foundation [71744, 27904] FX The authors gratefully acknowledge current and former U.S. Department of Health and Human Services (HHS)/Office of the Assistant Secretary for Health (OASH) colleagues for their leadership and efforts on Let's Move! Cities, Towns and Counties (LMCTC) during the last three years, in particular Dr. Howard Koh, Ms. Rosie Henson, Ms. Catherine McMahon, the HHS/OASH Regional Health Administrators, the Deputy Regional Health Administrators, and the regional Let's Move! Advisors; as well as Mr. Leon Andrews from the National League of Cities. The National League of Cities also acknowledges the support of the Robert Wood Johnson Foundation for technical assistance to local elected officials working to create healthier communities and prevent childhood obesity (grant #71744 and #27904). Finally, the authors thank Penny Randall-Levy for expert referencing assistance. NR 24 TC 1 Z9 1 U1 0 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2015 VL 130 IS 5 BP 426 EP 430 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR1KX UT WOS:000361084800003 PM 26327718 ER PT J AU Ford, CL Mulatu, MS Godette, DC Gaines, TL AF Ford, Chandra L. Mulatu, Mesfin S. Godette, Dionne C. Gaines, Tommi L. TI Trends in HIV Testing Among US Older Adults Prior to and Since Release of CDC's Routine HIV Testing Recommendations: National Findings from the BRFSS SO PUBLIC HEALTH REPORTS LA English DT Article ID HEALTH-CARE SETTINGS; PREVENTION CAPACITY; MEDICAL-CARE; AGE 50; HIV/AIDS; RISK; AIDS; COMMUNITIES; ACCESS; INTERVENTIONS AB Objective. This study examined temporal trends in HIV testing among U.S. older adults (50-64 years of age) before and after the release of CDC's routine HIV testing recommendations in 2006. Methods. The sample (n=872,797; 51.4% female) comprised 2003-2010 Behavioral Risk Factor Surveillance System respondents in the oldest categories to which the recommendations apply: 50-54 years (34.5%, n=301,519), 55-59 years (34.1%, n=297,865), and 60-64 years (31.3%, n=273,413). We calculated (1) four-year pooled prevalences of past-year HIV testing before and after 2006, when the recommendations were released; and (2) annual prevalences of HIV testing overall and by age category from 2003-2010. Using weighted, multivariable logistic regression analyses, we examined binary (pre- vs. post-recommendations) and annual changes in testing, controlling for covariates. We stratified the data by recent doctor visits, examined racial/ethnic differences, and tested for linear and quadratic temporal trends. Results. Overall and within age categories, the pooled prevalence of past-year HIV testing decreased following release of the recommendations (p<0.001). The annual prevalence decreased monotonically from 2003 (5.5%) to 2006 (3.6%) (beta=-0.16, p<0.001) and then increased immediately after release of the recommendations, but decreased to 3.7% after 2009 (beta=0.01, p<0.001). By race/ethnicity, testing increased over time among non-Hispanic black people only. Annual prevalence also increased among respondents with recent doctor visits. Conclusion. CDC's HIV testing recommendations were associated with a reversal in the downward trend in past-year HIV testing among older adults; however, the gains were neither universal nor sustained over time. C1 [Ford, Chandra L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90095 USA. [Mulatu, Mesfin S.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Godette, Dionne C.] NIAAA, NIH, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. [Gaines, Tommi L.] Univ Calif San Diego, Dept Med, Div Global Publ Hlth, San Diego, CA 92103 USA. RP Ford, CL (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Community Hlth Sci, Box 951772,650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM clford@ucla.edu FU University of California Los Angeles (UCLA) Faculty Career Development Award; Eunice Kennedy Shriver National Institute of Child Health and Human Development via the UCLA California Center for Population Research [5R24HD041022]; National Institute on Drug Abuse [K01DA034523-01] FX Chandra Ford received support from a University of California Los Angeles (UCLA) Faculty Career Development Award and the Eunice Kennedy Shriver National Institute of Child Health and Human Development via the UCLA California Center for Population Research (#5R24HD041022). Tommi Gaines received support from the National Institute on Drug Abuse (#K01DA034523-01). Mesfin Mulatu participated in this endeavor in his personal capacity. The authors acknowledge Ron Andersen, William Cunningham, Martin Shapiro, and Mignon Moore for feedback on an early draft of the article; and Julia T. Caldwell for assistance in preparing manuscript tables and figures. NR 47 TC 1 Z9 1 U1 0 U2 7 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2015 VL 130 IS 5 BP 514 EP 525 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR1KX UT WOS:000361084800014 PM 26327729 ER PT J AU Prasanna, PGS Narayanan, D Hallett, K Bernhard, EJ Ahmed, MM Evans, G Vikram, B Weingarten, M Coleman, CN AF Prasanna, Pataje G. S. Narayanan, Deepa Hallett, Kory Bernhard, Eric J. Ahmed, Mansoor M. Evans, Gregory Vikram, Bhadrasain Weingarten, Michael Coleman, C. Norman TI Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation SO RADIATION RESEARCH LA English DT Editorial Material ID DIABETIC FOOT ULCERS; THROMBIN PEPTIDE; LUNG-CANCER; ADVANCED TECHNOLOGIES; INDUCED FIBROSIS; ORAL MUCOSITIS; PROTECTS MICE; MASS-CASUALTY; NORMAL TISSUE; RADIOTHERAPY C1 [Prasanna, Pataje G. S.; Bernhard, Eric J.; Ahmed, Mansoor M.; Vikram, Bhadrasain; Coleman, C. Norman] NIH, Div Canc Treatment & Diag, Radiat Res Program, Bethesda, MD 20892 USA. [Narayanan, Deepa; Hallett, Kory; Evans, Gregory; Weingarten, Michael] NCI, Small Business Innovat Res SBIR Dev Ctr, Bethesda, MD 20892 USA. RP Prasanna, PGS (reprint author), NIH, Div Canc Treatment & Diag, Radiat Res Program, 9609 Med Ctr Dr,Room 3W230,MSC 9727, Bethesda, MD 20892 USA. EM pat.prasanna@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 59 TC 6 Z9 6 U1 0 U2 7 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 SEP PY 2015 VL 184 IS 3 BP 235 EP 248 DI 10.1667/RR14186.1 PG 14 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA CR3NB UT WOS:000361238600001 PM 26284423 ER PT J AU Adams, PS Tian, X Zahid, M Khalifa, O Leatherbury, L Lo, CW AF Adams, Phillip S. Tian, Xin Zahid, Maliha Khalifa, Omar Leatherbury, Linda Lo, Cecilia W. TI Establishing normative nasal nitric oxide values in infants SO RESPIRATORY MEDICINE LA English DT Article DE Primary ciliary dyskinesia; Nasal nitric oxide; Infant; Control values; Stratification method ID PRIMARY CILIARY DYSKINESIA; CONGENITAL HEART-DISEASE; GENETIC-ANALYSIS; CYSTIC-FIBROSIS; HETEROTAXY; DEFECTS; DYSFUNCTION; DIAGNOSIS; CHILDREN AB Introduction: Primary ciliary dyskinesia (PCD), a disease of impaired respiratory cilia motility, is often difficult to diagnose. Recent studies show low nasal nitric oxide (nNO) is closely linked to PCD, allowing the use of nNO measurement for PCD assessments. Nasal NO cutoff values for PCD are stratified by age, given nNO levels normally increase with age. However, normative values for nNO have not been established for infants less than 1 year old. In this study, we aim to establish normative values for nNO in infants and determine their utility in guiding infant PCD assessment. Methods and results: We obtained 42 nNO values from infants less than 1 year old without a history of PCD or recurrent sinopulmonary disease. Using regression analysis, we estimated the mean age-adjusted nNO values and established a 95% prediction interval (PI) for normal nNO. Using these findings, we were able to show 14 of 15 infant PCD patients had abnormally low nNO with values below the 95% PI. Conclusions: In this study we determined a regression model that best fits normative nNO values for infants less than 1 year old. This model identified the majority of PCD infants as having abnormally low nNO. These findings suggest nNO measurement can help guide PCD assessment in infants, and perhaps other pulmonary diseases with a link to low nNO. With early assessments, earlier clinical intervention may be possible to slow disease progression and help reduce pulmonary morbidity. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Adams, Phillip S.] Univ Pittsburgh, Div Pediat Anesthesiol, Dept Anesthesiol, Sch Med, Pittsburgh, PA 15224 USA. [Tian, Xin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Zahid, Maliha; Khalifa, Omar; Lo, Cecilia W.] Univ Pittsburgh, Dept Dev Biol, Sch Med, Pittsburgh, PA 15201 USA. [Leatherbury, Linda] Childrens Natl Med Ctr, Dept Pediat, Div Cardiol, Washington, DC 20310 USA. RP Lo, CW (reprint author), Univ Pittsburgh, Dept Dev Biol, Sch Med, 530 45th St,8120 Rangos Res Ctr, Pittsburgh, PA 15201 USA. EM adamsp@upmc.edu; tianx@nhlbi.nih.gov; maz7@pitt.edu; omk4@pitt.edu; lleather@childrensnational.org; cel36@pitt.edu FU PA Department of Health FX This work was supported by the PA Department of Health. NR 38 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD SEP PY 2015 VL 109 IS 9 BP 1126 EP 1130 DI 10.1016/j.rmed.2015.07.010 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA CQ9HY UT WOS:000360925800005 PM 26233707 ER PT J AU Taeger, D Pesch, B Kendzia, B Behrens, T Jockel, KH Dahmann, D Siemiatycki, J Kromhout, H Vermeulen, R Peters, S Olsson, A Bruske, I Wichmann, HE Stucker, I Guida, F Tardon, A Merletti, F Mirabelli, D Richiardi, L Pohlabeln, H Ahrens, W Landi, MT Caporaso, N Pesatori, AC Mukeriya, A Szeszenia-Dabrowska, N Lissowska, J Gustavsson, P Field, J Marcus, MW Fabianova, E 't Mannetje, A Pearce, N Rudnai, P Bencko, V Janout, V Dumitru, RS Foretova, L Forastiere, F McLaughlin, J Demers, P Bueno-de-Mesquita, B Schuz, J Straif, K Bruning, T AF Taeger, Dirk Pesch, Beate Kendzia, Benjamin Behrens, Thomas Joeckel, Karl-Heinz Dahmann, Dirk Siemiatycki, Jack Kromhout, Hans Vermeulen, Roel Peters, Susan Olsson, Ann Brueske, Irene Wichmann, Heinz-Erich Stuecker, Isabelle Guida, Florence Tardon, Adonina Merletti, Franco Mirabelli, Dario Richiardi, Lorenzo Pohlabeln, Hermann Ahrens, Wolfgang Landi, Maria Teresa Caporaso, Neil Pesatori, Angela Cecilia Mukeriya, Anush Szeszenia-Dabrowska, Neonila Lissowska, Jolanta Gustavsson, Per Field, John Marcus, Michael W. Fabianova, Eleonora 't Mannetje, Andrea Pearce, Neil Rudnai, Peter Bencko, Vladimir Janout, Vladimir Dumitru, Rodica Stanescu Foretova, Lenka Forastiere, Francesco McLaughlin, John Demers, Paul Bueno-de-Mesquita, Bas Schuez, Joachim Straif, Kurt Bruening, Thomas TI Lung cancer among coal miners, ore miners and quarrymen: smoking-adjusted risk estimates from the synergy pooled analysis of case-control studies SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE coal mining; histological subtype; mining; ore mining; population-based study ID FOLLOW-UP; UNITED-STATES; MORTALITY; EXPOSURE; DUST; HAZARD; QUARTZ AB Objectives Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen. Methods We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case-control study, controlling for smoking and employment in other at-risk occupations. Results Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34-1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21-3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18-1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure. Conclusions This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at-risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen. C1 [Taeger, Dirk; Pesch, Beate; Kendzia, Benjamin; Behrens, Thomas; Bruening, Thomas] Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, D-44789 Bochum, Germany. [Joeckel, Karl-Heinz] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Dahmann, Dirk] Ruhr Univ Bochum, Inst Res Hazardous Subst IGF, Bochum, Germany. [Siemiatycki, Jack] Univ Montreal Hosp Res Ctr CRCHUM, Montreal, PQ, Canada. [Siemiatycki, Jack] Sch Publ Hlth, Montreal, PQ, Canada. [Kromhout, Hans; Vermeulen, Roel; Peters, Susan] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, Utrecht, Netherlands. [Peters, Susan] Univ Western Australia, Sch Populat Hlth, Occupat Resp Epidemiol, Perth, WA 6009, Australia. [Olsson, Ann; Schuez, Joachim; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France. [Brueske, Irene; Wichmann, Heinz-Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany. [Wichmann, Heinz-Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, D-80290 Munich, Germany. [Stuecker, Isabelle; Guida, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc Team, Villejuif, France. [Tardon, Adonina] Univ Oviedo, Univ Inst Oncol, Mol Epidemiol Canc Unit, Oviedo, Spain. [Tardon, Adonina] CIBERESP, Barcelona, Spain. [Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] CPO Piemonte, Canc Epidemiol Unit, Turin, Italy. [Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] Univ Turin, Turin, Italy. [Pohlabeln, Hermann; Ahrens, Wolfgang] Leibniz Inst Prevent Res & Epidemiol BIPS GmbH, Bremen, Germany. [Ahrens, Wolfgang] Univ Bremen, Inst Stat, D-28359 Bremen, Germany. [Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA. [Pesatori, Angela Cecilia] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Pesatori, Angela Cecilia] Univ Milan, IRCCS Ca Granda Fdn, Milan, Italy. [Mukeriya, Anush] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland. [Olsson, Ann; Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland. [Olsson, Ann; Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Gustavsson, Per] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Field, John; Marcus, Michael W.] Univ Liverpool, Canc Res Ctr, Inst Translat Med, Roy Castle Lung Canc Res Programme,Dept Mol & Cli, Liverpool L69 3BX, Merseyside, England. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. ['t Mannetje, Andrea; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Pearce, Neil] London Sch Hyg & Trop Med, London WC1, England. [Rudnai, Peter] Natl Ctr Publ Hlth, Budapest, Hungary. [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic. [Dumitru, Rodica Stanescu] Natl Inst Publ Hlth, Bucharest, Romania. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Foretova, Lenka] MU, Fac Med, Brno, Czech Republic. [Forastiere, Francesco] ASL Roma E, Dept Epidemiol, Rome, Italy. [McLaughlin, John; Demers, Paul] Occupat Canc Res Ctr, Toronto, ON, Canada. [Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands. [Bueno-de-Mesquita, Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Bueno-de-Mesquita, Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Bueno-de-Mesquita, Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. RP Taeger, D (reprint author), Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, Burkle de la Camp Pl 1, D-44789 Bochum, Germany. EM taeger@ipa-dguv.de RI Szeszenia-Dabrowska, Neonila/F-7190-2010; Janout, Vladimir/M-5133-2014; Bruning, Thomas/G-8120-2015; Forastiere, Francesco/J-9067-2016; Vermeulen, Roel/F-8037-2011; OI Bruning, Thomas/0000-0001-9560-5464; Forastiere, Francesco/0000-0002-9162-5684; Vermeulen, Roel/0000-0003-4082-8163; richiardi, lorenzo/0000-0003-0316-9402; Taeger, Dirk/0000-0002-5340-5584; pesatori, angela/0000-0002-0261-3252; Ahrens, Wolfgang/0000-0003-3777-570X FU German Social Accident Insurance (DGUV) [FP 271]; Canadian Institutes of Health Research; Guzzo-SRC Chair in Environment and Cancer; Fondation de France; German Federal Ministry of Education, Science, Research, and Technology; Ministry of Labour and Social Affairs; EC's INCO-COPERNICUS Program; Polish State Committee for Science Research; Roy Castle Foundation; NIH/NCI/DCEG Intramural Research Program; Lombardy Region; INAIL; European Union Nuclear Fission Safety Program; Italian Association for Cancer Research; Region Piemont; Compagnia di San Paolo; Europe Against Cancer Program; Swedish Council for Work Life Research; Swedish EPA; University of Oviedo; CIBERESP; MH CZ-DRO (MMCI) [00209805]; [FISS-PI060604] FX This work was supported by the German Social Accident Insurance (DGUV) (grant FP 271). Grant sponsors of the individual studies were the Canadian Institutes of Health Research and Guzzo-SRC Chair in Environment and Cancer; the Fondation de France; the German Federal Ministry of Education, Science, Research, and Technology and the Ministry of Labour and Social Affairs; EC's INCO-COPERNICUS Program; Polish State Committee for Science Research; Roy Castle Foundation; NIH/NCI/DCEG Intramural Research Program; Lombardy Region; INAIL and the European Union Nuclear Fission Safety Program; Italian Association for Cancer Research, Region Piemont, Compagnia di San Paolo; Europe Against Cancer Program; the Swedish Council for Work Life Research and the Swedish EPA; the University of Oviedo, CIBERESP, and FISS-PI060604; MH CZ-DRO (MMCI, 00209805). NR 35 TC 3 Z9 3 U1 3 U2 15 PU SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 EI 1795-990X J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD SEP PY 2015 VL 41 IS 5 BP 467 EP 477 DI 10.5271/sjweh.3513 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR1IS UT WOS:000361079000006 PM 26153779 ER PT J AU Persoskie, A Ferrer, RA Taber, JM Klein, WMP Parascandola, M Harris, PR AF Persoskie, Alexander Ferrer, Rebecca A. Taber, Jennifer M. Klein, William M. P. Parascandola, Mark Harris, Peter R. TI Smoke-free air laws and quit attempts: Evidence for a moderating role of spontaneous self-affirmation SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Smoke-free; Tobacco control; Self-affirmation; Defensive processing; Reactance ID HEALTH-RISK INFORMATION; FREE LEGISLATION; PSYCHOLOGICAL REACTANCE; ANTISMOKING MESSAGES; WARNING LABELS; CESSATION; EXPOSURE; INTERVENTION; METAANALYSIS; COUNTERACTS AB Background: In addition to their primary goal of protecting nonsmokers from secondhand smoke, smoke-free air laws may also encourage intentions to quit smoking, quit attempts, and cessation among smokers. However, laws may not encourage quitting if smokers feel threatened by them and react defensively. Objective: This study examined whether spontaneous self-affirmation the extent to which people think about their values or strengths when they feel threatened may reduce smokers' reactance to smoke-free laws, enhancing the ability of the laws to encourage quitting. Method: We linked state-level information on the comprehensiveness of U.S. smoke-free laws (compiled in January, 2013 by the American Lung Association) with data from a U.S. health survey (Health Information National Trends Survey) collected from September December, 2013 (N = 345 current smokers; 587 former smokers). Results: Smoke-free laws interacted with self-affirmation to predict quit attempts in the past year and intentions to quit in the next six months: Smokers higher in self-affirmation reported more quit attempts and quit intentions if they lived in states with more comprehensive smoke-free laws. There was some evidence of a "boomerang" effect (i.e., less likelihood of making a quit attempt) among smokers low in self-affirmation if living in states with more comprehensive smoke-free laws, but this effect was significant only among smokers extremely low in self-affirmation. For quit intentions, there was no evidence for a boomerang effect of smoke-free laws even among smokers extremely low in self-affirmation. More comprehensive smoke-free laws were not associated with smoking status (former vs. current smoker) or average amount smoked per day, nor did they interact with self-affirmation to predict these outcomes. Conclusions: The impact of smoke-free policies on quit attempts and quit intentions may be moderated by psychological characteristics such as the tendency to spontaneously self-affirm. Follow-ups should experimentally manipulate self-affirmation and examine effects of smoke-free laws in controlled contexts. Published by Elsevier Ltd. C1 [Persoskie, Alexander; Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Bethesda, MD 20892 USA. [Taber, Jennifer M.; Klein, William M. P.] NCI, Off Associate Director, Behav Res Program, Bethesda, MD 20892 USA. [Parascandola, Mark] NCI, Tobacco Control Res Branch, Behav Res Program, Bethesda, MD 20892 USA. [Harris, Peter R.] Univ Sussex, Sch Psychol, Brighton BN1 9RH, E Sussex, England. RP Persoskie, A (reprint author), Bldg 75,Off 4472,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM persoskie@gmail.com NR 70 TC 2 Z9 2 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 2015 VL 141 BP 46 EP 55 DI 10.1016/j.socscimed.2015.07.015 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CR2MU UT WOS:000361165000006 PM 26246033 ER PT J AU Chaturvedi, S Turan, TN Lynn, MJ Derdeyn, CP Fiorella, D Janis, LS Chimowitz, MI AF Chaturvedi, Seemant Turan, Tanya N. Lynn, Michael J. Derdeyn, Colin P. Fiorella, David Janis, L. Scott Chimowitz, Marc I. CA SAMMPRIS Trial Investigators TI Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID? SO STROKE LA English DT Article DE atherosclerosis; dyslipidemia; intracranial atherosclerosis; stroke; warfarin ID INTRACRANIAL ARTERIAL-STENOSIS; TRANSIENT ISCHEMIC ATTACK; RECURRENT STROKE; BLOOD-PRESSURE; RISK; PREVENTION; MANAGEMENT; ASPIRIN; THERAPY; DESIGN AB Background and Purpose-The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses. Methods-Using proportional hazards regression, we compared the SAMMPRIS primary end point between SAMMPRIS medical patients and WASID patients meeting the same qualifying criteria adjusted for confounding baseline characteristics. Results-The unadjusted comparison of the SAMMPRIS primary end point showed a significantly higher risk for WASID patients (P=0.009, logrank test) with 12 month Kaplan-Meier estimates of 21.9% in WASID and 12.6% in SAMMPRIS and hazard ratio 1.9 (95% confidence interval = 1.2-3.0). The analyses identified the following confounding factors that varied between the studies and that conferred a higher risk: lack of statin use at enrollment (hazard ratio = 1.8, 95% confidence interval = 1.1-2.9, P=0.027) that was more prevalent among WASID patients (39% versus 14%, P<0.0001) and prior infarcts in the territory of the symptomatic vessel (hazard ratio = 1.8, 95% confidence interval = 1.1-2.9, P=0.023) that was more prevalent among SAMMPRIS patients (34% versus 22%, P=0.015). The hazard ratio for WASID versus SAMMPRIS adjusted for these 2 characteristics was 1.9 (95% confidence interval = 1.1-3.2). Conclusions-After adjustment for confounding baseline characteristics, WASID patients had an almost 2-fold higher risk of the SAMMPRIS primary end point, which supports the hypothesis that the lower rate of the primary end point in the medical arm of SAMMPRIS compared with WASID patients was as a result of the aggressive medical management used in SAMMPRIS. C1 [Chaturvedi, Seemant] Univ Miami, Dept Neurol, Miami, FL 33136 USA. [Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Lynn, Michael J.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA. RP Chaturvedi, S (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, 1120 NW 14th St,Room 1363, Miami, FL 33136 USA. EM SChaturvedi@med.miami.edu OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683 FU US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS) [U01 NS058728]; National Institutes of Health - Medical University of South Carolina [UL1RR029882]; National Institutes of Health - University of Florida [UL1RR029889]; National Institutes of Health - University of Cincinnati [UL1RR029890]; National Institutes of Health - University of California, San Francisco [UL1RR024131]; Stryker Neurovascular; AstraZeneca FX The SAMMPRIS trial was funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS). In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health, provided local support for the evaluation of patients in the trial: Medical University of South Carolina (UL1RR029882), University of Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and University of California, San Francisco (UL1RR024131). Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third party device distribution, site monitoring, and study auditing. This research is also supported by the Investigator-Sponsored Study Program of AstraZeneca that donates rosuvastatin (Crestor) to study patients. NR 12 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2015 VL 46 IS 9 BP 2562 EP 2567 DI 10.1161/STROKEAHA.115.009656 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CQ9FZ UT WOS:000360919700038 PM 26251251 ER PT J AU Lu, SY Deng, R Jiang, HM Song, HL Li, SA Shen, QC Huang, WK Nussinov, R Yu, JX Zhang, J AF Lu, Shaoyong Deng, Rong Jiang, Haiming Song, Huili Li, Shuai Shen, Qiancheng Huang, Wenkang Nussinov, Ruth Yu, Jianxiu Zhang, Jian TI The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation SO STRUCTURE LA English DT Article ID CRYSTAL-STRUCTURE; INSULIN-RESISTANCE; STRUCTURAL BASIS; CELL-SURVIVAL; PROTEINS; AKT/PKB; DOMAIN; SPECIFICITY; ACTIVATION; PROTEASE AB Kinases use ATP to phosphorylate substrates; recent findings underscore the additional regulatory roles of ATP. Here, we propose a mechanism for allosteric regulation of Akt1 kinase phosphorylation by ATP. Our 4.7-mu s molecular dynamics simulations of Akt1 and its mutants in the ATP/ADP bound/unbound states revealed that ATP occupancy of the ATP-binding site stabilizes the closed conformation, allosterically protecting pT308 by restraining phosphatase access and key interconnected residues on the ATP -> pT308 allosteric pathway. Following ATP -> ADP hydrolysis, pT308 is exposed and readily dephosphorylated. Site-directed mutagenesis validated these predictions and indicated that the mutations do not impair PDK1 and PP2A phosphatase recruitment. We further probed the function of residues around pT308 at the atomic level, and predicted and experimentally confirmed that Akt1(H194R/R273H) double mutant rescues pathology-related Akt1(R273H). Analysis of classical Akt homologs suggests that this mechanism can provide a general model of allosteric kinase regulation by ATP; as such, it offers a potential avenue for allosteric drug discovery. C1 [Lu, Shaoyong; Jiang, Haiming; Song, Huili; Li, Shuai; Shen, Qiancheng; Huang, Wenkang; Zhang, Jian] SJTU SM, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Dept Pathophysiol, Shanghai 200025, Peoples R China. [Deng, Rong; Yu, Jianxiu] SJTU SM, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China. [Deng, Rong; Yu, Jianxiu] SJTU SM, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China. [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Zhang, J (reprint author), SJTU SM, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Dept Pathophysiol, Shanghai 200025, Peoples R China. EM jianxiu.yu@gmail.com; jian.zhang@sjtu.edu.cn FU National Basic Research Program of China [2015CB910403]; National Natural Science Foundation of China [81322046, 81302689, 81473137]; Shanghai Rising-Star Program [13QA1402300]; Program for New Century Excellent Talents in University [NCET-12-0355]; China Postdoctoral Science Foundation [2014M551426]; National Cancer Institute; NIH [HHSN261200800001E]; Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research FX This work was supported by the National Basic Research Program of China (973 Program) (2015CB910403); National Natural Science Foundation of China (81322046, 81302689, 81473137); Shanghai Rising-Star Program (13QA1402300); Program for New Century Excellent Talents in University (NCET-12-0355); and China Postdoctoral Science Foundation (2014M551426). This work has also been funded in whole or in part with Federal funds from the National Cancer Institute, NIH, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 48 TC 13 Z9 13 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD SEP 1 PY 2015 VL 23 IS 9 BP 1725 EP 1734 DI 10.1016/j.str.2015.06.027 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CR1VJ UT WOS:000361113000017 PM 26256536 ER PT J AU Bharti, K AF Bharti, K. TI Induced to Cure: Engineering iPS Cell Derived RPE Scaffolds to Treat Degenerative Eye Diseases SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Bharti, K.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S173 EP S173 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201277 ER PT J AU Burks, S Bresler, M Nagle, M Nguyen, B Tebebi, P Kim, S Milo, B Frank, J AF Burks, S. Bresler, M. Nagle, M. Nguyen, B. Tebebi, P. Kim, S. Milo, B. Frank, J. TI Pulsed Focused Ultrasound Enhances Stem Cell Homing to Skeletal Muscle in a Murine Model of Muscular Dystrophy and Homing is Suppressed by Ibuprofen SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Burks, S.; Bresler, M.; Nagle, M.; Nguyen, B.; Tebebi, P.; Kim, S.; Milo, B.; Frank, J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S262 EP S262 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202117 ER PT J AU Burks, SR Bresler, M Nagle, M Kim, S Milo, B Frank, J AF Burks, S. R. Bresler, M. Nagle, M. Kim, S. Milo, B. Frank, J. TI Combining Mesenchymal Stromal Cell Infusions with Pulsed Focused Ultrasound to Kidneys Increases MSC Production of Interleukin 10 to Improve Acute Kidney Injury SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Burks, S. R.; Bresler, M.; Nagle, M.; Kim, S.; Milo, B.; Frank, J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S268 EP S268 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202141 ER PT J AU Hassan, S Burns, JC Oliver, ER Kiell, EP Yoo, JJ Jackson, JD Atala, AJ AF Hassan, S. Burns, J. C. Oliver, E. R. Kiell, E. P. Yoo, J. J. Jackson, J. D. Atala, A. J. TI In Vivo Myc Gene Delivery to Adult Mouse Inner Ear Stimulates Proliferation of Post mitotic Supporting Cells Leading to New Hair Cell Formation SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Hassan, S.; Yoo, J. J.; Jackson, J. D.; Atala, A. J.] Wake Forest Univ, Bowman Gray Sch Med, WFIRM, Winston Salem, NC USA. [Burns, J. C.] NIDCD, NIH, Bethesda, MD USA. [Oliver, E. R.; Kiell, E. P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Otolaryngol Head & Neck Surg, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S114 EP S114 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205201047 ER PT J AU Kim, S Milo, B Frank, J AF Kim, S. Milo, B. Frank, J. TI Effects of Pro-inflammatory Cytokine Pretreatment on MSC Potency, Survival, and Migration SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Kim, S.; Milo, B.; Frank, J.] NIH, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S331 EP S331 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202386 ER PT J AU King, LM AF King, L. M. TI National Institute of Dental and Craniofacial Research Support for Research Training in Tissue Engineering and Regenerative Medicine SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [King, L. M.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S378 EP S378 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202571 ER PT J AU Tebebi, PA Williams, R Kim, S Nguyen, B Burks, S Frenkel, V Frank, JA AF Tebebi, P. A. Williams, R. Kim, S. Nguyen, B. Burks, S. Frenkel, V. Frank, J. A. TI Reestablishment of Perfusion in Critical Limb Ischemia Model with Pulsed Focused Ultrasound (pfus) and Mesenchymal Stem Cells in Aged Mice SO TISSUE ENGINEERING PART A LA English DT Meeting Abstract CT 4th TERMIS World Congress CY SEP 08-11, 2015 CL Boston, MA SP TERMIS C1 [Tebebi, P. A.; Williams, R.; Kim, S.; Nguyen, B.; Burks, S.; Frenkel, V.; Frank, J. A.] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD SEP 1 PY 2015 VL 21 SU 1 BP S234 EP S235 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP9HR UT WOS:000360205202009 ER PT J AU Trabert, B Falk, RT Stanczyk, FZ McGlynn, KA Brinton, LA Xu, X AF Trabert, Britton Falk, Roni T. Stanczyk, Frank Z. McGlynn, Katherine A. Brinton, Louise A. Xu, Xia TI Reproducibility of an assay to measure serum progesterone metabolites that may be related to breast cancer risk using liquid chromatography-tandem mass spectrometry SO HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION LA English DT Article DE breast cancer risk; liquid chromatography-tandem mass spectrometry; reproducibility; serum progesterone assay ID MENOPAUSAL HORMONE-THERAPY; ESTROGEN PLUS PROGESTIN; COLORECTAL-CANCER; POSTMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; 20-ALPHA-DIHYDROPROGESTERONE; COHORT; CELLS AB Recent data suggest a novel role of progesterone in breast cancer etiology involving the progesterone metabolites 3 alpha-dihydroprogesterone (3 alpha HP), 5 alpha-dihydroprogesterone (5 alpha P), and 20 alpha-dihydroprogesterone (20 alpha HP). Accurate and precise measures of progesterone metabolites are needed for etiologic studies of hormonally related cancers. We have developed a high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) method to measure five hormones, including progesterone, its precursor pregnenolone, and three progesterone metabolites, 5 alpha P, 3 alpha HP, and 20 alpha HP. Hormone levels were measured in serum from 20 healthy volunteers (7 men, 5 premenopausal women, and 8 postmenopausal women). Two blinded, randomized aliquots per individual were assayed in each of four batches. The coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated from the individual components of variance. The overall laboratory CVs were <3% and ICCs were uniformly high (>98%) for all hormones measured across sex/menopausal status groups. Our HPLC-MS/MS assay of progesterone metabolites demonstrated excellent sensitivity, laboratory reproducibility, and interindividual variation, suggesting that this serum assay is suitable for epidemiologic research. The high sensitivity of the assay, and thus the ability to quantify concentrations among postmenopausal women and men, further supports that this novel assay is suitable for studies of serum progesterone metabolite concentrations and risk of breast cancer or other hormonally related cancer. C1 [Trabert, Britton; Falk, Roni T.; McGlynn, Katherine A.; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Xu, Xia] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Trabert, B (reprint author), 9609 Med Ctr Dr,Room 7E-228, Bethesda, MD 20892 USA. EM britton.trabert@nih.gov RI Trabert, Britton/F-8051-2015 FU Intramural NIH HHS [ZIA CP010126-16]; NCI NIH HHS [ZIA CP010126-14] NR 22 TC 0 Z9 0 U1 2 U2 5 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1868-1883 EI 1868-1891 J9 HORM MOL BIOL CLIN I JI Horm. Mol. Biol. Clin. Investig. PD SEP PY 2015 VL 23 IS 3 BP 79 EP 84 DI 10.1515/hmbci-2015-0026 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ9YU UT WOS:000360973800002 PM 26353176 ER PT J AU Shabalin, I Dauter, Z Jaskolski, M Minor, W Wlodawer, A AF Shabalin, Ivan Dauter, Zbigniew Jaskolski, Mariusz Minor, Wladek Wlodawer, Alexander TI Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY LA English DT Article DE cisplatin; carboplatin; crystal structure; error corrections; structural databases; structure re-refinement; validation; data reprocessing; reproducibility ID X-RAY-DIFFRACTION; EGG-WHITE LYSOZYME; CRYSTAL-STRUCTURES; ELECTRON-DENSITY; MACROMOLECULAR STRUCTURES; SUPEROXIDE-DISMUTASE; STRUCTURE VALIDATION; CHEMICAL CONVERSION; DATA-BANK; BINDING AB The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested. C1 [Shabalin, Ivan; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. [Dauter, Zbigniew] Argonne Natl Lab, NCI, Synchrotron Radiat Res Sect, MCL, Argonne, IL 60439 USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ, Fac Chem, Dept Crystallog, PL-60780 Poznan, Poland. [Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. [Wlodawer, Alexander] NCI, Prot Struct Sect, MCL, Frederick, MD 21702 USA. RP Dauter, Z (reprint author), Argonne Natl Lab, NCI, Synchrotron Radiat Res Sect, MCL, 9700 S Cass Ave, Argonne, IL 60439 USA. EM dauter@anl.gov; wlodawer@nih.gov RI Shabalin, Ivan/H-1902-2016; OI Shabalin, Ivan/0000-0003-3955-9242; Minor, Wladek/0000-0001-7075-7090 FU Intramural Research Program of the National Cancer Institute, Center for Cancer Research; National Science Center (Poland) [2013/10/M/NZ1/00251]; NIAID, NIH, Department of Health and Human Services [HHSN272200700058C]; NIGMS [GM094585, GM094662, GM093342] FX We would like to thank Nicholas P. Farrell and Przemek Porebski for valuable discussions and Joanna Raczynska for reading the manuscript. This project was supported in part by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. The collaboration of MJ and ZD was supported in part by a grant (2013/10/M/NZ1/00251) from the National Science Center (Poland). IS and WM were supported by federal funds from the NIAID, NIH, Department of Health and Human Services under Contract No. HHSN272200700058C and by NIGMS grants GM094585, GM094662 and GM093342. NR 63 TC 17 Z9 17 U1 2 U2 30 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 SEP PY 2015 VL 71 BP 1965 EP 1979 DI 10.1107/S139900471500629X PN 9 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA CQ5OH UT WOS:000360654300018 PM 26327386 ER PT J AU Bousleiman, SZ Rice, MM Moss, J Todd, A Rincon, M Mallett, G Milluzzi, C Allard, D Dorman, K Ortiz, F Johnson, F Reed, P Tolivaisa, S AF Bousleiman, Sabine Zoghbi Rice, Madeline Murguia Moss, Joan Todd, Allison Rincon, Monica Mallett, Gail Milluzzi, Cynthia Allard, Donna Dorman, Karen Ortiz, Felecia Johnson, Francee Reed, Peggy Tolivaisa, Susan CA Eunice Kennedy Shriver Natl Inst C TI Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE antenatal corticosteroids; evidence-based interventions; magnesium sulfate; Maternal-Fetal Medicine Units Network; progesterone ID MAGNESIUM-SULFATE EXPOSURE; TEAM CLIMATE INVENTORY; BIRTH-WEIGHT INFANTS; RANDOMIZED CONTROLLED-TRIALS; SPONTANEOUS PRETERM BIRTH; CEREBRAL-PALSY; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; INTRAVENTRICULAR HEMORRHAGE; MICRONIZED PROGESTERONE; DOUBLE-BLIND AB OBJECTIVE: We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. STUDY DESIGN: A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. RESULTS: A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P - .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection. C1 [Bousleiman, Sabine Zoghbi] Columbia Univ, Coll Phys & Surg, Dept Obstet, New York, NY 10027 USA. [Bousleiman, Sabine Zoghbi] Columbia Univ, Coll Phys & Surg, Dept Gynecol, New York, NY USA. [Moss, Joan] Univ Texas Med Branch, Galveston, TX 77555 USA. Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Rincon, Monica] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mallett, Gail] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Milluzzi, Cynthia] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Allard, Donna] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Dorman, Karen] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Ortiz, Felecia] Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA. [Johnson, Francee] Ohio State Univ, Sch Med, Columbus, OH 43210 USA. [Reed, Peggy] Univ Utah, Sch Med, Salt Lake City, UT USA. [Rice, Madeline Murguia] George Washington Univ, Biostat Ctr, Washington, DC USA. [Tolivaisa, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Bousleiman, SZ (reprint author), Columbia Univ, Coll Phys & Surg, Dept Obstet, New York, NY 10027 USA. EM sb1080@columbia.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD40485, HD53097, HD27869, HD53118, HD40512, HD40544, HD40560, HD40545, HD27915, HD34208, HD36801] FX This study was supported by grants HD40485, HD53097, HD27869, HD53118, HD40512, HD40544, HD40560, HD40545, HD27915, HD34208, and HD36801 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 73 TC 3 Z9 3 U1 0 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 SEP PY 2015 VL 213 IS 3 AR 398.e1 DI 10.1016/j.ajog.2015.05.005 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700034 PM 25957021 ER PT J AU Esplin, MS Manuck, TA Varner, MW Christensen, B Biggio, J Bukowski, R Parry, S Zhang, HP Huang, H Andrews, W Saade, G Sadovsky, Y Reddy, UM Ilekis, J AF Esplin, M. Sean Manuck, Tracy A. Varner, Michael W. Christensen, Bryce Biggio, Joseph Bukowski, Radek Parry, Samuel Zhang, Heping Huang, Hao Andrews, William Saade, George Sadovsky, Yoel Reddy, Uma M. Ilekis, John TI Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med DE cluster analysis; gene-based analysis; phenotype; spontaneous preterm birth ID GENOME-WIDE ASSOCIATION; GENETIC-ANALYSIS; INFLAMMATION; DELIVERY; RISK AB OBJECTIVE: We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. STUDY DESIGN: We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB <= 34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. RESULTS: One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by chi(2) analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P = .0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. CONCLUSION: We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. C1 [Esplin, M. Sean; Manuck, Tracy A.; Varner, Michael W.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA. [Esplin, M. Sean; Manuck, Tracy A.; Varner, Michael W.] Intermt Healthcare, Dept Maternal Fetal Med, Salt Lake City, UT USA. [Christensen, Bryce] Golden Helix, Bozeman, MT USA. [Biggio, Joseph; Andrews, William] Univ Alabama Birmingham, Dept Obstet & Gynecol, Sch Med, Birmingham, AL 35294 USA. [Bukowski, Radek; Saade, George] Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med, Galveston, TX 77555 USA. [Parry, Samuel] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Zhang, Heping; Huang, Hao] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Sadovsky, Yoel] Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Pittsburgh, PA USA. [Reddy, Uma M.; Ilekis, John] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA. RP Esplin, MS (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA. EM sean.esplin@imail.org OI Esplin, Sean/0000-0002-0856-4332 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research [U01-HD-050062, U01-HD-050078, U01-HD-050080, U01-HD-050088, U01-HD-050094]; NICHD grant [5K23HD067224] FX Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (U01-HD-050062, U01-HD-050078, U01-HD-050080, U01-HD-050088, U01-HD-050094; all authors) and by NICHD grant number 5K23HD067224 (T.A.M.). NR 28 TC 4 Z9 4 U1 4 U2 8 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 SEP PY 2015 VL 213 IS 3 AR 429.e1 DI 10.1016/j.ajog.2015.06.011 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700049 PM 26070700 ER PT J AU Pearce, MM Zilliox, MJ Rosenfeld, AB Thomas-White, KJ Richter, HE Nager, CW Visco, AG Nygaard, IE Barber, MD Schaffer, J Moalli, P Sung, VW Smith, AL Rogers, R Nolen, TL Wallace, D Meikle, SF Gai, XW Wolfe, AJ Brubaker, L AF Pearce, Meghan M. Zilliox, Michael J. Rosenfeld, Amy B. Thomas-White, Krystal J. Richter, Holly E. Nager, Charles W. Visco, Anthony G. Nygaard, Ingrid E. Barber, Matthew D. Schaffer, Joseph Moalli, Pamela Sung, Vivian W. Smith, Ariana L. Rogers, Rebecca Nolen, Tracy L. Wallace, Dennis Meikle, Susan F. Gai, Xiaowu Wolfe, Alan J. Brubaker, Linda CA Pelvic Floor Disorders Network TI The female urinary microbiome in urgency urinary incontinence SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE bacteria; microbiome; microbiota; urgency urinary incontinence; urinary tract infection ID BLADDER; BACTERIA AB OBJECTIVE: The purpose of this study was to characterize the urinary microbiota in women who are planning treatment for urgency urinary incontinence and to describe clinical associations with urinary symptoms, urinary tract infection, and treatment outcomes. STUDY DESIGN: Catheterized urine samples were collected from multisite randomized trial participants who had no clinical evidence of urinary tract infection; 16S ribosomal RNA gene sequencing was used to dichotomize participants as either DNA sequence-positive or sequence-negative. Associations with demographics, urinary symptoms, urinary tract infection risk, and treatment outcomes were determined. In sequence-positive samples, microbiotas were characterized on the basis of their dominant microorganisms. RESULTS: More than one-half (51.1%; 93/182) of the participants' urine samples were sequence-positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2 episodes; P < .0001), responded better to treatment (decrease in urgency urinary incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive samples, 8 major bacterial clusters were identified; 7 clusters were dominated not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella (17%), but also by other taxa (25%). The remaining cluster had no dominant genus (13%). CONCLUSION: DNA sequencing confirmed urinary bacterial DNA in many women with urgency urinary incontinence who had no signs of infection. Sequence status was associated with baseline urgency urinary incontinence episodes, treatment response, and posttreatment urinary tract infection risk. C1 [Pearce, Meghan M.; Thomas-White, Krystal J.; Wolfe, Alan J.] Loyola Univ Chicago, Stritch Sch Med, Dept Microbiol & Immunol, Maywood, IL USA. [Zilliox, Michael J.; Gai, Xiaowu] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL USA. [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol & Urol, Maywood, IL 60660 USA. [Rosenfeld, Amy B.] Columbia Univ Coll Phys & Surg, Microbiol & Immunol Dept, Hammer Hlth Sci, New York, NY 10032 USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Sch Med, Birmingham, AL 35294 USA. [Nager, Charles W.] UC San Diego Hlth Syst, Dept Reprod Med, San Diego, CA USA. [Visco, Anthony G.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Nolen, Tracy L.; Wallace, Dennis] RTI Int, Res Triangle Pk, NC USA. [Nygaard, Ingrid E.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Barber, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA. [Schaffer, Joseph] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Moalli, Pamela] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Smith, Ariana L.] Univ Penn, Perelman Sch Med, Dept Urol, Philadelphia, PA 19104 USA. [Sung, Vivian W.] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Rogers, Rebecca] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept & Reprod Hlth Branch, Ctr Populat Res, NIH, Bethesda, MD USA. RP Brubaker, L (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol & Urol, Maywood, IL 60660 USA. EM lbrubaker@luc.edu FU Department of Health and Human Services [1G20RR030939-0 1] FX We thank the Loyola University Chicago Health Sciences Division's Office of Informatics and Systems Development (which was developed through grant funds awarded by the Department of Health and Human Services as award number 1G20RR030939-0 1) for their expertise and for the computational resources used in support of this research. NR 18 TC 15 Z9 15 U1 1 U2 5 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 SEP PY 2015 VL 213 IS 3 AR 347.e1 DI 10.1016/j.ajog.2015.07.009 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ4CL UT WOS:000360551700014 PM 26210757 ER PT J AU Sturlaugsdottir, R Aspelund, T Bjornsdottir, G Sigurdsson, S Eiriksdottir, G Imai, CM Garcia, M Launer, LJ Harris, TB Gudnason, V AF Sturlaugsdottir, Ran Aspelund, Thor Bjornsdottir, Gudlaug Sigurdsson, Sigurdur Eiriksdottir, Gudny Imai, Cindy Mari Garcia, Melissa Launer, Lenore J. Harris, Tamara B. Gudnason, Vilmundur TI Carotid atherosclerosis and cardiovascular health metrics in old subjects from the AGES-Reykjavik study SO ATHEROSCLEROSIS LA English DT Article DE Carotid arteries; Imaging; Cardiovascular health score ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; RISK-FACTORS; PLAQUE AREA; ASSOCIATION; CALCIFICATION; PREDICTION; WOMEN; MEN AB Background: Ideal cardiovascular (CV) health by simultaneous presence of 7 ideal health metrics (blood pressure, cholesterol, glucose, smoking, BMI, physical activity and diet) has been defined by the American Heart Association. In the current study we investigated the association of a CV health score (range 0-14), on the extent and progression of carotid atherosclerosis, assessed as carotid intima-media thickness (cIMT) and total plaque area (TPA) by ultrasound at 5 years interval. Methods and results: A total of 219 participants (age 75.6 +/- 5.1) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were studied. Men with poor (low) CV health score had greater TPA than those with more optimal (high) score (61.5 (SD: 32.3), 44.4 (24.2) and 37.7 (23.2) mm(2) for those with CV health score <= 6, 7-9 and >= 10 respectively, p < 0.05). In linear analysis for men, log TPA was 0.088 mm(2) (SE: 0.040 p < 0.05) smaller for each additional point in the CV health score. CV health score was not associated with TPA in women, or cIMT in either sex. TPA increased in both sexes between visits. However, CV health score did not predict carotid atherosclerosis progression. Conclusions: CV health score is associated with TPA in older men but not in women. Men with poor CV health score at the baseline visit had more extensive carotid atherosclerosis than those with better CV health score, although it did not predict the progression of carotid atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Sturlaugsdottir, Ran; Aspelund, Thor; Bjornsdottir, Gudlaug; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Imai, Cindy Mari; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Sturlaugsdottir, Ran; Aspelund, Thor; Imai, Cindy Mari; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Garcia, Melissa; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Gudnason, V (reprint author), Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland. EM v.gudnason@hjarta.is RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institute on Aging [N01-AG-1-2100]; Intramural Research Program, Hjartavernd (Icelandic Heart Association); Althingi (Icelandic Parliament); RANNIS (The Icelandic Research Fund) [090452] FX This work was supported by the National Institute on Aging (N01-AG-1-2100), Intramural Research Program, Hjartavernd (Icelandic Heart Association), the Althingi (Icelandic Parliament) and RANNIS 090452 (The Icelandic Research Fund). NR 31 TC 5 Z9 5 U1 1 U2 3 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 SEP PY 2015 VL 242 IS 1 BP 65 EP 70 DI 10.1016/j.atherosclerosis.2015.06.043 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900011 PM 26184695 ER PT J AU Shah, RV Allison, MA Lima, JAC Bluemke, DA Abbasi, SA Ouyang, P Jerosch-Herold, M Ding, JZ Budoff, MJ Murthy, VL AF Shah, Ravi V. Allison, Matthew A. Lima, Joao A. C. Bluemke, David A. Abbasi, Siddique A. Ouyang, Pamela Jerosch-Herold, Michael Ding, Jingzhong Budoff, Matthew J. Murthy, Venkatesh L. TI Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE Imaging; Atherosclerosis; Statin ID METABOLIC SYNDROME; CARDIOVASCULAR EVENTS; INSULIN-RESISTANCE; HEPATIC STEATOSIS; DISEASE; POPULATION; RISK; ASSOCIATION; THERAPY; OBESITY AB Background and aims: To balance competing cardiovascular benefits and metabolic risks of statins, markers of type 2 diabetes (T2D) susceptibility are needed. We sought to define a competing risk/benefit of statin therapy on T2D and cardiovascular disease (CVD) events using liver attenuation and coronary artery calcification (CAC). Methods and results: 3153 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or baseline statin therapy had CT imaging for CAC and hepatic attenuation (hepatic steatosis). Cox models and rates of CVD and T2D were calculated to assess the role of liver attenuation in T2D and the relative risks/benefits of statins on CVD and T2D. 216 T2D cases were diagnosed at median 9.1 years follow-up. High liver fat and statin therapy were associated with diabetes (HR 2.06 [95% CI 1.52-2.79, P < 0.0001] and 2.01 [95% CI 1.46-2.77, P < 0.0001], respectively), after multivariable adjustment. With low liver fat and CAC = 0, the number needed to treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the number needed to harm (NNH) with an incident case of T2D (NNH 68). Conversely, those with CAC > 100 and low liver fat were more likely to benefit from statins for CVD reduction (NNT 29) relative to T2D risk (NNH 67). Among those with CAC > 100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less than incremental risk increase for T2D (NNH 24). Conclusions: Liver fat is associated with incident T2D and stratifies competing metabolic/CVD risks with statin therapy. Hepatic fat may inform T2D surveillance and lipid therapeutic strategies. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Shah, Ravi V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Cardiol & Med, Sch Med, Boston, MA 02215 USA. [Allison, Matthew A.] Univ Calif San Diego, Dept Family & Preventat Med, San Diego, CA 92103 USA. [Lima, Joao A. C.; Ouyang, Pamela] Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA. [Abbasi, Siddique A.] Brown Univ, Dept Cardiol & Med, Providence, RI 02912 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging, Boston, MA 02115 USA. [Ding, Jingzhong] Wake Forest Baptist Med Ctr, Dept Med, Winston Salem, NC USA. [Budoff, Matthew J.] Univ Calif Los Angeles, Dept Cardiol & Med, Los Angeles, CA USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Cardiovasc Med Div, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. RP Murthy, VL (reprint author), Univ Michigan, 1338 Cardiovasc Ctr,1500 E Med Ctr Dr,SPC 5873, Ann Arbor, MI 48109 USA. EM vlmurthy@med.umich.edu RI Murthy, Venkatesh/B-3448-2013; OI Murthy, Venkatesh/0000-0002-7901-1321; Bluemke, David/0000-0002-8323-8086; Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute (NHLBI) [NO1-HC-95159, N01-HC-95169]; American Heart Association; MESA Abdominal Body Composition Ancillary study from the National Heart, Lung, and Blood Institute [R01-HL088451]; NHLBI [R01-HL-085323, R01-HL-071739] FX MESA was supported by contracts NO1-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI). Dr. Shah is supported by a Fellow-to-Faculty Award from the American Heart Association. Dr. Allison was supported by funding for the MESA Abdominal Body Composition Ancillary study from the National Heart, Lung, and Blood Institute (R01-HL088451). Jingzhong Ding and Matthew J. Budoff are supported by R01-HL-085323 and R01-HL-071739, respectively, from NHLBI. Dr. Murthy had full access to all of the data in the study and takes responsibility for the integrity of the data, the accuracy of the data analysis, and acknowledgment of all persons vital to the production of this manuscript. Dr. Murthy has minor stock in General Electric. There are no other disclosures for any other authors relevant to the content of this manuscript. NR 30 TC 7 Z9 7 U1 2 U2 6 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 SEP PY 2015 VL 242 IS 1 BP 211 EP 217 DI 10.1016/j.atherosclerosis.2015.07.018 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900033 PM 26209814 ER PT J AU Lucero, D Svidirov, D Freeman, L Lopez, GI Fassio, E Remaley, AT Schreier, L AF Lucero, Diego Svidirov, Denis Freeman, Lita Lopez, Graciela I. Fassio, Eduardo Remaley, Alan T. Schreier, Laura TI Increased cholesterol efflux capacity in metabolic syndrome: Relation with qualitative alterations in HDL and LCAT SO ATHEROSCLEROSIS LA English DT Article DE Metabolic syndrome; HDL; Cholesterol efflux capacity; Pre-beta 1-HDL; LCAT ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; GEL-ELECTROPHORESIS; ADHESION MOLECULES; ATHEROSCLEROSIS; HYPERTRIGLYCERIDEMIA; SUBPOPULATIONS; PRECIPITATION AB Background: Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known. Objective: To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS. Methods: In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (d: 1.063-1.210 g/mL) was chemically characterized. Pre-beta 1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each). Results: Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 +/- 1.8 vs. 8.7 +/- 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-b1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = -0.51; p = 0.001), independently of obesity and insulin-resistance (beta = -0.40, p = 0.034). Conclusion: This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-beta 1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Lucero, Diego; Lopez, Graciela I.; Schreier, Laura] Univ Buenos Aires, Dept Clin Biochem, Fac Pharm & Biochem, Lab Lipids & Atherosclerosis,INFIBIOC, Buenos Aires, DF, Argentina. [Lucero, Diego; Svidirov, Denis; Freeman, Lita; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. [Fassio, Eduardo] Natl Hosp Prof A Posadas, Dept Gastroenterol, Buenos Aires, DF, Argentina. RP Lucero, D (reprint author), Univ Buenos Aires, Dept Clin Biochem, Fac Pharm & Biochem, Junin 956,C1113AAD, Buenos Aires, DF, Argentina. EM dmlucero@ffyb.uba.ar OI Lucero, Diego/0000-0003-2833-5681 FU University of Buenos Aires [B036] FX This study was supported by a grant from University of Buenos Aires (B036). NR 43 TC 6 Z9 8 U1 0 U2 3 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 SEP PY 2015 VL 242 IS 1 BP 236 EP 242 DI 10.1016/j.atherosclerosis.2015.07.019 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WU UT WOS:000360100900038 PM 26232163 ER PT J AU Heltshe, SL Kafadar, K Prorok, PC AF Heltshe, Sonya L. Kafadar, Karen Prorok, Philip C. TI Quantification of length-bias in screening trials with covariate-dependent test sensitivity SO BIOMETRICAL JOURNAL LA English DT Article DE Cancer; Length-bias; Randomized screening trial; Sojourn time; Test sensitivity ID EARLY-DETECTION PROGRAMS; ESTIMATING LEAD TIME; RANDOMIZED-TRIAL; SOJOURN TIME; LUNG-CANCER; NONPARAMETRIC-ESTIMATION; PROSTATE; MORTALITY; DISEASE; MODEL AB Length-biased sampling exists in screening programs where longer duration disease is detected during the preclinical stage because a longer sojourn time (preclinical duration) has a higher probability of being screen detected. By modeling the course of disease, we quantify the effect of length-biased sampling on clinical duration when cases are subject to periodic screening with variable test sensitivity. We use the highly flexible bivariate lognormal density to jointly model preclinical and clinical durations, and we model screening test sensitivity as a function of the sojourn time and number of previous false negative screens. We show that the mean clinical duration among screen-detected cases can be up to 40% higher, with shrinking standard deviation, than those among nonscreen-detected cases, due to biased sampling alone, irrespective of any possible benefit (increased survival time arising from earlier detection or reduction in mortality). These findings will aid in the design and interpretation of screening trials. C1 [Heltshe, Sonya L.] Univ Washington, Dept Pediat, Seattle, WA 98121 USA. [Kafadar, Karen] Univ Virginia, Dept Stat, Charlottesville, VA 22903 USA. [Prorok, Philip C.] NCI, Bethesda, MD 20892 USA. RP Heltshe, SL (reprint author), Univ Washington, Dept Pediat, Seattle, WA 98121 USA. EM heltshe@u.washington.edu 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 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD SEP PY 2015 VL 57 IS 5 BP 777 EP 796 DI 10.1002/bimj.201400152 PG 20 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA CQ7CA UT WOS:000360759200004 PM 25980962 ER PT J AU Grantz, KL AF Grantz, K. Laughon TI To induce or not to induce: what is the right question? SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Editorial Material C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, NIH, Rockville, MD 20892 USA. RP Grantz, KL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, NIH, Rockville, MD 20892 USA. OI Grantz, Katherine/0000-0003-0276-8534 NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD SEP PY 2015 VL 122 IS 10 BP 1294 EP 1294 DI 10.1111/1471-0528.13480 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ1QX UT WOS:000360374600002 ER PT J AU Jensen, ET Daniels, JL Sturmer, T Robinson, WR Williams, C Vejrup, K Magnus, P Longnecker, MP AF Jensen, E. T. Daniels, J. L. Stuermer, T. Robinson, W. R. Williams, C. J. Vejrup, K. Magnus, P. Longnecker, M. P. TI Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Hormonal contraceptives; Mother and child Cohort Study (MoBa); preterm birth; small for gestational age ID IN-VITRO FERTILIZATION; ORAL-CONTRACEPTIVES; EMBRYONIC-DEVELOPMENT; ENDOCRINE DISRUPTORS; FETAL-GROWTH; EXPOSURE; PREGNANCY; WEIGHT; OBESITY; RISK AB ObjectiveTo evaluate whether hormonal contraceptives, used before or in early pregnancy, confer increased risk of preterm birth or reduced fetal growth. DesignPopulation-based cohort study conducted by the Norwegian Institute of Public Health (Mother and Child Cohort Study, 1998-2008) with linkage to the Norwegian Prescription Registry and to the Medical Birth Registry of Norway. SettingNorway. PopulationOf the 48615 pregnancies meeting study inclusion criteria, 44734 pregnancies were included in the complete case analysis. MethodsWe characterised hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. We used generalised estimating equations to estimate the odds of adverse outcome according to formulation used. Several sensitivity analyses were conducted. Main outcome measuresPreterm birth, small for gestational age. ResultsWe observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (e.g. adjusted odds ratio 1.21, 95% confidence interval 1.04-1.41 for last use 12 to >4months before conception); combination contraceptives containing the progestin norethisterone were consistently related to risk. Other types of hormonal contraception were generally not associated with preterm birth; none were related to small for gestational age. Observed associations were robust to sensitivity analyses. ConclusionHormonally active agents may exert dose-, agent-, and timing-specific effects on growth and development. We found that the particular progestin component is important when assessing the potential for adverse effects among former users of hormonal contraceptives. C1 [Jensen, E. T.; Williams, C. J.; Longnecker, M. P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Jensen, E. T.; Daniels, J. L.; Stuermer, T.; Robinson, W. R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Vejrup, K.; Magnus, P.] Natl Inst Publ Hlth, Oslo, Norway. RP Jensen, ET (reprint author), POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM elizabeth.jensen@nih.gov RI Jensen, Elizabeth/L-1466-2016; OI Longnecker, Matthew/0000-0001-6073-5322 FU Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) [ES102985]; University of North Carolina [T32HD052468]; Carolina Population Center [R24 HD050924]; Norwegian Ministry of Health [N01-ES-75558]; NIH/NIEHS, NIH/National Institute of Neurological Disorders and Stroke [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Norwegian Research Council/FUGE [151918/S10] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) (ES102985 to CJW), the University of North Carolina institutional training grant award for reproductive, perinatal, and pediatric epidemiology (grant T32HD052468 to ETJ), and the Carolina Population Center (R24 HD050924 to WRR). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health, contract N01-ES-75558 with the NIH/NIEHS, NIH/National Institute of Neurological Disorders and Stroke (grant 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1), and the Norwegian Research Council/FUGE (grant 151918/S10). NR 58 TC 1 Z9 1 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD SEP PY 2015 VL 122 IS 10 BP 1349 EP 1361 DI 10.1111/1471-0528.13114 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ1QX UT WOS:000360374600010 PM 25318662 ER PT J AU Miller, R Smiley, R Thom, EA Grobman, WA Iams, JD Mercer, BM Saade, G Tita, AT Reddy, UM Rouse, DJ Sorokin, Y Blackwell, SC Esplin, MS Tolosa, JE Caritis, SN AF Miller, R. Smiley, R. Thom, E. A. Grobman, W. A. Iams, J. D. Mercer, B. M. Saade, G. Tita, A. T. Reddy, U. M. Rouse, D. J. Sorokin, Y. Blackwell, S. C. Esplin, M. S. Tolosa, J. E. Caritis, S. N. CA Eunice Kennedy Shriver Natl Inst C Human Dev Maternal Fetal Med Units TI The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Beta-2 adrenoceptor; genotype; short cervix ID ALLELE-SPECIFIC PCR; BETA(2)-ADRENERGIC RECEPTOR; BETA-2-ADRENERGIC RECEPTOR; GENETIC POLYMORPHISMS; DELIVERY; VARIANTS; ASTHMA; LABOR; RISK; RAT AB ObjectiveTo determine whether (2)-adrenoceptor ((2)AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DesignA case-control ancillary study to a multicentre randomised controlled trial. SettingFourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. PopulationFour hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. MethodsNulliparous women with cervical length <30mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths 40mm were studied. (2)AR genotype was determined at positions encoding for amino acid residues 16 and 27. Main outcome measuresGenotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37weeks. ResultsGenotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. Conclusions(2)AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with (2)AR genotype do not appear to involve a short cervix pathway. C1 [Miller, R.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY 10032 USA. [Smiley, R.] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, Div Obstet Anesthesiol, New York, NY 10032 USA. [Thom, E. A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Grobman, W. A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. [Grobman, W. A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. [Iams, J. D.] Ohio State Univ, Columbus, OH 43210 USA. [Mercer, B. M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Saade, G.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Tita, A. T.] Univ Alabama Birmingham, Birmingham, AL USA. [Reddy, U. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Rouse, D. J.] Brown Univ, Providence, RI 02912 USA. [Sorokin, Y.] Wayne State Univ, Detroit, MI USA. [Blackwell, S. C.] Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA. [Esplin, M. S.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Tolosa, J. E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Caritis, S. N.] Univ Pittsburgh, Pittsburgh, PA USA. RP Miller, R (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, 622 West 168th St,PH-16, New York, NY 10032 USA. EM rsm20@columbia.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [R01HD48805, HD21410, UL1 RR024153, UL1 TR000005, HD27869, HD27915, HD27917, HD34116, HD34208, 5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1 RR024989, HD40545, HD40560, HD40485, HD53097, HD53118] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (R01HD48805, HD21410, UL1 RR024153; UL1 TR000005; HD27869, HD27915, HD27917, HD34116, HD34208, 5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1 RR024989 (NCRR), HD40545, HD40560, HD40485, HD53097, HD53118). Comments and views of the authors do not necessarily represent views of the NICHD. NR 37 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD SEP PY 2015 VL 122 IS 10 BP 1387 EP 1394 DI 10.1111/1471-0528.13243 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CQ1QX UT WOS:000360374600015 PM 25600430 ER PT J AU Xue, M Zheng, J Zhou, Q Hejtmancik, JF Wang, Y Li, SL AF Xue, Min Zheng, Jie Zhou, Qing Hejtmancik, J. Fielding Wang, Yuan Li, Shouling TI Novel FOXL2 mutations in two Chinese families with blepharophimosis-ptosis-epicanthus inversus syndrome SO BMC MEDICAL GENETICS LA English DT Article ID TRANSCRIPTION FACTOR FOXL2; GENOTYPE-PHENOTYPE CORRELATION; PREMATURE OVARIAN FAILURE; SYNDROME BPES; PROTEIN AGGREGATION; IDENTIFICATION; IMPAIRMENT; EXPRESSION; EVOLUTION; GENE AB Background: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease. Mutations in the forkhead box L2 (FOXL2) gene cause two types of BPES distinguished by the presence (type I) and absence (type II) of premature ovarian failure (POF). The purpose of this study was to identify possible mutations in FOXL2 in two Chinese families with BPES. Methods: Two large autosomal dominant Chinese BPES families were enrolled in this study. Genomic DNA was obtained from the leukocytes in peripheral venous blood. Four overlapping sets of primers were used to amplify the entire coding region and nearby intron sequences of the FOXL2 gene for mutations detection using polymerase chain reaction (PCR) and sequencing analyses. The sequencing results were analyzed using DNAstar software. Results: All patients of the two families demonstrated typical features of BPES type II, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus without female infertility (POF). A novel FOXL2 heterozygous indel mutation c.675_690delinsT, including a 16-bp deletion and a 1-bp(T) insertion (p.Ala226_Ala230del), which would result in deletion of 5 alanine residues of a poly-alanine (poly-Ala) tract in the protein, was identified in all affected members of family A. A novel heterozygous missense mutation (c.223C > T, p.Leu75Phe) was identified in family B. Conclusions: Two novel FOXL2 mutations were identified in Chinese families with BPES. Our results expand the spectrum of FOXL2 mutations and provide additional structure-function insights into the FOXL2 protein. C1 [Xue, Min; Zheng, Jie; Li, Shouling] Anhui Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Hefei, Peoples R China. [Zhou, Qing; Wang, Yuan] Anhui Key Lab Genet Res, Natl MOE Key Lab Gene Resource Utilizat Important, Hefei, Peoples R China. [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Xue, Min] Anhui 2 Prov Peoples Hosp, Dept Ophthalmol, Hefei, Peoples R China. RP Li, SL (reprint author), Anhui Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Hefei, Peoples R China. EM shoulingli@126.com NR 27 TC 1 Z9 1 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD SEP 1 PY 2015 VL 16 AR 73 DI 10.1186/s12881-015-0217-7 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CQ5VT UT WOS:000360674500001 PM 26323275 ER PT J AU Gard, CC Bowles, EJA Miglioretti, DL Taplin, SH Rutter, CM AF Gard, Charlotte C. Bowles, Erin J. Aiello Miglioretti, Diana L. Taplin, Stephen H. Rutter, Carolyn M. TI Misclassification of Breast Imaging Reporting and Data System (BI-RADS) Mammographic Density and Implications for Breast Density Reporting Legislation SO BREAST JOURNAL LA English DT Article DE BI-RADS density; breast density reporting legislation; intra- and interradiologist agreement; misclassification; percent density ID CANCER RISK; SCREENING MAMMOGRAPHY; ACCURACY; VARIABILITY; CATEGORIES; AGREEMENT; AGE AB USA states have begun legislating mammographic breast density reporting to women, requiring that women undergoing screening mammography who have dense breast tissue (Breast Imaging Reporting and Data System [BI-RADS] density c or d) receive written notification of their breast density; however, the impact that misclassification of breast density will have on this reporting remains unclear. The aim of this study was to assess reproducibility of the four-category BI-RADS density measure and examine its relationship with a continuous measure of percent density. We enrolled 19 radiologists, experienced in breast imaging, from a single integrated health care system. Radiologists interpreted 341 screening mammograms at two points in time 6months apart. We assessed intra- and interobserver agreement in radiologists'; interpretations of BI-RADS density and explored whether agreement depended upon radiologist characteristics. We examined the relationship between BI-RADS density and percent density in a subset of 282 examinations. Intraradiologist agreement was moderate to substantial, with kappa varying across radiologists from 0.50 to 0.81 (mean=0.69, 95% CI [0.63, 0.73]). Intraradiologist agreement was higher for radiologists with 10years experience interpreting mammograms (difference in mean kappa=0.10, 95% CI [0.01, 0.24]). Interradiologist agreement varied widely across radiologist pairs from slight to substantial, with kappa ranging from 0.02 to 0.72 (mean=0.46, 95% CI [0.36, 0.55]). Of 145 examinations interpreted as nondense (BI-RADS density a or b) by the majority of radiologists, 82.8% were interpreted as dense (BI-RADS density c or d) by at least one radiologist. Of 187 examinations interpreted as dense by the majority of radiologists, 47.1% were interpreted as nondense by at least one radiologist. While the examinations of almost half of the women in our study were interpreted clinically as having BI-RADS density c or d, only about 10% of examinations had percent density >50%. Our results suggest that breast density reporting based on a single BI-RADS density interpretation may be misleading due to high interradiologist variability and a lack of correspondence between BI-RADS density and percent density. C1 [Gard, Charlotte C.] New Mexico State Univ, Dept Econ Appl Stat & Int Business, Las Cruces, NM 88003 USA. [Bowles, Erin J. Aiello; Miglioretti, Diana L.; Rutter, Carolyn M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Miglioretti, Diana L.] UC Davis Sch Med, Dept Publ Hlth Sci, Davis, CA USA. [Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA. RP Gard, CC (reprint author), New Mexico State Univ, Dept Econ Appl Stat & Int Business, Coll Business, POB 30001,MSC 3CQ, Las Cruces, NM 88003 USA. EM cgard@nmsu.edu FU National Cancer Institute [U01CA86076, U01CA63731] FX This work was supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (BCSC) cooperative agreement (U01CA86076, U01CA63731). A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: http://breastscreening.cancer.gov/. NR 29 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD SEP-OCT PY 2015 VL 21 IS 5 BP 481 EP 489 DI 10.1111/tbj.12443 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CQ7FK UT WOS:000360768200004 PM 26133090 ER PT J AU Gebauer, M Ruetten, H Raymond, RH Robertson, RP Savage, PJ Shankar, SS Stefanovski, D Vassileva, MT Vella, A Wright, KF Fryburg, DA AF Gebauer, M. Ruetten, H. Raymond, R. H. Robertson, R. P. Savage, P. J. Shankar, S. S. Stefanovski, D. Vassileva, M. T. Vella, A. Wright, K. F. Fryburg, D. A. CA Fdn NIH Beta Cell Project Team TI Enteroendocrine secretion after meal challenge is preserved across glucose tolerance spectrum: lack of correlation with beta cell function SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Gebauer, M.; Ruetten, H.] Sanofi Aventis Deutschland GmbH, Frankfurt, Germany. [Raymond, R. H.] RSquared Solut, Skillman, NJ USA. [Robertson, R. P.] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Savage, P. J.] NIDDK, NIH, Bethesda, MD USA. [Shankar, S. S.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Stefanovski, D.] Univ Penn, Philadelphia, PA 19104 USA. [Vassileva, M. T.] Fdn NIH, Bethesda, MD USA. [Vella, A.] Mayo Clin, Rochester, MN USA. [Wright, K. F.; Fryburg, D. A.] ROI BioPharma Consulting, East Lyme, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 554 BP S270 EP S270 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820901244 ER PT J AU Hjort, L Grunnet, LG Olsson, A Martino, D Hu, FB Zhang, C Saffery, R Olsen, S Vaag, A AF Hjort, L. Grunnet, L. Groth Olsson, A. Martino, D. Hu, F. B. Zhang, C. Saffery, R. Olsen, S. Vaag, A. TI Effects of a hyperglycaemic intrauterine environment on offsprings epigenome and risk of cardio-metabolic disease later in life SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Hjort, L.; Grunnet, L. Groth; Olsson, A.; Vaag, A.] Copenhagen Univ Hosp, Copenhagen, Denmark. [Martino, D.; Saffery, R.] Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Hu, F. B.] Harvard Univ, Med & Publ Hlth Sch, Boston, MA 02115 USA. [Zhang, C.] NICHHD, Bethesda, MD 20892 USA. [Olsen, S.] Statens Serum Inst, DK-2300 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 119 BP S59 EP S59 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900120 ER PT J AU Lernmark, A Larsson, HE Lee, HS Krischer, J Vehik, K Lynch, KF Haller, M Hagopian, WA Rewers, MJ She, JX Simell, OG Toppari, J Ziegler, AG Akolkar, B AF Lernmark, A. Larsson, H. Elding Lee, H. -S. Krischer, J. Vehik, K. Lynch, K. F. Haller, M. Hagopian, W. A. Rewers, M. J. She, J. -X. Simell, O. G. Toppari, J. Ziegler, A. -G. Akolkar, B. CA TEDDY Study Grp TI Factors affecting the risk for the first appearance of an islet autoantibody in The Environmental Determinants of Diabetes in the Young (TEDDY) study SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Lernmark, A.] Lund Univ, Univ Hosp MAS, S-22100 Lund, Sweden. [Larsson, H. Elding] Lund Univ, Univ Hosp SUS, Malmo, Sweden. [Lee, H. -S.; Krischer, J.; Vehik, K.; Lynch, K. F.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Haller, M.] Univ Gainesville, Dept Pediat, Seattle, WA USA. [Hagopian, W. A.] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Rewers, M. J.] Univ Colorado, Aurora, CO USA. [She, J. -X.] Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Simell, O. G.; Toppari, J.] Turku Univ Hosp, Dept Pediat, Turku, Finland. [Ziegler, A. -G.] Helmholtz Zentrum Munchen, Diabet Res Inst, Forschergrp Diabet eV, Neuherberg, Germany. [Ziegler, A. -G.] Klinikum Rechts Der Isar, Neuherberg, Germany. [Akolkar, B.] Univ Hosp MAS, NIDDKD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 44 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900045 ER PT J AU Raciti, GA Spinelli, R Desiderio, A Campitelli, M Parrillo, L Longo, M Zatterale, F Vastolo, V Ungaro, P Miele, C Pastan, I Beguinot, F AF Raciti, G. A. Spinelli, R. Desiderio, A. Campitelli, M. Parrillo, L. Longo, M. Zatterale, F. Vastolo, V. Ungaro, P. Miele, C. Pastan, I. Beguinot, F. TI Obesity modulates Ankrd26 gene expression by inducing epigenetic changes of its promoter SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Raciti, G. A.; Spinelli, R.; Desiderio, A.; Campitelli, M.; Parrillo, L.; Longo, M.; Zatterale, F.; Vastolo, V.; Ungaro, P.; Miele, C.; Beguinot, F.] Univ Naples Federico II, Dept Translat Med Sci DiSMeT, CNR Res Unit, Naples, Italy. [Pastan, I.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 342 BP S172 EP S172 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820901032 ER PT J AU Torn, C Lernmark, A Vehik, K Bonifacio, E Rewers, M Simell, O Toppari, J Ziegler, A Akolkar, B Hagopian, W Schatz, D She, JX Krischer, J AF Torn, C. Lernmark, A. Vehik, K. Bonifacio, E. Rewers, M. Simell, O. Toppari, J. Ziegler, A. Akolkar, B. Hagopian, W. Schatz, D. She, J. -X. Krischer, J. CA TEDDY Study Grp TI Maternal exposure of autoantibodies protects the child from islet autoimmunity in early childhood if the mother does not have type 1 diabetes (TEDDY) SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Torn, C.; Lernmark, A.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Vehik, K.; Krischer, J.] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Bonifacio, E.] Tech Univ Dresden, Fac Med, Ctr Regenerat Therapies, D-01062 Dresden, Germany. [Rewers, M.] Univ Colorado, Denver & Hlth Sci Ctr, Dept Pediat, Boulder, CO 80309 USA. [Simell, O.; Toppari, J.] Univ Turku, Dept Pediat, SF-20500 Turku, Finland. [Ziegler, A.] Diabet Res Inst, Dept Pediat, Munich, Germany. [Akolkar, B.] NIDDK, Bethesda, MD 20892 USA. [Hagopian, W.] Pacific North West Inst, Seattle, WA USA. [Schatz, D.] Univ Florida, Dept Pediat, Gainesville, FL USA. [She, J. -X.] Med Coll Georgia, Atlanta, GA USA. RI Bonifacio, Ezio/E-7700-2010 OI Bonifacio, Ezio/0000-0002-8704-4713 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 296 BP S149 EP S149 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900297 ER PT J AU van Leeuwen, N Wood, AR Jackson, A Jonsson, A Wang, N Smith, U Vilarino, LB Stancakova, A Walker, M Hanson, R Frayling, TM AF van Leeuwen, N. Wood, A. R. Jackson, A. Jonsson, A. Wang, N. Smith, U. Vilarino, L. Boquete Stancakova, A. Walker, M. Hanson, R. Frayling, T. M. CA GUINNESS Consortium TI A genome wide association study of IVGTT based measures of first phase insulin secretion reveals new physiology of known and novel variants SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [van Leeuwen, N.] LUMC, Mol Cell Biol, Leiden, Netherlands. [Wood, A. R.; Vilarino, L. Boquete; Frayling, T. M.] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England. [Jackson, A.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Jackson, A.] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Jonsson, A.] Univ Copenhagen, Fac Hlth & Med Sci, DK-1168 Copenhagen, Denmark. [Wang, N.] USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Smith, U.] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Smith, U.] Univ Gothenburg, Lundberg Lab Diabet Res, Gothenburg, Sweden. [Stancakova, A.] Univ Eastern Finland, Inst Clin Sci, Internal Med, Kuopio, Finland. [Stancakova, A.] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Walker, M.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Hanson, R.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 105 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900106 ER PT J AU Yin, P Gandasi, NR Riz, M Cortese, G Chibalina, M Rorsman, P Sherman, A Pedersen, MG Barg, S AF Yin, P. Gandasi, N. R. Riz, M. Cortese, G. Chibalina, M. Rorsman, P. Sherman, A. Pedersen, M. G. Barg, S. TI Clustering of L-type CA(2+)-channels promotes exocytosis of individual secretory granules SO DIABETOLOGIA LA English DT Meeting Abstract CT 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-18, 2015 CL Stockholm, SWEDEN SP European Assoc Study Diabet C1 [Yin, P.; Gandasi, N. R.; Barg, S.] Uppsala Univ, Inst Med Cell Biol, Uppsala, Sweden. [Riz, M.; Pedersen, M. G.] Univ Padua, Dept Informat Engn, I-35100 Padua, Italy. [Cortese, G.] Univ Padua, Dept Stat, I-35100 Padua, Italy. [Chibalina, M.; Rorsman, P.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England. [Sherman, A.] NIDDK, NIH, Bethesda, MD 20892 USA. RI Rorsman, Patrik/A-4331-2016; Pedersen, Morten/F-4134-2012 OI Rorsman, Patrik/0000-0001-7578-0767; Pedersen, Morten/0000-0002-2639-2394 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2015 VL 58 SU 1 MA 254 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP3ZE UT WOS:000359820900255 ER PT J AU Turkbey, B Choyke, PL AF Turkbey, Baris Choyke, Peter L. TI PIRADS 2.0: what is new? SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PROSTATE-CANCER; SCORING SYSTEM; BIOPSY C1 [Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov NR 12 TC 11 Z9 11 U1 0 U2 0 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP-OCT PY 2015 VL 21 IS 5 BP 382 EP 384 DI 10.5152/dir.2015.15099 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ4CE UT WOS:000360551000004 PM 26200484 ER PT J AU Polizzotto, MN Chen, G Tressler, RL Godfrey, C AF Polizzotto, Mark N. Chen, Grace Tressler, Randall L. Godfrey, Catherine TI Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions SO DRUGS LA English DT Article ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; HISTONE DEACETYLASE INHIBITORS; CHRONIC VIRAL-INFECTION; ANTIRETROVIRAL THERAPY; MULTIPLE-MYELOMA; LATENT RESERVOIR; VALPROIC ACID; DISEASE PROGRESSION; ANTIVIRAL THERAPY AB Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been "cured" of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment. C1 [Polizzotto, Mark N.] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Chen, Grace; Tressler, Randall L.] HJF DAIDS Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA. [Godfrey, Catherine] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Polizzotto, MN (reprint author), UNSW Australia, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia. EM mpolizzotto@kirby.unsw.edu.au; cgodfrey@niaid.nih.gov FU Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C]; Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Human Services FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800014C and by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Human Services. NR 105 TC 1 Z9 1 U1 1 U2 3 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0012-6667 EI 1179-1950 J9 DRUGS JI Drugs PD SEP PY 2015 VL 75 IS 13 BP 1447 EP 1459 DI 10.1007/s40265-015-0426-6 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CQ6GN UT WOS:000360702600001 PM 26224205 ER PT J AU Blakeslee, SB Parker, PA Gunn, CM Bandos, H Battaglia, TA Bevers, TB McCaskill-Stevens, W Muller-Nordhorn, J Holmberg, C AF Blakeslee, Sarah B. Parker, Patricia A. Gunn, Christine M. Bandos, Hanna Battaglia, Tracy A. Bevers, Therese B. McCaskill-Stevens, Worta Mueller-Nordhorn, Jacqueline Holmberg, Christine TI Casing uncertainty in LCIS recommendations through two patient narratives SO EUROPEAN JOURNAL OF CANCER CARE LA English DT Meeting Abstract ID CARCINOMA IN-SITU; MANAGEMENT; WOMEN; CARE C1 [Blakeslee, Sarah B.; Mueller-Nordhorn, Jacqueline; Holmberg, Christine] Charite, Berlin Sch Publ Hlth, D-13353 Berlin, Germany. [Parker, Patricia A.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Gunn, Christine M.; Battaglia, Tracy A.] Boston Med Ctr, Evans Dept Med, Boston, MA USA. [Gunn, Christine M.; Battaglia, Tracy A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bandos, Hanna] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Bandos, Hanna] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Bevers, Therese B.] Univ Texas MD Anderson Canc Ctr, Clin Canc Prevent, Houston, TX 77030 USA. [McCaskill-Stevens, Worta] NCI, Canc Prevent Div, Rockville, MD USA. NR 8 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-5423 EI 1365-2354 J9 EUR J CANCER CARE JI Eur. J. Cancer Care PD SEP PY 2015 VL 24 SU 2 SI SI MA P-09 BP 32 EP 32 PG 1 WC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation SC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation GA CQ7EM UT WOS:000360765800071 ER PT J AU DiPaola, RS Chen, YH Bubley, GJ Stein, MN Hahn, NM Carducci, MA Lattime, EC Gulley, JL Arlen, PM Butterfield, LH Wilding, G AF DiPaola, Robert S. Chen, Yu-Hui Bubley, Glenn J. Stein, Mark N. Hahn, Noah M. Carducci, Michael A. Lattime, Edmund C. Gulley, James L. Arlen, Philip M. Butterfield, Lisa H. Wilding, George TI A National Multicenter Phase 2 Study of Prostate-specific Antigen (PSA) Pox Virus Vaccine with Sequential Androgen Ablation Therapy in Patients with PSA Progression: ECOG 9802 SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Pox virus; Vaccine; PSA ID DEPRIVATION THERAPY; ONCOLOGY-GROUP; CANCER; IMMUNOTHERAPY; SURVIVAL; IMPACT; TRIAL AB Background: E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. Objective: To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Design, setting, and participants: Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte- macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Outcome measurements and statistical analysis: Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. Results and limitations: In step 1, 25 of 40 eligible patients (63%) were progression free at 6mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p = 0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade >= 4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. Conclusions: A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined withandrogenablation, supporting the feasibility of futurephase 3studies in thispopulation. Patient summary: These data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [DiPaola, Robert S.; Stein, Mark N.; Lattime, Edmund C.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hahn, Noah M.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Carducci, Michael A.] Johns Hopkins Univ, Baltimore, MD USA. [Gulley, James L.; Arlen, Philip M.] NCI, Bethesda, MD 20892 USA. [Butterfield, Lisa H.] Univ Pittsburgh, Pittsburgh, PA USA. [Wilding, George] Univ Wisconsin, UW Carbone Canc Ctr, Madison, WI USA. RP DiPaola, RS (reprint author), Rutgers Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM Robert.DiPaola@rutgers.edu RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Public Health Service [CA23318, CA66636, CA21115, CA80775, CA49883, CA16116, CA21076]; National Cancer Institute (NCI), National Institutes of Health; Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, group cochairs) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA80775, CA49883, CA16116, CA21076, and from the National Cancer Institute (NCI), National Institutes of Health, and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI. Only the first step of the study (step 1: vaccine alone) was presented at the Genitourinary American Society of Clinical Oncology Annual Meeting 2009; step 2 data (combined androgen ablation and vaccine) has not been presented. NR 19 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD SEP PY 2015 VL 68 IS 3 BP 365 EP 371 DI 10.1016/j.eururo.2014.12.010 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JZ UT WOS:000360572300013 PM 25533418 ER PT J AU Grazziotin, AL Vidal, NM Venancio, TM AF Grazziotin, Ana Laura Vidal, Newton M. Venancio, Thiago M. TI Uncovering major genomic features of essential genes in Bacteria and a methanogenic Archaea SO FEBS JOURNAL LA English DT Article DE essential genes; genome evolution; genome organization; operons; prokaryotes; transposon mutagenesis ID TRANSPOSON MUTANT LIBRARY; ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; BURKHOLDERIA-PSEUDOMALLEI; FRANCISELLA-NOVICIDA; NONESSENTIAL GENES; PROTEIN FAMILIES; CELL-DIVISION; EVOLUTION; OPERONS AB Identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. Although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. Here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for growth in vivo, encompassing 15 Bacteria and one Archaea. We refine and generalize important theories proposed using Escherichia coli. Essential genes are typically monogenic and more conserved than nonessential genes. Genes required in vivo are less conserved than those essential in vitro, suggesting that more divergent strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. We identified essential analogous pathways that would probably be missed by orthology-based essentiality prediction strategies. For example, Streptococcus sanguinis carries horizontally transferred isoprenoid biosynthesis genes that are widespread in Archaea. Genes specifically essential in Mycobacterium tuberculosis and Burkholderia pseudomallei are reported as potential drug targets. Moreover, essential genes are not only preferentially located in operons, but also occupy the first position therein, supporting the influence of their regulatory regions in driving transcription of whole operons. Finally, these important genomic features are shared between Bacteria and at least one Archaea, suggesting that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the prokaryotic domains. C1 [Grazziotin, Ana Laura; Vidal, Newton M.; Venancio, Thiago M.] Univ Estadual Norte Fluminense Darcy, Ctr Biociencias & Biotecnol, Lab Quim & Funcao Prot & Peptideos, BR-28013602 Rio De Janeiro, Brazil. [Grazziotin, Ana Laura; Vidal, Newton M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Venancio, TM (reprint author), Univ Estadual Norte Fluminense Darcy, Ctr Biociencias & Biotecnol, Lab Quim & Funcao Prot & Peptideos, Av Alberto Lamego 2000,P5-217, BR-28013602 Rio De Janeiro, Brazil. EM analauragrazziotin@gmail.com; thiago.venancio@gmail.com RI Venancio, Thiago/B-5003-2011 FU Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) [E-26/110.236/2011, E-26/102.259/2013]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF); CNPq; National Institutes of Health (NIH); National Library of Medicine, NIH FX We would like to thank the following institutions for funding our research: Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) (E-26/110.236/2011 and E-26/102.259/2013), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF) (A.L.G. PhD fellowship). N.M.V. postdoctoral fellowship is funded by a partnership between CNPq and National Institutes of Health (NIH). T.M.V. is a recipient of an established investigator fellowship award from CNPq. This research was supported in part by the Intramural Research Program of the National Library of Medicine, NIH. We would also like to thank Dr Robson Francisco de Souza for sharing the tjoin script and Dr Fenglou Mao for helping with DOOR2. NR 94 TC 1 Z9 1 U1 2 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD SEP PY 2015 VL 282 IS 17 BP 3395 EP 3411 DI 10.1111/febs.13350 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ5FR UT WOS:000360629200011 PM 26084810 ER PT J AU He, XM Syed, KS Tillo, D Mann, I Weirauch, MT Vinson, C AF He, Ximiao Syed, Khund Sayeed Tillo, Desiree Mann, Ishminder Weirauch, Matthew T. Vinson, Charles TI GABP alpha Binding to Overlapping ETS and CRE DNA Motifs Is Enhanced by CREB1: Custom DNA Microarrays SO G3-GENES GENOMES GENETICS LA English DT Article DE ETS; CRE; GABP alpha; CREB1; cooperative DNA binding ID TRANSCRIPTION-FACTOR-BINDING; GENOME-WIDE ANALYSIS; CRYSTAL-STRUCTURE; COOPERATIVE BINDING; IN-VIVO; SITES; MODEL; SPECIFICITY; PROTEINS; COMPLEX AB To achieve proper spatiotemporal control of gene expression, transcription factors cooperatively assemble onto specific DNA sequences. The ETS domain protein monomer of GABP alpha and the B-ZIP domain protein dimer of CREB1 cooperatively bind DNA only when the ETS (C/G CGGAAGT) and CRE (GTGACGTCAC) motifs overlap precisely, producing the ETS <-> CRE motif (C/G CGGAAGTGACGTCAC). We designed a Protein Binding Microarray (PBM) with 60-bp DNAs containing four identical sectors, each with 177,440 features that explore the cooperative interactions between GABP alpha and CREB1 upon binding the ETS <-> CRE motif. The DNA sequences include all 15-mers of the form C/G CGGA--CG-, the ETS <-> CRE motif, and all single nucleotide polymorphisms (SNPs), and occurrences in the human and mouse genomes. CREB1 enhanced GABP alpha binding to the canonical ETS <-> CRE motif CCGGAAGT two-fold, and up to 23-fold for several SNPs at the beginning and end of the ETS motif, which is suggestive of two separate and distinct allosteric mechanisms of cooperative binding. We show that the ETS-CRE array data can be used to identify regions likely cooperatively bound by GABP alpha and CREB1 in vivo, and demonstrate their ability to identify human genetic variants that might inhibit cooperative binding. C1 [He, Ximiao; Syed, Khund Sayeed; Tillo, Desiree; Mann, Ishminder; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Weirauch, Matthew T.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol,Div Biomed Informat, Cincinnati, OH 45229 USA. [Weirauch, Matthew T.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Pediat,Div Dev Biol, Cincinnati, OH 45229 USA. RP Weirauch, MT (reprint author), Cincinnati Childrens Hosp, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM matthew.weirauch@cchmc.org; vinsonc@mail.nih.gov OI He, Ximiao/0000-0003-1253-5275 NR 46 TC 1 Z9 1 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD SEP 1 PY 2015 VL 5 IS 9 BP 1909 EP 1918 DI 10.1534/g3.115.020248 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CQ6GS UT WOS:000360703200012 PM 26185160 ER PT J AU Deng, T Zhu, ZI Zhang, SF Postnikov, Y Huang, D Horsch, M Furusawa, T Beckers, J Rozman, J Klingenspor, M Amarie, O Graw, J Rathkolb, B Wolf, E Adler, T Busch, DH Gailus-Durner, V Fuchs, H de Angelis, MH van der Velde, A Tessarollo, L Ovcherenko, I Landsman, D Bustin, M AF Deng, Tao Zhu, Z. Iris Zhang, Shaofei Postnikov, Yuri Huang, Di Horsch, Marion Furusawa, Takashi Beckers, Johannes Rozman, Jan Klingenspor, Martin Amarie, Oana Graw, Jochen Rathkolb, Birgit Wolf, Eckhard Adler, Thure Busch, Dirk H. Gailus-Durner, Valerie Fuchs, Helmut de Angelis, Martin Hrabe van der Velde, Arjan Tessarollo, Lino Ovcherenko, Ivan Landsman, David Bustin, Michael TI Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers SO GENOME RESEARCH LA English DT Article ID CHROMOSOMAL-PROTEIN HMGN1; HISTONE H1; CHROMATIN COMPACTION; LINKER HISTONE; LIVING CELLS; HUMAN GENOME; MOBILITY; BINDING; NUCLEOSOMES; TRANSCRIPTION AB DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHS landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome-wide mapping of the DHSs in Hmgn1-/-, Hmgn2(-/-), and Hmgn1(-/-) n2(-/-) MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHS landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress-responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHS landscape, and the transcription fidelity and is necessary to retain wildtype phenotypes. Our study provides insight into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins. C1 [Deng, Tao; Zhang, Shaofei; Postnikov, Yuri; Furusawa, Takashi; Bustin, Michael] NCI, NIH, Ctr Canc Res, Prot Sect,Lab Metab, Bethesda, MD 20892 USA. [Zhu, Z. Iris; Huang, Di; van der Velde, Arjan; Ovcherenko, Ivan; Landsman, David] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20892 USA. [Horsch, Marion; Beckers, Johannes; Rozman, Jan; Amarie, Oana; Graw, Jochen; Rathkolb, Birgit; Adler, Thure; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabe] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, D-85764 Neuherberg, Germany. [Beckers, Johannes; de Angelis, Martin Hrabe] Tech Univ Munich, Ctr Life & Food Sci, Expt Genet, D-85354 Freising Weihenstephan, Germany. [Beckers, Johannes; Rathkolb, Birgit; de Angelis, Martin Hrabe] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany. [Klingenspor, Martin] Tech Univ Munich, Mol Nutr Med, D-85350 Freising Weihenstephan, Germany. [Klingenspor, Martin] Tech Univ Munich, Ctr Nutr & Food Sci, D-85350 Freising Weihenstephan, Germany. [Amarie, Oana; Graw, Jochen] IDG, D-85764 Neuherberg, Germany. [Rathkolb, Birgit; Wolf, Eckhard] Univ Munich, Gene Ctr, Inst Mol Anim Breeding & Biotechnol, D-81377 Munich, Germany. [Busch, Dirk H.] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Neural Dev Sect, Frederick, MD 21702 USA. RP Bustin, M (reprint author), NCI, NIH, Ctr Canc Res, Prot Sect,Lab Metab, Bethesda, MD 20892 USA. EM bustinm@mail.nih.gov RI Deng, Tao/J-2031-2015; Gailus-Durner, Valerie/M-7337-2014; Graw, Jochen/D-9336-2013; Hrabe de Angelis, Martin/F-5531-2012; Rozman, Jan/A-2540-2010; Beckers, Johannes/K-7237-2012; Bustin, Michael/G-6155-2015; OI Wolf, Eckhard/0000-0002-0430-9510; Klingenspor, Martin/0000-0002-4502-6664; van der Velde, Arjan/0000-0003-1086-0859; Landsman, David/0000-0002-9819-6675; Hrabe de Angelis, Martin/0000-0002-7898-2353; Rozman, Jan/0000-0002-8035-8904; Beckers, Johannes/0000-0001-7874-3822; Graw, Jochen/0000-0003-0298-9660 FU Intramural Research Programs of the CCR, NCI, NIH [ZIABC011154]; NCBI, NLM, NIH; German Federal Ministry of Education and Research [01KX1012]; Helmholtz Portfolio Theme "Metabolic Dysfunction and Common Disease"; Helmholtz Alliance "ICEMED"; German Center for Diabetes Research (DZD) FX This research was supported by the Intramural Research Programs of the CCR, NCI, NIH (grant ZIABC011154); by the NCBI, NLM, NIH; by the German Federal Ministry of Education and Research (Infrafrontier grant 01KX1012); by the Helmholtz Portfolio Theme "Metabolic Dysfunction and Common Disease"; by the Helmholtz Alliance "ICEMED"; and by the German Center for Diabetes Research (DZD). NR 48 TC 7 Z9 7 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD SEP PY 2015 VL 25 IS 9 BP 1295 EP 1308 DI 10.1101/gr.192229.115 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CQ6NK UT WOS:000360721000005 PM 26156321 ER PT J AU Ellis, EM Homish, GG Parks, KA Collins, RL Kiviniemi, MT AF Ellis, Erin M. Homish, Gregory G. Parks, Kathleen A. Collins, R. Lorraine Kiviniemi, Marc T. TI Increasing Condom Use by Changing People's Feelings About Them: An Experimental Study SO HEALTH PSYCHOLOGY LA English DT Article DE health decision making; affect/emotions; evaluative conditioning (EC); condom use ID AFFECTIVE ASSOCIATIONS; IMPLICIT ATTITUDES; PLANNED BEHAVIOR; I FEEL; METAANALYSIS; COGNITION; EXPLICIT; RISK; PROTECTION; INTERPLAY AB Objective: Given the well-documented efficacy of condoms as a means of preventing pregnancy and sexually transmitted infection transmission, the low rates of condom use among young adults necessitates a deeper understanding of the factors that influence condom use decision making. The central purpose of the current study was to examine how experimentally manipulated affective associations with condoms influence subsequent behavior in a condom selection task, thereby providing support for a causal relation of affective associations to behavior in this health domain. Method: Following a baseline assessment of cognitively based beliefs and affective associations, participants' (N = 171) affective associations with condoms were experimentally manipulated with an evaluative conditioning (EC) procedure. Images of condoms were paired repeatedly with positive or neutral affective stimuli. The key outcome measure was a behavioral choice task in which participants selected condoms upon completion of the experiment. Results: Participants in the positive condition reported more positive affective associations post-EC compared with those in the neutral condition, beta = 0.33, p = .025, 95% CI (0.041, 0.63). For participants who regularly used condoms at baseline, those in the positive condition also selected significantly more condoms, RR = 1.39, p = .015, 95% CI (1.07, 1.83). This condition effect on behavior was partially mediated by the change in affective associations. There was no effect of condition on condom selection among participants who rarely used condoms at baseline. Conclusion: The current study extends our theoretical understanding of the affect-behavior relation in the realm of condom use, and provides preliminary support for interventions that target affective associations with condoms. C1 [Ellis, Erin M.; Homish, Gregory G.; Collins, R. Lorraine; Kiviniemi, Marc T.] SUNY Buffalo, Dept Community Hlth & Hlth Behav, Buffalo, NY 14260 USA. [Parks, Kathleen A.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. [Kiviniemi, Marc T.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Ellis, EM (reprint author), 314 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. EM erinwals@buffalo.edu NR 48 TC 1 Z9 1 U1 6 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2015 VL 34 IS 9 BP 941 EP 950 DI 10.1037/hea0000205 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA CQ4OO UT WOS:000360584600007 PM 25581703 ER PT J AU Bodner, KE Engelhardt, CR Minshew, NJ Williams, DL AF Bodner, Kimberly E. Engelhardt, Christopher R. Minshew, Nancy J. Williams, Diane L. TI Making Inferences: Comprehension of Physical Causality, Intentionality, and Emotions in Discourse by High-Functioning Older Children, Adolescents, and Adults with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Inference; Theory of mind; Emotion; Language ID STRANGE STORIES TEST; ASPERGER-SYNDROME; READING-COMPREHENSION; SPECTRUM DISORDER; CONFIDENCE-INTERVALS; REVISED VERSION; BAYES FACTORS; EFFECT SIZES; MIND; LANGUAGE AB Studies investigating inferential reasoning in autism spectrum disorder (ASD) have focused on the ability to make socially-related inferences or inferences more generally. Important variables for intervention planning such as whether inferences depend on physical experiences or the nature of social information have received less consideration. A measure of bridging inferences of physical causation, mental states, and emotional states was administered to older children, adolescents, and adults with and without ASD. The ASD group had more difficulty making inferences, particularly related to emotional understanding. Results suggest that individuals with ASD may not have the stored experiential knowledge that specific inferences depend upon or have difficulties accessing relevant experiences due to linguistic limitations. Further research is needed to tease these elements apart. C1 [Bodner, Kimberly E.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. [Engelhardt, Christopher R.] Univ Missouri, Dept Hlth Psychol, Columbia, MO 65211 USA. [Engelhardt, Christopher R.] Thompson Ctr Autism & Neurodev Disorders, Columbia, MO 65211 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Williams, Diane L.] Duquesne Univ, Dept Speech Language Pathol, Rangos Sch Hlth Sci, Pittsburgh, PA 15282 USA. [Bodner, Kimberly E.; Minshew, Nancy J.; Williams, Diane L.] Univ Pittsburgh, Sch Med, NIH, Autism Ctr Excellence, Pittsburgh, PA USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Williams, DL (reprint author), Duquesne Univ, Dept Speech Language Pathol, Rangos Sch Hlth Sci, Fisher Hall 409,600 Forbes Ave, Pittsburgh, PA 15282 USA. EM kimberly.bodner@mail.mizzou.edu; engelhardtc@health.missouri.edu; minshewnj@upmc.edu; williamsd2139@duq.edu RI Williams, Diane/B-4128-2017 FU National Institute of Child Health and Human Development (NICHD) [HD055748]; National Institute on Deafness and other Communication Disorders (NIDCD) [K23DC006691] FX We acknowledge the support of the National Institute of Child Health and Human Development (NICHD) [HD055748, an Autism Center of Excellence, to N.J.M.]; and, the National Institute on Deafness and other Communication Disorders (NIDCD) [K23DC006691 to D.L.W.]. We are grateful to the participants and families who generously gave of their time and effort to this study. We acknowledge the contribution of Amanda Brening, Kelsey Woods, and Maureen McAniff in the development of the PIT. KEB would like to thank Denis McCarthy for his guidance and feedback on the development of the psychometric properties of the PIT. We thank Rob Mason for his contribution of stimuli that were important in the developmental process. NR 60 TC 2 Z9 2 U1 7 U2 29 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD SEP PY 2015 VL 45 IS 9 BP 2721 EP 2733 DI 10.1007/s10803-015-2436-3 PG 13 WC Psychology, Developmental SC Psychology GA CQ4AH UT WOS:000360545800006 PM 25821925 ER PT J AU Gaca, AO Kudrin, P Colomer-Winter, C Beljantseva, J Liu, KQ Anderson, B Wang, JD Rejman, D Potrykus, K Cashel, M Hauryliuk, V Lemos, JA AF Gaca, Anthony O. Kudrin, Pavel Colomer-Winter, Cristina Beljantseva, Jelena Liu, Kuanqing Anderson, Brent Wang, Jue D. Rejman, Dominik Potrykus, Katarzyna Cashel, Michael Hauryliuk, Vasili Lemos, Jose A. TI From (p)ppGpp to (pp)pGpp: Characterization of Regulatory Effects of pGpp Synthesized by the Small Alarmone Synthetase of Enterococcus faecalis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; STRINGENT RESPONSE; STAPHYLOCOCCUS-AUREUS; BACILLUS-SUBTILIS; REL PROTEINS; STREPTOCOCCUS-EQUISIMILIS; GUANOSINE TETRAPHOSPHATE; DIFFERENTIAL REGULATION; FUNCTIONAL-ANALYSIS; CRITICAL COMPONENT AB The bacterial stringent response (SR) is a conserved stress tolerance mechanism that orchestrates physiological alterations to enhance cell survival. This response is mediated by the intracellular accumulation of the alarmones pppGpp and ppGpp, collectively called (p) ppGpp. In Enterococcus faecalis, (p) ppGpp metabolism is carried out by the bifunctional synthetase/hydrolase E. faecalis Rel (Rel(Ef)) and the small alarmone synthetase (SAS) RelQ(Ef). Although Rel is the main enzyme responsible for SR activation in Firmicutes, there is emerging evidence that SASs can make important contributions to bacterial homeostasis. Here, we showed that RelQ(Ef) synthesizes ppGpp more efficiently than pppGpp without the need for ribosomes, tRNA, or mRNA. In addition to (p) ppGpp synthesis from GDP and GTP, RelQ(Ef) also efficiently utilized GMP to form GMP 3'-diphosphate (pGpp). Based on this observation, we sought to determine if pGpp exerts regulatory effects on cellular processes affected by (p) ppGpp. We found that pGpp, like (p) ppGpp, strongly inhibits the activity of E. faecalis enzymes involved in GTP biosynthesis and, to a lesser extent, transcription of rrnB by Escherichia coli RNA polymerase. Activation of E. coli RelA synthetase activity was observed in the presence of both pGpp and ppGpp, while RelQ(Ef) was activated only by ppGpp. Furthermore, enzymatic activity of RelQ(Ef) is insensitive to relacin, a (p) ppGpp analog developed as an inhibitor of "long" RelA/SpoT homolog (RSH) enzymes. We conclude that pGpp can likely function as a bacterial alarmone with target-specific regulatory effects that are similar to what has been observed for (p) ppGpp. IMPORTANCE Accumulation of the nucleotide second messengers (p) ppGpp in bacteria is an important signal regulating genetic and physiological networks contributing to stress tolerance, antibiotic persistence, and virulence. Understanding the function and regulation of the enzymes involved in (p) ppGpp turnover is therefore critical for designing strategies to eliminate the protective effects of this molecule. While characterizing the (p) ppGpp synthetase RelQ of Enterococcus faecalis (RelQ(Ef)), we found that, in addition to (p) ppGpp, RelQ(Ef) is an efficient producer of pGpp (GMP 3'-diphosphate). In vitro analysis revealed that pGpp exerts complex, target-specific effects on processes known to be modulated by (p) ppGpp. These findings provide a new regulatory feature of RelQ(Ef) and suggest that pGpp may represent a new member of the (pp) pGpp family of alarmones. C1 [Gaca, Anthony O.; Colomer-Winter, Cristina; Lemos, Jose A.] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA. [Gaca, Anthony O.; Colomer-Winter, Cristina; Lemos, Jose A.] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Kudrin, Pavel; Beljantseva, Jelena; Hauryliuk, Vasili] Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia. [Liu, Kuanqing; Anderson, Brent; Wang, Jue D.] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. [Rejman, Dominik] Acad Sci Czech Republ Vvi, Inst Organ Chem & Biochem, Prague, Czech Republic. [Potrykus, Katarzyna] Univ Gdansk, Dept Mol Biol, PL-80952 Gdansk, Poland. [Potrykus, Katarzyna; Cashel, Michael] Eunice Kennedy Shriver NICHD, Sect Mol Regulat, Program Genom Dev, NIH, Bethesda, MD USA. [Hauryliuk, Vasili] Umea Univ, Dept Mol Biol, Univ Hosp Area, Umea, Sweden. [Hauryliuk, Vasili] Umea Univ, Lab Mol Infect Med Sweden, Univ Hosp Area, Umea, Sweden. RP Hauryliuk, V (reprint author), Univ Tartu, Inst Technol, Ulikooli 18, EE-50090 Tartu, Estonia. EM vasili.hauryliuk@umu.se; jose_lemos@urmc.rochester.edu RI Rejman, Dominik/D-6901-2011; OI Gaca, Anthony/0000-0003-3476-7034; Hauryliuk, Vasili/0000-0003-2389-5057; Colomer Winter, Cristina/0000-0003-0103-4977 FU NIDCR training program in oral sciences [T90 DE021985]; NIH [R01GM084003]; Kennedy Shriver National Institute of Child Health and Human Development intramural program of the National Institutes of Health; Polish National Science Center [DEC-2013/10/E/NZ1/00657]; Czech Science Foundation [15-11711S]; European Regional Development Fund through the Centre of Excellence in Chemical Biology, Estonian Science Foundation [ETF9012, PUT37]; Ragnar Soderberg Foundation; Swedish Research Council; Kempe Foundation; Umea University FX A.O.G. was supported by the NIDCR training program in oral sciences, grant T90 DE021985. J.D.W. was supported by NIH grant R01GM084003. M.C. was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural program of the National Institutes of Health. K.P. was supported by grant DEC-2013/10/E/NZ1/00657 from the Polish National Science Center. D.R. was supported by funds from the Czech Science Foundation, grant 15-11711S. V.H. was supported by funds from the European Regional Development Fund through the Centre of Excellence in Chemical Biology, Estonian Science Foundation grants (ETF9012 and PUT37), the Ragnar Soderberg Foundation, the Swedish Research Council, the Kempe Foundation, and Umea University. NR 67 TC 10 Z9 10 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2015 VL 197 IS 18 BP 2908 EP 2919 DI 10.1128/JB.00324-15 PG 12 WC Microbiology SC Microbiology GA CQ6KH UT WOS:000360712700002 PM 26124242 ER PT J AU Brawner, CA Shafiq, A Aldred, HA Ehrman, JK Leifer, ES Selektor, Y Tita, C Velez, M Williams, CT Schairer, JR Lanfear, DE Keteyian, SJ AF Brawner, Clinton A. Shafiq, Ali Aldred, Heather A. Ehrman, Jonathan K. Leifer, Eric S. Selektor, Yelena Tita, Cristina Velez, Mauricio Williams, Celeste T. Schairer, John R. Lanfear, David E. Keteyian, Steven J. TI Comprehensive Analysis of Cardiopulmonary Exercise Testing and Mortality in Patients With Systolic Heart Failure: The Henry Ford Hospital Cardiopulmonary Exercise Testing (FIT-CPX) Project SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Cardiomyopathy; survival; prognosis; exercise test ID PEAK OXYGEN-CONSUMPTION; PROGNOSTIC VALUE; CARDIAC TRANSPLANTATION; DILATED CARDIOMYOPATHY; VENTILATORY RESPONSE; RISK STRATIFICATION; ELDERLY-PATIENTS; ASSOCIATION; INDEX; RECOMMENDATIONS AB Background: Many studies have shown a strong association between numerous variables from a cardiopulmonary exercise (CPX) test and prognosis in patients with heart failure with reduced ejection fraction (HFrEF). However, few studies have compared the prognostic value of a majority of these variables simultaneously, so controversy remains regarding optimal interpretation. Methods and Results: This was a retrospective analysis of patients with BFrEF (n = 1,201; age = 55 +/- 13 y; 33% female) and a CPX test from 1997 to 2010. Thirty variables from a CPX test were considered in separate adjusted Cox regression analyses to describe the strength of the relation of each to a composite end point of all-cause mortality, left ventricular assist device implantation, or heart transplantation. During a median follow-up of 3.8 years, there were 577 (48.0%) events. The majority of variables were highly significant (P < .001). Among these, percentage of predicted maximum (V)over dotO(2) (ppM(V)over dotO(2); Wald = 203; P < .001; C-index = 0.73). was similar to V-E-VCO2 slope (Wald = 201; P < .001; C = 0.72) and peak (V)over dotO(2) (Wald = 161; P <.001; C = 0.72). In addition, there was no significant interaction observed for peak respiratory exchange ratio <1 vs >= 1. Conclusions: Consistent with prior studies, many CPX test variables were strongly associated with prognosis in patients with HFrEF. The choice of which variable to use is up to the clinician. Renewed attention should be given to ppM(V)over dotO(2), which appears to be highly predictive of survival in these patients. C1 [Brawner, Clinton A.; Aldred, Heather A.; Ehrman, Jonathan K.; Selektor, Yelena; Tita, Cristina; Velez, Mauricio; Williams, Celeste T.; Schairer, John R.; Lanfear, David E.; Keteyian, Steven J.] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA. [Shafiq, Ali] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Leifer, Eric S.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Brawner, CA (reprint author), Henry Ford Hosp, Prevent Cardiol, 6525 Second Ave, Detroit, MI 48202 USA. EM cbrawne1@hfhs.org NR 38 TC 2 Z9 2 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD SEP PY 2015 VL 21 IS 9 BP 710 EP 718 DI 10.1016/j.cardfai1.2015.06.001 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ7JD UT WOS:000360778000005 PM 26067685 ER PT J AU Yu, PP Agbaegbu, C Malide, DA Wu, XF Katagiri, Y Hammer, JA Geller, HM AF Yu, Panpan Agbaegbu, Chinyere Malide, Daniela A. Wu, Xufeng Katagiri, Yasuhiro Hammer, John A. Geller, Herbert M. TI Cooperative interactions of LPPR family members in membrane localization and alteration of cellular morphology SO JOURNAL OF CELL SCIENCE LA English DT Article DE Membrane protrusion; Protein-protein interaction; Filopodia; Actin ID LIPID PHOSPHATE PHOSPHATASES; PROTEIN; GROWTH; BRAIN; PRG-1 AB The lipid phosphate phosphatase-related proteins (LPPRs), also known as plasticity-related genes (PRGs), are classified as a new brain-enriched subclass of the lipid phosphate phosphatase (LPP) superfamily. They induce membrane protrusions, neurite outgrowth or dendritic spine formation in cell lines and primary neurons. However, the exact roles of LPPRs and the mechanisms underlying their effects are not certain. Here, we present the results of a large-scale proteome analysis to determine LPPR1-interacting proteins using co-immunoprecipitation coupled to mass spectrometry. We identified putative LPPR1-binding proteins involved in various biological processes. Most interestingly, we identified the interaction of LPPR1 with its family member LPPR3, LPPR4 and LPPR5. Their interactions were characterized by co-immunoprecipitation and colocalization analysis using confocal and super-resolution microscopy. Moreover, co-expressing two LPPR members mutually elevated their protein levels, facilitated their plasma membrane localization and resulted in an increased induction of membrane protrusions as well as the phosphorylation of S6 ribosomal protein. Taken together, we revealed a new functional cooperation between LPPR family members and discovered for the first time that LPPRs likely exert their function through forming complex with its family members. C1 [Yu, Panpan; Agbaegbu, Chinyere; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Yu, Panpan] Jinan Univ, Guangdong Hongkong Macau Inst CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China. [Agbaegbu, Chinyere] Georgetown Univ, Interdisciplinary Program Neurosci, Washington, DC USA. [Malide, Daniela A.] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Wu, Xufeng; Hammer, John A.] NHLBI, Mol Cell Biol Sect, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. RP Yu, PP (reprint author), NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM yupanpan21@gmail.com; geller@helix.nih.gov FU Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health; National Instiutes of Health [R01 NS064250-05, T32 NS041218] FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. C.A. was supported by the National Instiutes of Health [grant numbers R01 NS064250-05 to Dr Jeffrey S. Urbach and T32 NS041218 to Georgetown University]. Deposited in PMC for release after 12 months. NR 22 TC 2 Z9 2 U1 2 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD SEP 1 PY 2015 VL 128 IS 17 BP 3210 EP 3222 DI 10.1242/jcs.169789 PG 13 WC Cell Biology SC Cell Biology GA CQ6LL UT WOS:000360715800006 PM 26183180 ER PT J AU Tonietto, M Veronese, M Rizzo, G Zanotti-Fregonara, P Lohith, TG Fujita, M Zoghbi, SS Bertoldo, A AF Tonietto, Matteo Veronese, Mattia Rizzo, Gaia Zanotti-Fregonara, Paolo Lohith, Talakad G. Fujita, Masahiro Zoghbi, Sami S. Bertoldo, Alessandra TI Improved models for plasma radiometabolite correction and their impact on kinetic quantification in PET studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain imaging; kinetic modeling; mathematical modeling; positron emission tomography; receptor imaging ID TEST-RETEST REPRODUCIBILITY; HUMAN BRAIN; HUMANS; LIGAND; RECEPTORS; BINDING; RADIOLIGAND; RADIOTRACER; DOPAMINE AB The quantification of dynamic positron emission tomography studies performed with arterial sampling usually requires correcting the input function for the presence of radiometabolites by using a model of the plasma parent fraction (PPf). Here, we show how to include the duration of radioligand injection in the PPf model formulations to achieve a more physiologic description of the plasma measurements. This formulation (here called convoluted model) was tested on simulated data and on three datasets with different parent kinetics: [C-11]NOP-1A, [C-11]MePPEP, and [C-11](R)-rolipram. Results showed that convoluted PPf models better described the fraction of unchanged parent in the plasma compared with standard models for all three datasets (weighted residuals sum of squares up to 25% lower). When considering the effect on tissue quantification, the overall impact on the total volume of distribution (V-T) was low. However, the impact was significant and radioligand-dependent on the binding potential (BP) and the microparameters (K-1, k(2), k(3), and k(4)). Simulated data confirmed that quantification is sensitive to different degrees to PPf model misspecification. Including the injection duration allows obtaining a more accurate correction of the input function for the presence of radiometabolites and this yields a more reliable quantification of the tissue parameters. C1 [Tonietto, Matteo; Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn DEI, I-35131 Padua, Italy. [Veronese, Mattia] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Zanotti-Fregonara, Paolo; Lohith, Talakad G.; Fujita, Masahiro; Zoghbi, Sami S.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Zanotti-Fregonara, Paolo] Univ Bordeaux, CNRS, INCIA, UMR 5287, Talence, France. RP Bertoldo, A (reprint author), Univ Padua, Dept Informat Engn DEI, Via G Gradenigo 6-B, I-35131 Padua, Italy. EM bertoldo@dei.unipd.it RI Veronese, Mattia/A-6012-2013; Rizzo, Gaia/A-8697-2013; OI Veronese, Mattia/0000-0003-3562-0683; Rizzo, Gaia/0000-0001-7272-8576; Tonietto, Matteo/0000-0001-9591-5710 FU Intramural Research Program, National Institute of Mental Health [MH002795-13]; UK Medical Research Council programme [G1100809/1] FX This work was supported in part by the Intramural Research Program, National Institute of Mental Health (MH002795-13), and by the UK Medical Research Council programme grant No. G1100809/1. Portions of this work were presented in preliminary form at the International Society of Nuclear Medicine meeting (Vancouver, 2013). NR 25 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2015 VL 35 IS 9 BP 1462 EP 1469 DI 10.1038/jcbfm.2015.61 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CQ6BN UT WOS:000360689500013 PM 25873424 ER PT J AU Saenz, C Reveiz, L Tisdale, JF AF Saenz, Carla Reveiz, Ludovic Tisdale, John F. TI Public titles of clinical trials should have ethics review SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Research ethics; Clinical trial registration; IRB review; Marketing; Bioethics; Bias AB A key aspect to guarantee that research with human subjects is ethical is being overlooked. Ethics review committees invest great effort examining the informed consent documents of research protocols to ensure that potential participants can provide consent validly and are not deluded into thinking that the experimental intervention they may sign up for is already known to be therapeutic. However, these efforts to avoid what is called the "therapeutic misconception" might be in vain if the title with which the studies are being introduced to the potential participants escapes ethics review. Research participants might be deceived by clinical trials entitled "novel therapy" when the point of the trial is precisely to find out whether the intervention at stake is therapeutic or not. Providing potential research participants with such misleading information hampers their ability to make informed decisions. The well-established scrutiny that ethics review committees exercise with regard to consent forms is limited if the registration of clinical trials, for which a public title is chosen, constitutes a process that is independent from the ethics review. In this article, we examine this problem, assess recent measures to integrate clinical trial registration with ethics review processes, and provide specific recommendations to solve the problem and ultimately enhance the accountability, transparency, and ethics of research with human subjects. (C) 2015 Pan American Health Organization. Published by Elsevier Inc. All rights reserved. C1 [Saenz, Carla; Reveiz, Ludovic] World Hlth Org, Pan Amer Hlth Org, Dept Knowledge Management Bioeth & Res, Washington, DC 20037 USA. [Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Saenz, C (reprint author), World Hlth Org, Pan Amer Hlth Org, Dept Knowledge Management Bioeth & Res, 525 23rd St NW, Washington, DC 20037 USA. EM saenzcar@paho.org FU World Health Organization [001] NR 10 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2015 VL 68 IS 9 BP 1105 EP 1107 DI 10.1016/j.jclinepi.2014.05.016 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CQ4TK UT WOS:000360597300021 PM 26279403 ER PT J AU Zhou, P Zhang, N Nussinov, R Ma, BY AF Zhou, Ping Zhang, Ning Nussinov, Ruth Ma, Buyong TI Defining the Domain Arrangement of the Mammalian Target of Rapamycin Complex Component Rictor Protein SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article; Proceedings Paper CT 7th Computational Structural Bioinformatics Workshop (CSBW) CY SEP 20, 2014 CL Newport Beach, CA DE mTOR; protein domain; protein-protein interactions; Raptor; Rictor ID T-LYMPHOPOIESIS; MTOR; PHOSPHORYLATION; RAPTOR; ACTIVATION; HOMOLOGY; CELLS; CLASSIFICATION; ASSOCIATION; SEQUENCES AB Mammalian target of rapamycin (mTOR) complexes play a pivotal role in the cell. Raptor and Rictor proteins interact with mTOR to form two distinct complexes, mTORC1 and mTORC2, respectively. While the domain structure of Raptor is known, current bioinformatics tools failed to classify the domains in Rictor. Here we focus on identifying specific domains in Rictor by searching for conserved regions. We scanned the pdb structural database and constructed three protein domain datasets. Next we carried out multiple pairwise sequence alignments of the proteins in the domain dataset. By analyzing the z-scores of Rictor sequence similarity to protein sequences in the dataset, we assigned the structural and functional domains of Rictor. We found that, like Raptor, Rictor also has HEAT and WD40 domains, which could be the common motif binding to mTORC. Rictor may also have pleckstrin homology domains, which mediate cellular localization and transmit signals to downstream targets, as well as a domain that is homologous to 50S protein L17 and human 39S protein L17. This putative ribosome binding domain could mediate mTORC2-ribosome interaction. C1 [Zhou, Ping; Zhang, Ning] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin, Peoples R China. [Zhou, Ping; Zhang, Ning] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China. [Nussinov, Ruth; Ma, Buyong] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Bldg 542, Frederick, MD 21702 USA. EM mabuyong@mail.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; Chinese NFSC [30772529]; 973 program [2011CB933100, 2010CB933900] FX The authors are funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. P.Z. and N.Z. thank Chinese NFSC grant 30772529 and 973 program grants 2011CB933100 and 2010CB933900. NR 33 TC 0 Z9 0 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PD SEP 1 PY 2015 VL 22 IS 9 BP 876 EP 886 DI 10.1089/cmb.2015.0103 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA CQ5RU UT WOS:000360664100008 PM 26176550 ER PT J AU Meany, HJ Seibel, NL Krailo, M Villaluna, D Chen, ZJ Gaynon, P Neglia, JP Park, JR Hutchinson, R Sato, JK Wells, RJ Woods, WG Reaman, G AF Meany, Holly J. Seibel, Nita L. Krailo, Mark Villaluna, Doojduen Chen, Zhengjia Gaynon, Paul Neglia, Joseph P. Park, Julie R. Hutchinson, Raymond Sato, Judith K. Wells, Robert J. Woods, William G. Reaman, Gregory TI Feasibility Study of a Novel Experimental Induction Protocol Combining B43-PAP (Anti-CD19) Immunotoxin With Standard Induction Chemotherapy in Children and Adolescents With Relapsed B-Lineage ALL: A Report From the Children's Oncology Group SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE anti-CD19 immunotoxin; immunotherapy; relapsed B-lineage ALL ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW RELAPSE; POKEWEED ANTIVIRAL PROTEIN; CANCER-GROUP; INTENSIVE CHEMOTHERAPY; MONOCLONAL-ANTIBODY; LYMPHOMA CELL; IN-VITRO; P-GP; THERAPY AB Background:B43-pokeweed antiviral protein (B43-PAP) is a high-affinity anti-CD19 immunotoxin that is capable of causing apoptotic death in B-lineage leukemic cells with a drug-resistant phenotype. B43-PAP exhibited in vivo antileukemic activity in preclinical studies as well as on a single-agent phase I clinical trial. This pediatric phase I/II study evaluated the toxicity profile and efficacy of B43-PAP immunotoxin in combination with standard induction chemotherapy in children and adolescents with relapsed CD19-positive B-lineage acute lymphoblastic leukemia (B-ALL). Pharmacokinetic profile and immunogenicity of B43-PAP were assessed.Experimental Design:B43-PAP in combination with standard 3 and 4-drug induction chemotherapy was administered on days 9-13 and 21-25 of a 28-day treatment course with vincristine, prednisone, l-asparaginase, daunomycin, and intrathecal methotrexate. Thirty patients with relapsed B-ALL were enrolled on study CCG-0957.Results:Grade III/IV nonhematologic dose-limiting toxicities were encountered in 4 patients evaluable for toxicity and included myalgias, motor dysfunction, pulmonary toxicity, and elevated liver transaminase. Dose-limiting toxicities occurred only with the 4-drug regimen. Fourteen patients achieved a complete remission at the end of induction among the 20 patients evaluable for response.Conclusions:B43-PAP in combination with standard induction chemotherapy can be safely administered and exhibits clinical antileukemic activity against relapsed B-ALL. C1 [Meany, Holly J.] George Washington Univ, Childrens Natl Med Ctr, Sch Med & Publ Hlth, Dept Pediat Hematol Oncol, Washington, DC USA. [Seibel, Nita L.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Reaman, Gregory] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Krailo, Mark] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Gaynon, Paul] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Villaluna, Doojduen] Childrens Oncol Grp, Arcadia, CA USA. [Sato, Judith K.] City Hope Natl Med Ctr, Dept Pediat, Duarte, CA 91010 USA. [Chen, Zhengjia] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Woods, William G.] Emory Univ, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorder Ctr, Atlanta, GA 30322 USA. [Neglia, Joseph P.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Park, Julie R.] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Hutchinson, Raymond] Univ Michigan, CS Mott Childrens Hosp, Pediat Hematol Oncol, Ann Arbor, MI 48109 USA. [Wells, Robert J.] Univ Texas MD Anderson Canc Ctr, Childrens Canc Hosp, Div Pediat, Houston, TX 77030 USA. RP Meany, HJ (reprint author), Childrens Natl Med Ctr, Dept Pediat Hematol Oncol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM hmeany@childrensnational.org FU NCTN Operation Center Grant [CA180886]; Statistics and Data Center Grant [CA98413]; NCTN Statistics and Data Center Grant [CA180899]; [CA98543] FX Supported by study grants CA98543 (Chair's Grant), CA180886 (NCTN Operation Center Grant), CA98413 (Statistics and Data Center Grant), CA180899 (NCTN Statistics and Data Center Grant). NR 45 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1524-9557 EI 1537-4513 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 2015 VL 38 IS 7 BP 299 EP 305 DI 10.1097/CJI.0000000000000088 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA CQ4QB UT WOS:000360588600006 PM 26261894 ER PT J AU Raval, DB Merideth, M Sloan, JL Braverman, NE Conway, RL Manoli, I Venditti, CP AF Raval, Donna B. Merideth, Melissa Sloan, Jennifer L. Braverman, Nancy E. Conway, Robert L. Manoli, Irini Venditti, Charles P. TI Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Review ID INBORN ERROR; MANAGEMENT; METABOLISM; ACIDURIA; DEFICIENCY; DIAGNOSIS; COBALAMIN; ACIDOSIS; PATIENT; MUT(-) AB Introduction Women with inherited metabolic disorders, including those with previously life-limiting conditions such as MMA, are reaching child-bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored. Methods Pregnancies affected by maternal MMA were ascertained through study 04-HG-0127 "Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders" (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed. Results Seventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut- (one cobalamin responsive, three non-responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5 % (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8 % (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57 % (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed. Conclusion Although there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population. C1 [Raval, Donna B.; Sloan, Jennifer L.; Manoli, Irini; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Raval, Donna B.] Medstar Washington Hosp Ctr, Dept Obstet & Gynecol, Maternal Fetal Med, Washington, DC USA. [Merideth, Melissa] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Braverman, Nancy E.] McGill Univ, Montreal Childrens Hosp Res Inst, Dept Human Genet & Pediat, Montreal, PQ, Canada. [Conway, Robert L.] Wayne State Univ, Sch Med, Dept Pediat, Div Genet Gen & Metabol Disorders,Childrens Hosp, Detroit, MI 48201 USA. RP Venditti, CP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 FU Intramural NIH HHS [ZIA HG200318-11] NR 21 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD SEP PY 2015 VL 38 IS 5 BP 839 EP 846 DI 10.1007/s10545-014-9802-8 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CQ2NC UT WOS:000360436700007 PM 25567501 ER PT J AU Ktena, YP Ramstad, T Baker, EH Sloan, JL Mannes, AJ Manoli, I Venditti, CP AF Ktena, Yiouli P. Ramstad, Trygg Baker, Eva H. Sloan, Jennifer L. Mannes, Andrew J. Manoli, Irini Venditti, Charles P. TI Propofol administration in patients with methylmalonic acidemia and intracellular cobalamin metabolism disorders: a review of theoretical concerns and clinical experiences in 28 patients SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article AB Background Methylmalonic acidemia and intracellular cobalamin metabolism disorders represent a heterogeneous group of inborn errors of metabolism. Most patients will require diagnostic and/or therapeutic procedures frequently requiring sedation or anesthetic management due to neurological and neurocognitive impairments. It has been stated that propofol is contraindicated in this population. We report our experience with propofol administration in a large series of patients. Methods Twenty eight patients (14 mut, seven cblC, three cblA, three cblB, one cblG) aged 2-35.6 years enrolled in a natural history study (ClinicalTrials.gov identifier: NCT00078078) and required anesthetics for 39 diagnostic or therapeutic procedures. Data were collected on the anesthetic technique, perianesthetic course, and adverse events related to propofol. Results Propofol was used as the sole induction agent in most cases (36/39) and as the primary maintenance agent in all cases. Infusion rates were 100-400 mcg kg(-1) min(-1) (mean = 214). Infusion duration was 60-325 min (mean = 158) and total doses ranged between 270-3610 mg (mean = 1217). Adverse events were recorded in two cases; neither appeared to be related to propofol administration. Conclusions Propofol is an effective, safe induction and maintenance agent for elective short procedures requiring anesthesia in patients with MMA and cobalamin metabolism disorders. Despite multiple comorbidities and propensity toward instability, those affected can receive anesthesia with an acceptable safety profile, if metabolically and hemodynamically stabilized prior to the event. Synopsis A review of the perianesthetic records of 28 patients with isolated MMA and intracellular cobalamin metabolism disorders suggests that propofol anesthesia can be administered safely to these patients, in the setting of metabolic stability. C1 [Ktena, Yiouli P.; Sloan, Jennifer L.; Manoli, Irini; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Ramstad, Trygg; Mannes, Andrew J.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 NR 0 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD SEP PY 2015 VL 38 IS 5 BP 847 EP 853 DI 10.1007/s10545-015-9816-x PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CQ2NC UT WOS:000360436700008 PM 25985870 ER PT J AU Zoon, KC Friedman, RM AF Zoon, Kathryn C. Friedman, Robert M. TI Samuel Baron (1928-2015) INMEMORIAM SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Biographical-Item C1 [Zoon, Kathryn C.] NIAID, NIH, Bethesda, MD 20892 USA. RP Zoon, KC (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD SEP 1 PY 2015 VL 35 IS 9 BP 667 EP 667 DI 10.1089/jir.2015.28999.sba PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CQ4QT UT WOS:000360590400001 PM 26280626 ER PT J AU Redeker, NS Anderson, R Bakken, S Corwin, E Docherty, S Dorsey, SG Heitkemper, M McCloskey, DJ Moore, S Pullen, C Rapkin, B Schiffman, R Waldrop-Valverde, D Grady, P AF Redeker, Nancy S. Anderson, Ruth Bakken, Suzanne Corwin, Elizabeth Docherty, Sharron Dorsey, Susan G. Heitkemper, Margaret McCloskey, Donna Jo Moore, Shirley Pullen, Carol Rapkin, Bruce Schiffman, Rachel Waldrop-Valverde, Drenna Grady, Patricia TI Advancing Symptom Science Through Use of Common Data Elements SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Cognition; fatigue; mood; pain; sleep disturbance; symptom management ID QUALITY-OF-LIFE; BREAST-CANCER; HEALTH AB BackgroundUse of common data elements (CDEs), conceptually defined as variables that are operationalized and measured in identical ways across studies, enables comparison of data across studies in ways that would otherwise be impossible. Although healthcare researchers are increasingly using CDEs, there has been little systematic use of CDEs for symptom science. CDEs are especially important in symptom science because people experience common symptoms across a broad range of health and developmental states, and symptom management interventions may have common outcomes across populations. PurposesThe purposes of this article are to (a) recommend best practices for the use of CDEs for symptom science within and across centers; (b) evaluate the benefits and challenges associated with the use of CDEs for symptom science; (c) propose CDEs to be used in symptom science to serve as the basis for this emerging science; and (d) suggest implications and recommendations for future research and dissemination of CDEs for symptom science. DesignThe National Institute of Nursing Research (NINR)-supported P20 and P30 Center directors applied published best practices, expert advice, and the literature to identify CDEs to be used across the centers to measure pain, sleep, fatigue, and affective and cognitive symptoms. FindingsWe generated a minimum set of CDEs to measure symptoms. ConclusionsThe CDEs identified through this process will be used across the NINR Centers and will facilitate comparison of symptoms across studies. We expect that additional symptom CDEs will be added and the list will be refined in future work. Clinical RelevanceSymptoms are an important focus of nursing care. Use of CDEs will facilitate research that will lead to better ways to assist people to manage their symptoms. C1 [Redeker, Nancy S.] Yale Univ, Sch Nursing, Nursing, New Haven, CT 06536 USA. [Anderson, Ruth] Univ N Carolina, Res, Chapel Hill, NC USA. [Bakken, Suzanne] Columbia Univ, Nursing, New York, NY USA. [Bakken, Suzanne] Columbia Univ, Biomed Informat, New York, NY USA. [Corwin, Elizabeth] Emory Univ, Res, Atlanta, GA 30322 USA. [Docherty, Sharron] Duke Univ, Durham, NC USA. [Dorsey, Susan G.] Univ Maryland, Dept Pain & Translat Symptom Sci, Baltimore, MD 21201 USA. [Heitkemper, Margaret] Univ Washington, Seattle, WA 98195 USA. [McCloskey, Donna Jo; Grady, Patricia] NINR, NIH, Bethesda, MD 20892 USA. [Moore, Shirley] Case Western Reserve Univ, Nursing, Cleveland, OH 44106 USA. [Moore, Shirley] Case Western Reserve Univ, Res, Cleveland, OH 44106 USA. [Pullen, Carol] Univ Nebraska Med Ctr, Omaha, NE USA. [Rapkin, Bruce] Albert Einstein Coll Med, Epidemiol & Populat Hlth, New York, NY USA. [Schiffman, Rachel] Univ Wisconsin, Res, Milwaukee, WI 53201 USA. [Waldrop-Valverde, Drenna] Emory Univ, Atlanta, GA 30322 USA. RP Redeker, NS (reprint author), Yale Univ, Sch Nursing, POB 27399, West Haven, CT 06516 USA. EM nancy.redeker@yale.edu RI Redeker, Nancy/Q-8252-2016 OI Redeker, Nancy/0000-0001-7817-2708 FU [P30NR014134]; [P30NR010677]; [P20NR01426]; [P30NR011396]; [P30NR014129]; [P30NR011400]; [P30NR014139-01] FX This work was supported through the following grants: P30NR014134 (Waldrop-Valverde, principal investigator [PI]); P30NR010677 (Bakken, PI); P20NR01426 (Redeker, PI); P30NR011396 (Dorsey, PI); P30NR014129 (Dorsey, PI); P30NR011400 (Heitkemper, PI); and P30NR014139-01 (Anderson/Docherty, PI). NR 31 TC 7 Z9 7 U1 12 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD SEP PY 2015 VL 47 IS 5 BP 379 EP 388 DI 10.1111/jnu.12155 PG 10 WC Nursing SC Nursing GA CQ7PV UT WOS:000360797000002 PM 26250061 ER PT J AU Hey-Mogensen, M Gram, M Jensen, MB Lund, MT Hansen, CN Scheibye-Knudsen, M Bohr, VA Dela, F AF Hey-Mogensen, Martin Gram, Martin Jensen, Martin Borch Lund, Michael Taulo Hansen, Christina Neigaard Scheibye-Knudsen, Morten Bohr, Vilhelm A. Dela, Flemming TI A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID AGE-RELATED-CHANGES; RESPIRATORY-CHAIN FUNCTION; OXYGEN SPECIES PRODUCTION; ELECTRON-TRANSPORT CHAIN; MODULAR KINETIC-ANALYSIS; INDUCED OXIDATIVE STRESS; H2O2 RELEASE; IN-VIVO; PHYSICAL-ACTIVITY; SUPEROXIDE-PRODUCTION AB Despite numerous studies, there is no consensus about whether mitochondrial function is altered with increased age. The novelty of the present study is the determination of mitochondrial function at submaximal activity rates, which is more physiologically relevant than the ex vivo functionality protocols used previously. Muscle biopsies were taken from 64 old or young male subjects (aged 60-70 or 20-30years). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for the isolation of mitochondria and subsequent measurements of DNA repair, anti-oxidant capacity and mitochondrial protein levels (complexes I-V). Mitochondrial function was determined by simultaneous measurement of oxygen consumption, membrane potential and hydrogen peroxide emission using pyruvate+malate (PM) or succinate+rotenone (SR) as substrates. Proton leak was lower in aged subjects when determined at the same membrane potential and was unaffected by training status. State 3 respiration was lower in aged untrained subjects. This effect, however, was alleviated in aged trained subjects. H2O2 emission with PM was higher in aged subjects, and was exacerbated by training, although it was not changed when using SR. However, with a higher manganese superoxide dismuthase content, the trained aged subjects may actually have lower or similar mitochondrial superoxide emission compared to the untrained subjects. We conclude that ageing and the physical activity level in aged subjects are both related to changes in the intrinsic functionality of the mitochondrion in skeletal muscle. Both of these changes could be important factors in determining the metabolic health of the aged skeletal muscle cell. C1 [Hey-Mogensen, Martin; Gram, Martin; Lund, Michael Taulo; Hansen, Christina Neigaard; Dela, Flemming] Univ Copenhagen, Dept Biomed Sci, Ctr Hlth Aging, Xlab, DK-2200 Copenhagen, Denmark. [Jensen, Martin Borch; Bohr, Vilhelm A.] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, DK-2200 Copenhagen, Denmark. [Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Dela, F (reprint author), Univ Copenhagen, Dept Biomed Sci, Ctr Hlth Aging, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark. EM fdela@sund.ku.dk OI Scheibye-Knudsen, Morten/0000-0002-6637-1280; Family Name Deactivated, Given Names Deactivated/0000-0003-4512-3314; Gram, Martin/0000-0002-0350-3506 FU Danish council for Independent Research - Medical Sciences; AP Moller Foundation - Fonden til Laegevidenskabens Fremme; Nordea Foundation (Centre for Healthy Aging) FX The work was supported financially by The Danish council for Independent Research - Medical Sciences, The AP Moller Foundation - Fonden til Laegevidenskabens Fremme and the Nordea Foundation (Centre for Healthy Aging). NR 62 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2015 VL 593 IS 17 BP 3991 EP 4010 DI 10.1113/JP270204 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CQ7GB UT WOS:000360769900023 PM 26096709 ER PT J AU Nicklett, EJ Rostant, OS Schantz, K Evans, L AF Nicklett, E. J. Rostant, O. S. Schantz, K. Evans, L. TI Neighborhood Context and Recurrent Falls among Older Adults Aging in Place SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT 4th Chinese Congress on Gerontology and Health Industry (CCGI) CY SEP 11-13, 2015 CL Suzhou, PEOPLES R CHINA SP Chinese Geriatr Soc C1 [Nicklett, E. J.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Rostant, O. S.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Schantz, K.; Evans, L.] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. EM enicklet@umich.edu; ola.rostant@nih.gov; schantka@umich.edu; laevans@umich.edu NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2015 VL 63 SU 2 SI SI MA P5 BP S324 EP S324 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CQ5DR UT WOS:000360624000007 ER PT J AU Antignac, C Calvet, JP Germino, GG Grantham, JJ Guay-Woodford, LM Harris, PC Hildebrandt, F Peters, DJM Somlo, S Torres, VE Walz, G Zhou, J Yu, ASL AF Antignac, Corinne Calvet, James P. Germino, Gregory G. Grantham, Jared J. Guay-Woodford, Lisa M. Harris, Peter C. Hildebrandt, Friedhelm Peters, Dorien J. M. Somlo, Stefan Torres, Vicente E. Walz, Gerd Zhou, Jing Yu, Alan S. L. TI The Future of Polycystic Kidney Disease Research-As Seen By the 12 Kaplan Awardees SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PLANAR CELL POLARITY; PROXIMAL TUBULAR INJURY; AUTOSOMAL-DOMINANT; CYST FORMATION; PRIMARY CILIA; MOUSE MODEL; ATUBULAR GLOMERULI; INTERSTITIAL NEPHRITIS; SIGNALING PATHWAYS; 2-HIT MODEL AB Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham's retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research. C1 [Antignac, Corinne] Paris Descartes Sorbonne Paris Cite Univ, Lab Inherited Kidney Dis, Natl Inst Hlth & Med Res, Paris, France. [Antignac, Corinne] Hop Necker Enfants Malad, Imagine Inst, Paris, France. [Antignac, Corinne] Hop Necker Enfants Malad, Dept Genet, Paris, France. [Calvet, James P.; Grantham, Jared J.; Yu, Alan S. L.] Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66160 USA. [Germino, Gregory G.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. [Guay-Woodford, Lisa M.] Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA. [Harris, Peter C.; Torres, Vicente E.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Peters, Dorien J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Somlo, Stefan] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Somlo, Stefan] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Walz, Gerd] Univ Med Ctr Freiburg, Dept Med, Div Renal, Freiburg, Germany. [Zhou, Jing] Harvard Univ, Brigham & Womens Hosp, Harvard Ctr Polycyst Kidney Dis Res, Renal Div,Dept Med,Med Sch, Boston, MA 02115 USA. RP Yu, ASL (reprint author), Univ Kansas, Med Ctr, Kidney Inst, WHE 6018,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM JCALVET@kumc.edu; ayu@kumc.edu FU PKD Foundation; Otsuka Pharmaceuticals; Recanati-Kaplan Foundation FX We wish to thank the sponsors of the 2014 Grantham Symposium for their generous support: The PKD Foundation, Otsuka Pharmaceuticals, and the Recanati-Kaplan Foundation. NR 111 TC 7 Z9 7 U1 3 U2 11 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2015 VL 26 IS 9 BP 2081 EP 2095 DI 10.1681/ASN.2014121192 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA CQ4NR UT WOS:000360582100006 PM 25952256 ER PT J AU Camp, JV Bagci, U Chu, YK Squier, B Fraig, M Uriarte, SM Guo, HX Mollura, DJ Jonsson, CB AF Camp, Jeremy V. Bagci, Ulas Chu, Yong-Kyu Squier, Brendan Fraig, Mostafa Uriarte, Silvia M. Guo, Haixun Mollura, Daniel J. Jonsson, Colleen B. TI Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE LUNG INJURY; MONOCLONAL-ANTIBODY KI-67; INNATE IMMUNE-RESPONSES; ACID-BINDING LECTINS; SMALL ANIMAL-MODELS; GENE-EXPRESSION; ALVEOLAR MACROPHAGES; PULMONARY INFECTION; EXTRACELLULAR TRAPS; EPITHELIAL-CELLS AB Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [F-18] fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCE Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs. C1 [Camp, Jeremy V.; Uriarte, Silvia M.; Jonsson, Colleen B.] Univ Louisville, Dept Microbiol & Immunol, Louisville, KY 40292 USA. [Camp, Jeremy V.; Chu, Yong-Kyu; Guo, Haixun; Jonsson, Colleen B.] Univ Louisville, Ctr Predict Med Infect Dis & Biodef, Louisville, KY 40292 USA. [Squier, Brendan] Univ Louisville, Sch Dent, Louisville, KY 40292 USA. [Fraig, Mostafa; Uriarte, Silvia M.] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Fraig, Mostafa] Univ Louisville, Dept Pathol, Louisville, KY 40292 USA. [Guo, Haixun] Univ Louisville, Dept Radiol, Louisville, KY 40292 USA. [Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Jonsson, CB (reprint author), Univ Louisville, Dept Microbiol & Immunol, Louisville, KY 40292 USA. EM cjonsson@utk.edu RI Fraig, Mostafa/I-1670-2016; OI Fraig, Mostafa/0000-0003-1119-3672; Bagci, Ulas/0000-0001-7379-6829 FU Commonwealth of Kentucky as a Clinical and Translational Science Pilot Project Program at the University of Louisville; U.S. National Institutes of Health [NIH]; Pfizer Inc.; Center for Infectious Disease Imaging in the Intramural Research Program of the NIH FX Financial support was provided in part by the Commonwealth of Kentucky as a Clinical and Translational Science Pilot Project Program at the University of Louisville (to C.B.J.), the Clinical Research Training Program (a public-private partnership supported jointly by the U.S. National Institutes of Health [NIH] and Pfizer Inc. via a grant to the Foundation for NIH from Pfizer Inc.), and the Center for Infectious Disease Imaging in the Intramural Research Program of the NIH. NR 108 TC 1 Z9 1 U1 2 U2 12 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 SEP PY 2015 VL 89 IS 17 BP 8733 EP 8748 DI 10.1128/JVI.00817-15 PG 16 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900008 PM 26063430 ER PT J AU Gohain, N Tolbert, WD Acharya, P Yu, L Liu, TY Zhao, PS Orlandi, C Visciano, ML Kamin-Lewis, R Sajadi, MM Martin, L Robinson, JE Kwong, PD DeVico, AL Ray, K Lewis, GK Pazgier, M AF Gohain, Neelakshi Tolbert, William D. Acharya, Priyamvada Yu, Lei Liu, Tongyun Zhao, Pingsen Orlandi, Chiara Visciano, Maria L. Kamin-Lewis, Roberta Sajadi, Mohammad M. Martin, Loic Robinson, James E. Kwong, Peter D. DeVico, Anthony L. Ray, Krishanu Lewis, George K. Pazgier, Marzena TI Cocrystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1 SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-MEDIATED CYTOTOXICITY; HUMAN MONOCLONAL-ANTIBODY; VACCINE EFFICACY TRIAL; ENVELOPE GLYCOPROTEIN; ANTIGENIC PROPERTIES; ADCC ACTIVITY; INFECTION; CD4; MACAQUES AB Accumulating evidence indicates a role for Fc receptor (FcR)-mediated effector functions of antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), in prevention of human immunodeficiency virus type 1 (HIV-1) acquisition and in postinfection control of viremia. Consequently, an understanding of the molecular basis for Env epitopes that constitute effective ADCC targets is of fundamental interest for humoral anti-HIV-1 immunity and for HIV-1 vaccine design. A substantial portion of FcR effector function of potentially protective anti-HIV-1 antibodies is directed toward nonneutralizing, transitional, CD4-inducible (CD4i) epitopes associated with the gp41-reactive region of gp120 (cluster A epitopes). Our previous studies defined the A32-like epitope within the cluster A region and mapped it to the highly conserved and mobile layers 1 and 2 of the gp120 inner domain within the C1-C2 regions of gp120. Here, we elucidate additional cluster A epitope structures, including an A32-like epitope, recognized by human monoclonal antibody (MAb) N60-i3, and a hybrid A32-C11-like epitope, recognized by rhesus macaque MAb JR4. These studies define for the first time a hybrid A32-C11-like epitope and map it to elements of both the A32-like subregion and the seven-layered beta-sheet of the gp41-interactive region of gp120. These studies provide additional evidence that effective antibody-dependent effector function in the cluster A region depends on precise epitope targeting-a combination of epitope footprint and mode of antibody attachment. All together these findings help further an understanding of how cluster A epitopes are targeted by humoral responses. IMPORTANCE HIV/AIDS has claimed the lives of over 30 million people. Although antiretroviral drugs can control viral replication, no vaccine has yet been developed to prevent the spread of the disease. Studies of natural HIV-1 infection, simian immunodeficiency virus (SIV)- or simian-human immunodeficiency virus (SHIV)-infected nonhuman primates (NHPs), and HIV-1-infected humanized mouse models, passive transfer studies in infants born to HIV-infected mothers, and the RV144 clinical trial have linked FcR-mediated effector functions of anti-HIV-1 antibodies with postinfection control of viremia and/or blocking viral acquisition. With this report we provide additional definition of the molecular determinants for Env antigen engagement which lead to effective antibody-dependent effector function directed to the nonneutralizing CD4-dependent epitopes in the gp41-reactive region of gp120. These findings have important implications for the development of an effective HIV-1 vaccine. C1 [Gohain, Neelakshi; Tolbert, William D.; Yu, Lei; Liu, Tongyun; Zhao, Pingsen; Orlandi, Chiara; Visciano, Maria L.; Kamin-Lewis, Roberta; Sajadi, Mohammad M.; DeVico, Anthony L.; Lewis, George K.; Pazgier, Marzena] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Gohain, Neelakshi; Tolbert, William D.; Ray, Krishanu; Pazgier, Marzena] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Acharya, Priyamvada; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Yu, Lei; Liu, Tongyun; Zhao, Pingsen; Orlandi, Chiara; Visciano, Maria L.; Kamin-Lewis, Roberta; Lewis, George K.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Sajadi, Mohammad M.; DeVico, Anthony L.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Sajadi, Mohammad M.] VA Maryland Hlth Care Ctr, Med Care Clin Ctr, Baltimore, MD USA. [Martin, Loic] CEA, IBiTecS, Serv Ingn Mol Prot, Gif Sur Yvette, France. [Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. RP Pazgier, M (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. EM mpazgier@ihv.umaryland.edu RI Gohain, Neelakshi/P-7493-2015; MARTIN, loic/E-1627-2011 OI MARTIN, loic/0000-0002-7940-2955 FU Bill and Melinda Gates Foundation [OPP1033109]; National Institute of Allergy and Infectious Diseases (NIAID)/NIH [R01 AI-084830, R01 AI-087181, K25-AI087968, 5K23AI084580-04]; Intramural Research Program of the VRC, National Institute of Allergy and Infectious Diseases, NIH; U.S. Department of Energy Office of Biological and Environmental Research; National Institutes of Health (NIH) National Center for Research Resources, Biomedical Technology Program [P41RR001209]; National Institute of General Medical Sciences FX Support for this work was provided by a grant from The Bill and Melinda Gates Foundation (OPP1033109 to G.K.L.), by National Institute of Allergy and Infectious Diseases (NIAID)/NIH grants R01 AI-084830 and R01 AI-087181 (to G.K.L), K25-AI087968 (to K.R.), and 5K23AI084580-04 (to M.M.S.), and by the Intramural Research Program of the VRC, National Institute of Allergy and Infectious Diseases, NIH. Crystallographic data were collected at the Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of the SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the U.S. Department of Energy Office of Biological and Environmental Research, by the National Institutes of Health (NIH) National Center for Research Resources, Biomedical Technology Program (P41RR001209), and by the National Institute of General Medical Sciences. NR 72 TC 13 Z9 13 U1 1 U2 7 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 SEP PY 2015 VL 89 IS 17 BP 8840 EP 8854 DI 10.1128/JVI.01232-15 PG 15 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900017 PM 26085162 ER PT J AU Geoghegan, JL Tan, LV Kuhnert, D Halpin, RA Lin, XD Simenauer, A Akopov, A Das, SR Stockwell, TB Shrivastava, S Ngoc, NM Uyen, LTT Tuyen, NTK Thanh, TT Hang, VTT Qui, PT Hung, NT Khanh, TH Thinh, LQ Nhan, LNT Van, HMT Viet, DC Tuan, HM Viet, HL Hien, TT Chau, NVV Thwaites, G Grenfell, BT Stadler, T Wentworth, DE Holmes, EC Van Doorn, HR AF Geoghegan, Jemma L. Le Van Tan Kuehnert, Denise Halpin, Rebecca A. Lin, Xudong Simenauer, Ari Akopov, Asmik Das, Suman R. Stockwell, Timothy B. Shrivastava, Susmita Nghiem My Ngoc Le Thi Tam Uyen Nguyen Thi Kim Tuyen Tran Tan Thanh Vu Thi Ty Hang Phan Tu Qui Nguyen Thanh Hung Truong Huu Khanh Le Quoc Thinh Le Nguyen Thanh Nhan Hoang Minh Tu Van Do Chau Viet Ha Manh Tuan Ho Lu Viet Tran Tinh Hien Nguyen Van Vinh Chau Thwaites, Guy Grenfell, Bryan T. Stadler, Tanja Wentworth, David E. Holmes, Edward C. Van Doorn, H. Rogier TI Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam SO JOURNAL OF VIROLOGY LA English DT Article ID POLIOMYELITIS-LIKE DISEASE; 71 VACCINE; POPULATION-DYNAMICS; EPIDEMIC; INFECTION; CHINA; RECOMBINATION; OUTBREAKS; CHILDREN; TAIWAN AB Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (R-e) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the R-e of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus. C1 [Geoghegan, Jemma L.; Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Marie Bashir Inst Infect Dis & Biosecur, Charles Perkins Ctr, Sydney, NSW 2006, Australia. [Geoghegan, Jemma L.; Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Le Van Tan; Nguyen Thi Kim Tuyen; Tran Tan Thanh; Vu Thi Ty Hang; Tran Tinh Hien; Thwaites, Guy; Van Doorn, H. Rogier] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam. [Kuehnert, Denise] Swiss Fed Inst Technol, Dept Environm Syst Sci, Zurich, Switzerland. [Kuehnert, Denise; Stadler, Tanja] Swiss Inst Bioinformat, Lausanne, Switzerland. [Halpin, Rebecca A.; Lin, Xudong; Simenauer, Ari; Akopov, Asmik; Das, Suman R.; Stockwell, Timothy B.; Shrivastava, Susmita] J Craig Venter Inst, Rockville, MD USA. [Nghiem My Ngoc; Le Thi Tam Uyen; Phan Tu Qui; Nguyen Van Vinh Chau] Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Nguyen Thanh Hung; Truong Huu Khanh; Le Quoc Thinh; Le Nguyen Thanh Nhan] Childrens Hosp 1, Ho Chi Minh City, Vietnam. [Do Chau Viet; Ha Manh Tuan; Ho Lu Viet] Childrens Hosp 2, Ho Chi Minh City, Vietnam. [Hoang Minh Tu Van; Thwaites, Guy; Van Doorn, H. Rogier] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford, England. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Stadler, Tanja] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Zurich, Switzerland. [Wentworth, David E.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Geoghegan, JL (reprint author), Univ Sydney, Sch Biol Sci, Marie Bashir Inst Infect Dis & Biosecur, Charles Perkins Ctr, Sydney, NSW 2006, Australia. RI Stadler, Tanja/J-4742-2013; OI Stadler, Tanja/0000-0001-6431-535X; Simenauer, Ari/0000-0003-0812-6049; Le Van, Tan/0000-0002-1791-3901; Wentworth, David/0000-0002-5190-980X; Thwaites, Guy/0000-0002-2858-2087; Holmes, Edward/0000-0001-9596-3552; Kuhnert, Denise/0000-0002-5657-018X FU Wellcome Trust [101104/Z/13/Z, 089276/Z/09/Z]; Li Ka Shing Foundation-University of Oxford Global Health Program strategic award [LG23]; Judith and David Coffey fellowship from the Charles Perkins Centre; University of Sydney; ECH, NHMRC Australia Fellowship [AF30]; ETH Zurich postdoctoral fellowship; European Research Council under the 7th Framework Programme of the European Commission (PhyPD) [335529]; Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate; U.S. Department of Homeland Security; Fogarty International Center; National Institutes of Health; Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200900007C] FX This research was supported by the Wellcome Trust (101104/Z/13/Z and 089276/Z/09/Z) and the Li Ka Shing Foundation-University of Oxford Global Health Program strategic award (LG23). J.L.G. is supported by the Judith and David Coffey fellowship from the Charles Perkins Centre, University of Sydney, and ECH by an NHMRC Australia Fellowship (AF30). D.K. is supported by an ETH Zurich postdoctoral fellowship, T.S. was supported in part by the European Research Council under the 7th Framework Programme of the European Commission (PhyPD; grant agreement 335529), and B.T.G. was supported by grants from the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, the U.S. Department of Homeland Security, the Fogarty International Center, and the National Institutes of Health and by the Bill and Melinda Gates Foundation. This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract HHSN272200900007C. NR 54 TC 8 Z9 9 U1 5 U2 9 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 SEP PY 2015 VL 89 IS 17 BP 8871 EP 8879 DI 10.1128/JVI.00706-15 PG 9 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900019 PM 26085170 ER PT J AU Kazemian, M Ren, M Lin, JX Liao, W Spolski, R Leonard, WJ AF Kazemian, Majid Ren, Min Lin, Jian-Xin Liao, Wei Spolski, Rosanne Leonard, Warren J. TI Possible Human Papillomavirus 38 Contamination of Endometrial Cancer RNA Sequencing Samples in The Cancer Genome Atlas Database SO JOURNAL OF VIROLOGY LA English DT Article ID BURROWS-WHEELER TRANSFORM; CERVICAL-CANCER; VIRAL EXPRESSION; READ ALIGNMENT; PROJECT; SEQ; IDENTIFICATION; TRANSCRIPTS; LANDSCAPE; VIRUS AB Viruses are causally associated with a number of human malignancies. In this study, we sought to identify new virus-cancer associations by searching RNA sequencing data sets from > 2,000 patients, encompassing 21 cancers from The Cancer Genome Atlas (TCGA), for the presence of viral sequences. In agreement with previous studies, we found human papillomavirus 16 (HPV16) and HPV18 in oropharyngeal cancer and hepatitis B and C viruses in liver cancer. Unexpectedly, however, we found HPV38, a cutaneous form of HPV associated with skin cancer, in 32 of 168 samples from endometrial cancer. In 12 of the HPV38-positive (HPV38(+)) samples, we observed at least one paired read that mapped to both human and HPV38 genomes, indicative of viral integration into the host DNA, something not previously demonstrated for HPV38. The expression levels of HPV38 transcripts were relatively low, and all 32 HPV38(+) samples belonged to the same experimental batch of 40 samples, whereas none of the other 128 endometrial carcinoma samples were HPV38(+), raising doubts about the significance of the HPV38 association. Moreover, the HPV38(+) samples contained the same 10 novel single nucleotide variations (SNVs), leading us to hypothesize that one patient was infected with this new isolate of HPV38, which was integrated into his/her genome and may have cross-contaminated other TCGA samples within batch 228. Based on our analysis, we propose guidelines to examine the batch effect, virus expression level, and SNVs as part of next-generation sequencing (NGS) data analysis for evaluating the significance of viral/ pathogen sequences in clinical samples. IMPORTANCE High-throughput RNA sequencing (RNA-Seq), followed by computational analysis, has vastly accelerated the identification of viral and other pathogenic sequences in clinical samples, but cross-contamination during the processing of the samples remain a major problem that can lead to erroneous conclusions. We found HPV38 sequences specifically present in RNA-Seq samples from endometrial cancer patients from TCGA, a virus not previously associated with this type of cancer. However, multiple lines of evidence suggest possible cross-contamination in these samples, which were processed together in the same batch. Despite this potential cross-contamination, our data indicate that we have detected a new isolate of HPV38 that appears to be integrated into the human genome. We also provide general guidelines for computational detection and interpretation of pathogen-disease associations. C1 [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov OI Kazemian, Majid/0000-0001-7080-8820 FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health; NIH [K22-KHL125593A] FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, and a grant to M.K. from the NIH (K22-KHL125593A). NR 31 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2015 VL 89 IS 17 BP 8967 EP 8973 DI 10.1128/JVI.00822-15 PG 7 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900027 PM 26085148 ER PT J AU Russell, RF McDonald, JU Ivanova, M Zhong, ZY Bukreyev, A Tregoning, JS AF Russell, Ryan F. McDonald, Jacqueline U. Ivanova, Maria Zhong, Ziyun Bukreyev, Alexander Tregoning, John S. TI Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1 beta Responses SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; SH-GENE; ALVEOLAR MACROPHAGES; IN-VITRO; VACCINE CANDIDATE; INFLUENZA VACCINE; INNATE IMMUNITY; LUNG INJURY; ION-CHANNEL; G-PROTEIN AB The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV Delta SH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV Delta SH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV Delta SH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1 beta (IL-1 beta) response to RSV Delta SH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1 beta was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1 beta response to RSV Delta SH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1 beta response in vivo, the first demonstration of neutrophilic IL-1 beta production in response to viral lung infection. In this study, we describe an increased IL-1 beta response to RSV Delta SH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines. IMPORTANCE There is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1 beta response to RSV Delta SH is greater in spite of a lower viral load, which contributes to the attenuation in vivo. This potentially suggests a novel method by which viruses can evade the host response. As all Pneumovirinae and some Paramyxovirinae carry similar SH genes, this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of the Paramyxoviridae. C1 [Russell, Ryan F.; McDonald, Jacqueline U.; Ivanova, Maria; Zhong, Ziyun; Tregoning, John S.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Mucosal Infect & Immun Grp, Virol Sect, London, England. [Bukreyev, Alexander] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tregoning, JS (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Med, Mucosal Infect & Immun Grp, Virol Sect, St Marys Campus, London, England. EM john.tregoning@imperial.ac.uk FU Innovative Medicines Initiative Joint Undertaking [115308 Biovacsafe]; European Union; European Community [HEALTH-F4-2011-18 280873] FX The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115308 Biovacsafe, the resources of which are composed of financial contributions from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA members' in-kind contributions. This work was supported by the European Community's European Seventh Framework Program ADITEC (HEALTH-F4-2011-18 280873). NR 58 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 2015 VL 89 IS 17 BP 8974 EP 8981 DI 10.1128/JVI.01070-15 PG 8 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900028 PM 26085154 ER PT J AU Guzzo, C Fox, JC Miao, H Volkman, BF Lusso, P AF Guzzo, Christina Fox, Jamie C. Miao, Huiyi Volkman, Brian F. Lusso, Paolo TI Structural Determinants for the Selective Anti-HIV-1 Activity of the All-beta Alternative Conformer of XCL1 SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; C-CHEMOKINE LYMPHOTACTIN; PLATELET FACTOR-IV; ENVELOPE GLYCOPROTEIN; HIV-1; RECOGNITION; BINDING; POTENT; IDENTIFICATION; NEUTRALIZATION AB HIV-1 replication is regulated in vivo by a complex network of cytokines and chemokines. XCL1/lymphotactin, a unique metamorphic chemokine, was recently identified as a broad-spectrum endogenous HIV-1 inhibitor that blocks viral entry via direct interaction with the gp120 envelope glycoprotein. HIV-1 inhibition by XCL1 requires access to the alternative all-beta conformation, which interacts with glycosaminoglycans (GAGs) but not with the specific XCL1 receptor, XCR1. To investigate the structural determinants of the HIV-inhibitory function of XCL1, we performed a detailed structure-function analysis of a stabilized all-beta variant, XCL1 W55D. Individual alanine substitutions of two basic residues within the 40s' loop, K42 and R43, abrogated the ability of XCL1 to bind to the viral envelope and block HIV-1 infection; moreover, a loss of HIV-inhibitory function, albeit less marked, was seen upon individual mutation of three additional basic residues: R18, R35, and K46. In contrast, mutation of K42 to arginine did not cause any loss of function, suggesting that the interaction with gp120 is primarily electrostatic in nature. Strikingly, four of these five residues cluster to form a large (similar to 350 angstrom(2)) positively charged surface in the all-beta XCL1 conformation, whereas they are dissociated in the classic chemokine fold, which is inactive against HIV-1, providing a structural basis for the selective antiviral activity of the alternatively folded XCL1. Furthermore, we observed that changes to the N-terminal domain, which is proximal to the cluster of putative HIV-1 gp120-interacting residues, also affect the antiviral activity of XCL1. Interestingly, the complement of residues involved in HIV-1 blockade is partially overlapping, but distinct from those involved in the GAG-binding function of XCL1. These data identify key structural determinants of anti-HIV activity in XCL1, providing new templates for the development of HIV-1 entry inhibitors. IMPORTANCE The host immune system controls HIV-1 infection through a wide array of inhibitory responses, including the induction of cytotoxic effector cells and the secretion of noncytolytic soluble antiviral factors such as cytokines and chemokines. We recently identified XCL1/lymphotactin, a chemokine primarily produced by CD8(+) T cells, as a novel endogenous factor with broad anti-HIV activity. Strikingly, only one of the two conformations that XCL1 can adopt in solution, the alternative all-beta fold, mediates antiviral activity. At variance with the classic HIV-inhibitory chemokines such as CCL5/RANTES, XCL1 acts via direct interaction with the external viral envelope glycoprotein, gp120. Here, we identify the interactive surface of XCL1 that is implicated in binding to the HIV-1 envelope and HIV-1 inhibition, providing a structural basis to explain why only the all-beta XCL1 conformer is effective against HIV-1. Our findings may be useful in guiding the rational design of new inhibitors of HIV-1 entry. C1 [Guzzo, Christina; Miao, Huiyi; Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Fox, Jamie C.; Volkman, Brian F.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. RP Lusso, P (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM plusso@niaid.nih.gov FU Canadian Institutes of Health Research; Intramural AIDS Targeted Antiviral Program (IATAP); National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) FX This study was supported by a Fellowship from the Canadian Institutes of Health Research to C.G., a research grant from the Intramural AIDS Targeted Antiviral Program (IATAP), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). NR 28 TC 4 Z9 4 U1 0 U2 6 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 SEP PY 2015 VL 89 IS 17 BP 9061 EP 9067 DI 10.1128/JVI.01285-15 PG 7 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900035 PM 26085164 ER PT J AU Bukh, J Engle, RE Faulk, K Wang, RY Farci, P Alter, HJ Purcell, RH AF Bukh, Jens Engle, Ronald E. Faulk, Kristina Wang, Richard Y. Farci, Patrizia Alter, Harvey J. Purcell, Robert H. TI Immunoglobulin with High-Titer In Vitro Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CULTURE SYSTEMS; GENOTYPE NEUTRALIZATION; ENVELOPE GLYCOPROTEINS; E2 GLYCOPROTEIN; IMMUNE-RESPONSE; MOLECULAR CLONE; INFECTION; VACCINE; LIVER; PREVENTION AB The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected patient and challenged with genotype strains efficiently neutralized by H06 in vitro. Genotype 1a NAbs afforded no protection against genotype 4a or 5a. Protection against homologous 1a lasted 18 weeks, but infection emerged when NAb titers waned. However, 6a infection was prevented. The differential in vivo neutralization patterns have implications for HCV vaccine development. C1 [Bukh, Jens] Univ Copenhagen, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, Copenhagen, Denmark. [Bukh, Jens] Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, Copenhagen, Denmark. [Bukh, Jens] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark. [Bukh, Jens; Engle, Ronald E.; Faulk, Kristina; Farci, Patrizia; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Wang, Richard Y.; Alter, Harvey J.] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Bukh, J (reprint author), Univ Copenhagen, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, Copenhagen, Denmark. EM jbukh@sund.ku.dk FU Intramural Research Program of the NIAID, NIH; NIAID [NO1-AO-62713]; Danish Council for Independent Research-Medical Sciences; Lundbeck Foundation; Novo Nordisk Foundation; Advanced-Top Researcher grant from the Danish Council for Independent Research; Novo Nordisk Prize FX This study was supported by the Intramural Research Program of the NIAID, NIH, and by NIAID contract NO1-AO-62713, as well as by research grants to J.B. from the Danish Council for Independent Research-Medical Sciences, the Lundbeck Foundation, and the Novo Nordisk Foundation. J.B. is the recipient of an Advanced-Top Researcher grant from the Danish Council for Independent Research (2014) and the 2015 Novo Nordisk Prize. NR 54 TC 4 Z9 4 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 SEP PY 2015 VL 89 IS 17 BP 9128 EP 9132 DI 10.1128/JVI.01194-15 PG 5 WC Virology SC Virology GA CQ6GZ UT WOS:000360703900043 PM 26085160 ER PT J AU Platts-Mills, JA Babji, S Bodhidatta, L Gratz, J Haque, R Havt, A McCormick, BJJ McGrath, M Olortegui, MP Samie, A Shakoor, S Mondal, D Lima, IFN Hariraju, D Rayamajhi, BB Qureshi, S Kabir, F Yori, PP Mufamadi, B Amour, C Carreon, JD Richard, SA Lang, D Bessong, P Mduma, E Ahmed, T Lima, AAAM Mason, CJ Zaidi, AKM Bhutta, ZA Kosek, M Guerrant, RL Gottlieb, M Miller, M Kang, G Houpt, ER AF Platts-Mills, James A. Babji, Sudhir Bodhidatta, Ladaporn Gratz, Jean Haque, Rashidul Havt, Alexandre McCormick, Benjamin J. J. McGrath, Monica Olortegui, Maribel Paredes Samie, Amidou Shakoor, Sadia Mondal, Dinesh Lima, Ila F. N. Hariraju, Dinesh Rayamajhi, Bishnu B. Qureshi, Shahida Kabir, Furqan Yori, Pablo P. Mufamadi, Brenda Amour, Caroline Carreon, J. Daniel Richard, Stephanie A. Lang, Dennis Bessong, Pascal Mduma, Esto Ahmed, Tahmeed Lima, Aldo A. A. M. Mason, Carl J. Zaidi, Anita K. M. Bhutta, Zulfiqar A. Kosek, Margaret Guerrant, Richard L. Gottlieb, Michael Miller, Mark Kang, Gagandeep Houpt, Eric R. CA MAL-ED Network Investigators TI Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED) SO LANCET GLOBAL HEALTH LA English DT Article ID GLOBAL ENTERIC MULTICENTER; CHILDHOOD DIARRHEA; ATTRIBUTABLE RISK; CHILDREN; DISEASE; GROWTH; MALNUTRITION; INFECTION; ETIOLOGY; SITE AB Background Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community. Methods We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through twice-weekly home visits by fieldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1-12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea. Findings Between Nov 26, 2009, and Feb 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0-24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5.2%, 95% CI 3.0-7.1), rotavirus (4.8%, 4.5-5.0), Campylobacter spp (3.5%, 0.4-6.3), astrovirus (2.7%, 2.2-3.1), and Cryptosporidium spp (2.0%, 1.3-2.6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7.9%, 3.1-12.1), norovirus GII (5.4%, 2.1-7.8), rotavirus (4.9%, 4.4-5.2), astrovirus (4.2%, 3.5-4.7), and Shigella spp (4.0%, 3.6-4.3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fifth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation There was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited. C1 [Platts-Mills, James A.; Gratz, Jean; Guerrant, Richard L.; Houpt, Eric R.] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Havt, Alexandre; Lima, Ila F. N.; Lima, Aldo A. A. M.] Univ Fed Ceara, Clin Res Unit, Fortaleza, Ceara, Brazil. [Havt, Alexandre; Lima, Ila F. N.; Lima, Aldo A. A. M.] Univ Fed Ceara, Inst Biomed, Fortaleza, Ceara, Brazil. [Haque, Rashidul; Mondal, Dinesh; Ahmed, Tahmeed] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Babji, Sudhir; Hariraju, Dinesh; Kang, Gagandeep] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Bodhidatta, Ladaporn; Rayamajhi, Bishnu B.; Mason, Carl J.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [Yori, Pablo P.; Kosek, Margaret] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Olortegui, Maribel Paredes; Yori, Pablo P.; Kosek, Margaret] Asociac Benef PRISMA, Iquitos, Peru. [Shakoor, Sadia; Qureshi, Shahida; Kabir, Furqan; Zaidi, Anita K. M.; Bhutta, Zulfiqar A.] Aga Khan Univ, Karachi, Pakistan. [Samie, Amidou; Mufamadi, Brenda; Bessong, Pascal] Univ Venda, Thohoyandou, South Africa. [Gratz, Jean; Amour, Caroline; Mduma, Esto] Haydom Lutheran Hosp, Haydom, Tanzania. [Lang, Dennis; Gottlieb, Michael] Fdn Natl Inst Hlth, Bethesda, MD USA. [McCormick, Benjamin J. J.; McGrath, Monica; Carreon, J. Daniel; Richard, Stephanie A.; Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Houpt, ER (reprint author), Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. EM erh6k@virginia.edu RI Strand, Tor/D-9836-2016; OI Strand, Tor/0000-0002-4038-151X; Lima de Moraes, Milena/0000-0003-1222-8400 FU Bill & Melinda Gates Foundation; Foundation for the NIH; National Institutes of Health, Fogarty International Center FX The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health, Fogarty International Center. The authors thank the staff and participants of the MAL-ED Network Project for their important contributions. NR 36 TC 57 Z9 57 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD SEP PY 2015 VL 3 IS 9 BP E564 EP E575 DI 10.1016/S2214-109X(15)00151-5 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ4FJ UT WOS:000360559500022 PM 26202075 ER PT J AU Kohli, A Kapoor, R Sims, Z Nelson, A Sidharthan, S Lam, B Silk, R Kotb, C Gross, C Teferi, G Sugarman, K Pang, PS Osinusi, A Polis, MA Rustgi, V Masur, H Kottilil, S AF Kohli, Anita Kapoor, Rama Sims, Zayani Nelson, Amy Sidharthan, Sreetha Lam, Brian Silk, Rachel Kotb, Colleen Gross, Chloe Teferi, Gebeyehu Sugarman, Kate Pang, Phillip S. Osinusi, Anu Polis, Michael A. Rustgi, Vinod Masur, Henry Kottilil, Shyam TI Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study SO LANCET INFECTIOUS DISEASES LA English DT Article ID VIRUS-INFECTION; RIBAVIRIN; EPIDEMIOLOGY; PREDICTION; FIBROTEST; FIBROSIS; TRIAL AB Background Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections. Methods In this single-centre, open-label cohort, phase 2a trial, patients with HCV genotype 4 who were treatment naive or interferon treatment experienced (HIV-negative) were sequentially enrolled at the Clinical Center of the National Institutes of Health, Bethesda, MD, USA. We gave patients 12 weeks of ledipasvir (90 mg) and sofosbuvir (400 mg) as a single combination tablet once per day. The primary efficacy endpoint was sustained viral response at 12 weeks (SVR12), as measured by the proportion of patients with HCV RNA concentrations less than the lower limit of quantification (COBAS TaqMan HCV test, version 1.0, 43 IU/mL). The primary safety endpoint was the frequency and severity of adverse events. We did our analyses on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01805882. Findings Between Sept 16, 2013, and Nov 2, 2014, we recruited 21 patients. 20 (95%) of 21 patients completed 12 weeks of treatment and achieved SVR12 (95% CI 76-100), including seven patients with cirrhosis. One patient was non-adherent to study drugs and withdrew from the study, but was included in the intention-to-treat analysis. No patients discontinued treatment because of adverse events and no grade 3 or 4 adverse events occurred that were related to study medications. The most common adverse events were diarrhoea (two patients), fatigue (three patients), nausea (two patients), and upper respiratory infections (two patients). Interpretation Ledipasvir and sofosbuvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 100% SVR for all patients who received all 12 weeks of study drugs, irrespective of previous treatment status and underlying liver fibrosis. This is the first report of a single-pill, all-oral, interferon-free, ribavirin-free treatment for patients with HCV genotype 4. C1 [Kohli, Anita; Sims, Zayani; Sidharthan, Sreetha; Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Polis, Michael A.] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Kohli, Anita; Kapoor, Rama; Silk, Rachel; Kotb, Colleen; Gross, Chloe] Frederick Natl Lab Canc Res, Leidos Biomed Res, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA. [Nelson, Amy; Kottilil, Shyam] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Lam, Brian] INOVA Fairfax Hosp, Fairfax, VA USA. [Teferi, Gebeyehu; Sugarman, Kate] Unity Hlth Care, Washington, DC USA. [Pang, Phillip S.; Osinusi, Anu] Gilead Sci, Foster City, CA USA. [Rustgi, Vinod] Univ Pittsburgh, Med Ctr, Thomas E Starlz Transplantat Inst, Div Hepatol, Pittsburgh, PA USA. RP Kottilil, S (reprint author), Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. EM skottilil@niaid.nih.gov FU NIAID, National Cancer Institute and Clinical Center Intramural Program; NIH; Gilead Sciences FX NIAID, National Cancer Institute and Clinical Center Intramural Program. The study was also supported in part by a Cooperative Research and Development Agreement between NIH and Gilead Sciences. NR 22 TC 32 Z9 32 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2015 VL 15 IS 9 BP 1049 EP 1054 DI 10.1016/S1473-3099(15)00157-7 PG 6 WC Infectious Diseases SC Infectious Diseases GA CQ4AZ UT WOS:000360547800032 PM 26187031 ER PT J AU Launer, LJ AF Launer, Lenore J. TI Preventing Alzheimer's disease is difficult SO LANCET NEUROLOGY LA English DT Editorial Material C1 NIA, Intramural Res Program, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Intramural Res Program, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov NR 3 TC 1 Z9 1 U1 1 U2 7 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 SEP PY 2015 VL 14 IS 9 BP 872 EP 874 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CP4YZ UT WOS:000359889800005 PM 26293557 ER PT J AU An, L Shen, J AF An, Li Shen, Jun TI Image-guided spatial localization of heterogeneous compartments for magnetic resonance SO MEDICAL PHYSICS LA English DT Article DE SLIM; SPLASH; Tikhonov regularization; SRF ID SPECTRAL LOCALIZATION; SLIM; SPECTROSCOPY AB Purpose: Image-guided localization SPectral Localization Achieved by Sensitivity Heterogeneity (SPLASH) allows rapid measurement of signals from irregularly shaped anatomical compartments without using phase encoding gradients. Here, the authors propose a novel method to address the issue of heterogeneous signal distribution within the localized compartments. Methods: Each compartment was subdivided into multiple subcompartments and their spectra were solved by Tikhonov regularization to enforce smoothness within each compartment. The spectrum of a given compartment was generated by combining the spectra of the components of that compartment. The proposed method was first tested using Monte Carlo simulations and then applied to reconstructing in vivo spectra from irregularly shaped ischemic stroke and normal tissue compartments. Results: Monte Carlo simulations demonstrate that the proposed regularized SPLASH method significantly reduces localization and metabolite quantification errors. In vivo results show that the intracompartment regularization results in similar to 40% reduction of error in metabolite quantification. Conclusions: The proposed method significantly reduces localization errors and metabolite quantification errors caused by intracompartment heterogeneous signal distribution. C1 [An, Li; Shen, Jun] NIMH, Sect Magnet Resonance Spect, Mol Imaging Branch, NIH, Bethesda, MD 20854 USA. RP An, L (reprint author), Bldg 10,Room 3D46,10 Ctr Dr,MSC 1216, Bethesda, MD 20892 USA. EM li.an@nih.gov FU National Institute of Mental Health, National Institutes of Health [IRP-NIMH-NIH] FX This work was supported by the intramural research program of National Institute of Mental Health, National Institutes of Health (No. IRP-NIMH-NIH). Ioline Henter provided invaluable editorial assistance. NR 17 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2015 VL 42 IS 9 BP 5278 EP 5286 DI 10.1118/1.4928398 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CQ5LG UT WOS:000360645000028 PM 26328977 ER PT J AU Sun, WY Chatterjee, B Wang, YH Stevenson, HS Edelman, DC Meltzer, PS Barr, FG AF Sun, Wenyue Chatterjee, Bishwanath Wang, Yonghong Stevenson, Holly S. Edelman, Daniel C. Meltzer, Paul S. Barr, Frederic G. TI Distinct methylation profiles characterize fusion-positive and fusion-negative rhabdomyosarcoma SO MODERN PATHOLOGY LA English DT Article ID CHILDRENS ONCOLOGY GROUP; DNA METHYLATION; GENE-EXPRESSION; EMBRYONAL RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; GENOME; CANCER; PROMOTER; REVEALS; CLASSIFICATION AB Rhabdomyosarcoma comprises two major subtypes, fusion positive (PAX3-FOXO1 or PAX7-FOXO1) and fusion negative. To investigate the significance of DNA methylation in these subtypes, we analyzed methylation profiles of 37 rhabdomyosarcoma tumors and 10 rhabdomyosarcoma cell lines, as well as 8 normal tissues. Unsupervised clustering of DNA methylation clearly distinguished the fusion-positive and fusion-negative subsets. The fusion-positive tumors showed substantially lower overall levels of methylation compared with fusion-negative tumors. Comparison with the methylation pattern of normal skeletal muscle and bone marrow indicates that fusion-negative rhabdomyosarcoma is more similar to these normal tissues compared with fusion-positive rhabdomyosarcoma, and suggests that many of the methylation differences between these subtypes arise from 'aberrant' hyper- and hypomethylation events in fusion-positive rhabdomyosarcoma. Integrative methylation and gene expression analysis revealed that methylation differences between fusion-positive and fusion-negative tumors could either be positively or negatively associated with mRNA expression. There was no significant difference in the distribution of PAX3-FOXO1-binding sites between genes with and without differential methylation. However, the finding that PAX3-FOXO1-binding sites were enriched among genes that were both differentially methylated and differentially expressed suggests that the fusion protein interacts with DNA methylation to regulate target gene expression. An 11-gene DNA methylation signature, classifying the rhabdomyosarcoma tumors into fusion-positive and fusion-negative subsets, was established and validated by pyrosequencing assays. Notably, EMILIN1 (part of the 11-gene signature) showed higher methylation and lower mRNA expression in fusion-positive compared with fusion-negative tumors, and demonstrated demethylation and re-expression in multiple fusion-positive cell lines after treatment with 5-aza-2'-deoxycytidine. In conclusion, our study demonstrates that fusion-positive and fusion-negative rhabdomyosarcoma tumors possess characteristic methylation profiles that contribute to the expression differences between these fusion subtypes. These findings indicate an important relationship between fusion status and epigenetic changes in rhabdomyosarcoma, present a novel approach for ascertaining fusion status, and may identify new therapeutic targets in rhabdomyosarcoma. C1 [Sun, Wenyue; Chatterjee, Bishwanath; Barr, Frederic G.] NCI, Pathol Lab, Canc Mol Pathol, Bethesda, MD 20892 USA. [Wang, Yonghong; Stevenson, Holly S.; Edelman, Daniel C.; Meltzer, Paul S.] NCI, Clin Mol Profiling Core, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Barr, FG (reprint author), NCI, Pathol Lab, 10 Ctr Dr,Room 3B55,MSC1500, Bethesda, MD 20892 USA. EM barrfg@mail.nih.gov FU National Cancer Institute; NIH [R21-CA150091] FX We thank Donna Gustafson, Mark Bowser, and Stephen Master for technical assistance and consultation. This research was supported by the Intramural Research Program of the National Cancer Institute. Preliminary data collection was supported by NIH Grant R21-CA150091. NR 38 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2015 VL 28 IS 9 BP 1214 EP 1224 DI 10.1038/modpathol.2015.82 PG 11 WC Pathology SC Pathology GA CQ5RV UT WOS:000360664200006 PM 26226845 ER PT J AU Law, MH Bishop, DT Lee, JE Brossard, M Martin, NG Moses, EK Song, FJ Barrett, JH Kumar, R Easton, DF Pharoah, PDP Swerdlow, AJ Kypreou, KP Taylor, JC Harland, M Randerson-Moor, J Akslen, LA Andresen, PA Avril, MF Azizi, E Scarra, GB Brown, KM Debniak, T Duffy, DL Elder, DE Fang, SY Friedman, E Galan, P Ghiorzo, P Gillanders, EM Goldstein, AM Gruis, NA Hansson, J Helsing, P Hocevar, M Hoiom, V Ingvar, C Kanetsky, PA Chen, WV Landi, MT Lang, J Lathrop, GM Lubinski, J Mackie, RM Mann, GJ Molven, A Montgomery, GW Novakovic, S Olsson, H Puig, S Puig-Butille, JA Qureshi, AA Radford-Smith, GL van der Stoep, N van Doorn, R Whiteman, DC Craig, JE Schadendorf, D Simms, LA Burdon, KP Nyholt, DR Pooley, KA Orr, N Stratigos, AJ Cust, AE Ward, SV Hayward, NK Han, JL Schulze, HJ Dunning, AM Bishop, JAN Demenais, F Amos, CI MacGregor, S Iles, MM AF Law, Matthew H. Bishop, D. Timothy Lee, Jeffrey E. Brossard, Myriam Martin, Nicholas G. Moses, Eric K. Song, Fengju Barrett, Jennifer H. Kumar, Rajiv Easton, Douglas F. Pharoah, Paul D. P. Swerdlow, Anthony J. Kypreou, Katerina P. Taylor, John C. Harland, Mark Randerson-Moor, Juliette Akslen, Lars A. Andresen, Per A. Avril, Marie-Franoise Azizi, Esther Scarra, Giovanna Bianchi Brown, Kevin M. Debniak, Tadeusz Duffy, David L. Elder, David E. Fang, Shenying Friedman, Eitan Galan, Pilar Ghiorzo, Paola Gillanders, Elizabeth M. Goldstein, Alisa M. Gruis, Nelleke A. Hansson, Johan Helsing, Per Hocevar, Marko Hoeiom, Veronica Ingvar, Christian Kanetsky, Peter A. Chen, Wei V. Landi, Maria Teresa Lang, Julie Lathrop, G. Mark Lubinski, Jan Mackie, Rona M. Mann, Graham J. Molven, Anders Montgomery, Grant W. Novakovic, Srdjan Olsson, Hakan Puig, Susana Puig-Butille, Joan Anton Qureshi, Abrar A. Radford-Smith, Graham L. van der Stoep, Nienke van Doorn, Remco Whiteman, David C. Craig, Jamie E. Schadendorf, Dirk Simms, Lisa A. Burdon, Kathryn P. Nyholt, Dale R. Pooley, Karen A. Orr, Nick Stratigos, Alexander J. Cust, Anne E. Ward, Sarah V. Hayward, Nicholas K. Han, Jiali Schulze, Hans-Joachim Dunning, Alison M. Bishop, Julia A. Newton Demenais, Florence Amos, Christopher I. MacGregor, Stuart Iles, Mark M. CA GenoMEL Consortium Essen-Heidelberg Investigators SDH Study Grp Q-MEGA QTWIN Investigators AMFS Investigators ATHENS Melanoma Study Grp TI Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma SO NATURE GENETICS LA English DT Article ID MEAN TELOMERE LENGTH; GENOTYPE IMPUTATION; CANCER-RISK; PHENOTYPIC CHARACTERISTICS; SEQUENCE VARIANTS; CELL CARCINOMA; FIELD SYNOPSIS; SKIN-CANCER; STEM-CELLS; ASSOCIATION AB Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 x 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology. C1 [Law, Matthew H.; MacGregor, Stuart] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia. [Bishop, D. Timothy; Barrett, Jennifer H.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Bishop, Julia A. Newton; Iles, Mark M.] Univ Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England. [Lee, Jeffrey E.; Fang, Shenying] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Brossard, Myriam; Demenais, Florence] INSERM, Genet Variat & Human Dis Unit, UMR 946, Paris, France. [Brossard, Myriam; Demenais, Florence] Univ Paris Diderot, Sorbonne Paris Cite, Inst Univ Hematol, Paris, France. [Martin, Nicholas G.; Duffy, David L.] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia. [Moses, Eric K.; Ward, Sarah V.] Univ Western Australia, Fac Med Dent & Hlth Sci, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia. [Song, Fengju] Tianjin Med Univ, Dept Epidemiol & Biostat, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Canc,Canc Inst & Hosp, Tianjin, Peoples R China. [Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany. [Easton, Douglas F.; Pooley, Karen A.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Kypreou, Katerina P.; Stratigos, Alexander J.] Univ Athens, Sch Med, Andreas Sygros Hosp, Dept Dermatol, GR-11527 Athens, Greece. [Akslen, Lars A.] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers CCBIO, Bergen, Norway. [Akslen, Lars A.; Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Andresen, Per A.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Pathol,Mol Pathol, N-0027 Oslo, Norway. [Avril, Marie-Franoise] Univ Paris 05, AP HP, Hop Cochin, Serv Dermatol, Paris, France. [Azizi, Esther] Sheba Med Ctr, Dept Dermatol, Tel Hashomer, Israel. [Azizi, Esther; Friedman, Eitan] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Azizi, Esther; Friedman, Eitan] Sheba Med Ctr, Oncogenet Unit, Tel Hashomer, Israel. [Scarra, Giovanna Bianchi; Ghiorzo, Paola] Univ Genoa, Dept Internal Med & Med Specialties, Genoa, Italy. [Scarra, Giovanna Bianchi; Ghiorzo, Paola] Azienda Osped Univ IRCCS AOU, Lab Genet Rare Canc, Ist Ricovero & Cura Carattere Sci, San Martino Ist Sci Tumori,Ist Nazl Ricerca Cancr, Genoa, Italy. [Brown, Kevin M.; Goldstein, Alisa M.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Debniak, Tadeusz; Lubinski, Jan] Pomeranian Med Univ, Int Hereditary Canc Ctr, Szczecin, Poland. [Elder, David E.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Galan, Pilar] Univ Paris 13, Ctr Rech Epidemiol & Stat, Communaute Univ Sorbonne Paris Cite,U1153, Conservatoire Natl Arts & Metiers,INSERM,EREN,U11, Bobigny, France. [Gillanders, Elizabeth M.] NHGRI, Inherited Dis Res Branch, US Natl Inst Hlth, Baltimore, MD USA. [Gruis, Nelleke A.; van Doorn, Remco] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. [Hansson, Johan; Hoeiom, Veronica] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Helsing, Per] Univ Oslo, Rikshosp, Dept Dermatol, Oslo Univ Hosp, N-0027 Oslo, Norway. [Hocevar, Marko] Inst Oncol Ljubljana, Dept Surg Oncol, Ljubljana, Slovenia. [Ingvar, Christian] Lund Univ, Clin Sci, Dept Surg, Lund, Sweden. [Kanetsky, Peter A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Chen, Wei V.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Lang, Julie; Mackie, Rona M.] Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland. [Lathrop, G. Mark] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Mackie, Rona M.] Univ Glasgow, Dept Publ Hlth, Glasgow, Lanark, Scotland. [Mann, Graham J.] Univ Sydney Westmead, Ctr Canc Res, Millennium Inst Med Res, Sydney, NSW, Australia. [Mann, Graham J.] Melanoma Inst Australia, Sydney, NSW, Australia. [Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway. [Montgomery, Grant W.; Nyholt, Dale R.] QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld, Australia. [Novakovic, Srdjan] Inst Oncol Ljubljana, Dept Mol Diagnost, Ljubljana, Slovenia. [Olsson, Hakan] Lund Univ, Clin Sci, Dept Oncol Pathol, Lund, Sweden. [Olsson, Hakan] Lund Univ, Clin Sci, Dept Canc Epidemiol, Lund, Sweden. [Puig, Susana; Puig-Butille, Joan Anton] Univ Barcelona, Dept Dermatol, Melanoma Unit, Barcelona, Spain. [Puig, Susana; Puig-Butille, Joan Anton] Univ Barcelona, Dept Biochem, Hosp Clin, Inst Invest Biomed August Pi Sune, Barcelona, Spain. [Puig, Susana; Puig-Butille, Joan Anton] Univ Barcelona, Dept Mol Genet, Hosp Clin, Inst Invest Biomed August Pi Sune, Barcelona, Spain. [Puig, Susana; Puig-Butille, Joan Anton] Inst Salud Carlos III, Ctr Invest Biomed Red CIBER Enfermedades Raras, Barcelona, Spain. [Qureshi, Abrar A.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Radford-Smith, Graham L.; Simms, Lisa A.] QIMR Berghofer Med Res Inst, Inflammatory Bowel Dis, Brisbane, Qld, Australia. [Radford-Smith, Graham L.] Royal Brisbane & Womens Hosp, Dept Gastroenterol & Hepatol, Brisbane, Qld, Australia. [Radford-Smith, Graham L.] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [van der Stoep, Nienke] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Dept Clin Genet, Leiden, Netherlands. [Whiteman, David C.] QIMR Berghofer Med Res Inst, Canc Control Grp, Brisbane, Qld, Australia. [Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, Essen, Germany. [Schadendorf, Dirk] German Consortium Translat Canc Res DKTK, Heidelberg, Germany. [Burdon, Kathryn P.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Nyholt, Dale R.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Cust, Anne E.] Univ Sydney, Sydney Sch Publ Hlth, Canc Epidemiol & Serv Res, Sydney, NSW 2006, Australia. [Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Oncogen, Brisbane, Qld, Australia. [Han, Jiali] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA. [Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Schulze, Hans-Joachim] Univ Munster, Dept Dermatol, Fachklin Hornheide, Inst Tumors Skin, D-48149 Munster, Germany. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA. RP Law, MH (reprint author), QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia. EM matthew.law@qimrberghofer.edu.au; m.m.iles@leeds.ac.uk RI Akslen, Lars /C-1202-2017; Demenais, Florence/G-3298-2013; Montgomery, Grant/B-7148-2008; Macgregor, Stuart/C-6442-2009; hayward, nicholas/C-1367-2015; Duffy, David/B-7392-2013; Hoiom, Veronica/F-4153-2012 OI Puig, Susana/0000-0003-1337-9745; , Srdjan/0000-0002-8888-4810; Whiteman, David/0000-0003-2563-9559; Akslen, Lars /0000-0003-2710-9543; Demenais, Florence/0000-0001-8361-0936; Barrett, Jenny/0000-0002-1720-7724; Dunning, Alison Margaret/0000-0001-6651-7166; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802; Montgomery, Grant/0000-0002-4140-8139; Macgregor, Stuart/0000-0001-6731-8142; hayward, nicholas/0000-0003-4760-1033; Duffy, David/0000-0001-7227-632X; FU Cancer Research UK [10124, A10589, A4994]; Medical Research Council [MR/L01629X/1]; NCATS NIH HHS [UL1 TR001108]; NCI NIH HHS [P30 CA016672, P30 CA023108, P50 CA093459, R01 CA083115, R01 CA088363, R01 CA100264, R01 CA122838, R01 CA133996, R03 CA167741] NR 92 TC 33 Z9 33 U1 4 U2 18 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 SEP PY 2015 VL 47 IS 9 BP 987 EP + DI 10.1038/ng.3373 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CQ1XQ UT WOS:000360394100008 PM 26237428 ER PT J AU Chan, K Roberts, SA Klimczak, LJ Sterling, JF Saini, N Malc, EP Kim, J Kwiatkowski, DJ Fargo, DC Mieczkowski, PA Getz, G Gordenin, DA AF Chan, Kin Roberts, Steven A. Klimczak, Leszek J. Sterling, Joan F. Saini, Natalie Malc, Ewa P. Kim, Jaegil Kwiatkowski, David J. Fargo, David C. Mieczkowski, Piotr A. Getz, Gad Gordenin, Dmitry A. TI An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers SO NATURE GENETICS LA English DT Article ID DNA-POLYMERASE-ZETA; BREAST-CANCER; DELETION POLYMORPHISM; MUTATIONAL PROCESSES; CYTIDINE DEAMINASES; GENE-EXPRESSION; CARCINOMA; YEAST; GENOMES; DAMAGE AB Elucidation of mutagenic processes shaping cancer genomes is a fundamental problem whose solution promises insights into new treatment, diagnostic and prevention strategies(1). Single-strand DNA-specific APOBEC cytidine deaminase(s) are major source(s) of mutation in several cancer types(2-4). Previous indirect evidence implicated APOBEC3B as the more likely major mutator deaminase, whereas the role of APOBEC3A is not established(5,6). Using yeast models enabling the controlled generation of long single-strand genomic DNA substrates(7), we show that the mutation signatures of APOBEC3A and APOBEC3B are statistically distinguishable. We then apply three complementary approaches to identify cancer samples with mutation signatures resembling either APOBEC. Strikingly, APOBEC3A-like samples have over tenfold more APOBEC-signature mutations than APOBEC3B-like samples. We propose that APOBEC3A-mediated mutagenesis is much more frequent because APOBEC3A itself is highly proficient at generating DNA breaks(8-10), whose repair can trigger the formation of single-strand hypermutation substrates. C1 [Chan, Kin; Roberts, Steven A.; Sterling, Joan F.; Saini, Natalie; Gordenin, Dmitry A.] NIEHS, Genome Integr & Struct Biol Lab, US NIH, Res Triangle Pk, NC 27709 USA. [Roberts, Steven A.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. [Klimczak, Leszek J.; Fargo, David C.] NIEHS, Integrat Bioinformat Support Grp, US NIH, Res Triangle Pk, NC 27709 USA. [Malc, Ewa P.; Mieczkowski, Piotr A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Kim, Jaegil; Kwiatkowski, David J.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kwiatkowski, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Getz, Gad] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gordenin, DA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, US NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM gordenin@niehs.nih.gov FU US National Institutes of Health Intramural Research Program [Z1AES103266]; US National Institutes of Health [U24CA143845, R01GM052319, 1P01CA120964, R00ES022633, K99ES024424] FX We thank T.A. Kunkel, S.A. Lujan and D.V. Zaykin for critical reading of the manuscript. This work was supported by US National Institutes of Health Intramural Research Program Project Z1AES103266 to D.A.G. and US National Institutes of Health grants U24CA143845 to G.G., R01GM052319 to P.A.M., 1P01CA120964 to D.J.K., R00ES022633 to S.A.R. and K99ES024424 to K.C. NR 55 TC 38 Z9 38 U1 3 U2 10 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 SEP PY 2015 VL 47 IS 9 BP 1067 EP + DI 10.1038/ng.3378 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CQ1XQ UT WOS:000360394100018 PM 26258849 ER PT J AU Grunewald, TGP Bernard, V Gilardi-Hebenstreit, P Raynal, V Surdez, D Aynaud, MM Mirabeau, O Cidre-Aranaz, F Tirode, F Zaidi, S Perot, G Jonker, AH Lucchesi, C Le Deley, MC Oberlin, O Marec-Berard, P Veron, AS Reynaud, S Lapouble, E Boeva, V Frio, TR Alonso, J Bhatia, S Pierron, G Cancel-Tassin, G Cussenot, O Cox, DG Morton, LM Machiela, MJ Chanock, SJ Charnay, P Delattre, O AF Gruenewald, Thomas G. P. Bernard, Virginie Gilardi-Hebenstreit, Pascale Raynal, Virginie Surdez, Didier Aynaud, Marie-Ming Mirabeau, Olivier Cidre-Aranaz, Florencia Tirode, Franck Zaidi, Sakina Perot, Gaelle Jonker, Anneliene H. Lucchesi, Carlo Le Deley, Marie-Cecile Oberlin, Odile Marec-Berard, Perrine Veron, Amelie S. Reynaud, Stephanie Lapouble, Eve Boeva, Valentina Frio, Thomas Rio Alonso, Javier Bhatia, Smita Pierron, Gaelle Cancel-Tassin, Geraldine Cussenot, Olivier Cox, David G. Morton, Lindsay M. Machiela, Mitchell J. Chanock, Stephen J. Charnay, Patrick Delattre, Olivier TI Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SEQ DATA-ANALYSIS; EXPRESSION; TRANSCRIPTION; COMMON; TUMORS; DNA; CHROMATIN; ELEMENTS; REVEALS AB Deciphering the ways in which somatic mutations and germline susceptibility variants cooperate to promote cancer is challenging. Ewing sarcoma is characterized by fusions between EWSR1 and members of the ETS gene family, usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors that bind DNA at GGAA motifs(1-3). A recent genome-wide association study(4) identified susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited proliferation, clonogenicity and spheroidal growth in vitro and induced regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the EGR2 locus in affected subjects and controls identified 291 Ewing-associated SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by converting an interspaced GGAT motif into a GGAA motif, thereby increasing the number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer activity of this sequence, with epigenetic characteristics of an active regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which increased global and allele-specific EGR2 expression. Collectively, our findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesis. C1 [Gruenewald, Thomas G. P.; Raynal, Virginie; Surdez, Didier; Aynaud, Marie-Ming; Mirabeau, Olivier; Tirode, Franck; Zaidi, Sakina; Jonker, Anneliene H.; Lucchesi, Carlo; Delattre, Olivier] PSL Res Univ, Inst Curie, Genet & Biol Canc Unit, Paris, France. [Gruenewald, Thomas G. P.; Raynal, Virginie; Surdez, Didier; Aynaud, Marie-Ming; Mirabeau, Olivier; Tirode, Franck; Zaidi, Sakina; Jonker, Anneliene H.; Lucchesi, Carlo; Delattre, Olivier] Inst Curie, Res Ctr, INSERM, U830, Paris, France. [Bernard, Virginie; Raynal, Virginie; Frio, Thomas Rio; Delattre, Olivier] Inst Curie, Res Ctr, Inst Curie Genom Excellence ICGex Platform, Paris, France. [Gilardi-Hebenstreit, Pascale; Charnay, Patrick] Ecole Normale Super, CNRS, INSERM, Inst Biol ENS IBENS,U1024,UMR8197, Paris, France. [Cidre-Aranaz, Florencia; Alonso, Javier] Inst Salud Carlos III, Inst Invest Enfermedades Raras, Madrid, Spain. [Perot, Gaelle] INSERM, Biol Sarcomas U916, Inst Bergonie, Bordeaux, France. [Le Deley, Marie-Cecile] Inst Gustave Roussy, Dept Epidemiol & Biostat, Villejuif, France. [Oberlin, Odile] Inst Gustave Roussy, Dept Pediat, Villejuif, France. [Marec-Berard, Perrine] Univ Lyon, Leon Berard Canc Ctr, Inst Pediat Hematol & Oncol, Lyon, France. [Veron, Amelie S.; Cox, David G.] Canc Res Ctr Lyon, Leon Berard Canc Ctr, U1052, INSERM, Lyon, France. [Reynaud, Stephanie; Lapouble, Eve; Pierron, Gaelle; Delattre, Olivier] Inst Curie Ctr Hosp, UGS, Paris, France. [Boeva, Valentina] Inst Curie, Res Ctr, INSERM, Bioinformat Biostat Epidemiol & Computat Syst Bio, Paris, France. [Boeva, Valentina] Mines ParisTech, Fontainebleau, France. [Bhatia, Smita] Univ Alabama Birmingham, Sch Med, Inst Canc Outcomes & Survivorship, Birmingham, AL USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier] Univ Paris 06, Hop Tenon, Ctr Rech Pathol Prostat CeRePP, Lab Urol,Res Team 2, Paris, France. [Morton, Lindsay M.; Machiela, Mitchell J.; Chanock, Stephen J.] NCI, DCEG, Bethesda, MD 20892 USA. RP Delattre, O (reprint author), PSL Res Univ, Inst Curie, Genet & Biol Canc Unit, Paris, France. EM olivier.delattre@curie.fr RI Tirode, Franck/B-4586-2009; Alonso, Javier/B-6012-2013; Grunewald, Thomas/O-2317-2013; Cox, David/A-2023-2009; Boeva, Valentina/C-2855-2017 OI Tirode, Franck/0000-0003-4731-7817; Machiela, Mitchell/0000-0001-6538-9705; Cancel-Tassin, Geraldine/0000-0002-9583-6382; Alonso, Javier/0000-0002-6287-8391; Grunewald, Thomas/0000-0003-0920-7377; Cox, David/0000-0002-2152-9259; Boeva, Valentina/0000-0002-4382-7185 FU German Research Foundation [DFG GR3728/2-1]; Daimler and Benz Foundation; LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative; Mehr LEBEN fur krebskranke Kinder-Bettina-Bruu-Stiftung; Institut Curie-SIRIC (Site de Recherche Integree en Cancerologie) program; Asociacion Pablo Ugarte; Instituto de Salud Carlos III [RTICC RD12/0036/0027]; InfoSarcomes Association; National Cancer Institute [CA55727]; Intramural Research Program of the National Institutes of Health, National Cancer Institute; Institut Curie; INSERM; Agence Nationale de la Recherche (Investissements d'Avenir) [ANR-10-EQPX-03]; Canceropole Ile-de-France [ANR10-INBS-09-08]; Ligue Nationale Contre le Cancer (Equipe labellisee); Institut National du Cancer [PLBIO14-237]; European PROVABES project [ERA-649 NET TRANSCAN JTC-2011]; ASSET project [FP7-HEALTH-2010-259348]; EEC project [HEALTH-F2-2013-602856]; Societe Francaise des Cancers de l'Enfant; CNRS; Ministere de la Recherche et Technologie; Fondation pour la Recherche Medicale; program "Investissements d'Avenir" [ANR-10-LABX-54 MEMOLIFE, ANR-11-IDEX-0001-02 PSLstar] FX T.G.P.G. is supported by a grant from the German Research Foundation (DFG GR3728/2-1), by the Daimler and Benz Foundation in cooperation with the Reinhard Frank Foundation, by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative and by the Mehr LEBEN fur krebskranke Kinder-Bettina-Bruu-Stiftung. D.S. is supported by the Institut Curie-SIRIC (Site de Recherche Integree en Cancerologie) program. F.C.-A. is supported by a grant from the Asociacion Pablo Ugarte and Instituto de Salud Carlos III RTICC RD12/0036/0027. D.G.C. is supported by a grant from the InfoSarcomes Association. The Childhood Cancer Survivor Study is supported by the National Cancer Institute (CA55727, G.T. Armstrong), with funding for genotyping from the Intramural Research Program of the National Institutes of Health, National Cancer Institute. This work was supported by grants from the Institut Curie; INSERM; the Agence Nationale de la Recherche (Investissements d'Avenir) (ANR-10-EQPX-03); the Canceropole Ile-de-France (ANR10-INBS-09-08); the Ligue Nationale Contre le Cancer (Equipe labellisee); the Institut National du Cancer (PLBIO14-237); the European PROVABES (ERA-649 NET TRANSCAN JTC-2011), ASSET (FP7-HEALTH-2010-259348) and EEC (HEALTH-F2-2013-602856) projects; and the Societe Francaise des Cancers de l'Enfant. The following associations supported this work: Courir pour Mathieu, Dans les pas du Geant, Olivier Chape, Les Bagouzamanon, Enfants et Sante, and les Amis de Claire. The Charnay laboratory was financed by INSERM, the CNRS, the Ministere de la Recherche et Technologie, and the Fondation pour la Recherche Medicale. It has received support under the program "Investissements d'Avenir" launched by the French Government and implemented by the ANR, with the references ANR-10-LABX-54 MEMOLIFE and ANR-11-IDEX-0001-02 PSLstar Research University. We thank J. Maris for providing genotype information for the neuroblastoma data set, and we thank L. Liang and W. Cookson for providing access to genotype data on the LCL data set. We thank H. Kovar (Children's Cancer Research Institute Vienna, Vienna, Austria) for providing cell lines STA-ET-1, STA-ET-3 and STA-ET-8, and F. Redini (University of Nantes, Nantes, France) for providing cell line TC-32. Human MSC lines L87 and V54-2 were kindly provided by P. Nelson (University Hospital LMU, Munich, Germany). We also thank the following clinicians and pathologists for providing samples used in this work: I. Aerts, P. Anract, C. Bergeron, L. Boccon-Gibod, F. Boman, F. Bourdeaut, C. Bouvier, R. Bouvier, L. Brugieres, E. Cassagnau, J. Champigneulle, C. Cordonnier, J. M. Coindre, N. Corradini, A. Coulomb-Lhermine, A. De Muret, G. De Pinieux, A.S. Defachelles, A. Deville, F. Dijoud, F. Doz, C. Dufour, K. Fernandez, N. Gaspard, L. Galmiche-Rolland, C. Glorion, A. Gomez-Brouchet, J. M. Guinebretiere, H. Jouan, C. Jeanne-Pasquier, B. Kantelip, F. Labrousse, V. Laithier, F. Larousserie, G. Leverger, C. Linassier, P. Mary, G. Margueritte, E. Mascard, A. Moreau, J. Michon, C. Michot, F. Millot, Y. Musizzano, M. Munzer, B. Narciso, O. Oberlin, D. Orbach, H. Pacquement, Y. Perel, B. Petit, M. Peuchmaur, J. Y. Pierga, C. Piguet, S. Piperno-Neumann, E. Plouvier, D. Ranchere-Vince, J. Rivel, C. Rouleau, H. Rubie, H. Sartelet, G. Schleiermacher, C. Schmitt, N. Sirvent, D. Sommelet, P. Terrier, R. Tichit, J. Vannier, J.M. Vignaud and V. Verkarre. We also thank D. Darmon for technical assistance, S. Grossetete-Lalami for bioinformatic assistance, and V.R. Buchholz and E.; Butt for critical reading of the manuscript. NR 60 TC 16 Z9 17 U1 2 U2 20 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 SEP PY 2015 VL 47 IS 9 BP 1073 EP + DI 10.1038/ng.3363 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CQ1XQ UT WOS:000360394100019 PM 26214589 ER PT J AU Paull, D Sevilla, A Zhou, HY Hahn, AK Kim, H Napolitano, C Tsankov, A Shang, LS Krumholz, K Jagadeesan, P Woodard, CM Sun, B Vilboux, T Zimmer, M Forero, E Moroziewicz, DN Martinez, H Malicdan, MCV Weiss, KA Vensand, LB Dusenberry, CR Polus, H Sy, KTL Kahler, DJ Gahl, WA Solomon, SL Chang, S Meissner, A Eggan, K Noggle, SA AF Paull, Daniel Sevilla, Ana Zhou, Hongyan Hahn, Aana Kim Kim, Hesed Napolitano, Christopher Tsankov, Alexander Shang, Linshan Krumholz, Katie Jagadeesan, Premlatha Woodard, Chris M. Sun, Bruce Vilboux, Thierry Zimmer, Matthew Forero, Eliana Moroziewicz, Dorota N. Martinez, Hector Malicdan, May Christine V. Weiss, Keren A. Vensand, Lauren B. Dusenberry, Carmen R. Polus, Hannah Sy, Karla Therese L. Kahler, David J. Gahl, William A. Solomon, Susan L. Chang, Stephen Meissner, Alexander Eggan, Kevin Noggle, Scott A. TI Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells SO NATURE METHODS LA English DT Article ID EFFICIENT GENERATION; MESSENGER-RNA; HUMAN SKIN; DISEASE; CULTURE; IPSC; MAINTENANCE; INDUCTION; EXPANSION; PLATFORM AB Induced pluripotent stem cells (iPSCSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSCSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSCSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines. C1 [Paull, Daniel; Sevilla, Ana; Zhou, Hongyan; Hahn, Aana Kim; Kim, Hesed; Napolitano, Christopher; Shang, Linshan; Krumholz, Katie; Jagadeesan, Premlatha; Woodard, Chris M.; Sun, Bruce; Zimmer, Matthew; Forero, Eliana; Moroziewicz, Dorota N.; Martinez, Hector; Weiss, Keren A.; Vensand, Lauren B.; Dusenberry, Carmen R.; Polus, Hannah; Sy, Karla Therese L.; Kahler, David J.; Solomon, Susan L.; Chang, Stephen; Noggle, Scott A.] New York Stem Cell Fdn Res Inst, New York, NY 10023 USA. [Tsankov, Alexander; Meissner, Alexander; Eggan, Kevin] Broad Inst, Cambridge, MA USA. [Tsankov, Alexander; Meissner, Alexander; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tsankov, Alexander; Meissner, Alexander; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Vilboux, Thierry; Malicdan, May Christine V.; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Vilboux, Thierry] Inova Hlth Syst, Inova Translat Med Inst, Div Med Genom, Falls Church, VA USA. [Gahl, William A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA. [Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Eggan, Kevin] Howard Hughes Med Inst, Cambridge, MA USA. RP Paull, D (reprint author), New York Stem Cell Fdn Res Inst, New York, NY 10023 USA. EM dpaull@nyscf.org; snoggle@nyscf.org RI zhou, hongyan/B-3689-2011 OI zhou, hongyan/0000-0001-5919-7715 FU US National Institutes of Health grant [P01GM099117] FX We thank L. Rubin, Z. Hall and S. Lipnick for critical reading of the manuscript. This work would not have been possible without S. Solomon's leadership, vision, continual encouragement and unstinting support. The authors also thank The Genomics Core, National Human Genome Research Institute, for performing the SNP arrays and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, USA for their contributions. A.M. receives support as a New York Stem Cell Foundation Robertson Investigator, with additional funding through US National Institutes of Health grant P01GM099117. NR 41 TC 28 Z9 28 U1 6 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD SEP PY 2015 VL 12 IS 9 BP 885 EP + DI 10.1038/NMETH.3507 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ4PI UT WOS:000360586700036 PM 26237226 ER PT J AU Liu, ZB Lin, KS Benard, F Pourghiasian, M Kiesewetter, DO Perrin, DM Chen, XY AF Liu, Zhibo Lin, Kuo-Shyan Benard, Francois Pourghiasian, Maral Kiesewetter, Dale O. Perrin, David M. Chen, Xiaoyuan TI One-step F-18 labeling of biomolecules using organotrifluoroborates SO NATURE PROTOCOLS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CARBONIC-ANHYDRASE IX; IN-VIVO EVALUATION; PET; PEPTIDES; TARGET; KIT; RADIOSYNTHESIS; CHELATION; AZIDES AB Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous F-18 fluoride (F-18-) and used for positron emission tomography (PETPETPET) imaging. Among the beta+-emitting radionuclides, fluorine-18 (F-18) is the isotope of choice for PETPETPET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be F-18-labeled in one step in aqueous conditions via F-18-F-19 isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step F-18-labeling method that obviates the need for HPLCPLCPLC purification. Within 30 min, F-18-labeled PETPETPET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (> 98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/mmol (1.1-3.0 Ci/mu mol). The entire procedure, including the precursor preparation and F-18 radiolabeling, takes 7-10 d. C1 [Liu, Zhibo; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Lin, Kuo-Shyan; Benard, Francois; Pourghiasian, Maral] British Columbia Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 4E6, Canada. [Perrin, David M.] Univ British Columbia, Dept Chem, Vancouver, BC, Canada. RP Liu, ZB (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM zhibo.liu@nih.gov; dperrin@chem.ubc.ca; shawn.chen@nih.gov RI Benard, Francois/M-7720-2015; OI Benard, Francois/0000-0001-7995-3581; Lin, Kuo-Shyan/0000-0002-0739-0780 FU National Sciences and Engineering Research Council; Canadian Cancer Society Research Institute FX This work was supported by the National Sciences and Engineering Research Council, and the Canadian Cancer Society Research Institute, with contributions from the intramural research program at National Institute of Biomedical Imaging and Bioengineering, US National Institutes of Health. NR 44 TC 8 Z9 8 U1 8 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD SEP PY 2015 VL 10 IS 9 BP 1423 EP 1432 DI 10.1038/nprot.2015.090 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CQ3HQ UT WOS:000360493200011 PM 26313478 ER PT J AU Nugent, AC Robinson, SE Coppola, R Furey, ML Zarate, CA AF Nugent, Allison C. Robinson, Stephen E. Coppola, Richard Furey, Maura L. Zarate, Carlos A., Jr. TI Group differences in MEG-ICA derived resting state networks: Application to major depressive disorder SO NEUROIMAGE LA English DT Article DE Magnetoencephalography (MEG); Depression; Network ID INDEPENDENT COMPONENT ANALYSIS; TREATMENT-RESISTANT DEPRESSION; RAPID ANTIDEPRESSANT RESPONSE; ANTERIOR CINGULATE CORTEX; FUNCTIONAL CONNECTIVITY; GLUCOSE-METABOLISM; DEFAULT MODE; BRAIN NETWORKS; MAGNETOENCEPHALOGRAPHY; KETAMINE AB Functional magnetic resonance imaging (fMRI) studies have revealed the existence of robust, interconnected brain networks exhibiting correlated low frequency fluctuations during rest, which can be derived by examining inherent spatio-temporal patterns in functional scans independent of any a priori model. In order to explore the electrophysiological underpinnings of these networks, analogous techniques have recently been applied to magnetoencephalography (MEG) data, revealing similar networks that exhibit correlated low frequency fluctuations in the power envelope of beta band (14-30 Hz) power. However, studies to date using this technique have concentrated on healthy subjects, and no method has yet been presented for group comparisons. We extended the ICA resting state MEG method to enable group comparisons, and demonstrate the technique in a sample of subjects with major depressive disorder (MDD). We found that the intrinsic resting state networks evident in fMRI appeared to be disrupted in individuals with MDD compared to healthy participants, particularly in the subgenual cingulate, although the electrophysiological correlates of this are unknown. Networks extracted from a combined group of healthy and MDD participants were examined for differences between groups. Individuals with MDD showed reduced correlations between the subgenual anterior cingulate (sgACC) and hippocampus in a network with primary nodes in the precentral and middle frontal gyri. Individuals with MDD also showed increased correlations between insulo-temporal nodes and amygdala compared to healthy controls. To further support our methods and findings, we present test/re-test reliability on independent recordings acquired within the same session. Our results demonstrate that group analyses are possible with the resting state MEG-independent component analysis (ICA) technique, highlighting a new pathway for analysis and discovery. This study also provides the first evidence of altered sgACC connectivity with a motor network. This finding, reliable across multiple sessions, suggests that the sgACC may partially mediate the psychomotor symptoms of MDD via synchronized changes in beta-band power, and expands the idea of the sgACC as a hub region mediating cognitive and emotional symptomatic domains in MDD. Findings of increased connectivity between the amygdala and cortical nodes further support the role of amygdalar networks in mediated depressive symptomatology. Published by Elsevier Inc. C1 [Nugent, Allison C.; Furey, Maura L.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Robinson, Stephen E.; Coppola, Richard] NIMH, NIMH Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA. RP Nugent, AC (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 9000 Rockville Pike,MSC 1030, Bethesda, MD 20892 USA. EM nugenta@mail.nih.gov OI Nugent, Allison/0000-0003-2569-2480 FU Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); NARSAD Independent Investigator; Brain & Behavior Mood Disorders Research Award; 7SE research unit FX Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator to CAZ, and by the Brain & Behavior Mood Disorders Research Award to CAZ. The authors thank the 7SE research unit and staff for their support. Ioline Henter, MA (NIMH) provided invaluable editorial assistance. We are also grateful to Matthew Brookes for many helpful conversations regarding the techniques implemented herein. NR 69 TC 8 Z9 8 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2015 VL 118 BP 1 EP 12 DI 10.1016/j.neuroimage.2015.05.051 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CQ5GB UT WOS:000360630200001 PM 26032890 ER PT J AU Saar, G Cheng, N Belluscio, L Koretsky, AP AF Saar, Galit Cheng, Ning Belluscio, Leonardo Koretsky, Alan P. TI Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model SO NEUROIMAGE LA English DT Article DE Manganese enhanced MRI; Olfaction; Alzheimer's disease; Molecular imaging ID MANGANESE-ENHANCED MRI; MILD COGNITIVE IMPAIRMENT; AXONAL-TRANSPORT RATES; AMYLOID-BETA; BULB VOLUME; TRANSGENIC MICE; BRAIN; HIPPOCAMPAL; ATROPHY; PHASE AB Manganese enhanced MRI (MEMRI) was used to detect specific laminar changes in the olfactory bulb (OB) to follow the progression of amyloid precursor protein (APP)-induced neuronal pathology and its recovery in a reversible olfactory based Alzheimer's disease (AD) mouse model. Olfactory dysfunction is an early symptom of AD, which suggests that olfactory sensory neurons (OSNs) may be more sensitive to AD related factors than neurons in other brain areas. Previously a transgenic mouse model was established that causes degeneration of OSNs by over-expressing humanized APP (hAPP), which results in a disruption of the olfactory circuitry with changes in the glomerular structure. In the present work, OB volume and manganese enhancement of the glomerular layer in the OB were decreased in mutant mice. Turning off APP overexpression with doxycycline produced a significant increase in manganese enhancement of the glomerular layer after only 1 week, and further recovery after 3 weeks, while treatment with A beta antibody produced modest improvement with MRI measurements. Thus, MEMRI enables a direct tracking of laminar specific neurodegeneration through a non-invasive in vivo measurement. The use of MRI will enable assessment of the ability of different pharmacological reagents to block olfactory neuronal loss and can serve as a unique in vivo screening tool to both identify potential therapeutics and test their efficacy. Published by Elsevier Inc. C1 [Saar, Galit; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Cheng, Ning; Belluscio, Leonardo] NINDS, Dev Neuronal Plast Unit, NIH, Bethesda, MD 20892 USA. [Cheng, Ning] Univ Calgary, Cumming Sch Med, Alberta Childrens Hosp Res Inst ACHRI, Calgary, AB T2N 4N1, Canada. RP Koretsky, AP (reprint author), NINDS, NIH, 10 Ctr Dr,Bldg 10,Rm B1D728,MSC 1065, Bethesda, MD 20892 USA. EM saarg@mail.nih.gov; ncheng@ucalgary.ca; belluscl@mail.nih.gov; koretskya@ninds.nih.gov FU Intramural Research Program of the NIH, NINDS FX This research was supported by the Intramural Research Program of the NIH, NINDS. We thank Nadia Bouraoud and Li Bai for assistance with animal procedures and animal handling. We also thank Dr. Steve Dodd for providing MRI technical support. NR 54 TC 2 Z9 2 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2015 VL 118 BP 183 EP 192 DI 10.1016/j.neuroimage.2015.05.045 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CQ5GB UT WOS:000360630200018 PM 26021215 ER PT J AU Klein, MM Treister, R Raij, T Pascual-Leone, A Park, L Nurmikko, T Lenz, F Lefaucheur, JP Lang, M Hallett, M Fox, M Cudkowicz, M Costello, A Carr, DB Ayache, SS Oaklander, AL AF Klein, Max M. Treister, Roi Raij, Tommi Pascual-Leone, Alvaro Park, Lawrence Nurmikko, Turo Lenz, Fred Lefaucheur, Jean-Pascal Lang, Magdalena Hallett, Mark Fox, Michael Cudkowicz, Merit Costello, Ann Carr, Daniel B. Ayache, Samar S. Oaklander, Anne Louise TI Transcranial magnetic stimulation of the brain: guidelines for pain treatment research SO PAIN LA English DT Review DE Neuropathic pain; Neuromodulation; Treatment; Human; Device ID MOTOR CORTEX STIMULATION; SHAM-CONTROLLED TRIAL; SPINAL-CORD-INJURY; CHRONIC NEUROPATHIC PAIN; SYNDROME TYPE-I; THETA-BURST STIMULATION; CENTRAL POSTSTROKE PAIN; SMALL-FIBER NEUROPATHY; DOUBLE-BLIND; MULTIPLE-SCLEROSIS AB Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials. C1 [Klein, Max M.; Treister, Roi; Lang, Magdalena; Fox, Michael; Cudkowicz, Merit; Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Raij, Tommi; Fox, Michael] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Boston, MA 02114 USA. [Pascual-Leone, Alvaro; Fox, Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02114 USA. [Park, Lawrence; Costello, Ann] US FDA, Ctr Devices & Radiol Hlth, Div Neurol & Phys Med Devices, Off Device Evaluat, Bethesda, MD 20014 USA. [Park, Lawrence] NIMH, US Natl Inst Hlth, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Nurmikko, Turo] Walton Ctr NHS Fdn Trust, Pain Res Inst, Neurosci Res Ctr, Liverpool, Merseyside, England. [Lenz, Fred] Johns Hopkins Med Inst, Dept Neurosurg, Baltimore, MD 21205 USA. [Lefaucheur, Jean-Pascal; Ayache, Samar S.] Henri Mondor Hosp, Assistance Publ Hop Paris, Dept Physiol, Creteil, France. [Lefaucheur, Jean-Pascal; Ayache, Samar S.] Paris Est Creteil Univ, Fac Med, Nerve Excitabil & Therapeut Team, EA 4391, Creteil, France. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Anesthesiol, Boston, MA 02111 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Klein, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 275 Charles St Warren Bldg 310, Boston, MA 02114 USA. EM mklein@mgh.harvard.edu FU Radcliffe Institute for Advanced Study; Samuels Family Foundation; Public Health Service [K24NS059892, K23NS083741, NS38493, R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, U01NS077179]; NINDS; UK National Institute of Health Research [PB-PG-0110-20321]; Hopkins Neurosurgery Pain Research Institute; American Academy of Neurology/American Brain Foundation; Sidney R. Baer Foundation; Harvard Catalyst-Clinical and Translational Science Center [UL1 RR025758] FX Supported in part by the Radcliffe Institute for Advanced Study and the Samuels Family Foundation, the Public Health Service (K24NS059892, K23NS083741, NS38493, R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, and U01NS077179) and NINDS intramural support to M. Hallett, the UK National Institute of Health Research (PB-PG-0110-20321) to T. Nurmikko, the Hopkins Neurosurgery Pain Research Institute, the American Academy of Neurology/American Brain Foundation, the Sidney R. Baer Foundation, the Harvard Catalyst-Clinical and Translational Science Center (UL1 RR025758). NR 117 TC 16 Z9 16 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD SEP PY 2015 VL 156 IS 9 BP 1601 EP 1614 DI 10.1097/j.pain.0000000000000210 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CQ4MQ UT WOS:000360579400007 PM 25919472 ER PT J AU Siqueira, L Smith, VC AF Siqueira, Lorena Smith, Vincent C. CA Comm Subst Abuse TI Binge Drinking SO PEDIATRICS LA English DT Article ID HEALTH-RISK BEHAVIORS; HIGH-SCHOOL-STUDENTS; ALCOHOL-CONSUMPTION; UNITED-STATES; UNDERAGE DRINKING; COLLEGE-STUDENTS; SELF-EFFICACY; ADOLESCENTS; PREDICTORS; INTERVENTIONS AB Alcohol is the substance most frequently abused by children and adolescents in the United States, and its use is associated with the leading causes of death and serious injury at this age (ie, motor vehicle accidents, homicides, and suicides). Among youth who drink, the proportion who drink heavily is higher than among adult drinkers, increasing from approximately 50% in those 12 to 14 years of age to 72% among those 18 to 20 years of age. In this clinical report, the definition, epidemiology, and risk factors for binge drinking; the neurobiology of intoxication, blackouts, and hangovers; genetic considerations; and adverse outcomes are discussed. The report offers guidance for the pediatrician. As with any high-risk behavior, prevention plays a more important role than later intervention and has been shown to be more effective. In the pediatric office setting, it is important to ask every adolescent about alcohol use. C1 [Siqueira, Lorena] NIAAA, Orlando, FL 32832 USA. [Smith, Vincent C.] Amer Acad Child & Adolescent Psychiat, New York, NY USA. RP Siqueira, L (reprint author), NIAAA, Orlando, FL 32832 USA. NR 71 TC 5 Z9 5 U1 9 U2 34 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 SEP PY 2015 VL 136 IS 3 BP E718 EP E726 DI 10.1542/peds.2015-2337 PG 9 WC Pediatrics SC Pediatrics GA CQ6IN UT WOS:000360708100025 PM 26324872 ER PT J AU Chughtai, AA Kassak, F Kostrouchova, M Novotny, JP Krause, MW Saudek, V Kostrouch, Z Kostrouchova, M AF Chughtai, Ahmed Ali Kassak, Filip Kostrouchova, Marketa Novotny, Jan Philipp Krause, Michael W. Saudek, Vladimir Kostrouch, Zdenek Kostrouchova, Marta TI Perilipin-related protein regulates lipid metabolism in C-elegans SO PEERJ LA English DT Article DE Perilipin; Perilipin-related protein in C. elegans; Caenorhabditis elegans; Lipid droplets; Fat metabolism ID ADIPOSE TRIGLYCERIDE LIPASE; CAENORHABDITIS-ELEGANS; DROPLET PROTEINS; HOMOLOG LSD2; FAT STORAGE; PAT-FAMILY; DROSOPHILA; AUTOPHAGY; LIPOLYSIS; GENE AB Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. Inmutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism. C1 [Chughtai, Ahmed Ali; Kassak, Filip; Kostrouchova, Marketa; Novotny, Jan Philipp; Kostrouch, Zdenek; Kostrouchova, Marta] Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, Prague, Czech Republic. [Kostrouchova, Marketa] Charles Univ Prague, Dept Pathol, Fac Med 3, Prague, Czech Republic. [Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Saudek, Vladimir] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Wellcome Trust Med Res Council, Cambridge, England. RP Saudek, V (reprint author), Univ Cambridge, Metab Res Labs, Inst Metab Sci, Wellcome Trust Med Res Council, Cambridge, England. EM vs317@cam.ac.uk; marta.kostrouchova@lf1.cuni.cz OI Krause, Michael/0000-0001-6127-3940 FU European Regional Development Fund "BIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec" [CZ.1.05/1.1.00/02.0109]; Charles University in Prague [PRVOUK-P27/LF1/1, SVV 260023/2014, SVV 260149/2015]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, USA; MediCentrum Praha a.s. FX This work was supported by the European Regional Development Fund "BIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec" (CZ.1.05/1.1.00/02.0109); the grant PRVOUK-P27/LF1/1 from Charles University in Prague; the grants SVV 260023/2014 and SVV 260149/2015 from Charles University in Prague. MWK is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, USA. The authors received funds from MediCentrum Praha a.s. to support the work reported in this publication. ZK and MK contributed personal funds to this work. The funders (excluding the authors) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 3 Z9 3 U1 0 U2 9 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD SEP 1 PY 2015 VL 3 AR e1213 DI 10.7717/peerj.1213 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ8HX UT WOS:000360849100001 PM 26357594 ER PT J AU Becnel, LB Darlington, YF Ochsner, SA Easton-Marks, JR Watkins, CM McOwiti, A Kankanamge, WH Wise, MW DeHart, M Margolis, RN McKenna, NJ AF Becnel, Lauren B. Darlington, Yolanda F. Ochsner, Scott A. Easton-Marks, Jeremy R. Watkins, Christopher M. McOwiti, Apollo Kankanamge, Wasula H. Wise, Michael W. DeHart, Michael Margolis, Ronald N. McKenna, Neil J. TI Nuclear Receptor Signaling Atlas: Opening Access to the Biology of Nuclear Receptor Signaling Pathways SO PLOS ONE LA English DT Article ID BREAST-CANCER CELLS; GENE-EXPRESSION; ER-ALPHA; ESTROGEN; COREGULATORS; NETWORKS; RESOURCE AB Signaling pathways involving nuclear receptors (NRs), their ligands and coregulators, regulate tissue-specific transcriptomes in diverse processes, including development, metabolism, reproduction, the immune response and neuronal function, as well as in their associated pathologies. The Nuclear Receptor Signaling Atlas (NURSA) is a Consortium focused around a Hub website (www.nursa.org) that annotates and integrates diverse 'omics datasets originating from the published literature and NURSA-funded Data Source Projects (NDSPs). These datasets are then exposed to the scientific community on an Open Access basis through user-friendly data browsing and search interfaces. Here, we describe the redesign of the Hub, version 3.0, to deploy "Web 2.0" technologies and add richer, more diverse content. The Molecule Pages, which aggregate information relevant to NR signaling pathways from myriad external databases, have been enhanced to include resources for basic scientists, such as post-translational modification sites and targeting miRNAs, and for clinicians, such as clinical trials. A portal to NURSA's Open Access, PubMed-indexed journal Nuclear Receptor Signaling has been added to facilitate manuscript submissions. Datasets and information on reagents generated by NDSPs are available, as is information concerning periodic new NDSP funding solicitations. Finally, the new website integrates the Transcriptomine analysis tool, which allows for mining of millions of richly annotated public transcriptomic data points in the field, providing an environment for dataset re-use and citation, bench data validation and hypothesis generation. We anticipate that this new release of the NURSA database will have tangible, long term benefits for both basic and clinical research in this field. C1 [Becnel, Lauren B.; Darlington, Yolanda F.; Easton-Marks, Jeremy R.; Watkins, Christopher M.; McOwiti, Apollo; Kankanamge, Wasula H.; DeHart, Michael] Dan L Duncan Comprehens Canc Ctr, Biomed Informat Grp, Houston, TX USA. [Ochsner, Scott A.; McKenna, Neil J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Wise, Michael W.; Margolis, Ronald N.] NIDDK, Div Diabet & Metab Dis, Bethesda, MD USA. [Becnel, Lauren B.; Darlington, Yolanda F.; Ochsner, Scott A.; Easton-Marks, Jeremy R.; Watkins, Christopher M.; McOwiti, Apollo; Kankanamge, Wasula H.; Wise, Michael W.; DeHart, Michael; McKenna, Neil J.] Nucl Receptor Signaling Atlas NURSA Informat Hub, Bethesda, MD USA. RP McKenna, NJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, One Baylor Plaza, Houston, TX 77030 USA. EM nmckenna@bcm.edu OI Margolis, Ronald/0000-0002-8956-0455; Ochsner, Scott/0000-0003-1099-7863 FU National Institute of Diabetes Digestive and Kidney Diseases; Eunice Kennedy Shriver National Institute of Child Health and Development [DK097748]; National Institutes of Health Big Data To Knowledge (BD2K) program [DK097748-S1] FX NURSA is supported by grants from the National Institute of Diabetes Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Development (DK097748) and by the National Institutes of Health Big Data To Knowledge (BD2K) program (DK097748-S1). NR 30 TC 5 Z9 5 U1 0 U2 4 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 SEP 1 PY 2015 VL 10 IS 9 AR e0135615 DI 10.1371/journal.pone.0135615 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ2NK UT WOS:000360437700022 PM 26325041 ER PT J AU Hill, MD Martin, RH Palesch, YY Moy, CS Tamariz, D Ryckborst, KJ Jones, EB Weisman, D Pettigrew, C Ginsberg, MD AF Hill, Michael D. Martin, Renee H. Palesch, Yuko Y. Moy, Claudia S. Tamariz, Diego Ryckborst, Karla J. Jones, Elizabeth B. Weisman, David Pettigrew, Creed Ginsberg, Myron D. TI Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial SO PLOS ONE LA English DT Article ID MARKED NEUROPROTECTIVE EFFICACY; FOCAL CEREBRAL-ISCHEMIA; LOCAL VASCULAR DYNAMICS; TROPONIN-T; MYOCARDIAL-INFARCTION; DOSE-ESCALATION; RAT MODEL; THERAPY; THROMBOLYSIS; FIBRINOGEN AB Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18-83 and a baseline NIHSS >= 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01-5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3-26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. C1 [Hill, Michael D.] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Hill, Michael D.] Univ Calgary, Dept Med, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada. [Hill, Michael D.] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Dept Radiol, Calgary, AB, Canada. [Hill, Michael D.] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Dept Community Hlth Sci, Calgary, AB, Canada. [Martin, Renee H.; Palesch, Yuko Y.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Moy, Claudia S.] NINDS, Off Clin Res, NIH, Bethesda, MD 20892 USA. [Tamariz, Diego; Ginsberg, Myron D.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Ryckborst, Karla J.] Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada. [Jones, Elizabeth B.] Univ Texas Hlth Sci Ctr Houston, Dept Emergency Med, Houston, TX 77030 USA. [Weisman, David] Abington Neurol Associates, Abington, PA USA. [Pettigrew, Creed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Pettigrew, Creed] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Hill, MD (reprint author), Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. EM michael.hill@ucalgary.ca FU National Institute of Neurological Disorders and Stroke, National Institutes of Health [U01NS040406, U01NS054630, U01NS056975, U10NS058967] FX This work was supported by cooperative agreements from the National Institute of Neurological Disorders and Stroke, National Institutes of Health (U01NS040406, University of Miami; U01NS054630, Medical University of South Carolina; U01NS056975, University of Michigan; U10NS058967, University of Kentucky). NR 28 TC 2 Z9 2 U1 0 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 SEP 1 PY 2015 VL 10 IS 9 AR e0131390 DI 10.1371/journal.pone.0131390 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ2NK UT WOS:000360437700003 PM 26325387 ER PT J AU Pomeroy, LW Bjornstad, ON Kim, H Jumbo, SD Abdoulkadiri, S Garabed, R AF Pomeroy, Laura W. Bjornstad, Ottar N. Kim, Hyeyoung Jumbo, Simon Dickmu Abdoulkadiri, Souley Garabed, Rebecca TI Serotype-Specific Transmission and Waning Immunity of Endemic Foot-and-Mouth Disease Virus in Cameroon SO PLOS ONE LA English DT Article ID ECONOMIC-IMPACTS; GREAT-BRITAIN; INFECTION; LIVESTOCK; EPIDEMIC; DYNAMICS; SPREAD; CATTLE; FORCE; AUSTRALIA AB Foot-and-mouth disease virus (FMDV) causes morbidity and mortality in a range of animals and threatens local economies by acting as a barrier to international trade. The outbreak in the United Kingdom in 2001 that cost billions to control highlighted the risk that the pathogen poses to agriculture. In response, several mathematical models have been developed to parameterize and predict both transmission dynamics and optimal disease control. However, a lack of understanding of the multi-strain etiology prevents characterization of multi-strain dynamics. Here, we use data from FMDV serology in an endemic setting to probe strain-specific transmission and immunodynamics. Five serotypes of FMDV affect cattle in the Far North Region of Cameroon. We fit both catalytic and reverse catalytic models to serological data to estimate the force of infection and the rate of waning immunity, and to detect periods of sustained transmission. For serotypes SAT2, SAT3, and type A, a model assuming life-long immunity fit better. For serotypes SAT1 and type O, the better-fit model suggests that immunity may wane over time. Our analysis further indicates that type O has the greatest force of infection and the longest duration of immunity. Estimates for the force of infection were time-varying and indicated that serotypes SAT1 and O displayed endemic dynamics, serotype A displayed epidemic dynamics, and SAT2 and SAT3 did not sustain local chains of transmission. Since these results were obtained from the same population at the same time, they highlight important differences in transmission specific to each serotype. They also show that immunity wanes at rates specific to each serotype, which influences patterns of local persistence. Overall, this work shows that viral serotypes can differ significantly in their epidemiological and immunological characteristics. Patterns and processes that drive transmission in endemic settings must consider complex viral dynamics for accurate representation and interpretation. C1 [Pomeroy, Laura W.; Garabed, Rebecca] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. [Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Bjornstad, Ottar N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Kim, Hyeyoung] Ohio State Univ, Dept Geog, Columbus, OH 43210 USA. [Jumbo, Simon Dickmu; Abdoulkadiri, Souley] Lanavet, Lab Natl Vet, Garoua, Cameroon. [Garabed, Rebecca] Ohio State Univ, Publ Hlth Preparedness Infect Dis Program, Columbus, OH 43210 USA. RP Pomeroy, LW (reprint author), Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. EM pomeroy.26@osu.edu FU Eunice Kennedy Shriver National Institute of Child Health & Human Development [R24-HD058484]; National Science Foundation [DEB-1015908]; Ohio State University Initiative in Population Research FX This work was supported by award R24-HD058484 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (http://www.nichd.nih.gov/Pages/index.aspx), awarded to the Ohio State University Initiative in Population Research and RG, and by award DEB-1015908 from the National Science Foundation (http://www.nsf.gov), awarded to RG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 3 Z9 3 U1 3 U2 6 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 SEP 1 PY 2015 VL 10 IS 9 AR e0136642 DI 10.1371/journal.pone.0136642 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ2NK UT WOS:000360437700051 PM 26327324 ER PT J AU Senkevicha, TG Bruno, D Martens, C Porcella, SF Wolf, YI Moss, B AF Senkevicha, Tatiana G. Bruno, Daniel Martens, Craig Porcella, Stephen F. Wolf, Yuri I. Moss, Bernard TI Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vaccinia virus; DNA replication; DNA replication fork; DNA replication origin; Okazaki fragments ID OKAZAKI FRAGMENT MATURATION; VIRAL-DNA; GENOME; INITIATION; RESOLUTION; JUNCTION; PRIMASE; CHROMOSOME; FACTORIES; REQUIRES AB Poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded DNA genomes. Nevertheless, the mode of poxvirus DNA replication and the nature and location of the replication origins remain unknown. A current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subsequently resolved into unit genomes. The existence of specific origins has been questioned because any plasmid can replicate in cells infected by vaccinia virus (VACV), the prototype poxvirus. We applied directional deep sequencing of short single-stranded DNA fragments enriched for RNA-primed nascent strands isolated from the cytoplasm of VACV-infected cells to pinpoint replication origins. The origins were identified as the switching points of the fragment directions, which correspond to the transition from continuous to discontinuous DNA synthesis. Origins containing a prominent initiation point mapped to a sequence within the hairpin loop at one end of the VACV genome and to the same sequence within the concatemeric junction of replication intermediates. These findings support a model for poxvirus genome replication that involves leading and lagging strand synthesis and is consistent with the requirements for primase and ligase activities as well as earlier electron microscopic and biochemical studies implicating a replication origin at the end of the VACV genome. C1 [Senkevicha, Tatiana G.; Moss, Bernard] NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. [Bruno, Daniel; Martens, Craig; Porcella, Stephen F.] NIAID, Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Moss, B (reprint author), NIAID, Lab Viral Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Wolfgang Resch of the Scientific Computing Branch, Center for Information Technology, for useful suggestions on sequence analysis and Eugene Koonin of the National Center for Biotechnology Information of the National Library of Medicine for helpful discussions and critical reading of the manuscript. The research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 43 TC 0 Z9 0 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2015 VL 112 IS 35 BP 10908 EP 10913 DI 10.1073/pnas.1514809112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200042 PM 26286988 ER PT J AU Maruotti, J Sripathi, SR Bharti, K Fuller, J Wahlin, KJ Ranganathan, V Sluch, VM Berlinicke, CA Davis, J Kim, C Zhao, LJ Wan, J Qian, J Corneo, B Temple, S Dubey, R Olenyuk, BZ Bhutto, I Lutty, GA Zack, DJ AF Maruotti, Julien Sripathi, Srinivas R. Bharti, Kapil Fuller, John Wahlin, Karl J. Ranganathan, Vinod Sluch, Valentin M. Berlinicke, Cynthia A. Davis, Janine Kim, Catherine Zhao, Lijun Wan, Jun Qian, Jiang Corneo, Barbara Temple, Sally Dubey, Ramin Olenyuk, Bogdan Z. Bhutto, Imran Lutty, Gerard A. Zack, Donald J. TI Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE retinal pigment epithelium; pluripotent stem cells; high-throughput screening; differentiation; age-related macular degeneration ID DIFFERENTIATION; EXPRESSION; DERIVATION; MEMBRANE; PATHWAY; DISEASE; RPE AB Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule-only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE. C1 [Maruotti, Julien; Sripathi, Srinivas R.; Fuller, John; Wahlin, Karl J.; Ranganathan, Vinod; Sluch, Valentin M.; Berlinicke, Cynthia A.; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Bhutto, Imran; Lutty, Gerard A.; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Bharti, Kapil; Davis, Janine] NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA. [Corneo, Barbara] Columbia Univ, Stem Cell Core Facil, New York, NY 10032 USA. [Temple, Sally] Neural Stem Cell Inst, Rensselaer, NY 12144 USA. [Dubey, Ramin] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Dubey, Ramin] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. [Olenyuk, Bogdan Z.] Univ So Calif, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. [Zack, Donald J.] Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD 21287 USA. [Zack, Donald J.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21287 USA. [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Inst Genet Med, Baltimore, MD 21287 USA. RP Zack, DJ (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. EM dzack@jhmi.edu RI Wan, Jun/H-7132-2013; OI Wan, Jun/0000-0001-9286-6562; Fuller, John/0000-0002-6587-146X; Jaskula-Ranga, Vinod/0000-0003-1202-634X FU Foundation Fighting Blindness Wynn-Gund Translational Acceleration Program; Bright Focus Macular Degeneration Research Program; NIH [5R21EY023812-02, P30EY001765]; Research to Prevent Blindness, Inc. FX We thank Dr. Linzhao Cheng (The Johns Hopkins University) for providing hiPSC BC1, and Dr. Emeline Nandrot (Institut de la Vision) for providing FITC-POS. This work was supported by grants from Foundation Fighting Blindness Wynn-Gund Translational Acceleration Program, Bright Focus Macular Degeneration Research Program, NIH Grants 5R21EY023812-02 and P30EY001765, unrestricted funds from Research to Prevent Blindness, Inc., and generous gifts from the Guerrieri Family Foundation, Mr. and Mrs. Robert and Clarice Smith, and the Raab Family Foundation. NR 30 TC 8 Z9 8 U1 0 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2015 VL 112 IS 35 BP 10950 EP 10955 DI 10.1073/pnas.1422818112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200049 PM 26269569 ER PT J AU Massoud, R Enose-Akahata, Y Tagaya, Y Azimi, N Basheer, A Jacobson, S AF Massoud, Raya Enose-Akahata, Yoshimi Tagaya, Yutaka Azimi, Nazli Basheer, Asjad Jacobson, Steven TI Common gamma-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human T-cell lymphotropic virus type 1; HAM/TSP; gamma chain; IL-15 ID T-CELLS; SPONTANEOUS LYMPHOPROLIFERATION; NEUROLOGIC DISEASE; IL-15; LYMPHOCYTES; INFECTION; HAM/TSP; PROTEIN; LOAD AB Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive inflammatory myelopathy occurring in a subset of HTLV-1-infected individuals. Despite advances in understanding its immunopathogenesis, an effective treatment remains to be found. IL-2 and IL-15, members of the gamma chain (gamma c) family of cytokines, are prominently deregulated in HAM/TSP and underlie many of the characteristic immune abnormalities, such as spontaneous lymphocyte proliferation (SP), increased STAT5 phosphorylation in the lymphocytes, and increased frequency and cytotoxicity of virus-specific cytotoxic CD8(+) T lymphocytes (CTLs). In this study, we describe a novel immunomodulatory strategy consisting of selective blockade of certain gamma c family cytokines, including IL-2 and IL-15, with a gamma c antagonistic peptide. In vitro, a PEGylated form of the peptide, named BNZ132-1-40, reduced multiple immune activation markers such as SP, STAT5 phosphorylation, spontaneous degranulation of CD8(+) T cells, and the frequency of transactivator protein (Tax)-specific CD8(+) CTLs, thought to be major players in the immunopathogenesis of the disease. This strategy is thus a promising therapeutic approach to HAM/TSP with the potential of being more effective than single monoclonal antibodies targeting either IL-2 or IL-15 receptors and safer than inhibitors of downstream signaling molecules such as JAK1 inhibitors. Finally, selective cytokine blockade with antagonistic peptides might be applicable to multiple other conditions in which cytokines are pathogenic. C1 [Massoud, Raya; Enose-Akahata, Yoshimi; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Tagaya, Yutaka] Univ Maryland, Sch Med, Div Basic Sci & Vaccine Res, Cell Biol Lab, Baltimore, MD 21201 USA. [Azimi, Nazli; Basheer, Asjad] Bioniz LLC, Irvine, CA 92618 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 24 TC 4 Z9 4 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2015 VL 112 IS 35 BP 11030 EP 11035 DI 10.1073/pnas.1412626112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200063 PM 26283355 ER PT J AU Wesolowski, A Metcalf, CJE Eagle, N Kombich, J Grenfell, BT Bjornstad, ON Lessler, J Tatem, AJ Buckee, CO AF Wesolowski, Amy Metcalf, C. J. E. Eagle, Nathan Kombich, Janeth Grenfell, Bryan T. Bjornstad, Ottar N. Lessler, Justin Tatem, Andrew J. Buckee, Caroline O. TI Quantifying seasonal population fluxes driving rubella transmission dynamics using mobile phone data SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE rubella; mobile phones; population mobility; Kenya; seasonality ID INFECTIOUS-DISEASES; HUMAN MOVEMENT; MEASLES; MALARIA; EPIDEMIOLOGY; VACCINATION; AFRICA; PATTERNS; MODEL; RISK AB Changing patterns of human aggregation are thought to drive annual and multiannual outbreaks of infectious diseases, but the paucity of data about travel behavior and population flux over time has made this idea difficult to test quantitatively. Current measures of human mobility, especially in low-income settings, are often static, relying on approximate travel times, road networks, or cross-sectional surveys. Mobile phone data provide a unique source of information about human travel, but the power of these data to describe epidemiologically relevant changes in population density remains unclear. Here we quantify seasonal travel patterns using mobile phone data from nearly 15 million anonymous subscribers in Kenya. Using a rich data source of rubella incidence, we show that patterns of population travel (fluxes) inferred from mobile phone data are predictive of disease transmission and improve significantly on standard school term time and weather covariates. Further, combining seasonal and spatial data on travel from mobile phone data allows us to characterize seasonal fluctuations in risk across Kenya and produce dynamic importation risk maps for rubella. Mobile phone data therefore offer a valuable previously unidentified source of data for measuring key drivers of seasonal epidemics. C1 [Wesolowski, Amy; Eagle, Nathan; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wesolowski, Amy; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Wesolowski, Amy; Tatem, Andrew J.; Buckee, Caroline O.] Flowminder Fdn, SE-11355 Stockholm, Sweden. [Metcalf, C. J. E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Metcalf, C. J. E.; Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA. [Metcalf, C. J. E.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Eagle, Nathan] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Kombich, Janeth] Univ Kabianga, Dept Biol Sci, Kericho Country, Kenya. [Bjornstad, Ottar N.] Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA 16801 USA. [Lessler, Justin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton SO17 1BJ, Hants, England. RP Wesolowski, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM awesolow@hsph.harvard.edu; cmetcalf@princeton.edu OI Lessler, Justin/0000-0002-9741-8109 FU National Science Foundation [0750271]; James S. McDonnell Foundation; Bill and Melinda Gates Foundation [49446, OPP1032350]; National Institutes of Health (NIH)/National Institute of Allergy and Infectious Disease [U19AI089674]; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, NIH; Models of Infectious Disease Agent Study program [1U54GM088558]; Bill and Melinda Gates Foundation; Science and Technology Directorate, Department of Homeland Security [HSHQDC-12-C-00058]; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Wellcome Trust [106866/Z/15/Z] FX A.W. was supported by the National Science Foundation (Grant 0750271) and the James S. McDonnell Foundation. A.J.T. acknowledges support from Bill and Melinda Gates Foundation (Grants 49446 and OPP1032350); National Institutes of Health (NIH)/National Institute of Allergy and Infectious Disease (U19AI089674); and the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, NIH. C.O.B. was supported by the Models of Infectious Disease Agent Study program (Cooperative Agreement 1U54GM088558). This work was funded by the Bill and Melinda Gates Foundation; the Science and Technology Directorate, Department of Homeland Security, Contract HSHQDC-12-C-00058 (to B.T.G., C.J.E.M., J.L., and O.N.B.); and the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, NIH (C.J.E.M., B.T.G., and O.N.B.). C.J.E.M., A.J.T., and C.O.B. acknowledge support from the Wellcome Trust Sustaining Health Grant (106866/Z/15/Z). NR 37 TC 8 Z9 8 U1 4 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2015 VL 112 IS 35 BP 11114 EP 11119 DI 10.1073/pnas.1423542112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1TV UT WOS:000360383200077 PM 26283349 ER PT J AU Heitmann, RJ Hill, MJ James, AN Schimmel, T Segars, JH Csokmay, JM Cohen, J Payson, MD AF Heitmann, Ryan J. Hill, Micah J. James, Aidita N. Schimmel, Tim Segars, James H. Csokmay, John M. Cohen, Jacques Payson, Mark D. TI Live births achieved via IVF are increased by improvements in air quality and laboratory environment SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE air quality; implantation; IVF; laboratory environment; live birth ID IN-VITRO FERTILIZATION; SINGLE-BLASTOCYST TRANSFER; TROPHECTODERM MORPHOLOGY; OUTCOMES; INDUCTION; PREGNANCY; OVULATION; CULTURE AB Infertility is a common disease, which causes many couples to seek treatment with assisted reproduction techniques. Many factors contribute to successful assisted reproduction technique outcomes. One important factor is laboratory environment and air quality. Our facility had the unique opportunity to compare consecutively used, but separate assisted reproduction technique laboratories, as a result of a required move. Environmental conditions were improved by strategic engineering designs. All other aspects of the IVF laboratory, including equipment, physicians, embryologists, nursing staff and protocols, were kept constant between facilities. Air quality testing showed improved air quality at the new IVF site. Embryo implantation (32.4% versus 24.3%; P < 0.01) and live birth (39.3% versus 31.8%, P < 0.05) were significantly increased in the new facility compared with the old facility. More patients met clinical criteria and underwent mandatory single embryo transfer on day 5 leading to both a reduction in multiple gestation pregnancies and increased numbers of vitrified embryos per patient with supernumerary embryos available. Improvements in IVF laboratory conditions and air quality had profound positive effects on laboratory measures and patient outcomes. This study further strengthens the importance of the laboratory environment and air quality in the success of an IVF programme. Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd. C1 [Heitmann, Ryan J.; Hill, Micah J.; Segars, James H.; Csokmay, John M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Heitmann, Ryan J.; Hill, Micah J.; Csokmay, John M.; Payson, Mark D.] Walter Reed Natl Mil Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Bethesda, MD 20889 USA. [James, Aidita N.; Schimmel, Tim; Cohen, Jacques] ART Inst Washington Inc, Bethesda, MD 20889 USA. [Payson, Mark D.] Domin Fertil, Arlington, VA 22204 USA. RP Heitmann, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 CRC,10 Ctr Dr, Bethesda, MD 20892 USA. EM ryan.j.heitmann.mil@mail.mil FU intramural research program of the Program in Reproductive and Adult Endocrinology, NICHD, NIH FX The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense or the United States Government. This research was supported, in part, by the intramural research program of the Program in Reproductive and Adult Endocrinology, NICHD, NIH. NR 26 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1472-6483 EI 1472-6491 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD SEP PY 2015 VL 31 IS 3 BP 364 EP 371 DI 10.1016/j.rbmo.2015.04.011 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CQ5OU UT WOS:000360655700008 PM 26194882 ER PT J AU Mammen, JS McGready, J Oxman, R Chia, CW Ladenson, PW Simonsick, EM AF Mammen, Jennifer S. McGready, John Oxman, Rachael Chia, Chee W. Ladenson, Paul W. Simonsick, Eleanor M. TI Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging SO THYROID LA English DT Article ID CORONARY-HEART-DISEASE; SUBCLINICAL HYPOTHYROIDISM; CARDIOVASCULAR HEALTH; ATRIAL-FIBRILLATION; EUTHYROID MAN; DYSFUNCTION; MORTALITY; EVENTS; ASSOCIATION; PREVALENCE AB Background: Both endogenous and exogenous thyrotoxicosis has been associated with atrial fibrillation and low bone mineral density. Therefore, this study investigated the risk factors associated with prevalent and incident thyrotoxicosis and the initiation of thyroid hormone therapy in a healthy, aging cohort. Methods: A total of 1450 ambulatory community volunteer participants in the Baltimore Longitudinal Study of Aging examined at the NIA Clinical Research Unit in Baltimore, MD, have undergone longitudinal monitoring of serum thyrotropin (TSH) and thyroid hormone (free thyroxine and free triiodothryonine) levels as well as medication use every one to four years, depending on age, between 2003 and 2014. Results: The prevalence of low TSH was 9.6% for participants on thyroid hormone and 0.8% for nontreated individuals (p < 0.001). New cases occurred at a rate of 17.7/1000 person-years of exposure to thyroid hormone therapy [CI 9-32/1000] and 1.5/1000 person-years in the unexposed population [CI 0.7-2.9/1000]. Women were more likely to be treated and more often overtreated than men were. The adjusted hazard ratio (HR) for thyrotoxicosis between treated and untreated women was 27.5 ([CI 7.2-105.4]; p < 0.001) and 3.8 for men ([CI 1.2-6.3]; p < 0.01). White race/ethnicity and older age were risk factors for thyroid hormone therapy but not overtreatment. Body mass index was not associated with starting therapy (HR = 1.0). Thyroid hormone initiation was highest among women older than 80 years of age (3/100 person-years). For one-third of treated participants with follow-up data, overtreatment persisted at least two years. Conclusions: Iatrogenic thyrotoxicosis accounts for approximately half of both prevalent and incident low TSH events in this community-based cohort, with the highest rates among older women, who are vulnerable to atrial fibrillation and osteoporosis. Physicians should be particularly cautious in treating subclinical hypothyroidism in elderly women in light of recent studies demonstrating no increased risk of cardiovascular morbidity or death for individuals with elevated TSH levels <10 mIU/L. C1 [Mammen, Jennifer S.] Johns Hopkins Bayview Med Ctr, Div Endocrinol, Baltimore, MD 21224 USA. [Oxman, Rachael] Johns Hopkins Bayview Med Ctr, Div Internal Med, Baltimore, MD 21224 USA. [McGready, John] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Chia, Chee W.; Simonsick, Eleanor M.] NIA, NIH, Baltimore, MD 21224 USA. [Ladenson, Paul W.] Johns Hopkins Univ, Dept Med, Div Endocrinol, Baltimore, MD USA. RP Mammen, JS (reprint author), Johns Hopkins Bayview Med Ctr, 5200 Eastern Ave,MFL Ctr Tower Suite 4300, Baltimore, MD 21224 USA. EM jmammen1@jhmi.edu FU Passano Foundation; Walton Family Foundation; NIH [K23DK095954]; NIH Intramural Research Program, National Institute on Aging FX We thank Dr. David Cooper for his close reading of the manuscript. Financial support came from the Passano Foundation, the Walton Family Foundation, NIH grant K23DK095954 to J.S.M., and the NIH Intramural Research Program, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the NIA. NR 38 TC 9 Z9 9 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD SEP 1 PY 2015 VL 25 IS 9 BP 979 EP 986 DI 10.1089/thy.2015.0180 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ0VB UT WOS:000360314600001 PM 26177259 ER PT J AU Feng, ZW Hu, GX Ma, SF Xie, XQ AF Feng, Zhiwei Hu, Guanxing Ma, Shifan Xie, Xiang-Qun TI Computational Advances for the Development of Allosteric Modulators and Bitopic Ligands in G Protein-Coupled Receptors SO AAPS JOURNAL LA English DT Review DE allosteric modulators; bitopic ligands; computational approaches; drug discovery; drug target discovery; G protein-coupled receptors ID MOLECULAR-DYNAMICS APPROACH; DRUG DISCOVERY; HISTORICAL-PERSPECTIVE; FUNCTIONAL SELECTIVITY; MUSCARINIC RECEPTOR; GABA(B) RECEPTOR; BIVALENT LIGANDS; STRUCTURAL BASIS; BINDING-SITES; GPCRS AB Allosteric modulators of G protein-coupled receptors (GPCRs), which target at allosteric sites, have significant advantages against the corresponding orthosteric compounds including higher selectivity, improved chemical tractability or physicochemical properties, and reduced risk of receptor oversensitization. Bitopic ligands of GPCRs target both orthosteric and allosteric sites. Bitopic ligands can improve binding affinity, enhance subtype selectivity, stabilize receptors, and reduce side effects. Discovering allosteric modulators or bitopic ligands for GPCRs has become an emerging research area, in which the design of allosteric modulators is a key step in the detection of bitopic ligands. Radioligand binding and functional assays ([S-35] GTP gamma S and ERK1/2 phosphorylation) are used to test the effects for potential modulators or bitopic ligands. High-throughput screening (HTS) in combination with disulfide trapping and fragment-based screening are used to aid the discovery of the allosteric modulators or bitopic ligands of GPCRs. When used alone, these methods are costly and can often result in too many potential drug targets, including false positives. Alternatively, low-cost and efficient computational approaches are useful in drug discovery of novel allosteric modulators and bitopic ligands to help refine the number of targets and reduce the false-positive rates. This review summarizes the state-of-the-art computational methods for the discovery of modulators and bitopic ligands. The challenges and opportunities for future drug discovery are also discussed. C1 [Feng, Zhiwei; Hu, Guanxing; Ma, Shifan; Xie, Xiang-Qun] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Feng, Zhiwei; Hu, Guanxing; Ma, Shifan; Xie, Xiang-Qun] Univ Pittsburgh, Sch Pharm, Computat Chem Genom Screening Ctr, Pittsburgh, PA 15261 USA. [Feng, Zhiwei; Hu, Guanxing; Ma, Shifan; Xie, Xiang-Qun] NIDA, Natl Ctr Excellence Computat Drug Abuse Res, Pittsburgh, PA USA. [Feng, Zhiwei; Hu, Guanxing; Ma, Shifan; Xie, Xiang-Qun] Drug Discovery Inst, Pittsburgh, PA USA. [Xie, Xiang-Qun] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15261 USA. [Xie, Xiang-Qun] Univ Pittsburgh, Dept Biol Struct, Pittsburgh, PA 15261 USA. RP Xie, XQ (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 3501 Terrace St,529 Salk Hall, Pittsburgh, PA 15261 USA. EM xix15@pitt.edu FU NIDA [P30DA035778A1]; NIH [R01DA025612] FX The authors would like to acknowledge the funding support for the Xie laboratory at the University of Pittsburgh from the NIDA P30DA035778A1 and NIH R01DA025612. We also thank our lab members Ms. Xiaole Yang and Ms. Xiaomeng Xu for their effort on literature studies and data collection on the compounds reported and marketed. Dr. James Lyons-Weiler provided pre-submission editorial review and comment. NR 99 TC 4 Z9 4 U1 4 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2015 VL 17 IS 5 BP 1080 EP 1095 DI 10.1208/s12248-015-9776-y PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CQ1NN UT WOS:000360364500004 PM 25940084 ER PT J AU Rocco, MV Daugirdas, JT Greene, T Lockridge, RS Chan, C Pierratos, A Lindsay, R Larive, B Chertow, GM Beck, GJ Eggers, PW Kliger, AS AF Rocco, Michael V. Daugirdas, John T. Greene, Tom Lockridge, Robert S. Chan, Christopher Pierratos, Andreas Lindsay, Robert Larive, Brett Chertow, Glenn M. Beck, Gerald J. Eggers, Paul W. Kliger, Alan S. CA FHN Trial Grp TI Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Nocturnal hemodialysis; frequent hemodialysis; extended hemodialysis; frequent-long dialysis schedule; clinical trial; mortality; hemodialysis prescription; dialysis dose; dialysis adequacy; dialysis regimen; end-stage renal disease (ESRD); renal replacement therapy; Frequent Hemodialysis Network (FHN) Nocturnal Trial ID IN-CENTER HEMODIALYSIS; CONVENTIONAL HEMODIALYSIS; HOME HEMODIALYSIS; RANDOMIZED-TRIALS; 3 TIMES; SURVIVAL; HEALTH AB Background: Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis. Study Design: Posttrial observational study. Setting & Participants: Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up. Intervention: The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription. Outcomes & Measurements: We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment. Results: Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P = 0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P = 0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P = 0.7). Limitations: These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes. Conclusions: Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Rocco, Michael V.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. [Daugirdas, John T.] Univ Illinois, Dept Med, Chicago, IL USA. [Greene, Tom] Univ Utah, Sch Med, Dept Biostat, Salt Lake City, UT USA. [Lockridge, Robert S.] Univ Virginia, Lynchburg Nephrol Phys, Lynchburg, VA USA. [Chan, Christopher] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Pierratos, Andreas] Univ Toronto, Humber River Hosp, Toronto, ON, Canada. [Lindsay, Robert] London Hlth Sci Ctr, London, ON, Canada. [Larive, Brett; Beck, Gerald J.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Eggers, Paul W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kliger, Alan S.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Kliger, Alan S.] Yale Univ, Sch Med, New Haven, CT USA. RP Rocco, MV (reprint author), Wake Forest Sch Med, Dept Internal Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mrocco@wakehealth.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; Centers for Medicare & Medicaid Services; National Institutes of Health (NIH) Research Foundation; NIH Research Foundation-Amgen Inc; Baxter; Dialysis Clinics Inc-; Fresenius Medical Care FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Centers for Medicare & Medicaid Services, and the National Institutes of Health (NIH) Research Foundation. The investigators and sponsors are grateful for the support of contributors to the NIH Research Foundation-Amgen Inc, Baxter, and Dialysis Clinics Inc-and support from Fresenius Medical Care. The funders of this study did not have any role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. NR 28 TC 19 Z9 19 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2015 VL 66 IS 3 BP 459 EP 468 DI 10.1053/j.ajkd.2015.02.331 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CP8BG UT WOS:000360115400019 PM 25863828 ER PT J AU Prince, LK Abbott, KC Lee, JJ Oliver, DK Olson, SW AF Prince, Lisa K. Abbott, Kevin C. Lee, Jessica J. Oliver, David K. Olson, Stephen W. TI Creatine Kinase, Coenzyme Q10, Race, and Risk of Rhabdomyolysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID ACUTE KIDNEY INJURY; MYOPATHY C1 [Prince, Lisa K.; Oliver, David K.; Olson, Stephen W.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Abbott, Kevin C.] NIH, Bethesda, MD 20892 USA. [Lee, Jessica J.] Naval Med Ctr San Diego, San Diego, CA USA. RP Olson, SW (reprint author), Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. EM stephen.w.olson.mil@mail.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 10 TC 0 Z9 0 U1 0 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2015 VL 66 IS 3 BP 541 EP 542 DI 10.1053/j.ajkd.2015.04.045 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CP8BG UT WOS:000360115400031 PM 26060183 ER PT J AU Glenn, KR Slaughter, JC Fowke, JH Buchowski, MS Matthews, CE Signorello, LB Blot, WJ Lipworth, L AF Glenn, Kimberly R. Slaughter, James C. Fowke, Jay H. Buchowski, Maciej S. Matthews, Charles E. Signorello, Lisa B. Blot, William J. Lipworth, Loren TI Physical activity, sedentary behavior and all-cause mortality among blacks and whites with diabetes SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Physical activity; Diabetes; Low income; Sedentary behaviors; Cardiovascular disease; Mortality ID SOUTHERN COMMUNITY COHORT; CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-HEART-DISEASE; LEISURE-TIME; EXERCISE CAPACITY; HEALTH DISPARITIES; AFRICAN-AMERICANS; OLDER-ADULTS; MELLITUS; RISK AB Purpose: The study objective was to examine the role of physical activity (PA) and sedentary time (ST) on mortality risk among a population of low-income adults with diabetes. Methods: Black (n = 11,137) and white (n = 4508) men and women with diabetes from the Southern Community Cohort Study self-reported total PA levels and total ST. Participants were categorized into quartiles of total PA and total ST. Hazard ratios (HRs) and 95% confidence intervals (CIs) for subsequent mortality risk were estimated from Cox proportional hazards analysis with adjustment for potential confounders. Results: During follow-up, 2370 participants died. The multivariable risk of mortality was lower among participants in the highest quartile of PA compared with those in the lowest quartile (HR, 0.64; 95% CI: 0.57-0.73). Mortality risk was significantly increased among participants in the highest compared with the lowest quartile of ST after adjusting for PA (HR, 1.21; 95% CI: 1.08-1.37). Across sex and race groups, similar trends of decreasing mortality with rising PA and increasing mortality with rising ST were observed. Conclusions: Although causality cannot be established from these observational data, the current findings suggest that increasing PA and decreasing ST may help extend survival among individuals with diabetes irrespective of race and sex. (C) 2015 Elsevier Inc. All rights reserved. C1 [Glenn, Kimberly R.; Fowke, Jay H.; Blot, William J.; Lipworth, Loren] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA. [Slaughter, James C.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37212 USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Signorello, Lisa B.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. RP Glenn, KR (reprint author), Off Healthcare Stat Policy Planning & Assessment, Tennessee Dept Hlth, 710 James Robertson Pkwy, Nashville, TN 37243 USA. EM kimberly.glenn@tn.gov RI Dey, Kamalesh/E-6568-2017; OI Glenn, Kimberly/0000-0002-6765-5592; Slaughter, James/0000-0002-8770-980X FU NCI NIH HHS [R01 CA092447]; NIDDK NIH HHS [P30 DK092986] NR 37 TC 4 Z9 4 U1 1 U2 11 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 SEP PY 2015 VL 25 IS 9 BP 649 EP 655 DI 10.1016/j.annepidem.2015.04.006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP9AV UT WOS:000360187000003 PM 26141652 ER PT J AU Muntner, P Whittle, J Lynch, AI Colantonio, LD Simpson, LM Einhorn, PT Levitan, EB Whelton, PK Cushman, WC Louis, GT Davis, BR Oparil, S AF Muntner, Paul Whittle, Jeff Lynch, Amy I. Colantonio, Lisandro D. Simpson, Lara M. Einhorn, Paula T. Levitan, Emily B. Whelton, Paul K. Cushman, William C. Louis, Gail T. Davis, Barry R. Oparil, Suzanne TI Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; LONG-TERM; CARDIOVASCULAR EVENTS; FOLLOW-UP; EUROPEAN LACIDIPINE; REGRESSION DILUTION; AFRICAN-AMERICANS; RISK-FACTOR; HYPERTENSION AB Background: Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient's underlying BP. Objective: To examine the association of visit-to-visit variability (VVV) of systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and mortality outcomes. Design: Prospective cohort study. Setting: Post hoc analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). Participants: 25 814 ALLHAT participants. Measurements: The VVV of SBP was defined as the SD across SBP measurements obtained at 7 visits conducted from 6 to 28 months after ALLHAT enrollment. Participants without CVD events during the first 28 months of follow-up were followed from the 28-month visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and heart failure. Results: During follow-up, 1194 fatal CHD or nonfatal MI events, 1948 deaths, 606 strokes, and 921 heart failure events occurred. After multivariable adjustment, including for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (>= 14.4 mm Hg vs. <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was also associated with CVD events and mortality. Limitation: Long-term outcomes were not available. Conclusion: Higher VVV of SBP is associated with an increased risk for CVD and mortality. Future studies should examine whether reducing VVV of BP lowers this risk. C1 [Muntner, Paul; Lynch, Amy I.; Levitan, Emily B.; Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Whittle, Jeff] Clement J Zablocki Vet Affairs Med Ctr, Milwaukee, WI 53295 USA. [Colantonio, Lisandro D.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Simpson, Lara M.; Davis, Barry R.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Einhorn, Paula T.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Whelton, Paul K.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN 38104 USA. [Louis, Gail T.] Tulane Univ, Res Off, New Orleans, LA 70118 USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, 1700 Univ Blvd,Suite 450, Birmingham, AL 35294 USA. EM pmuntner@uab.edu OI Colantonio, Lisandro/0000-0001-8742-1788 FU National Institutes of Health FX National Institutes of Health. NR 33 TC 30 Z9 31 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 2015 VL 163 IS 5 BP 329 EP U42 DI 10.7326/M14-2803 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA CQ0OM UT WOS:000360296000004 PM 26215765 ER PT J AU Nayak, RK Wendler, D Miller, FG Kim, SYH AF Nayak, Rahul K. Wendler, David Miller, Franklin G. Kim, Scott Y. H. TI Pragmatic Randomized Trials Without Standard Informed Consent? A National Survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEALTH INFORMATION; MECHANICAL TURK; CLINICAL-TRIALS; ETHICS; INTERNET; QUALITY AB Background: Significant debate surrounds the issue of whether written consent is necessary for pragmatic randomized, controlled trials (RCTs) with low risk. Objective: To assess the U.S. public's views on alternatives to written consent for low-risk pragmatic RCTs. Design: National experimental survey (2 x 2 factorial design) examining support for written consent versus general notification or verbal consent in 2 research scenarios. Setting: Web-based survey conducted in December 2014. Participants: 2130 U.S. adults sampled from a nationally representative, probability-based online panel (response rate, 64.0%). Measurements: Respondent's recommendation to an ethics review board and personal preference as a potential participant on how to obtain consent or notification in the 2 research scenarios. Results: Most respondents in each of the 4 groups (range, 60.3% to 71.5%) recommended written informed consent, and personal preferences were generally in accord with that advice. Most (78.9%) believed that the pragmatic RCTs did not pose additional risks, but 62.5% of these respondents would still recommend written consent. In contrast, a substantial minority in all groups (28.5% to 39.7%) recommended the alternative option (general notification or verbal consent) over written consent. Limitation: Framing effects could have affected respondents' attitudes, and nonrespondents may have differed in levels of trust toward research or health care institutions. Conclusion: Most of the public favored written informed consent over the most widely advocated alternatives for low-risk pragmatic RCTs; however, a substantial minority favored general notification or verbal consent. C1 [Nayak, Rahul K.; Wendler, David; Miller, Franklin G.; Kim, Scott Y. H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM scott.kim@nih.gov FU National Institutes of Health Clinical Center FX Time-sharing Experiments for the Social Sciences and Intramural Research Program of the National Institutes of Health Clinical Center. NR 23 TC 6 Z9 6 U1 0 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 2015 VL 163 IS 5 BP 356 EP U81 DI 10.7326/M15-0817 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CQ0OM UT WOS:000360296000007 PM 26215125 ER PT J AU Goldenholz, DM Moss, R Scott, J Auh, S Theodore, WH AF Goldenholz, Daniel M. Moss, Robert Scott, Jonathan Auh, Sungyoung Theodore, William H. TI Confusing placebo effect with natural history in epilepsy: A big data approach SO ANNALS OF NEUROLOGY LA English DT Article ID PARTIAL-ONSET SEIZURES; ANTIEPILEPTIC DRUGS; REFRACTORY EPILEPSY; PATIENT AWARENESS; METAANALYSIS; POPULATION; REMISSION; TRIALS AB For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using , a patient-centered database of 684,825 seizures, we simulated placebo and drug trials. These simulations were employed to clarify the sources of placebo effects in epilepsy, and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6-week baseline and 6-week test period, starting at time 0, 3, 6...24 months. Here, placebo reduced seizures regardless of study start time. Regression-to-the-mean persisted only for 3 to 6 months. Simulation 2 comprised a 6-week baseline and then 2 years of follow-up. Seizure frequencies continued to improve throughout follow-up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo-controlled drug trial, to explore methods of placebo response reduction. An efficacious drug failed to demonstrate a significant effect compared with placebo (p=0.12), although modifications either in study start time (p=0.025) or baseline population reduction (p=0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In epilepsy clinical trials, some seizure reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329-336 C1 [Goldenholz, Daniel M.; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Goldenholz, Daniel M.; Scott, Jonathan; Theodore, William H.] NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. [Moss, Robert] NINDS, Seizuretracker Com, NIH, Bethesda, MD 20892 USA. [Auh, Sungyoung] NINDS, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Goldenholz, DM (reprint author), NINDS, NIH, Clin Epilepsy Sect, CNP,DIR, 10 Ctr Dr 10 CRC,Room 7-5644,MSC1404, Bethesda, MD 20892 USA. EM daniel.goldenholz@nih.gov OI Goldenholz, Daniel/0000-0002-8370-2758 FU NIH National Institute of Neurological Disorders and Stroke Division of Intramural Research FX This study was supported by the NIH National Institute of Neurological Disorders and Stroke Division of Intramural Research. NR 28 TC 5 Z9 5 U1 6 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2015 VL 78 IS 3 BP 329 EP 336 DI 10.1002/ana.24470 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CP9MQ UT WOS:000360218800001 PM 26150090 ER PT J AU Percopo, CM Rice, TA Brenner, TA Dyer, KD Luo, JL Kanakabandi, K Sturdevant, DE Porcella, SF Domachowske, JB Keicher, JD Rosenberg, HF AF Percopo, Caroline M. Rice, Tyler A. Brenner, Todd A. Dyer, Kimberly D. Luo, Janice L. Kanakabandi, Kishore Sturdevant, Daniel E. Porcella, Stephen F. Domachowske, Joseph B. Keicher, Jesse D. Rosenberg, Helene F. TI Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection SO ANTIVIRAL RESEARCH LA English DT Article DE Inflammation; Cytokines; Pneumovirus; Pattern-recognition receptors ID SYNCYTIAL VIRUS; PNEUMOVIRUS INFECTION; INFLAMMATORY RESPONSES; EXPERIMENTAL COLITIS; CYTOKINE RESPONSES; TRACT INFECTIONS; TRAINED IMMUNITY; VIRAL-INFECTION; PNEUMONIA VIRUS; INNATE IMMUNITY AB We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24 h after virus challenge. Survival in response to L plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airwajrs. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L plantarum, as are mice devoid of type I interferon receptors. Taken together, L plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. Published by Elsevier B.V. C1 [Percopo, Caroline M.; Rice, Tyler A.; Brenner, Todd A.; Dyer, Kimberly D.; Luo, Janice L.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Kanakabandi, Kishore; Sturdevant, Daniel E.; Porcella, Stephen F.] NIAID, Genom Unit, Technol Branch, NIH, Hamilton, MT USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. [Keicher, Jesse D.] Glaxo Smith Kline Inc, Infect Dis, Drug Discovery, Res Triangle Pk, NC USA. RP Rosenberg, HF (reprint author), NIAID, Inflammat Immunobiol Sect, NIH, Bldg 10,Room 11C215,MSC 1883,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov OI Brenner, Todd/0000-0003-0541-2234 FU Division of Intramural Research [AI000943] FX The authors thank Dr. Kimmo Virtaneva of the Genomics Unit, RTS, for his assistance with experimental design and sample processing, and Dr. Kirk M. Druey (MSTS/LAD/NIAID) for critical review of this manuscript. This research was funded by Division of Intramural Research AI000943 to H.F.R. and Collaborative Research and Development Agreement 2013-0510 between NIAID and GlaxoSmithKline. NR 77 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 2015 VL 121 BP 109 EP 119 DI 10.1016/j.antiviral.2015.07.001 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA CQ3OI UT WOS:000360511500013 PM 26145728 ER PT J AU Fontana, J Steven, AC AF Fontana, Juan Steven, Alasdair C. TI Influenza virus-mediated membrane fusion: Structural insights from electron microscopy SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE Influenza virus; Viral fusion; Hemagglutinin; Cryo-electron microscopy; Cryo-electron tomography; Subtomogram averaging ID MATRIX PROTEIN M1; LOW-PH; CRYOELECTRON TOMOGRAPHY; A VIRUS; CONFORMATIONAL-CHANGE; FUSOGENIC ACTIVITY; HEMAGGLUTININ; PARTICLES; RIBONUCLEOPROTEINS; ENTRY AB Influenza virus, the causative agent of flu, enters the host cell by endocytosis. The low pH encountered inside endosomes triggers conformational changes in the viral glycoprotein hemagglutinin (HA), that mediate fusion of the viral and cellular membranes. This releases the viral genome into the cytoplasm of the infected cell, establishing the onset of the replication cycle. To investigate the structural basis of HA-mediated membrane fusion, a number of techniques have been employed. These include X-ray crystallography, which has provided atomic models of the HA ectodomain in its initial (pre-fusion) state and of part of HA in its final (post-fusion) state. However, this left an information deficit concerning many other aspects of the fusion process. Electron microscopy (EM) approaches are helping to fill this void. For example, influenza virions at neutral pH have been imaged by cryo-EM and cryo-electron tomography (cryo-ET); thin section EM has shown that influenza viruses enter the cell by endocytosis; the large-scale structural changes in HA when virions are exposed to low pH (pre-fusion to post-fusion states) have been visualized by negative staining and cryo-EM; acidification also induces structural changes in the M1 matrix layer and its separation from the viral envelope; intermediate HA conformations between its pre- and post-fusion states have been detected by cryo-ET supplemented with subtomogram averaging; and fusion of influenza virions with liposomes has been visualized by cryo-ET. In this review, we survey EM-based contributions towards the characterization of influenza virus-mediated membrane fusion and anticipate the potential for future developments. Published by Elsevier Inc. C1 [Fontana, Juan; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Fontana, J (reprint author), NIAMS, Struct Biol Res Lab, NIH, 50 South Dr,Bldg 50,Room 1517, Bethesda, MD 20892 USA. EM fontana@mail.nih.gov; stevena@mail.nih.gov OI Fontana, Juan/0000-0002-9084-2927 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 67 TC 3 Z9 3 U1 4 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2015 VL 581 SI SI BP 86 EP 97 DI 10.1016/j.abb.2015.04.011 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CP9BC UT WOS:000360187700011 PM 25958107 ER PT J AU Chen, HF Shi, BY Feng, XB Kong, W Chen, WW Geng, LY Chen, JY Liu, R Li, X Chen, WJ Gao, X Sun, LY AF Chen, Haifeng Shi, Bingyu Feng, Xuebing Kong, Wei Chen, Weiwei Geng, Linyu Chen, Jinyun Liu, Rui Li, Xia Chen, WanJun Gao, Xiang Sun, Lingyun TI Leptin and Neutrophil-Activating Peptide 2 Promote Mesenchymal Stem Cell Senescence Through Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway in Patients With Systemic Lupus Erythematosus SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID REPLICATIVE SENESCENCE; DISEASE-ACTIVITY; T-CELLS; CHEMOKINE RECEPTORS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; IN-VITRO; EXPRESSION; APOPTOSIS; MICE AB Objective. Mesenchymal stem cells (MSCs) derived from patients with systemic lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has been reported to be induced by several inflammatory cytokines, including interferon-alpha (IFN alpha) and IFN gamma, that are involved in the pathogenesis of SLE. We undertook this study to investigate whether the inflammatory environment in SLE could affect MSC senescence. Methods. Cellular senescence was measured by staining of senescence-associated beta-galactosidase and by expression of the cell cycle inhibitors p53 and p21. Eighty cytokines and chemokines in serum from healthy controls and patients with SLE were identified by cytokine antibody array. Results. SLE serum promoted senescence of MSCs, which was reversed by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling inhibitor LY294002 but not by the JAK/STAT inhibitor AG490 and not by the MEK/ERK inhibitor PD98059. Cytokine antibody array analysis revealed that leptin and neutrophil-activating peptide 2 (NAP-2) were the 2 factors most significantly elevated in SLE serum compared with normal serum. Blockade of leptin or NAP-2 in MSC cultures abolished SLE serum-induced senescence, while direct addition of these 2 factors could promote senescence in cultures of normal MSCs. Inhibition of PI3K/Akt signaling with LY294002 reduced leptin- and NAP-2-induced senescence in MSCs. Conclusion. Taken together, our data show that leptin and NAP-2 act synergistically to promote MSC senescence through enhancement of the PI3K/Akt signaling pathway in SLE patients. C1 [Chen, Haifeng; Shi, Bingyu; Feng, Xuebing; Kong, Wei; Chen, Weiwei; Geng, Linyu; Chen, Jinyun; Liu, Rui; Sun, Lingyun] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Li, Xia] Dalian Med Univ, Dalian, Peoples R China. [Chen, WanJun] NIDCR, NIH, Bethesda, MD USA. [Gao, Xiang; Sun, Lingyun] Nanjing Univ, Nanjing 210008, Jiangsu, Peoples R China. RP Sun, LY (reprint author), Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Rheumatol & Immunol, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM lingyunsun@nju.edu.cn FU National Natural Science Foundation of China [81120108021, 30972736]; NIH (Intramural Research Program of the National Institute of Dental and Craniofacial Research) FX Supported by the National Natural Science Foundation of China (grants 81120108021 and 30972736 to Dr. Sun). Dr. WanJun Chen's work was supported by the NIH (Intramural Research Program of the National Institute of Dental and Craniofacial Research). NR 41 TC 9 Z9 11 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2015 VL 67 IS 9 BP 2383 EP 2393 DI 10.1002/art.39196 PG 11 WC Rheumatology SC Rheumatology GA CQ1SP UT WOS:000360379500012 PM 25989537 ER PT J AU Zhou, Q Aksentijevich, I Wood, GM Walts, AD Hoffmann, P Remmers, EF Kastner, DL Ombrello, AK AF Zhou, Qing Aksentijevich, Ivona Wood, Geryl M. Walts, Avram D. Hoffmann, Patrycja Remmers, Elaine F. Kastner, Daniel L. Ombrello, Amanda K. TI Cryopyrin-Associated Periodic Syndrome Caused by a Myeloid-Restricted Somatic NLRP3 Mutation SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID MULTISYSTEM INFLAMMATORY DISEASE; LOW-LEVEL MOSAICISM; ARTICULAR SYNDROME; AUTOINFLAMMATORY DISEASES; CIAS1 MUTATIONS; PATIENT AB Objective. To identify the cause of disease in an adult patient presenting with recent-onset fevers, chills, urticaria, fatigue, and profound myalgia, who was found to be negative for cryopyrin-associated periodic syndrome (CAPS) NLRP3 mutations by conventional Sanger DNA sequencing. Methods. We performed whole-exome sequencing and targeted deep sequencing using DNA from the patient's whole blood to identify a possible NLRP3 somatic mutation. We then screened for this mutation in subcloned NLRP3 amplicons from fibroblasts, buccal cells, granulocytes, negatively selected monocytes, and T and B lymphocytes and further confirmed the somatic mutation by targeted sequencing of exon 3. Results. We identified a previously reported CAPS-associated mutation, p.Tyr570Cys, with a mutant allele frequency of 15% based on exome data. Targeted sequencing and subcloning of NLRP3 amplicons confirmed the presence of the somatic mutation in whole blood at a ratio similar to the exome data. The mutant allele frequency was in the range of 13.3-16.8% in monocytes and 15.2-18% in granulocytes. Notably, this mutation was either absent or present at a very low frequency in B and T lymphocytes, in buccal cells, and in the patient's cultured fibroblasts. Conclusion. Our findings indicate the possibility of myeloid-restricted somatic mosaicism in the pathogenesis of CAPS, underscoring the emerging role of massively parallel sequencing in clinical diagnosis. C1 [Zhou, Qing; Aksentijevich, Ivona; Wood, Geryl M.; Hoffmann, Patrycja; Remmers, Elaine F.; Kastner, Daniel L.; Ombrello, Amanda K.] NHGRI, NIH, Bethesda, MD 20892 USA. [Walts, Avram D.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Aksentijevich, I (reprint author), NHGRI, Bldg 10-CRC,Room B2-5235,10 Ctr Dr, Bethesda, MD 20892 USA. EM aksen-tii@mail.nih.gov; kastnerd@mail.nih.gov RI Yu, Xiaomin/I-6407-2016 FU Intramural Research Programs of the National Human Genome Research Institute; National Heart, Lung, and Blood Institute, NIH FX Supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Heart, Lung, and Blood Institute, NIH. NR 14 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2015 VL 67 IS 9 BP 2482 EP 2486 DI 10.1002/art.39190 PG 5 WC Rheumatology SC Rheumatology GA CQ1SP UT WOS:000360379500026 PM 25988971 ER PT J AU Schaffer, A Isometsa, ET Tondo, L Moreno, DH Sinyor, M Kessing, LV Turecki, G Weizman, A Azorin, JM Ha, K Reis, C Cassidy, F Goldstein, T Rihmer, Z Beautrais, A Chou, YH Diazgranados, N Levitt, AJ Zarate, CA Yatham, L AF Schaffer, Ayal Isometsae, Erkki T. Tondo, Leonardo Moreno, Doris H. Sinyor, Mark Kessing, Lars Vedel Turecki, Gustavo Weizman, Abraham Azorin, Jean-Michel Ha, Kyooseob Reis, Catherine Cassidy, Frederick Goldstein, Tina Rihmer, Zoltan Beautrais, Annette Chou, Yuan-Hwa Diazgranados, Nancy Levitt, Anthony J. Zarate, Carlos A., Jr. Yatham, Lakshmi TI Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Review DE Bipolar disorder; suicide or suicide attempts; pharmacotherapy; prevalence; neurobiology ID PSYCHIATRY WFSBP GUIDELINES; SEROTONIN TRANSPORTER GENE; MAJOR DEPRESSIVE DISORDER; RISK-FACTORS; ANTIEPILEPTIC DRUGS; MOOD DISORDERS; PREFRONTAL CORTEX; ANXIETY DISORDERS; STEP-BD; 5-HTTLPR POLYMORPHISM AB Objectives: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results: The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval=[5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4-14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23-26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion: This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. C1 [Schaffer, Ayal] Int Soc Bipolar Disorders, Task Force Suicide, Pittsburgh, PA USA. [Schaffer, Ayal; Reis, Catherine] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Program, Toronto, ON M4N 3M5, Canada. [Schaffer, Ayal; Sinyor, Mark; Levitt, Anthony J.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Isometsae, Erkki T.] Univ Helsinki, Dept Psychiat, Inst Clin Med, SF-00180 Helsinki, Finland. [Tondo, Leonardo] Lucio Bini Ctr, Cagliari, Italy. [Tondo, Leonardo] Harvard Univ, Sch Med, Boston, MA USA. [Tondo, Leonardo] McLean Hosp, Belmont, MA 02178 USA. [Moreno, Doris H.] Univ Sao Paulo, Dept & Inst Psychiat, Sect Psychiat Epidemiol, Sao Paulo, Brazil. [Moreno, Doris H.] Univ Sao Paulo, Dept & Inst Psychiat, Mood Disorders Unit, Sao Paulo, Brazil. [Sinyor, Mark; Levitt, Anthony J.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON M4N 3M5, Canada. [Kessing, Lars Vedel] Univ Copenhagen, Fac Hlth Sci, Psychiat Ctr Copenhagen, Copenhagen, Denmark. [Turecki, Gustavo] McGill Univ, Dept Psychiat, Res & Acad Affairs, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Grp Suicide Studies, Montreal, PQ, Canada. [Turecki, Gustavo] Douglas Inst, Depress Disorders Program, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Weizman, Abraham] Felsenstein Med Res Ctr, Lab Biol Psychiat, Petah Tiqwa, Israel. [Weizman, Abraham] Geha Mental Hlth Ctr, Res Unit, Petah Tiqwa, Israel. [Weizman, Abraham] Tel Aviv Univ, Sackler Fac Med, Dept Psychiat, IL-69978 Tel Aviv, Israel. [Azorin, Jean-Michel] Sainte Marguerite Hosp, Dept Adult Psychiat, Marseille, France. [Azorin, Jean-Michel] Univ Aix Marseille 2, F-13284 Marseille 07, France. [Ha, Kyooseob] Seoul Natl Univ, Bundang Hosp, Mood Disorders Clin, Songnam, South Korea. [Ha, Kyooseob] Seoul Natl Univ, Bundang Hosp, Affect Neurosci Lab, Songnam, South Korea. [Ha, Kyooseob] Korea Assoc Suicide Prevent, Seoul, South Korea. [Cassidy, Frederick] Duke Univ, Dept Psychiat & Behav Sci, Div Brain Stimulat & Neurophysiol, Durham, NC USA. [Goldstein, Tina] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Child & Adolescent Psychiat, Pittsburgh, PA USA. [Rihmer, Zoltan] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Budapest, Hungary. [Rihmer, Zoltan] Semmelweis Univ, Dept Psychiat & Psychotherapy, Budapest, Hungary. [Beautrais, Annette] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Chou, Yuan-Hwa] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Dept Psychiat, Sect Psychosomat Med, Taipei 112, Taiwan. [Diazgranados, Nancy] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Yatham, Lakshmi] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. RP Schaffer, A (reprint author), Sunnybrook Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Program, 2075 Bayview Ave,Room FG 52, Toronto, ON M4N 3M5, Canada. EM ayal.schaffer@sunnybrook.ca FU Brenda Smith Bipolar Disorder Research Fund; Sunnybrook Health Sciences Centre; University of Toronto FX Partial support for this project was provided by the Brenda Smith Bipolar Disorder Research Fund, Sunnybrook Health Sciences Centre and University of Toronto. NR 174 TC 3 Z9 4 U1 5 U2 22 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2015 VL 49 IS 9 BP 785 EP 802 DI 10.1177/0004867415594427 PG 18 WC Psychiatry SC Psychiatry GA CQ2FE UT WOS:000360414000007 PM 26185269 ER PT J AU Bjelobaba, I Janjic, MM Stojilkovic, SS AF Bjelobaba, Ivana Janjic, Marija M. Stojilkovic, Stanko S. TI Purinergic signaling pathways in endocrine system SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Review DE Hypothalamus; Pituitary; Thyroid gland; Adrenal gland; Ovary; Testis ID ANTERIOR-PITUITARY-CELLS; RAT SERTOLI-CELLS; GRANULOSA-LUTEAL CELLS; ADRENOCORTICAL-FASCICULATA CELLS; FOLLICLE-STIMULATING-HORMONE; ADENYLATE-CYCLASE ACTIVITY; A(1) ADENOSINE RECEPTORS; THYROID FRTL-5 CELLS; MOUSE LEYDIG-CELLS; GATED ION CHANNELS AB Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V. C1 [Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stojilks@mail.nih.gov FU Intramural Research Program of the National Institute of Child Health and Human Development FX Grant Information: This work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development NR 234 TC 0 Z9 0 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 EI 1872-7484 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD SEP PY 2015 VL 191 BP 102 EP 116 DI 10.1016/j.autneu.2015.04.010 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CP9YA UT WOS:000360250600010 PM 25960051 ER PT J AU Sobecks, RM Wang, T Askar, M Gallagher, MM Haagenson, M Spellman, S Fernandez-Vina, M Malmberg, KJ Muller, C Battiwalla, M Gajewski, J Verneris, MR Ringden, O Marino, S Davies, S Dehn, J Bornhauser, M Inamoto, Y Woolfrey, A Shaw, P Pollack, M Weisdorf, D Milller, J Hurley, C Lee, SJ Hsu, K AF Sobecks, Ronald M. Wang, Tao Askar, Medhat Gallagher, Meighan M. Haagenson, Michael Spellman, Stephen Fernandez-Vina, Marcelo Malmberg, Karl-Johan Mueller, Carlheinz Battiwalla, Minoo Gajewski, James Verneris, Michael R. Ringden, Olle Marino, Susana Davies, Stella Dehn, Jason Bornhaeuser, Martin Inamoto, Yoshihiro Woolfrey, Ann Shaw, Peter Pollack, Marilyn Weisdorf, Daniel Milller, Jeffrey Hurley, Carolyn Lee, Stephanie J. Hsu, Katharine TI Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Killer immunoglobulin-like receptor (KIR); Reduced-intensity conditioning; HCT; AML/MDS ID ACUTE MYELOGENOUS LEUKEMIA; NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTORS; HOST-DISEASE; NK CELLS; UNRELATED TRANSPLANTATION; ANTILEUKEMIA ACTIVITY; INHIBITORY RECEPTORS; INTERNATIONAL-BLOOD; SIBLING DONORS AB Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor CURD) HCT. We studied 909 patients undergoing RIC-URD HCT: Patients with acute myeloid leukemia (AML, n = 612) lacking >= 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P =.005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD Ha recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Sobecks, Ronald M.] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. [Wang, Tao] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Askar, Medhat] Cleveland Clin, Transplant Ctr, Cleveland, OH 44195 USA. [Gallagher, Meighan M.] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY 10021 USA. [Haagenson, Michael; Spellman, Stephen] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Fernandez-Vina, Marcelo] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Malmberg, Karl-Johan] Oslo Univ Hosp, Oslo, Norway. [Mueller, Carlheinz] Zent Knochenmarkspender Register Deutschland, Ulm, Germany. [Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Gajewski, James] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Verneris, Michael R.; Weisdorf, Daniel; Milller, Jeffrey] Univ Minnesota, Blood & Marrow Transplantat, Minneapolis, MN USA. [Ringden, Olle] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Therapeut Immunol, Stockholm, Sweden. [Marino, Susana] Univ Chicago Hosp, Dept Pathol, Chicago, IL 60637 USA. [Davies, Stella] Cincinnati Childrens Hosp, Dept Pediat, Div Bone Marrow Transplant & Immune Deficiency, Cincinnati, OH USA. [Dehn, Jason] Natl Marrow Donor Program, Immunogenet Operat & Res, Minneapolis, MN USA. [Bornhaeuser, Martin] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Inamoto, Yoshihiro; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Woolfrey, Ann] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Pediat, Seattle, WA 98195 USA. [Shaw, Peter] Childrens Hosp Westrnead, Westmead, NSW, Australia. [Pollack, Marilyn] Childrens Hosp, Histocompatibil & Immunogenet Lab, Dept Pathol, Oakland, CA 94609 USA. [Hurley, Carolyn] Georgetown Univ Hosp, Dept Oncol, Washington, DC 20007 USA. [Hsu, Katharine] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Hsu, Katharine] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Sobecks, RM (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA. EM sobeckr@ccf.org OI Mueller, Carlheinz/0000-0002-5359-9606; Malmberg, Karl-Johan/0000-0002-8718-9373 FU Public Health Service from the National Cancer Institute [U24-CA076518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute [5U10HL069294]; National Cancer Institute; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; NMDP; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah; WellPoint; Anonymous donation to the Medical College of Wisconsin FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; a Grant/Cooperative Agreement 5U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute; a contract HHSH250201200016C with Health Resources and Services Administration; 2 grants (N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; and grants from Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; Anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; NMDP; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah; and WellPoint. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the U.S. Government. NR 51 TC 7 Z9 7 U1 0 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 SEP PY 2015 VL 21 IS 9 BP 1589 EP 1596 DI 10.1016/j.bbmt.2015.05.002 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CQ0AB UT WOS:000360255900009 PM 25960307 ER PT J AU Del Bello, F Sakloth, F Partilla, JS Baumann, MH Glennon, RA AF Del Bello, Fabio Sakloth, Farhana Partilla, John S. Baumann, Michael H. Glennon, Richard A. TI Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE MDMA; MDMC; DAT; SERT; NET ID PARASUBSTITUTED METHCATHINONE ANALOGS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; MONOAMINE TRANSPORTERS; BATH SALTS; IN-VITRO; ECSTASY; PHARMACOLOGY; MEPHEDRONE; RELEASE; HUMANS AB N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; 'Ecstasy'; 1) and its beta-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and beta-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(-) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a beta-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Del Bello, Fabio; Sakloth, Farhana; Glennon, Richard A.] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. [Partilla, John S.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Glennon, RA (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Box 980540, Richmond, VA 23298 USA. EM glennon@vcu.edu OI Del Bello, Fabio/0000-0001-6538-6029 FU PHS Grant [DA033930]; Intramural Program of the National Institute on Drug Abuse FX This work was supported in part by PHS Grant DA033930 and by the Intramural Program of the National Institute on Drug Abuse. NR 27 TC 0 Z9 0 U1 2 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 1 PY 2015 VL 23 IS 17 BP 5574 EP 5579 DI 10.1016/j.bmc.2015.07.035 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CQ1IG UT WOS:000360349900034 PM 26233799 ER PT J AU Wang, SB Wang, XF Qin, BJ Ohkoshi, E Hsieh, KY Hamel, E Cui, MT Zhu, DQ Goto, M Morris-Natschke, SL Lee, KH Xie, L AF Wang, Sheng-Biao Wang, Xiao-Feng Qin, Bingjie Ohkoshi, Emika Hsieh, Kan-Yen Hamel, Ernest Cui, Mu-Tian Zhu, Dong-Qing Goto, Masuo Morris-Natschke, Susan L. Lee, Kuo-Hsiung Xie, Lan TI Optimization of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines as tubulin polymerization inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE N-Aryl 1,2,3,4-tetrahydroquinolines; Cytotoxic activity; Tubulin polymerization inhibitors; Colchicine binding inhibitors ID TUMOR-CELL LINES; COLCHICINE SITE; ANTITUMOR AGENTS; DIVERSE PANEL; CANCER-CELLS; DISCOVERY; INSIGHT; ANALOGS; DESIGN; DOMAIN AB Thirteen new N-aryl 1,2,3,4-tetrahydroquinoline compounds (4a-f, 6a-c, and 8a-d) were synthesized and evaluated for antitumor activity and drug-like properties. Compound 4a exhibited high inhibitory potency with low nanomolar GI(50) values of 16-20 nM in cellular assays, including excellent activity against the P-glycoprotein overexpressing cell line KBvin. Compound 4a inhibited colchicine binding to tubulin and tubulin assembly with an IC50 value of 0.85 mu M, superior to the reference compound CA4 (1.2 mu M) in the same assay. In addition, 4a also exhibited highly improved water solubility (75 mu g/mL) and a suitable log P value (3.43) at pH 7.4. With a good balance between antitumor potency and drug-like properties, compound 4a could be a new potential drug candidate for further development. Current results on SAR studies and molecular modeling provided more insight about this class of compounds as tubulin polymerization inhibitors targeting the colchicine site. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Wang, Sheng-Biao; Wang, Xiao-Feng; Qin, Bingjie; Cui, Mu-Tian; Zhu, Dong-Qing; Xie, Lan] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China. [Ohkoshi, Emika; Hsieh, Kan-Yen; Goto, Masuo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA. [Hsieh, Kan-Yen] Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. [Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan. RP Lee, KH (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA. EM khlee@unc.edu; lanxieshi@yahoo.com FU Natural Science Foundation of China (NSFC) [81120108022, 30930106]; NIH from the National Cancer Institute [CA177584]; Taiwan Department of Health, China Medical University Hospital Cancer Research Center of Excellence [DOH100-TD-C-111-005]; Teaching and Learning Excellence Program from Kaohsiung Medical University FX This investigation was supported by grants 81120108022 and 30930106 from the Natural Science Foundation of China (NSFC) awarded to L. Xie and NIH grant CA177584 from the National Cancer Institute awarded to K. H. Lee. This study was also supported in part by the Taiwan Department of Health, China Medical University Hospital Cancer Research Center of Excellence (DOH100-TD-C-111-005) awarded to K.H. Lee. K.Y. Hsieh was supported by the Teaching and Learning Excellence Program from Kaohsiung Medical University. NR 30 TC 5 Z9 5 U1 3 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 1 PY 2015 VL 23 IS 17 BP 5740 EP 5747 DI 10.1016/j.bmc.2015.07.016 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CQ1IG UT WOS:000360349900052 PM 26242242 ER PT J AU Singh, NS Bernier, M Camandola, S Khadeer, MA Moaddel, R Mattson, MP Wainer, IW AF Singh, Nagendra S. Bernier, Michel Camandola, Simonetta Khadeer, Mohammed A. Moaddel, Ruin Mattson, Mark P. Wainer, Irving W. TI Enantioselective inhibition of D-serine transport by (S)-ketamine SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; REGIONAL PAIN SYNDROME; HEALTHY-VOLUNTEERS; CAPILLARY-ELECTROPHORESIS; SH-SY5Y CELLS; CONCISE GUIDE; OLD DRUG; KETAMINE; PHARMACOLOGY; RELEASE AB Background and Purpose Patients with major depressive disorder receiving racemic ketamine, (R,S)-ketamine, experience transient increases in Clinician-Administered Dissociative States Scale scores and a coincident drop in plasma d-serine levels. The results suggest that (R,S)-ketamine produces an immediate, concentration-dependent pharmacological effect on d-serine plasma concentrations. One potential source of this effect is (R,S)-ketamine-induced inhibition of the transporter ASCT2, which regulates intracellular d-serine concentrations. In this study, we tested this hypothesis by examining the effect of (S)- and (R)-ketamine on ASCT2-mediated transport of d-serine in PC-12 and 1321N1 cells and primary neuronal cells in culture. Experimental Approach Intracellular and extracellular d-serine levels were determined using capillary electrophoresis-laser-induced fluorescence and liquid chromatography-mass spectrometry respectively. Expression of ASCT2, Asc-1 and serine racemase was determined utilizing Western blotting. Key Results (S)-Ketamine produced a concentration-dependent increase in intracellular d-serine and reduced extracellular d-serine accumulation. In contrast, (R)-ketamine decreased both intracellular and extracellular d-serine levels. The ASCT2 inhibitor, benzyl-d-serine (BDS), and ASCT2 gene knockdown mimicked the action of (S)-ketamine on d-serine in PC-12 cells, while the Asc-1 agonist d-isoleucine reduced intracellular d-serine and increased extracellular d-serine accumulation. This response to d-isoleucine was not affected by BDS or (S)-ketamine. Primary cultures of rat neuronal cells expressed ASCT2 and were responsive to (S)-ketamine and BDS. (S)- and (R)-ketamine increased the expression of monomeric serine racemase in all the cells studied, with (S)-ketamine having the greatest effect. Conclusions and Implications (S)-Ketamine decreased cellular export of d-serine via selective inhibition of ASCT2, and this could represent a possible source of dissociative effects observed with (R,S)-ketamine. C1 [Singh, Nagendra S.; Khadeer, Mohammed A.; Moaddel, Ruin; Wainer, Irving W.] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Bernier, Michel] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Camandola, Simonetta; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Lab Clin Invest, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM wainerir@grc.nia.nih.gov RI Singh, Nagendra/K-8966-2015 FU Intramural Research Program of National Institute on Aging/NIH; NIA [HHSN271201000008I] FX This work was supported by funding from the Intramural Research Program of the National Institute on Aging/NIH and by NIA Contract No. HHSN271201000008I. NR 45 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2015 VL 172 IS 18 BP 4546 EP 4559 DI 10.1111/bph.13239 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CQ3GT UT WOS:000360490800009 ER PT J AU Stratakis, CA AF Stratakis, Constantine A. TI And the GIST is: When one has a GIST, think of an association! SO CANCER LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; CARNEY-STRATAKIS-SYNDROME; SUCCINATE-DEHYDROGENASE; MOLECULAR-GENETICS; PDGFRA MUTATIONS; LACKING KIT; HYPERMETHYLATION; PHENOTYPE; DEFECTS; GENES AB Patients with gastrointestinal stromal tumors have been found to have other cancers more frequently than expected by chance in a population study. The findings are supportive of a genetic predisposition being more frequent in gastrointestinal stromal tumors, although other reasons cannot be excluded; clinicians need to bear in mind the possible association of a gastrointestinal stromal tumor with another primary cancer. C1 [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NIH, Interinst Pediat Endocrinol Training Program, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH,East Labs, 10 Ctr Dr,Room 1-3330,Bldg 10-CRC, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS NR 20 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2015 VL 121 IS 17 BP 2871 EP 2873 DI 10.1002/cncr.29435 PG 3 WC Oncology SC Oncology GA CP9VU UT WOS:000360244100007 PM 25931207 ER PT J AU Hall, KD Bemis, T Brychta, R Chen, KY Courville, A Crayner, EJ Goodwin, S Guo, J Howard, L Knuth, ND Miller, BV Prado, CM Siervo, M Skarulis, MC Walter, M Walter, PJ Yannai, L AF Hall, Kevin D. Bemis, Thomas Brychta, Robert Chen, Kong Y. Courville, Amber Crayner, Emma J. Goodwin, Stephanie Guo, Juen Howard, Lilian Knuth, Nicolas D. Miller, Bernard V., III Prado, Carla M. Siervo, Mario Skarulis, Monica C. Walter, Mary Walter, Peter J. Yannai, Laura TI Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity SO CELL METABOLISM LA English DT Article ID WEIGHT-LOSS; ENERGY-EXPENDITURE; REDUCTION; METABOLISM; NUTRITION; OXIDATION; BALANCE; PROTEIN; WOMEN; TRIAL AB Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 +/- 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 +/- 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. C1 [Hall, Kevin D.; Bemis, Thomas; Brychta, Robert; Chen, Kong Y.; Crayner, Emma J.; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Miller, Bernard V., III; Skarulis, Monica C.; Walter, Mary; Walter, Peter J.; Yannai, Laura] NIDDK, NIH, Bethesda, MD 20892 USA. [Courville, Amber] NIH, Clin Ctr Nutr Dept, Bethesda, MD 20892 USA. [Knuth, Nicolas D.] Towson Univ, Towson, MD 21252 USA. [Prado, Carla M.] Univ Alberta, Edmonton, AB T6G 2R3, Canada. [Siervo, Mario] Newcastle Univ, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England. RP Hall, KD (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov OI Chen, Kong/0000-0002-0306-1904 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. We thank the nursing and nutrition staff at the NIH MCRU for their invaluable assistance with this study. We thank Terri Wakefield, Dwayne Staton, and Erica Vass for their support in managing the study. We are most thankful to the study subjects who volunteered to participate in this demanding protocol. NR 38 TC 19 Z9 19 U1 6 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD SEP 1 PY 2015 VL 22 IS 3 BP 427 EP 436 DI 10.1016/j.cmet.2015.07.021 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CQ2TJ UT WOS:000360453900015 PM 26278052 ER PT J AU Krebs-Smith, SM Subar, AF Reedy, J AF Krebs-Smith, Susan M. Subar, Amy F. Reedy, Jill TI Examining Dietary Patterns in Relation to Chronic Disease Matching Measures and Methods to Questions of Interest SO CIRCULATION LA English DT Editorial Material DE Editorials; diet; epidemiology; outcome assessment (health care) ID QUALITY; INDEX; RISK; WOMEN C1 [Krebs-Smith, Susan M.; Subar, Amy F.; Reedy, Jill] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. RP Subar, AF (reprint author), US Naval Hosp, NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E140, Bethesda, MD 20814 USA. EM subara@mail.nih.gov NR 12 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 2015 VL 132 IS 9 BP 790 EP 793 DI 10.1161/CIRCULATIONAHA.115.018010 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ0VE UT WOS:000360315000002 PM 26260734 ER PT J AU Lauer, MS Mensah, GA AF Lauer, Michael S. Mensah, George A. TI Power of the Cluster SO CIRCULATION LA English DT Editorial Material DE Editorials; delivery of health care; hypertension; randomized trial ID BLOOD-PRESSURE CONTROL; TRIALS C1 [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 2015 VL 132 IS 9 BP 794 EP 795 DI 10.1161/CIRCULATIONAHA.115.018142 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ0VE UT WOS:000360315000003 PM 26187184 ER PT J AU Lindsey, ML Mayr, M Gomes, AV Delles, C Arrell, DK Murphy, AM Lange, RA Costello, CE Jin, YF Laskowitz, DT Sam, F Terzic, A Van Eyk, J Srinivas, PR AF Lindsey, Merry L. Mayr, Manuel Gomes, Aldrin V. Delles, Christian Arrell, D. Kent Murphy, Anne M. Lange, Richard A. Costello, Catherine E. Jin, Yu-Fang Laskowitz, Daniel T. Sam, Flora Terzic, Andre Van Eyk, Jennifer Srinivas, Pothur R. CA Amer Heart Assoc Council Council Cardiovasc Dis Young Council Clinical Cardiology Council Cardiovasc Stroke Nursing Council Hypertension Stroke Council TI Transformative Impact of Proteomics on Cardiovascular Health and Disease A Scientific Statement From the American Heart Association SO CIRCULATION LA English DT Editorial Material DE AHA Scientific Statements; biomarkers; mass spectrometry; proteome; systems biology; translational research ID PROTEIN POSTTRANSLATIONAL MODIFICATIONS; DOWN MASS-SPECTROMETRY; 3RD UNIVERSAL DEFINITION; CARDIAC TROPONIN-I; TOP-DOWN; QUANTITATIVE PROTEOMICS; MYOCARDIAL-INFARCTION; PLASMA-PROTEOME; BIOMARKER DISCOVERY; SYSTEMS BIOLOGY AB The year 2014 marked the 20th anniversary of the coining of the term proteomics. The purpose of this scientific statement is to summarize advances over this period that have catalyzed our capacity to address the experimental, translational, and clinical implications of proteomics as applied to cardiovascular health and disease and to evaluate the current status of the field. Key successes that have energized the field are delineated; opportunities for proteomics to drive basic science research, facilitate clinical translation, and establish diagnostic and therapeutic healthcare algorithms are discussed; and challenges that remain to be solved before proteomic technologies can be readily translated from scientific discoveries to meaningful advances in cardiovascular care are addressed. Proteomics is the result of disruptive technologies, namely, mass spectrometry and database searching, which drove protein analysis from 1 protein at a time to protein mixture analyses that enable large-scale analysis of proteins and facilitate paradigm shifts in biological concepts that address important clinical questions. Over the past 20 years, the field of proteomics has matured, yet it is still developing rapidly. The scope of this statement will extend beyond the reaches of a typical review article and offer guidance on the use of next-generation proteomics for future scientific discovery in the basic research laboratory and clinical settings. C1 [Lindsey, Merry L.] Univ Mississippi, Med Ctr, University, MS 38677 USA. [Mayr, Manuel] Kings Coll London, London WC2R 2LS, England. [Arrell, D. Kent; Terzic, Andre] Mayo Clin, Rochester, MN USA. [Costello, Catherine E.; Sam, Flora] Boston Univ, Sch Med, Boston, MA 02215 USA. [Delles, Christian] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. [Gomes, Aldrin V.] Univ Calif Davis, Davis, CA USA. [Jin, Yu-Fang] Univ Texas San Antonio, San Antonio, TX USA. [Lange, Richard A.] Texas Tech Univ Hlth Sci Ctr, El Paso, TX USA. [Laskowitz, Daniel T.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Murphy, Anne M.; Van Eyk, Jennifer] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Srinivas, Pothur R.] NIH, Bethesda, MD USA. Univ Wisconsin Madison, Madison, WI USA. Univ Louisville, Louisville, KY 40292 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Scripps Res Inst, La Jolla, CA USA. RP Lindsey, ML (reprint author), Univ Mississippi, Med Ctr, University, MS 38677 USA. OI Sam, Flora/0000-0001-8442-9362; Mayr, Manuel/0000-0002-0597-829X NR 163 TC 22 Z9 22 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 2015 VL 132 IS 9 BP 852 EP 872 DI 10.1161/CIR.0000000000000226 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ0VE UT WOS:000360315000010 PM 26195497 ER PT J AU Havranek, EP Mujahid, MS Barr, DA Blair, IV Cohen, MS Cruz-Flores, S Davey-Smith, G Dennison-Himmelfarb, CR Lauer, MS Lockwood, DW Rosal, M Yancy, CW AF Havranek, Edward P. Mujahid, Mahasin S. Barr, Donald A. Blair, Irene V. Cohen, Meryl S. Cruz-Flores, Salvador Davey-Smith, George Dennison-Himmelfarb, Cheryl R. Lauer, Michael S. Lockwood, Debra W. Rosal, Milagros Yancy, Clyde W. CA Amer Heart Assoc Council Quality Council Epidemiology Prevention Council Cardiovasc Stroke Nursing Council Lifestyle Cardiometab Hlth Stroke Council TI Social Determinants of Risk and Outcomes for Cardiovascular Disease A Scientific Statement From the American Heart Association SO CIRCULATION LA English DT Editorial Material DE AHA Scientific Statements; cardiovascular diseases; healthcare disparities; health services accessibility; prejudice; psychosocial deprivation; social determinants of health; socioeconomic factors ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; OF-THE-LITERATURE; BODY-MASS INDEX; NATIONALLY REPRESENTATIVE SAMPLE; COURSE SOCIOECONOMIC POSITION; TYPE-2 DIABETES-MELLITUS; COMMUNITY-HEALTH CENTERS C1 [Havranek, Edward P.] Denver Hlth, Denver, CO 80204 USA. [Mujahid, Mahasin S.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Barr, Donald A.] Stanford Univ, Stanford, CA 94305 USA. [Blair, Irene V.] Univ Colorado, Boulder, CO 80309 USA. [Cohen, Meryl S.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Cruz-Flores, Salvador] Texas Tech Univ Hlth Sci Ctr, El Paso, TX USA. [Davey-Smith, George] Univ Bristol, Bristol BS8 1TH, Avon, England. [Dennison-Himmelfarb, Cheryl R.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Lauer, Michael S.] NHLBI, Bethesda, MD USA. [Lockwood, Debra W.] Provident Resources Grp Inc, Baton Rouge, LA USA. [Rosal, Milagros] Univ Massachusetts Med, Worcester, MA USA. [Yancy, Clyde W.] Northwestern Univ, Evanston, IL 60208 USA. RP Havranek, EP (reprint author), Denver Hlth, Denver, CO 80204 USA. RI Davey Smith, George/A-7407-2013 OI Davey Smith, George/0000-0002-1407-8314 FU Medical Research Council [MC_UU_12013/1] NR 339 TC 49 Z9 49 U1 8 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 2015 VL 132 IS 9 BP 873 EP 898 DI 10.1161/CIR.0000000000000228 PG 26 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CQ0VE UT WOS:000360315000011 PM 26240271 ER PT J AU Abraham, SB Abel, BS Sinaii, N Saverino, E Wade, M Nieman, LK AF Abraham, Smita Baid Abel, Brent S. Sinaii, Ninet Saverino, Elizabeth Wade, Matthew Nieman, Lynnette K. TI Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ADRENOCORTICOTROPIN; CORTICOTROPIN AB ObjectivesTo validate the diagnostic utility of Cortrosyn stimulated aldosterone in the differentiation of primary (PAI) and secondary adrenal insufficiency (SAI) and to evaluate the effect of urine sodium levels and posture on test performance. DesignCross-sectional study. MethodsHealthy volunteers (HV; n=46) and patients with PAI (n=26) and SAI (n=29) participated in the study. Testing included cortisol and aldosterone (by liquid-chromatography tandem mass spectrometry) measurements at baseline and 30 and 60min after 250g Cortrosyn. Plasma corticotropin (ACTH), renin activity (PRA) and urine spot sodium as a proxy for 24-h urine sodium excretion were measured at baseline. The effect of a sitting or semifowlers posture was evaluated in healthy volunteers. ResultsA Cortrosyn-stimulated aldosterone level of 5ng/dl (014nmol/l) had 88% sensitivity and positive predictive value and 897% specificity and negative predictive value for distinguishing PAI from SAI. Spot urine sodium levels showed a strong correlation with peak aldosterone levels (r=-055, P=002, n=18) in the SAI but not PAI or HV groups. Posture did not have a significant effect on results. ConclusionsOnce diagnosed with adrenal insufficiency, a stimulated aldosterone value of 5ng/dl (014nmol/l) works well to differentiate PAI from SAI. However, clinicians should be aware of the possible effect of total body sodium as reflected by spot urine sodium levels on aldosterone results. A 24-h urine sodium measurement may be helpful in interpretation. C1 [Abraham, Smita Baid; Abel, Brent S.; Saverino, Elizabeth; Wade, Matthew; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), CRC, Rm 1-3140,MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Clinical Center, National Institutes of Health FX This work was supported in part by the intramural programme of The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Clinical Center, National Institutes of Health. NR 17 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2015 VL 83 IS 3 BP 308 EP 314 DI 10.1111/cen.12726 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ2VH UT WOS:000360459600004 PM 25620457 ER PT J AU Arduc, A Dogan, BA Tuna, MM Tutuncu, Y Isik, S Berker, D Guler, S AF Arduc, Ayse Dogan, Bercem Aycicek Tuna, Mazhar Muslum Tutuncu, Yasemin Isik, Serhat Berker, Dilek Guler, Serdar TI Higher body mass index and larger waist circumference may be predictors of thyroid carcinoma in patients with Hurthle-cell lesion/neoplasm fine-needle aspiration diagnosis SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CANCER-RISK; ANTHROPOMETRIC FACTORS; POOLED ANALYSIS; PHYSICAL-ACTIVITY; NEW-CALEDONIA; OBESITY; COHORT; SIZE; MALIGNANCY; WOMEN AB ObjectiveHigh body mass index (BMI) has been found to be associated with raised thyroid cancer risk, particularly in women. We examined the associations for BMI and waist circumference (WC) with thyroid cancer risk among women with Hurthle-cell lesion/neoplasm (HLN) on fine-needle aspiration biopsy (FNAB) with the hypothesis that BMI and WC could guide the management of these challenging indeterminate lesions. MethodsThis cross-sectional study included 224 women with HLN who underwent thyroidectomy. In all patients, TSH and thyroid auto-antibodies were evaluated, and thyroid nodule features were recorded. Patients were grouped according to BMI (<30 or 30kg/m(2)) and WC (<88 or 88cm). Relationships of thyroid cancer with BMI and WC were assessed using logistic regression analysis. ResultsMean weight, BMI (312651 vs 2647 +/- 59, P<0001), WC (9823 +/- 76 vs 8618 +/- 11, P=0001), and proportion of patients with high BMI (30kg/m(2)) (659 vs 338%, P<0001) or large WC (88cm) (841 vs 479%, P<0001) were significantly higher in malignant group compared to benign group. In regression analysis, BMI and WC significantly associated with existence of malignancy. Malignancy risk was 3819-fold higher (95% CI: 2068-7054) in BMI30kg/m(2) group compared to BMI<30kg/m(2), which was independent of TSH and age. Large WC was also associated with increased risk (OR=5593, 95% CI: 2736-11434). Baseline tumour characteristics were similar according to BMI and WC groups. ConclusionsA great BMI and large WC were associated with higher thyroid cancer risk in patients with FNAB diagnosis of HLN. Further studies are needed to use BMI or WC in the management of patients with HLN. C1 [Arduc, Ayse] NIDDK, NIH, Diabet Endocrine & Obes Branch, Bethesda, MD 20892 USA. [Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Tutuncu, Yasemin; Isik, Serhat; Berker, Dilek] Minist Hlth, Ankara Numune Res & Training Hosp, Dept Endocrinol & Metab, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Fac Med, Dept Endocrinol & Metab, Corum, Turkey. RP Arduc, A (reprint author), 1778 Dawson St, Vienna, VA 22182 USA. EM ayse_arduc@yahoo.com NR 37 TC 1 Z9 1 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2015 VL 83 IS 3 BP 405 EP 411 DI 10.1111/cen.12628 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ2VH UT WOS:000360459600020 PM 25296952 ER PT J AU Hayashi, PH Fontana, RJ Chalasani, NP Stolz, AA Talwalkar, JA Navarro, VJ Lee, WM Davern, TJ Kleiner, DE Gu, JZ Hoofnagle, JH AF Hayashi, Paul H. Fontana, Robert J. Chalasani, Naga P. Stolz, Andrew A. Talwalkar, Jay A. Navarro, Victor J. Lee, William M. Davern, Timothy J. Kleiner, David E. Gu, Jiezhun Hoofnagle, Jay H. CA US Drug-Induced Liver Injury TI Under-reporting and Poor Adherence to Monitoring Guidelines for Severe Cases of Isoniazid Hepatotoxicity SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Adverse Reaction; Antibiotics; Drug-Induced Liver Injury; Hepatotoxicity; Tuberculosis ID LATENT TUBERCULOSIS INFECTION; INDUCED LIVER-INJURY; UNITED-STATES; ANTITUBERCULOSIS TREATMENT; PREVENTIVE THERAPY; DRUG; HEPATITIS; REINTRODUCTION; NETWORK AB BACKGROUND & AIMS: Isoniazid is a leading cause of liver injury but it is not clear how many cases are reported or how many clinicians and patients adhere to American Thoracic Society (ATS) guidelines. We collected data on cases of isoniazid hepatotoxicity and assessed adherence to ATS guidelines and reports to the Centers for Disease Control's (CDC) isoniazid severe adverse events program. METHODS: We analyzed Drug-Induced Liver Injury Network (DILIN) cases considered definite, highly likely, or probable for isoniazid injury from 2004 through 2013. We assessed the delays in isoniazid discontinuance according to ATS criteria and hepatotoxicity severity by Severity Index Score. We checked reporting to the CDC by matching cases based on age, latency, indication, reporting period, and comorbidities. RESULTS: Isoniazid was the second most commonly reported agent in the DILIN, with 69 cases; 60 of these met inclusion criteria. The median age of cases was 49 years (range, 4-68 y), 70% were female, 97% had latent tuberculosis, and 62% were hospitalized. Patients took a median of 9 days to stop taking isoniazid (range, 0-99 days). Thirty-three cases (55%) continued taking isoniazid for more than 7 days after the ATS criteria for stopping were met. Twenty-four cases (40%) continued isoniazid for more than 14 days after meeting criteria for stopping. A delay in stopping was associated with more severe injury (P < .05). Of 13 patients who died or underwent liver transplantation, 9 (70%) continued taking isoniazid for more than 7 days after meeting criteria for stopping. Only 1 of 25 cases of isoniazid hepatotoxicity eligible for reporting to the CDC was reported. CONCLUSIONS: Poor adherence to ATS guidelines is common in cases of hepatotoxicity and is associated with more severe outcomes including hospitalization, death, and liver transplantation. Isoniazid continues to be a leading cause of DILI in the United States, and its hepatotoxicity is under-reported significantly. C1 [Hayashi, Paul H.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. [Fontana, Robert J.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Chalasani, Naga P.] Indiana Univ Sch Med, Div Gastroenterol, Indianapolis, IN 46202 USA. [Stolz, Andrew A.] Univ So Calif, Div Gastroenterol, Los Angeles, CA USA. [Talwalkar, Jay A.] Mayo Clin, Div Gastroenterol, Rochester, MN USA. [Navarro, Victor J.] Einstein Healthcare Network, Div Gastroenterol, Philadelphia, PA USA. [Navarro, Victor J.] Univ Penn, Philadelphia, PA 19104 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Gastroenterol, Dallas, TX 75390 USA. [Davern, Timothy J.] Calif Pacific Med Ctr, Div Gastroenterol, San Francisco, CA USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Gu, Jiezhun] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hayashi, PH (reprint author), Univ N Carolina, Ctr Liver, Div Gastroenterol & Hepatol, CB 7584 Burnett Womack Bldg,Room 8011, Chapel Hill, NC 27599 USA. EM paul_hayashi@med.unc.edu FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR001105, UL1 TR001108]; NCRR NIH HHS [UL1 RR025747, UL1 RR024134, UL1 RR024150, UL1 RR024982, UL1 RR024986, UL1 RR025761]; NIDDK NIH HHS [1U01-DK082992-01, 1U01-DK083020-01, 1U01-DK083023-01, 1U01-DK083027-01, 2U01-DK065176-06, 2U01-DK065184-06, 2U01-DK065201-06, 2U01-DK065211-06, 5U01-DK065238-08, 5U01DK065193-04, P30 DK034989, U01 DK065176, U01 DK065184, U01 DK065193, U01 DK065201, U01 DK065211, U01 DK065238, U01 DK082992, U01 DK083020, U01 DK083023, U01 DK083027] NR 24 TC 7 Z9 7 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2015 VL 13 IS 9 BP 1676 EP + DI 10.1016/j.cgh.2015.02.024 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP7TG UT WOS:000360090400025 PM 25724701 ER PT J AU Paul, WE AF Paul, William E. TI History of interleukin-4 SO CYTOKINE LA English DT Review DE Cytokine; Cytokine receptor; Interleukins; Th2 cells; Innate lymphoid cells ID STIMULATORY FACTOR-I; CD4(+) T-CELLS; TRANSCRIPTION FACTOR GATA-3; CYTOKINE GENE-EXPRESSION; TH2 DIFFERENTIATION; IL-4 RECEPTOR; B-CELLS; MOUSE LYMPHOCYTES; MESSENGER-RNA; BIOCHEMICAL-CHARACTERIZATION AB The history of the discovery and the development of our knowledge of IL-4 exemplifies the path of progress in biomedical science. There are unanticipated twists and turns although progress is made, sometimes quickly, other times far too slowly. Illustrative is the extended time from the first report of IL-4 in 1982 to the establishment of the efficacy of blocking IL-4 and its congener IL-13 in the treatment of moderate to severe asthma and atopic dermatitis, a period of 31 years. The author was "present at the creation" and has been a participant or a witness to virtually all the major advances and recounts here his recollection of this history. Published by Elsevier Ltd. C1 [Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIH, Bldg 10,Rm 11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases FX The work cited in this paper from my research group was supported by funding from the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. All animal experiments were conducted under the approval of the NIAID Animal Care and Use Committee. NR 80 TC 10 Z9 11 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD SEP PY 2015 VL 75 IS 1 BP 3 EP 7 DI 10.1016/j.cyto.2015.01.038 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CQ3NZ UT WOS:000360510600002 PM 25814340 ER PT J AU Zhu, JF AF Zhu, Jinfang TI T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production SO CYTOKINE LA English DT Review DE Type 2 T helper cells (Th2); Type 2 innate lymphoid cells (ILC2); Interleukin-4; Interleukin-13; GATA3 ID CD4(+) T-CELLS; LOCUS-CONTROL REGION; TRANSCRIPTION FACTOR GATA3; THYMIC STROMAL LYMPHOPOIETIN; CYTOKINE GENE-EXPRESSION; RANGE INTRACHROMOSOMAL INTERACTIONS; INTERFERON-GAMMA PRODUCTION; T(H)2 LINEAGE COMMITMENT; ANTIGEN-PRESENTING CELLS; FOLLICULAR HELPER-CELLS AB Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these "type 2 immune response-related" cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naive CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. Published by Elsevier Ltd. C1 [Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), 10 Ctr Dr,Bldg 10,Room 11D02, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 FU Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), USA FX The work is supported by the Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), USA. NR 264 TC 15 Z9 16 U1 7 U2 28 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD SEP PY 2015 VL 75 IS 1 BP 14 EP 24 DI 10.1016/j.cyto.2015.05.010 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CQ3NZ UT WOS:000360510600004 PM 26044597 ER PT J AU Hartman, RL Brown, TL Milavetz, G Spurgin, A Pierce, RS Gorelick, DA Gaffney, G Huestis, MA AF Hartman, Rebecca L. Brown, Timothy L. Milavetz, Gary Spurgin, Andrew Pierce, Russell S. Gorelick, David A. Gaffney, Gary Huestis, Marilyn A. TI Cannabis effects on driving lateral control with and without alcohol SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cannabis; Alcohol; Driving; Lateral control; THC; Oral fluid ID CONTROLLED SMOKED CANNABIS; MOTOR-VEHICLE CRASHES; ORAL FLUID; MASS-SPECTROMETRY; BLOOD; MARIJUANA; DRUGS; PERFORMANCE; DRIVERS; IMPAIRMENT AB Background: Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Delta(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. Methods: Current occasional (>= 1 x /last 3 months, <= 3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (similar to 0.8 h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17 h, 0.42 h) and after (1.4h, 2.3 h) driving that occurred 0.5-1.3 h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. Results: In N = 18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1 mu g/L during driving increased SDLP similar to 0.05 and 0.08 g/210 L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5 mu g/L THC+ 0.05 g/210 L alcohol showing similar SDLP to 0.08 g/210 L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. Conclusions: SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC >= 8.2 mu g/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. Published by Elsevier Ireland Ltd. C1 [Hartman, Rebecca L.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD USA. [Hartman, Rebecca L.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA. [Brown, Timothy L.] Univ Iowa, Natl Adv Driving Simulator, Iowa City, IA USA. [Milavetz, Gary; Spurgin, Andrew] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. [Pierce, Russell S.] Variable Solut, Salt Lake City, UT USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Gaffney, Gary] Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Huestis, MA (reprint author), Biomed Res Ctr, Suite 200 Room 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU United States Office of National Drug Control Policy; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health; National Highway Traffic Safety Administration; National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program [U54TR001013] FX This research was funded by the United States Office of National Drug Control Policy; the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health; and the National Highway Traffic Safety Administration. Additionally, the Institute for Clinical and Translational Science at the University of Iowa is supported by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, grant U54TR001013. The CTSA program is led by the NIH's National Center for Advancing Translational Sciences (NCATS). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 67 TC 11 Z9 11 U1 3 U2 33 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2015 VL 154 BP 25 EP 37 DI 10.1016/j.drugalcdep.2015.06.015 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CQ2HB UT WOS:000360419600003 PM 26144593 ER PT J AU Berlin, I Singleton, EG Heishman, SJ AF Berlin, Ivan Singleton, Edward G. Heishman, Stephen J. TI Cross validation of the prognostic and diagnostic utility of tobacco craving in a general and a pregnant sample of treatment-seeking smokers SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Tobacco craving; Smoking relapse; Diagnosis; Prognosis; Pregnant smokers; Screening ID NICOTINE-REPLACEMENT THERAPY; FAGERSTROM TEST; CIGARETTE DEPENDENCE; SMOKING-CESSATION; QUESTIONNAIRE; WITHDRAWAL; COTININE; URGES; TRIAL; METAANALYSIS AB Background: Valid and reliable brief measures of tobacco craving are necessary for research and clinical purposes. However, comparisons of the utility of single-item and brief multidimensional craving measures are scarce. Methods: We analyzed two tobacco craving measures, the French versions of the 12-item Tobacco Craving Questionnaire (FTCQ-12) and the single craving item on the Minnesota Nicotine Withdrawal Scale, in pregnant and non-pregnant (females and males) French smokers from two independent smoking cessation trials. Using data from pregnant smokers, we estimated first a prognostic model for each measure and compared their ability to predict relapse from one visit to the next. We next used cutoff values for both measures to determine how well craving distinguished current smokers from abstainers. For cross-validation, we tested how well the same cut-off values generalized to non-pregnant smokers. Results: Two FTCQ-12 factors (Expectancy and Purposefulness) predicted smoking status; scores were higher in pregnant non-abstainers than abstainers. The sum of these two factors, FTCQ-12 risk score (RS), yielded higher sensitivity both in prognostic and diagnostic models than single-item MNWS craving. FTCQ-12 RS had higher sensitivity among pregnant than non-pregnant smokers. Specificity of both tobacco craving measures was similar among pregnant smokers, but higher with MNWS craving than with FTCQ-12 RS in non-pregnant smokers. Conclusions: FTCQ-12 RS and MNWS craving can be used together in clinical practice to rapidly predict smoking status. Interventions targeting Expectancy and Purposefulness may result in higher likelihood of abstinence, especially among pregnant smokers. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Berlin, Ivan] Univ Paris 06, Hop Pitie Salpetriere, Fac Med, INSERM,U1178, F-75013 Paris, France. [Singleton, Edward G.] Interact Profess Serv, Catonsville, MD 21218 USA. [Heishman, Stephen J.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Berlin, I (reprint author), Univ Paris 06, Hop Pitie Salpetriere, Fac Med, Dept Pharmacol, 47 Bd Hop, F-75013 Paris, France. EM ivan.berlin@psl.aphp.fr; e4d3g2s1@verizon.net; heishman@nih.gov OI Singleton, Edward G./0000-0003-3442-877X FU French Ministry of Health Program Hospitalier de Recherche Clinique [AOR04001//P040406, 050558]; Agence francaise de securite sanitaire des produits de sante; Convention Pharmacologie Clinique et Therapeutique [RAF02020]; Ministry of Health, France [MA05 001050] FX The ADONIS study was supported by the French Ministry of Health Program Hospitalier de Recherche Clinique Loco-regional 2004 (AOR04001//P040406, registration number: 050558); by the Agence francaise de securite sanitaire des produits de sante, Convention Pharmacologie Clinique et Therapeutique 2003, RAF02020. The SNIPP study was funded by the Ministry of Health, France, Grant Number MA05 001050. Contribution of E.G. Singleton was partly funded by the same research grant. NR 44 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2015 VL 154 BP 174 EP 183 DI 10.1016/j.drugalcdep.2015.06.034 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CQ2HB UT WOS:000360419600023 PM 26160457 ER PT J AU Leal, LF Szarek, E Faucz, F Stratakis, CA AF Leal, Leticia Ferro Szarek, Eva Faucz, Fabio Stratakis, Constantine A. TI Phosphodiesterase 8B and cyclic AMP signaling in the adrenal cortex SO ENDOCRINE LA English DT Review DE PDE8B; PRKAR1A; PRKACA; cAMP signaling; Adrenal ID PROTEIN-KINASE-A; NODULAR ADRENOCORTICAL DISEASE; CARNEY COMPLEX; CUSHINGS-SYNDROME; PRKAR1A GENE; NUCLEOTIDE PHOSPHODIESTERASES; ACTIVATING MUTATION; CATALYTIC SUBUNIT; HYPERPLASIA; TUMORS AB Bilateral adrenocortical hyperplasia (BAH) in humans and mice has been recently linked to phosphodiesterase (PDE) 8B (PDE8B) and 11 (PDE11A) defects. These findings have followed the discovery that defects of primary genes of the cyclic monophosphatase (cAMP) signaling pathway, such as guanine nucleotide binding alpha subunit and PRKAR1A, are involved in the pathogenesis of BAH in humans; complete absence of Prkar1a in the adrenal cortex of mice also led to pathology that mimicked the human disease. Here, we review the most recent findings in human and mouse studies on PDE8B, a cAMP-specific PDE that appears to be highly expressed in the adrenal cortex and whose deficiency may underlie predisposition to BAH and possibly other human diseases. C1 [Leal, Leticia Ferro; Szarek, Eva; Faucz, Fabio; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. RP Szarek, E (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3216, Bethesda, MD 20892 USA. EM eva.szarek@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. No research was conducted involving human articipants and/or animals (we only reviewed the relevant literature) in the present report. NR 36 TC 2 Z9 2 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD SEP PY 2015 VL 50 IS 1 BP 27 EP 31 DI 10.1007/s12020-015-0621-y PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9CY UT WOS:000360192500006 PM 25971952 ER PT J AU Moberg, M Elango, P Ferrucci, L Spruit, MA Wouters, EF Rutten, EPA AF Moberg, Mia Elango, Palchamy Ferrucci, Luigi Spruit, Martijn A. Wouters, Emiel F. Rutten, Erica P. A. TI Vitamin D deficiency and airflow limitation in the Baltimore Longitudinal Study of Ageing SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Airflow limitation; airway obstruction; cardiovascular disease; comorbidities; physical activity; vitamin D ID OBSTRUCTIVE PULMONARY-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; PLASMA 25-HYDROXYVITAMIN D; CARDIOVASCULAR-DISEASE; SERUM 25-HYDROXYVITAMIN-D; D SUPPLEMENTATION; RANDOMIZED-TRIAL; OBESE-PATIENTS; US POPULATION AB BackgroundVitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and has also been linked to comorbidities often present in COPD. AimThe aim of this study was to investigate whether vitamin D deficiency was related specifically to airflow limitation or whether vitamin D deficiency was determined by conditions that frequently coexist with COPD: insulin resistance, hypertension, anaemia, obesity and hypercholesterolaemia. MethodsFor this cross-sectional analysis, we included 897 subjects from the Baltimore Longitudinal Study of Aging. Subjects taking vitamin D supplements were excluded. Airflow limitation was defined as FEV1/FVC30kg/m(2)) (OR: 19, P<0002) were significantly associated with vitamin D deficiency in the adjusted multivariate regression analysis. Physical activity was associated with a decreased risk of vitamin D deficiency. ConclusionsAirflow limitation was not an independent determinant of vitamin D deficiency. The effect of weight loss and increased physical activity on vitamin D levels should be investigated further in intervention studies. C1 [Moberg, Mia] Hvidovre Univ Hosp, Sect Resp Med, DK-2650 Hvidovre, Denmark. [Elango, Palchamy; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Spruit, Martijn A.; Wouters, Emiel F.; Rutten, Erica P. A.] Ctr Expertise Chron Organ Failure, CIRO, Dept Res & Educ, Horn, Netherlands. [Spruit, Martijn A.] Hasselt Univ, BIOMED Biomed Res Inst, REVAL Rehabil Res Ctr, Fac Med & Life Sci, Diepenbeek, Belgium. RP Moberg, M (reprint author), Holbaek Univ Hosp, Dept Med, DK-4300 Holbaek, Denmark. EM miamoberg@hotmail.com FU TrygFonden FX We would like to thank Jorgen Vestbo for valuable advice and insight during the writing of this manuscript. Mia Moberg was funded by TrygFonden. NR 47 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD SEP PY 2015 VL 45 IS 9 BP 955 EP 963 DI 10.1111/eci.12498 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CP9NI UT WOS:000360220700009 PM 26173468 ER PT J AU Gonzalez, N Moreno, P Jensen, RT AF Gonzalez, Nieves Moreno, Paola Jensen, Robert T. TI Bombesin receptor subtype 3 as a potential target for obesity and diabetes SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE bombesin receptors; BRS-3; diabetes mellitus; obesity ID NEUROMEDIN-B RECEPTOR; HUMAN ORPHAN RECEPTOR; LUNG-CANCER CELLS; PANCREATIC ACINAR-CELLS; PEPTIDE RECEPTOR; BRS-3 AGONISTS; TYROSINE PHOSPHORYLATION; SUBTYPE-3-DEFICIENT MICE; DOWN-REGULATION; NERVOUS-SYSTEM AB Introduction: Diabetes mellitus and obesity are important health issues; increasing in prevalence, both in the USA and globally. There are only limited pharmacological treatments, and although bariatric surgery is effective, new effective pharmacologic treatments would be of great value. This review covers one area of increasing interest that could yield new novel treatments of obesity/diabetes mellitus. It involves recognition of the central role the G-protein-coupled receptor, bombesin receptor subtype 3 (BRS-3) plays in energy/glucose metabolism. Areas covered: Since the initial observation that BRS-3 knockout mice develop obesity, hypertension, impaired glucose metabolism and hyperphagia, there have been numerous studies of the mechanisms involved and the development of selective BRS-3 agonists/antagonists, which have marked effects on body weight, feeding and glucose/insulin homeostasis. In this review, each of these areas is briefly reviewed. Expert opinion: BRS-3 plays an important role in glucose/energy homeostasis. The development of potent, selective BRS-3 agonists demonstrates promise as a novel approach to treat obesity/diabetic states. One important question that needs to be addressed is whether BRS-3 agonists need to be centrally acting. This is particularly important in light of recent animal and human studies that report transient cardiovascular side effects with centrally acting oral BRS agonists. C1 [Gonzalez, Nieves] Autonomous Univ Madrid, IIS Jimenez Diaz Fdn, Renal Vasc & Diabet Res Lab, Spanish Biomed Res Network Diabet & Associated Me, E-28049 Madrid, Spain. [Moreno, Paola; Jensen, Robert T.] NIDDK, NIH, Cell Biol Sect, Digest Dis Branch, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, Cell Biol Sect, Digest Dis Branch, Bldg 10,Rm 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK, NIH FX This study was partially supported by intramural funds of the NIDDK, NIH. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. NR 133 TC 3 Z9 3 U1 4 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD SEP PY 2015 VL 19 IS 9 BP 1153 EP 1170 DI 10.1517/14728222.2015.1056154 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP9AG UT WOS:000360185500002 PM 26066663 ER PT J AU Wang, HJ Murray, GJ Jung, MK AF Wang, He Joe Murray, Gary J. Jung, Mary Katherine TI Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE alcohol metabolism; alcoholic liver disease; AMP protein kinase; animal models; autophagy; cellular stress; c-Jun N-terminal kinases; homeostatic response; macrophage polarity; oxidative stress ID ACTIVATED PROTEIN-KINASE; INDUCED FATTY LIVER; N-TERMINAL KINASE; MITOCHONDRIAL PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM STRESS; CHRONIC ETHANOL INGESTION; OXIDATIVE STRESS; RAT HEPATOCYTES; AMPK PHOSPHORYLATION; SIGNALING PATHWAY AB Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed. C1 [Wang, He Joe; Murray, Gary J.; Jung, Mary Katherine] NIAAA, Div Metab & Hlth Effect, NIH, Bethesda, MD 20892 USA. RP Wang, HJ (reprint author), NIAAA, Div Metab & Hlth Effect, NIH, 5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM joe.wang1@nih.gov; Kathy.jung@nih.gov NR 97 TC 0 Z9 0 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD SEP PY 2015 VL 9 IS 9 BP 1193 EP 1205 DI 10.1586/17474124.2015.1069705 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0GN UT WOS:000360273500007 PM 26293978 ER PT J AU Xanthakos, SA Jenkins, TM Kleiner, DE Boyce, TW Mourya, R Karns, R Brandt, ML Harmon, CM Helmrath, MA Michalsky, MP Courcoulas, AP Zeller, MH Inge, TH AF Xanthakos, Stavra A. Jenkins, Todd M. Kleiner, David E. Boyce, Tawny W. Mourya, Reena Karns, Rebekah Brandt, Mary L. Harmon, Carroll M. Helmrath, Michael A. Michalsky, Marc P. Courcoulas, Anita P. Zeller, Meg H. Inge, Thomas H. CA Teen-LABS Consortium TI High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery SO GASTROENTEROLOGY LA English DT Article DE Pediatric; Severe Obesity; Microarray; Inflammation ID VERTICAL SLEEVE GASTRECTOMY; HEPATIC GENE-EXPRESSION; CONTROLLED-TRIAL; OBESE SUBJECTS; BILE-ACIDS; STEATOHEPATITIS; CHILDREN; ASSOCIATION; FIBROSIS; SPECTRUM AB BACKGROUND & AIMS: Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. METHODS: We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 +/- 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. RESULTS: NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P <.01), and white blood cell count (P = .04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93 - 6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. CONCLUSIONS: More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism. C1 [Xanthakos, Stavra A.; Mourya, Reena] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Gastroenterol Hepatol & Nutr,Dept Pediat, Cincinnati, OH 45229 USA. [Jenkins, Todd M.; Helmrath, Michael A.; Inge, Thomas H.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Pediat Surg, Cincinnati, OH 45229 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Boyce, Tawny W.] Univ New Mexico, Ctr Canc, Biostat Shared Resource, Albuquerque, NM 87131 USA. [Karns, Rebekah] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Biomed Informat, Cincinnati, OH 45229 USA. [Brandt, Mary L.] Texas Childrens Hosp, Baylor Coll Med, Michael E DeBakey Dept Surg, Div Pediat Surg, Houston, TX 77030 USA. [Harmon, Carroll M.] SUNY Buffalo, Women & Childrens Hosp Buffalo, Sch Med & Biomed Sci, Div Pediat Surg, Buffalo, NY 14260 USA. [Michalsky, Marc P.] Ohio State Univ, Coll Med, Dept Pediat Surg, Columbus, OH 43210 USA. [Michalsky, Marc P.] Nationwide Childrens Hosp, Columbus, OH USA. [Courcoulas, Anita P.] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Zeller, Meg H.] Cincinnati Childrens Hosp Med Ctr, Div Behav Med, Cincinnati, OH 45229 USA. RP Xanthakos, SA (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Gastroenterol Hepatol & Nutr,Dept Pediat, 3333 Burnet Ave,MLC 2010, Cincinnati, OH 45229 USA. EM Stavra.xanthakos@cchmc.org OI michalsky, marc/0000-0002-7119-3634 FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR001425, UL1 TR000005]; NIDDK NIH HHS [P30 DK078392, UM1 DK072493, U01 DK072493/ UM1 DK072493, U01 DK072493, UM1 DK095710, R01 DK100429, K23 DK080888, U01 DK066557] NR 41 TC 9 Z9 9 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2015 VL 149 IS 3 BP 623 EP + DI 10.1053/j.gastro.2015.05.039 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ0FE UT WOS:000360269800032 PM 26026390 ER PT J AU Mannisto, T Mendola, P Grantz, KL Leishear, K Sundaram, R Sherman, S Ying, Q Liu, DP AF Mannisto, Tuija Mendola, Pauline Grantz, Katherine Laughon Leishear, Kira Sundaram, Rajeshwari Sherman, Seth Ying, Qi Liu, Danping TI Acute and recent air pollution exposure and cardiovascular events at labour and delivery SO HEART LA English DT Article ID HOSPITAL CARDIAC-ARREST; CASE-CROSSOVER ANALYSIS; MYOCARDIAL-INFARCTION; MORTALITY; PREGNANCY; INFLAMMATION; POLLUTANTS; DISEASE; STROKE; COHORT AB Objective To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. Methods The Consortium on Safe Labor (2002-2008), an observational US cohort with 223 502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7 days preceding delivery. Results Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6 days prior to delivery (OR= 1.17, 99% CI 1.04 to 1.30 and OR= 1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR= 1.50, 1.08 to 2.09), m-xylene (OR= 1.54, 1.11 to 2.13), o-xylene (OR= 1.51, 1.09 to 2.09), p-xylene (OR= 1.43, 1.03 to 1.99) and toluene (OR= 1.42, 1.02 to 1.97) at 5 days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. Conclusions Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission. C1 [Mannisto, Tuija; Mendola, Pauline; Grantz, Katherine Laughon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. [Mannisto, Tuija] Ctr NordLab, Northern Finland Lab, Oulu, Finland. [Mannisto, Tuija] Univ Oulu, Dept Clin Chem, Oulu, Finland. [Mannisto, Tuija] Oulu Univ Hosp, Med Res Ctr Oulu, Oulu, Finland. [Mannisto, Tuija] Univ Oulu, Oulu, Finland. [Mannisto, Tuija] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Oulu, Finland. [Leishear, Kira] Glotech Inc, Rockville, MD USA. [Leishear, Kira] US FDA, Silver Spring, MD USA. [Sundaram, Rajeshwari; Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. [Sherman, Seth] EMMES Corp, Rockville, MD USA. [Ying, Qi] Texas A&M Univ, Zachry Dept Civil Engn, College Stn, TX USA. RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA. EM Pauline.Mendola@nih.gov OI Sherman, Seth/0000-0003-3667-9898; Mannisto, Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844; Sundaram, Rajeshwari/0000-0002-6918-5002; Grantz, Katherine/0000-0003-0276-8534 NR 28 TC 1 Z9 1 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD SEP PY 2015 VL 101 IS 18 BP 1491 EP 1498 DI 10.1136/heartjnl-2014-307366 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ0SP UT WOS:000360307600014 PM 26105036 ER PT J AU Magnani, JW AF Magnani, Jared W. TI Risk assessment for atrial fibrillation: Enter the P-wave SO HEART RHYTHM LA English DT Editorial Material ID RECLASSIFICATION; DISEASE; HUMANS C1 [Magnani, Jared W.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, NHLBI, Sect Cardiovasc Med,Boston Med Ctr,Framingham Hea, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu FU NIA NIH HHS [R03AG045075] NR 13 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD SEP PY 2015 VL 12 IS 9 BP 1896 EP 1897 DI 10.1016/j.hrthm.2015.05.007 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LK UT WOS:000360359000010 PM 25962804 ER PT J AU Ji, JF Zheng, X Forgues, M Yamashita, T Wauthier, EL Reid, LM Wen, XY Song, Y Wei, JS Khan, J Thorgeirsson, SS Wang, XW AF Ji, Junfang Zheng, Xin Forgues, Marshonna Yamashita, Taro Wauthier, Eliane L. Reid, Lola M. Wen, Xinyu Song, Young Wei, Jun S. Khan, Javed Thorgeirsson, Snorri S. Wang, Xin Wei TI Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma SO HEPATOLOGY LA English DT Article ID CANCER STEM-CELLS; HEPATIC PROGENITOR CELLS; LIVER-CANCER; CYTOKERATIN-19 EXPRESSION; MESENCHYMAL TRANSITION; TGF-BETA; EPCAM; PROGRESSION; METASTASIS; SURVIVAL AB Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted owing to their similarities to CSCs. It is established that epithelial cell adhesion molecule (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM(+)AFP(+) hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not expressed in normal HpSCs. We performed a pair-wise comparison of the miRNA transcriptome of EpCAM(+) and corresponding EpCAM(-) cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors by small RNA deep sequencing. We found that miR-150, miR-155, and miR-223 were preferentially highly expressed in EpCAM(+) HCC cells, which was further validated. Their gene surrogates, identified using miRNA and messenger RNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM(+) HCC cells, compared to corresponding EpCAM(-) HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM(+) fraction in HCC cells and reduced HCC cell colony formation, migration, and invasion in vitro. The reduced levels of identified miR-155 targets predicted the shortened overall survival and time to recurrence of HCC patients. Conclusion: miR-155 is highly elevated in EpCAM(+) HCC cells and might serve as a molecular target to eradicate the EpCAM(+) CSC population in human HCCs. (Hepatology 2015;62:829-840) C1 [Ji, Junfang] Zhejiang Univ, Inst Life Sci, Hangzhou 310003, Zhejiang, Peoples R China. [Ji, Junfang] Univ Hawaii, Ctr Canc, Canc Biol Program, Honolulu, HI 96822 USA. [Zheng, Xin] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Ji, Junfang; Forgues, Marshonna; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yamashita, Taro] Kanazawa Univ Hosp, Dept Gastroenterol, Kanazawa, Ishikawa, Japan. [Wauthier, Eliane L.; Reid, Lola M.] UNC Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC USA. [Wauthier, Eliane L.; Reid, Lola M.] UNC Sch Med, Program Mol Biol & Biotechnol, Chapel Hill, NC USA. [Wen, Xinyu; Song, Young; Wei, Jun S.; Khan, Javed] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, 37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. EM jji@cc.hawaii.edu; xw3u@nih.gov RI Khan, Javed/P-9157-2014; Wang, Xin/B-6162-2009 OI Khan, Javed/0000-0002-5858-0488; FU center for cancer research, the U.S. National Cancer Institute [Z01-BC 010313, Z01-BC010876]; UNC School of Medicine (Chapel Hill, NC) - SRA from Vesta Therapeutics (Bethesda, MD); National Institutes of Health (NIH) [R21CA182322]; NIH [P30DK34987]; National Institute of Diabetes and Digestive and Kidney Diseases [DK34987]; Cancer Center grant [CA016086] FX This work was supported by the intramural research program of the center for cancer research, the U.S. National Cancer Institute (Z01-BC 010313 and Z01-BC010876), collaborators at the UNC School of Medicine (Chapel Hill, NC) funded by an SRA from Vesta Therapeutics (Bethesda, MD), by a National Institutes of Health (NIH) grant (R21CA182322), and with core services support from several center grants: NIH (P30DK34987); National Institute of Diabetes and Digestive and Kidney Diseases (DK34987); and a Cancer Center grant (CA016086). NR 45 TC 9 Z9 10 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2015 VL 62 IS 3 BP 829 EP 840 DI 10.1002/hep.27886 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1RB UT WOS:000360375100020 PM 25953724 ER PT J AU Chung, RT Davis, GL Jensen, DM Masur, H Saag, MS Thomas, DL Aronsohn, AI Charlton, MR Feld, JJ Fontana, RJ Ghany, MG Godofsky, EW Graham, CS Kim, AY Kiser, JJ Kottilil, S Marks, KM Martin, P Mitruka, K Morgan, TR Naggie, S Raymond, D Reau, NS Schooley, RT Sherman, KE Sulkowski, MS Vargas, HE Ward, JW Wyles, DL AF Chung, Raymond T. Davis, Gary L. Jensen, Donald M. Masur, Henry Saag, Michael S. Thomas, David L. Aronsohn, Andrew I. Charlton, Michael R. Feld, Jordan J. Fontana, Robert J. Ghany, Marc G. Godofsky, Eliot W. Graham, Camilla S. Kim, Arthur Y. Kiser, Jennifer J. Kottilil, Shyam Marks, Kristen M. Martin, Paul Mitruka, Kiren Morgan, Timothy R. Naggie, Susanna Raymond, Daniel Reau, Nancy S. Schooley, Robert T. Sherman, Kenneth E. Sulkowski, Mark S. Vargas, Hugo E. Ward, John W. Wyles, David L. CA AASLD IDSA HCV Guidance Panel TI Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus SO HEPATOLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; SOFOSBUVIR PLUS RIBAVIRIN; GENOTYPE 1 INFECTION; TREATMENT-EXPERIENCED PATIENTS; ALL-CAUSE MORTALITY; LIVER FIBROSIS; ANTIVIRAL THERAPY; UNITED-STATES; NATURAL-HISTORY; TREATMENT-NAIVE C1 [Chung, Raymond T.] Massachusetts Gen Hosp, Hepatol, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. [Davis, Gary L.] Baylor Univ, Med Ctr, Hepatol, Dallas, TX USA. [Davis, Gary L.] Baylor Univ, Med Ctr, Liver Transplantat, Dallas, TX USA. [Jensen, Donald M.; Reau, Nancy S.] Univ Chicago, Med Ctr, Med, Chicago, IL 60637 USA. [Masur, Henry] NIH, Dept Crit Care Med, Med, Bethesda, MD 20892 USA. [Saag, Michael S.] Univ Alabama Birmingham, Sch Med, Med, Birmingham, AL USA. [Saag, Michael S.] Univ Alabama Birmingham, Sch Med, Global Hlth, Birmingham, AL USA. [Thomas, David L.; Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Med, Baltimore, MD USA. [Thomas, David L.] Johns Hopkins Univ, Sch Med, Infect Dis, Baltimore, MD USA. [Aronsohn, Andrew I.] Univ Chicago, Med Ctr, Med, Chicago, IL 60637 USA. [Charlton, Michael R.] Intermt Med Ctr, Hepatol, Murray, KY USA. [Charlton, Michael R.] Intermt Med Ctr, Liver Transplantat, Murray, KY USA. [Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Med, Toronto, ON M5T 2S8, Canada. [Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Med, Gastroenterol, Toronto, ON M5T 2S8, Canada. [Fontana, Robert J.] Univ Michigan, Sch Med, Med, Ann Arbor, MI USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Liver Transplantat, Ann Arbor, MI USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Godofsky, Eliot W.] Bach & Godofsky, Infect Dis, Bradenton, FL USA. [Graham, Camilla S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Med, Boston, MA 02215 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, ID Div, Viral Hepatitis Clin, Boston, MA 02114 USA. [Kiser, Jennifer J.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Pharmacol, Aurora, CO USA. [Kiser, Jennifer J.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Ctr Translat Pharmacokinet & Pharmacogen, Aurora, CO USA. [Kottilil, Shyam] Univ Maryland, Inst Human Virol, Med, Baltimore, MD 21201 USA. [Kottilil, Shyam] Univ Maryland, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA. [Marks, Kristen M.] Weill Cornell Med Coll, Med, New York, NY USA. [Martin, Paul] Univ Miami, Sch Med, Med, Miami, FL USA. [Martin, Paul] Univ Miami, Sch Med, Div Hepatol, Miami, FL USA. [Mitruka, Kiren; Ward, John W.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Morgan, Timothy R.] Vet Affairs Long Beach Healthcare Syst, Hepatol, Long Beach, CA USA. [Naggie, Susanna] Duke Univ, Sch Med, Durham, NC USA. [Naggie, Susanna] Duke Clin Res Inst, Infect Dis Res, Durham, NC USA. [Raymond, Daniel] Community Representat, Harm Reduct Coalit, New York, NY USA. [Schooley, Robert T.] Univ Calif San Diego, Med, La Jolla, CA 92093 USA. [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA. [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Med, Cincinnati, OH USA. [Sherman, Kenneth E.] Univ Cincinnati, Div Digest Dis, Coll Med, Cincinnati, OH USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Viral Hepatitis Ctr, Baltimore, MD USA. [Vargas, Hugo E.] Mayo Clin, Coll Med, Med, Phoenix, AZ USA. [Wyles, David L.] Univ Calif San Diego, Med, La Jolla, CA 92093 USA. RP Davis, GL (reprint author), 201 S Ocean Grande Dr,PH4, Ponte Vedra Beach, FL 32082 USA. EM rtchung@partners.org; davisgl@sbcglobal.net NR 127 TC 169 Z9 171 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2015 VL 62 IS 3 BP 932 EP 954 DI 10.1002/hep.27950 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ1RB UT WOS:000360375100028 ER PT J AU Liu, SY Erkkinen, MG Healey, ML Xu, YS Swett, KE Chow, HM Braun, AR AF Liu, Siyuan Erkkinen, Michael G. Healey, Meghan L. Xu, Yisheng Swett, Katherine E. Chow, Ho Ming Braun, Allen R. TI Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process SO HUMAN BRAIN MAPPING LA English DT Article DE creativity; poetry composition; fMRI; neurocognitive model; cognitive disinhibition ID PREFRONTAL CORTEX; FUNCTIONAL-ORGANIZATION; COGNITIVE NEUROSCIENCE; DECISION-MAKING; DEFAULT NETWORK; BASAL GANGLIA; FMRI; IMPROVISATION; GENERATION; INSIGHT AB Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase-dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re-engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain. Hum Brain Mapp 36:3351-3372, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Liu, Siyuan; Xu, Yisheng; Chow, Ho Ming; Braun, Allen R.] NIDCD, Language Sect, NIH, Bethesda, MD 20892 USA. [Erkkinen, Michael G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Healey, Meghan L.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA. [Swett, Katherine E.] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Chow, Ho Ming] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Braun, AR (reprint author), NIH, 10 Ctr Dr,Bldg 10,5D-37, Bethesda, MD 20892 USA. EM brauna@nidcd.nih.gov FU NIH intramural research funds [DC-000031-19] FX Contract grant sponsor: NIH intramural research funds; Contract grant number: DC-000031-19 (to A. R. B.) NR 71 TC 8 Z9 9 U1 7 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2015 VL 36 IS 9 BP 3351 EP 3372 DI 10.1002/hbm.22849 PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP9IY UT WOS:000360209000005 PM 26015271 ER PT J AU Stek, A Best, BM Wang, JJ Capparelli, EV Burchett, SK Kreitchmann, R Rungruengthanakit, K Cressey, TR Mofenson, LM Smith, E Shapiro, D Mirochnick, M AF Stek, Alice Best, Brookie M. Wang, Jiajia Capparelli, Edmund V. Burchett, Sandra K. Kreitchmann, Regis Rungruengthanakit, Kittipong Cressey, Tim R. Mofenson, Lynne M. Smith, Elizabeth Shapiro, David Mirochnick, Mark TI Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article ID ANTIRETROVIRAL PHARMACOLOGY; PROTEIN-BINDING; PLASMA-LEVELS; LOPINAVIR; RITONAVIR; DARUNAVIR/RITONAVIR; EXPOSURE; DOSAGE; WOMAN; POSTPARTUM AB Objective: To describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women. Design: Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily. Methods: Intensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 mu g/mL). Results: Pharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration-time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0-0.82). Conclusions: DRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations. C1 [Stek, Alice] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Los Angeles, CA 90033 USA. [Best, Brookie M.; Wang, Jiajia; Capparelli, Edmund V.; Cressey, Tim R.; Shapiro, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Burchett, Sandra K.] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, HIV AIDS Res Dept, Porto Alegre, RS, Brazil. [Rungruengthanakit, Kittipong] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Cressey, Tim R.] Chiang Mai Univ, Fac Associated Med Sci, Dept Med Technol, Chiang Mai 50000, Thailand. [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Bethesda, MD USA. [Smith, Elizabeth] NIAID, Bethesda, MD 20892 USA. [Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. RP Mirochnick, M (reprint author), Boston Med Ctr, 771 Albany St,Dowling 4N, Boston, MA 02118 USA. EM markm@bu.edu FU National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [UM1AI068632, UM1AI068616, UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) FX 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 Nos. 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). NR 36 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2015 VL 70 IS 1 BP 33 EP 41 DI 10.1097/QAI.0000000000000668 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CQ1HM UT WOS:000360347900005 PM 25950206 ER PT J AU Nakigozi, G Makumbi, FE Bwanika, JB Atuyambe, L Reynolds, SJ Kigozi, G Nalugoda, F Chang, LW Kiggundu, V Serwadda, D Wawer, MJ Gray, RH Kamya, MR AF Nakigozi, Gertrude Makumbi, Fredrick E. Bwanika, John B. Atuyambe, Lynn Reynolds, Steven J. Kigozi, Godfrey Nalugoda, Fred Chang, Larry W. Kiggundu, Valerian Serwadda, David Wawer, Maria J. Gray, Ronald H. Kamya, Moses R. TI Impact of Patient-Selected Care Buddies on Adherence to HIV Care, Disease Progression, and Conduct of Daily Life Among Pre-antiretroviral HIV-Infected Patients in Rakai, Uganda: A Randomized Controlled Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article ID SUB-SAHARAN AFRICA; SOUTH-AFRICA; RURAL UGANDA; FOLLOW-UP; THERAPY; DIAGNOSIS; JOHANNESBURG; MORTALITY; VIOLENCE; PROGRAM AB Background: Data are limited on effects of household or community support persons ("care buddies") on enrollment into and adherence to pre-antiretroviral HIV care. We assessed the impact of care buddies on adherence to HIV clinic appointments, HIV progression, and conduct of daily life among pre-antiretroviral therapy (pre-ART) HIV-infected individuals in Rakai, Uganda. Methods: A total of 1209 HIV-infected pre-ART patients aged >= 15 years were randomized to standard of care (SOC) (n = 604) or patient-selected care buddy (PSCB) (n = 605) and followed at 6 and 12 months. Outcomes were adherence to clinic visits, HIV disease progression, and self-reported conduct of daily life. Incidence and prevalence rate ratios and 95% confidence intervals (CIs) were used to assess outcomes in the intent-to-treat and as-treated analyses. Results: Baseline characteristics were comparable. In the intent to treat analysis, both arms were comparable with respect to adherence to CD4 monitoring visits [adjusted prevalence risk ratio (adjPRR), 0.98; 95% CI: 0.93 to 1.04; P = 0.529], and ART eligibility (adjPRR, 1.00; 95% CI: 0.77 to 1.31; P = 0.946). Good conduct of daily life was significantly higher in the PSCB than the SOC arm (adjPRR, 1.08; 95% CI: 1.03 to 1.13; P = 0.001). More men (61%) compared with women (30%) selected spouses/partners as buddies (P < 0.0001). Twenty-two percent of PSCB arm participants discontinued use of buddies. Conclusions: In pre-ART persons, having care buddies improved the conduct of daily life of the HIV-infected patients but had no effect on HIV disease progression and only limited effect on clinic appointment adherence. C1 [Nakigozi, Gertrude; Bwanika, John B.; Kigozi, Godfrey; Nalugoda, Fred; Kiggundu, Valerian] Rakai Hlth Sci Program, Kalisizo, Uganda. [Makumbi, Fredrick E.; Atuyambe, Lynn; Serwadda, David] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda. [Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Reynolds, Steven J.; Chang, Larry W.] Johns Hopkins Sch Med, Div Infect Dis, Dept Med, Baltimore, MD USA. [Reynolds, Steven J.; Chang, Larry W.; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kamya, Moses R.] Makerere Univ, Coll Hlth Sci, Dept Med, Kampala, Uganda. RP Nakigozi, G (reprint author), Rakai Hlth Sci Program, Kalisizo, Uganda. EM gnakigozi@rhsp.org FU Fogarty International Center, NIH [2 D43 TW001508-10]; African Doctoral dissertation fellowship award; President's Emergency Plan for AIDS Relief through the Centers for Disease Control, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases; NIH FX Supported by Fogarty International Center, NIH Grant 2 D43 TW001508-10, and in part by the African Doctoral dissertation fellowship award. The study was conducted through the Rakai Health Sciences Program, a research collaboration between the Uganda Virus Research Institute and researchers at Makerere and Johns Hopkins University. HIV care was supported by the President's Emergency Plan for AIDS Relief through the Centers for Disease Control, Uganda.; S.J.R. was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and NIH. The remaining authors have no conflicts of interest to disclose. NR 31 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2015 VL 70 IS 1 BP 75 EP 82 DI 10.1097/QAI.0000000000000710 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CQ1HM UT WOS:000360347900010 PM 26039929 ER PT J AU Soenjaya, Y Foster, BL Nociti, FH Ao, M Holdsworth, DW Hunter, GK Somerman, MJ Goldberg, HA AF Soenjaya, Y. Foster, B. L. Nociti, F. H., Jr. Ao, M. Holdsworth, D. W. Hunter, G. K. Somerman, M. J. Goldberg, H. A. TI Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE bone sialoprotein; cementum; periodontal ligament; bone; mechanotransduction; malocclusion ID ORTHODONTIC TOOTH MOVEMENT; BONE SIALOPROTEIN; ALVEOLAR BONE; ENAMEL DEFECTS; LIGAMENT; DENTIN; HYDROXYAPATITE; OSTEOPONTIN; PROTEINS; CEMENTUM AB Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp(-/-) mice. C1 [Soenjaya, Y.; Holdsworth, D. W.; Hunter, G. K.; Goldberg, H. A.] Univ Western Ontario, Biomed Engn Program, London, ON N6A 5C1, Canada. [Soenjaya, Y.; Holdsworth, D. W.; Hunter, G. K.; Goldberg, H. A.] Univ Western Ontario, Schulich Sch Med & Dent, Sch Dent, London, ON N6A 5C1, Canada. [Foster, B. L.; Nociti, F. H., Jr.; Ao, M.; Somerman, M. J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Nociti, F. H., Jr.] Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, Piracicaba, Brazil. [Holdsworth, D. W.] Univ Western Ontario, Robarts Res Inst, Imaging Res Labs, London, ON N6A 5C1, Canada. [Hunter, G. K.; Goldberg, H. A.] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. RP Goldberg, HA (reprint author), Univ Western Ontario, Schulich Sch Med & Dent, Sch Dent, London, ON N6A 5C1, Canada. EM hagoldbe@uwo.ca RI Holdsworth, David/F-6315-2012; Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 FU Canadian Institutes for Health Research [FRN130572]; Intramural Research Program of NIAMS of the NIH; NIAMS [AR 066110]; Canadian Institutes for Health Research; AO Foundation (Davos, Switzerland) FX We thank Dr. Kamila Kantovitz (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] / National Institutes of Health [NIH]) for preparation of histological samples for analyses, Dr. Jane E. Aubin (University of Toronto) for providing the Bsp-null mice and for critical discussions of the work, Dr. James Simmer (University of Michigan, Ann Arbor) for insights on mouse incisor eruption, and Dr. Michael Wolf (University of Bonn, Germany) and Dr. Vivek Thumbigere-Math (NIAMS) for assistance in applying composite resin. This research was supported by the Canadian Institutes for Health Research (FRN130572; H.A.G.), the Intramural Research Program of NIAMS of the NIH (M.J.S.), and NIAMS (grant AR 066110; B.L.F.). Y.S. was supported by the Joint Motion Program, a Canadian Institutes for Health Research-funded Strategic Training Initiative in Health Research and the AO Foundation (Davos, Switzerland). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 38 TC 3 Z9 3 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2015 VL 94 IS 9 BP 1276 EP 1285 DI 10.1177/0022034515592581 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CP9BO UT WOS:000360188900013 PM 26130257 ER PT J AU Lyons, C Kaufman, AR Rima, B AF Lyons, Claire Kaufman, Annette R. Rima, Brandi TI Implicit theories of the body among college women: Implications for physical activity SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE exercise; implicit theories; physical activity; weight discrepancy ID EXERCISE MOTIVATION; WEIGHT-GAIN; ADOLESCENCE; TRANSITION; ENTITY; HEALTH; INTERVENTIONS; REGRESSION; ADULTHOOD; BELIEFS AB This study explored the relationship between implicit theories of the body (ITB) and self-reported physical activity. ITB are beliefs about the malleability of the body. Individuals may hold entity ITB (that body appearance is fixed) or incremental ITB (that body appearance can be changed). Female undergraduate students (N = 313) completed an online survey assessing ITB, physical activity, and discrepancy between actual and ideal body weight. Participants endorsing incremental ITB reported more physical activity. A significant ITB by weight discrepancy interaction emerged. Developing interventions targeting implicit theories of the body may be one way to increase physical activity. C1 [Lyons, Claire] Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. [Kaufman, Annette R.] NIH, Baltimore, MD USA. [Rima, Brandi] CUNY, Bronx Community Coll, Dept Social Sci, Bronx, NY USA. RP Kaufman, AR (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,3-E-546, Rockville, MD 20850 USA. EM kaufmana@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 37 TC 1 Z9 1 U1 2 U2 12 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 EI 1461-7277 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD SEP PY 2015 VL 20 IS 9 BP 1142 EP 1153 DI 10.1177/1359105313508997 PG 12 WC Psychology, Clinical SC Psychology GA CQ0WP UT WOS:000360318800002 PM 24271689 ER PT J AU Boularan, C Hwang, IY Kamenyeva, O Park, C Harrison, K Huang, Z Kehrl, JH AF Boularan, Cedric Hwang, Il-Young Kamenyeva, Olena Park, Chung Harrison, Kathleen Huang, Zhen Kehrl, John H. TI B Lymphocyte-Specific Loss of Ric-8A Results in a G alpha Protein Deficit and Severe Humoral Immunodeficiency SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; ASYMMETRIC CELL-DIVISION; NUCLEOTIDE EXCHANGE FACTOR; SPLENIC MARGINAL ZONE; GERMINAL CENTER; T-LYMPHOCYTE; MICE; LOCALIZATION; ACTIVATION; MIGRATION AB Resistance to inhibitors of cholinesterase 8A (Ric-8A) is a highly evolutionarily conserved cytosolic protein initially identified in Caenorhabditis elegans, where it was assigned a regulatory role in asymmetric cell divisions. It functions as a guanine nucleotide exchange factor for G(alpha i), G(alpha q), and G(alpha 12/13) and as a molecular chaperone required for the initial association of nascent G alpha subunits with cellular membranes in embryonic stem cell lines. To test its role in hematopoiesis and B lymphocytes specifically, we generated ric8(fl/fl)vav1-cre and ric8(fl/fl)mb1-cre mice. The major hematopoietic cell lineages developed in the ric8(fl/fl) vav1-cre mice, notwithstanding severe reduction in G(alpha i2/3), G(alpha q), and G(alpha 13) proteins. B lymphocyte-specific loss of Ric-8A did not compromise bone marrow B lymphopoiesis, but splenic marginal zone B cell development failed, and B cells underpopulated lymphoid organs. The ric8(fl/fl)mb1-cre B cells exhibited poor responses to chemokines, abnormal trafficking, improper in situ positioning, and loss of polarity components during B cell differentiation. The ric8(fl/fl)mb1-cre mice had a severely disrupted lymphoid architecture and poor primary and secondary Ab responses. In B lymphocytes, Ric-8A is essential for normal Ga protein levels and is required for B cell differentiation, trafficking, and Ab responses. C1 [Boularan, Cedric; Hwang, Il-Young; Kamenyeva, Olena; Park, Chung; Harrison, Kathleen; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Huang, Zhen] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Huang, Zhen] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov FU intramural program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases. NR 56 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2015 VL 195 IS 5 BP 2090 EP 2102 DI 10.4049/jimmunol.1500523 PG 13 WC Immunology SC Immunology GA CP6QY UT WOS:000360014200021 PM 26232433 ER PT J AU Anuradha, R Munisankar, S Dolla, C Kumaran, P Nutman, TB Babu, S AF Anuradha, Rajamanickam Munisankar, Saravanan Dolla, Chandrakumar Kumaran, Paul Nutman, Thomas B. Babu, Subash TI Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-RESPONSE; T-CELLS; LYMPHATIC FILARIASIS; SCHISTOSOMIASIS; IMMUNOPATHOGENESIS; INTERLEUKIN-4; TUBERCULOSIS; SENSITIVITY; INTERFERON; MECHANISMS AB Chronic helminth infections are known to be associated with modulation of Ag-specific CD4(+) T responses. However, the role of CD4(+) T cell responses in human infection with Strongyloides stercoralis is not well defined. To examine the role of CD4(+) T cells expressing Th1, Th2, and Th17 cytokines in strongyloidiasis, we compared the frequency (F-o) of these subsets in infected (INF) individuals with F-o in S. stercoralis-uninfected (UN) individuals. INF individuals exhibited a significant decrease in the spontaneous and Ag-specific F-o of both monofunctional and dual-functional Th1 cells compared with UN. Similarly, INF individuals also exhibited significantly decreased F-o of monofunctional and dual-functional Th17 cells upon Ag stimulation compared with UN. In contrast, both the spontaneous and the Ag-induced F-o of monofunctional and dual-functional Th2 cells was significantly increased in INF compared with UN individuals. This differential T cell response was predominantly Ag specific because it was abrogated upon control Ag or mitogen stimulation. The regulation of Th1, Th2, and Th17 cells was predominantly dependent on IL-10, whereas the regulation of Th2, but not Th1 or Th17, cells was also dependent on TGF-beta. In addition, treatment of S. stercoralis infection significantly increased the Ag-specific F-o of Th1 and Th17 cells and decreased the F-o of Th2 cells in INF individuals. Thus, S. stercoralis infection is characterized by a parasite Ag-dependent regulation of monofunctional and dual-functional Th1, Th2, and Th17 cells, a regulation also reversible by antihelminthic treatment. C1 [Anuradha, Rajamanickam; Munisankar, Saravanan; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras 600031, Tamil Nadu, India. [Dolla, Chandrakumar; Kumaran, Paul] Natl Inst Res TB, Madras 600031, Tamil Nadu, India. [Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, Madras 600031, Tamil Nadu, India. EM sbabu@mail.nih.gov FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 32 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2015 VL 195 IS 5 BP 2241 EP 2250 DI 10.4049/jimmunol.1500745 PG 10 WC Immunology SC Immunology GA CP6QY UT WOS:000360014200037 PM 26202988 ER PT J AU Raznahan, A AF Raznahan, A. TI PARALLEL NEUROIMAGING GENOMICS OF SEX CHROMOSOME ANEUPLOIDY IN HUMANS AND MICE SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Meeting Abstract DE brain anatomy; gene expression; sex chromosome aneuploidy; systems biology C1 [Raznahan, A.] NIMH, Dev Neurogen Unit, Child Psychiat Branch, IRP,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD SEP PY 2015 VL 59 IS 9 BP 796 EP 797 PG 2 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA CP9KS UT WOS:000360213600021 ER PT J AU Jin, XT Freeman, SR Vaisman, B Liu, Y Chang, J Varsano, N Addadi, L Remaley, A Kruth, HS AF Jin, Xueting Freeman, Sebastian R. Vaisman, Boris Liu, Ying Chang, Janet Varsano, Neta Addadi, Lia Remaley, Alan Kruth, Howard S. TI ABCA1 contributes to macrophage deposition of extracellular cholesterol SO JOURNAL OF LIPID RESEARCH LA English DT Article DE atherosclerosis; apolipoprotein A-I; high density lipoprotein; probucol; TO901317; ATP binding cassette transporter A1; ATP binding cassette transporter G1 ID HIGH-DENSITY-LIPOPROTEIN; CELLULAR LIPID EFFLUX; APOLIPOPROTEIN-A-I; ANTIBODY RECOGNITION; PLASMA-MEMBRANE; APOA-I; DOMAINS; HDL; BINDING; TRANSPORT AB We previously reported that cholesterol-enriched macrophages excrete cholesterol into the extracellular matrix. A monoclonal antibody that detects cholesterol microdomains labels the deposited extracellular particles. Macrophage deposition of extracellular cholesterol depends, in part, on ABCG1, and this cholesterol can be mobilized by HDL components of the reverse cholesterol transport process. The objective of the current study was to determine whether ABCA1 also contributes to macrophage deposition of extracellular cholesterol. ABCA1 functioned in extracellular cholesterol deposition. The liver X receptor agonist, TO901317 (TO9), an ABCA1-inducing factor, restored cholesterol deposition that was absent in cholesterol-enriched ABCG1(-/-) mouse macrophages. In addition, the ABCA1 inhibitor, probucol, blocked the increment in cholesterol deposited by TO9-treated wild-type macrophages, and completely inhibited deposition from TO9-treated ABCG1(-/-) macrophages. Lastly, ABCA1(-/-) macrophages deposited much less extracellular cholesterol than wild-type macrophages. These findings demonstrate a novel function of ABCA1 in contributing to macrophage export of cholesterol into the extracellular matrix. C1 [Jin, Xueting; Freeman, Sebastian R.; Liu, Ying; Chang, Janet; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Vaisman, Boris; Remaley, Alan] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. [Varsano, Neta; Addadi, Lia] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health; Binational Science Foundation [2013045] FX This work was supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, and by the Binational Science Foundation (Grant 2013045). NR 36 TC 6 Z9 7 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2015 VL 56 IS 9 BP 1720 EP 1726 DI 10.1194/jlr.M060053 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ1ZQ UT WOS:000360399500008 PM 26203076 ER PT J AU Schwendeman, A Sviridov, DO Yuan, WM Guo, YH Morin, EE Yuan, Y Stonik, J Freeman, L Ossoli, A Thacker, S Killion, S Pryor, M Chen, YE Turner, S Remaley, AT AF Schwendeman, Anna Sviridov, Denis O. Yuan, Wenmin Guo, Yanhong Morin, Emily E. Yuan, Yue Stonik, John Freeman, Lita Ossoli, Alice Thacker, Seth Killion, Salena Pryor, Milton Chen, Y. Eugene Turner, Scott Remaley, Alan T. TI The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties SO JOURNAL OF LIPID RESEARCH LA English DT Article DE high density lipoprotein; apolipoprotein A-I; sphingomyelin; peptides; inflammation; atherosclerosis ID HIGH-DENSITY-LIPOPROTEIN; RANDOMIZED CONTROLLED-TRIAL; CELLULAR FREE-CHOLESTEROL; REVERSE LIPID TRANSPORT; A-I; CORONARY ATHEROSCLEROSIS; MICE; SPHINGOMYELIN; RELEVANCE; VIVO AB The goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid (PL) composition affects its cholesterol efflux and anti-inflammatory properties. An ApoA-I mimetic peptide, 5A, was combined with either SM or POPC. Both lipid formulations exhibited similar in vitro cholesterol efflux by ABCA1, but 5A-SM exhibited higher ABCG1- and SR-BI-mediated efflux relative to 5A-POPC (P < 0.05). Injection of both rHDLs in rats resulted in mobilization of plasma cholesterol, although the relative potency was 3-fold higher for the same doses of 5A-SM than for 5A-POPC. Formation of pre HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing a higher extent of pre formation relative to 5A-POPC. Both rHDLs exhibited anti-inflammatory properties, but 5A-SM showed higher inhibition of TNF-, IL-6, and IL-1 release than did 5A-POPC (P < 0.05). Both 5A-SM and 5A-POPC showed reduction in total plaque area in ApoE(-/-) mice, but only 5A-SM showed a statistically significant reduction over placebo control and baseline (P < 0.01). The type of PL used to reconstitute peptide has significant influence on rHDL's anti-inflammatory and anti-atherosclerosis properties. C1 [Schwendeman, Anna; Yuan, Wenmin; Morin, Emily E.; Yuan, Yue] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. [Schwendeman, Anna; Yuan, Wenmin; Morin, Emily E.; Yuan, Yue] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA. [Guo, Yanhong; Chen, Y. Eugene] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Sviridov, Denis O.; Stonik, John; Freeman, Lita; Ossoli, Alice; Thacker, Seth; Pryor, Milton; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Yuan, Yue] Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China. [Killion, Salena; Turner, Scott] KineMed Inc, Emeryville, CA 94608 USA. RP Schwendeman, A (reprint author), Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. EM annaschw@umich.edu RI Ossoli, Alice/K-5917-2016 OI Ossoli, Alice/0000-0002-9902-252X FU American Heart Association [13SDG17230049, R01 GM113832, R01 HL068878, R01 HL117491]; Cellular Biotechnology Training Program [T32 GM008353]; National Natural Science for Youth Foundation of China [81202481]; Scientific Research Foundation for the Returned Overseas Chinese Scholars by Shenyang Pharmaceutical University [GGJJ2014102] FX This research was funded in part by American Heart Association Grants 13SDG17230049, R01 GM113832, R01 HL068878, and R01 HL117491. E.E.M. was supported by a Cellular Biotechnology Training Program T32 GM008353. Y.Y. was supported by grant 81202481 of the National Natural Science for Youth Foundation of China and grant GGJJ2014102 of the Scientific Research Foundation for the Returned Overseas Chinese Scholars by Shenyang Pharmaceutical University. NR 36 TC 8 Z9 8 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2015 VL 56 IS 9 BP 1727 EP 1737 DI 10.1194/jlr.M060285 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ1ZQ UT WOS:000360399500009 PM 26117661 ER PT J AU Phillips, J Wendler, D AF Phillips, John Wendler, David TI Clarifying substituted judgement: the endorsed life approach SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID SURROGATE DECISION-MAKING; INTERESTS; AUTONOMY; FAMILY; MAKERS AB A primary goal of clinical practice is to respect patient autonomy. To promote this goal for patients who have lost the ability to make their own decisions, commentators recommend that surrogates make their treatment decisions based on the substituted judgment standard. This standard is commonly interpreted as directing surrogates to make the decision the patient would have made in the circumstances, if the patient were competent. However, recent commentators have argued that this approach-attempting to make the decision the patient would have made if competent-is theoretically problematic, practically infeasible, and ignores the interests of the patient's family and loved ones. These commentators conclude that the substituted judgment standard should be revised significantly, or abandoned altogether. While this response would avoid the cited problems, it also would require substantial changes to clinical practice and would raise significant problems of its own. The present paper thus considers the possibility that the criticisms do not point to problems with the substituted judgment standard itself; instead, they point to problems with the way it is most commonly interpreted. This analysis suggests that the substituted judgment standard need not be dramatically revised or abandoned. Instead, it should be interpreted in a way that effectively promotes respect for the autonomy of incompetent patients. The 'endorsed life' interpretation described here helps clinicians and surrogates to achieve this important goal. To clarify this approach, we explain how it differs from three other recently proposed alternatives to the standard interpretation of the substituted judgment standard. C1 [Phillips, John] Univ N Carolina, Dept Philosophy, Chapel Hill, NC 27599 USA. [Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural Research Program of NIH Clinical Center FX This work was supported by the Intramural Research Program of the NIH Clinical Center. NR 23 TC 4 Z9 4 U1 2 U2 4 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 SEP PY 2015 VL 41 IS 9 BP 723 EP 730 DI 10.1136/medethics-2013-101852 PG 8 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CQ1QE UT WOS:000360372400001 PM 25360029 ER PT J AU Klabunde, C Blom, J Bulliard, JL Garcia, M Hagoel, L Mai, V Patnick, J Rozjabek, H Senore, C Tornberg, S AF Klabunde, Carrie Blom, Johannes Bulliard, Jean-Luc Garcia, Montse Hagoel, Lea Mai, Verna Patnick, Julietta Rozjabek, Heather Senore, Carlo Tornberg, Sven TI Participation rates for organized colorectal cancer screening programmes: an international comparison SO JOURNAL OF MEDICAL SCREENING LA English DT Article DE Colorectal; neoplasm; screening; population; FOBT; organized programmes; participation; uptake ID OCCULT BLOOD-TEST; IMPLEMENTATION; PERFORMANCE; POPULATION; INDICATORS; COUNTRIES; COVERAGE; FINLAND; BREAST AB Objective: Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. Methods: Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. Results: Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30-100%, coverage by the screening programme from 7-67.7%, overall uptake/participation rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. Conclusion: Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously. C1 [Klabunde, Carrie] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Blom, Johannes] Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden. [Bulliard, Jean-Luc] Univ Lausanne Hosp, Div Chron Dis, Inst Social & Prevent Med, Lausanne, Switzerland. [Garcia, Montse] IDIBELL, Catalan Inst Oncol, Canc Prevent & Control Program, Lhospitalet De Llobregat, Spain. [Hagoel, Lea] Technion Israel Inst Technol, Fac Med, Dept Community Med & Epidemiol, IL-32000 Haifa, Israel. [Hagoel, Lea] Carmel Med Ctr Haifa, Haifa, Israel. [Mai, Verna] Canadian Partnership Canc, Toronto, ON, Canada. [Patnick, Julietta] Publ Hlth England, NHS Canc Screening Programmes, Sheffield, S Yorkshire, England. [Rozjabek, Heather] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Senore, Carlo] AOU Citta Salute & Sci, Ctr Prevenz ne Oncol Piemonte, Turin, Italy. [Tornberg, Sven] Karolinska Inst, Dept Oncol Pathol, S-10401 Stockholm, Sweden. [Tornberg, Sven] Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden. RP Blom, J (reprint author), Karolinska Univ Hosp, Div Coloproctol, Ctr Surg Gastroenterol, P9 03, S-17176 Stockholm, Sweden. EM johannes.blom@ki.se OI Garcia, Montse/0000-0002-3437-3185; Senore, Carlo/0000-0003-1023-7477 NR 22 TC 6 Z9 6 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0969-1413 EI 1475-5793 J9 J MED SCREEN JI J. Med. Screen. PD SEP PY 2015 VL 22 IS 3 BP 119 EP 126 DI 10.1177/0969141315584694 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ0NN UT WOS:000360293200003 PM 25967088 ER PT J AU Pinsky, PF Zhu, CS Kramer, BS AF Pinsky, Paul F. Zhu, Claire S. Kramer, Barnett S. TI Lung cancer risk by years since quitting in 30+pack year smokers SO JOURNAL OF MEDICAL SCREENING LA English DT Article DE lung cancer; low-dose CT; smoking; years since quit ID SMOKING-CESSATION; CHEST RADIOGRAPH; SCREENING TRIAL; EXCESS RISK; MORTALITY AB Objective: Current United States recommendations for low-dose computed tomography (LDCT) lung cancer screening limit eligibility to ever-smokers with 30+ pack-years, with former smokers eligible only within 15 years of quitting. The 15 year limit is partly based on perceived decreases in lung cancer risk as years since quitting (YSQ) increase. We examine the relationship between lung cancer risk and YSQ among 30+ pack-year former smokers. Methods: In the Prostate, Lung, Colorectal, and Ovarian trial, participants aged 55-74 were randomized to screening or usual care; screened subjects received annual chest-radiographs for lung cancer screening. Subjects completed a baseline questionnaire; smoking history included average cigarettes per day and age at starting and stopping smoking. Subjects were followed 13 years. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) associated with YSQ, with YSQ treated as a time-varying covariate. The models adjusted for age and sex. Results: Of 154899 subjects randomized, 27101 were former smokers with 30+ pack-years, and 69182 were never smokers. HRs relative to never smokers ranged from 30.8 (95% CI: 23.4-40.5) for YSQ 45 to 6.4 (95% CI: 5.1-8.0) for YSQ > 30. For YSQ of > 10-15, > 15-20, and > 20-25, HRs were 14.8 (95% CI: 11.9-18.2), 13.5 (95% CI: 11.3-16.2), and 9.9 (95% CI: 8.1-12.0), respectively. Conclusions: Lung cancer risk decreases gradually with YSQ in 30+ pack year former smokers. A range of upper limits on YSQ may be supportable for LDCT screening. C1 [Pinsky, Paul F.; Zhu, Claire S.; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr,Rm 5E108, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 15 TC 6 Z9 6 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0969-1413 EI 1475-5793 J9 J MED SCREEN JI J. Med. Screen. PD SEP PY 2015 VL 22 IS 3 BP 151 EP 157 DI 10.1177/0969141315579119 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ0NN UT WOS:000360293200007 PM 25926339 ER PT J AU Fields, RL Gainer, H AF Fields, R. L. Gainer, H. TI The-216-to-100-bp Sequence in the 5-Flanking Region of the Oxytocin Gene Contains a Cell-Type Specific Regulatory Element for its Selective Expression in Oxytocin Magnocellular Neurones SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE oxytocin; vasopressin; gene expression; supraoptic nucleus; hypothalamus; enhancer; repressor; magnocellular neurone ID HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; RESPONSE ELEMENT; VASOPRESSIN; RECEPTORS; PROMOTER; RAT; IDENTIFICATION; NEUROPHYSIN; BINDING AB The oxytocin (OXT) gene is abundantly and highly selectively expressed in magnocellular neurones (MCNs) of the hypothalamic-neurohypophysial system. Previous DNA sequence deletion studies invivo have shown that the -216- to -100-bp sequence in the 5-flanking region of the oxytocin gene was required for its cell-type specific expression in the rat supraoptic nucleus. In the present study, we test the coupled hypotheses that this -216- to -100-bp sequence is responsible for (i) the selective expression of the OXT gene in OXT-MNCs and (ii) its selective repression in vasopressin (AVP)-MCNs. We show that, consistent with hypothesis 1, removal of the -216- to -100-bp sequence from the OXT gene completely eliminates its expression in OXT-MCNs invivo but, in contrast to the prediction of hypothesis 2, there was no appearance of OXT gene expression in AVP-MCNs. Taken together, these and other data demonstrate that the -216- to -100-bp sequence in the 5-flanking region of the oxytocin gene contains only an activator of transcription operating in the OXT-MCNs. C1 [Fields, R. L.; Gainer, H.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU NINDS, NIH FX This research was supported by the Intramural Research Program of the NINDS, NIH. We thank Dr W. Scott Young (NIMH) for access to his unpublished transgenic mouse data and his critical reading of a draft of this manuscript. NR 24 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 EI 1365-2826 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD SEP PY 2015 VL 27 IS 9 BP 702 EP 707 DI 10.1111/jne.12299 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CP9IM UT WOS:000360207600003 PM 26177679 ER PT J AU McLaughlin, KA Peverill, M Gold, AL Alves, S Sheridan, MA AF McLaughlin, Katie A. Peverill, Matthew Gold, Andrea L. Alves, Sonia Sheridan, Margaret A. TI Child Maltreatment and Neural Systems Underlying Emotion Regulation SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE child maltreatment; child abuse; trauma; emotion regulation; amygdala ID AMYGDALA RESPONSE; PREFRONTAL CORTEX; ANXIETY DISORDER; NEGATIVE EMOTION; NATIONAL SAMPLE; YOUNG-ADULTS; ABUSE; STRESS; THREAT; REACTIVITY AB Objective: The strong associations between child maltreatment and psychopathology have generated interest in identifying neurodevelopmental processes that are disrupted following maltreatment. Previous research has focused largely on neural response to negative facial emotion. We determined whether child maltreatment was. associated with neural responses during passive viewing of negative and positive emotional stimuli and effortful attempts to regulate emotional responses. Method: A total of 42 adolescents aged 13 to 19 years, half with exposure to physical and/or sexual abuse, participated. Blood oxygen level dependent (BOLD) response was measured during passive viewing of negative and positive emotional stimuli and attempts to modulate emotional responses using cognitive reappraisal. Results: Maltreated adolescents exhibited heightened response in multiple nodes of the salience network, including amygdala, putamen, and anterior insula, to negative relative to neutral stimuli. During attempts to decrease responses to negative stimuli relative to passive viewing, maltreatment was associated with greater recruitment of superior frontal gyrus, dorsal anterior cingulate cortex, and frontal pole; adolescents with and without maltreatment down-regulated amygdala response to a similar degree. No associations were observed between maltreatment and neural response to positive emotional stimuli during passive viewing or effortful regulation. Conclusion: Child maltreatment heightens the salience of negative emotional stimuli. Although maltreated adolescents modulate amygdala responses to negative cues to a degree similar to that of non-maltreated youths, they use regions involved in effortful control to a greater degree to do so, potentially because greater effort is required to modulate heightened amygdala responses. These findings are promising, given the centrality of cognitive restructuring in trauma-focused treatments for children. C1 [McLaughlin, Katie A.; Peverill, Matthew] Univ Washington, Seattle, WA 98195 USA. [Gold, Andrea L.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Alves, Sonia] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Sheridan, Margaret A.] Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP McLaughlin, KA (reprint author), Univ Washington, Psychol, Box 351525, Seattle, WA 98195 USA. EM mclaughk@uw.edu OI Gold, Andrea/0000-0003-4447-776X FU National Institutes of Health [K01-MH092526, K01-MH092555]; Child Health Young Investigator Award from the Charles H. Hood-Foundation; Intramural Research Program of the National Institutes of Health FX This research was supported by grants from the National Institutes of Health (K01-MH092526 and K01-MH092555) and a Child Health Young Investigator Award from the Charles H. Hood-Foundation. These funders provided support for all data collection and analysis. In addition, this research was supported in part by the Intramural Research Program of the National Institutes of Health. NR 53 TC 12 Z9 12 U1 7 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2015 VL 54 IS 9 BP 753 EP 762 DI 10.1016/j.jaac.2015.06.010 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CQ0BL UT WOS:000360259500010 PM 26299297 ER PT J AU Pichard, DC Freeman, AF Cowen, EW AF Pichard, Dominique C. Freeman, Alexandra F. Cowen, Edward W. TI Primary immunodeficiency update Part I. Syndromes associated with eczematous dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HYPER-IGE SYNDROME; HYPERIMMUNOGLOBULIN-E SYNDROME; X-LINKED SYNDROME; STEM-CELL TRANSPLANTATION; DOCK8 DEFICIENCY; IMMUNE DYSREGULATION; ATOPIC-DERMATITIS; TYROSINE-KINASE-2 DEFICIENCY; STAPHYLOCOCCUS-AUREUS; STAT3 MUTATIONS AB In the past decade, the availability of powerful molecular techniques has accelerated the pace of discovery of several new primary immunodeficiencies (PIDs) and revealed the biologic basis of other established PIDs. These genetic advances, in turn, have facilitated more precise phenotyping of associated skin and systemic manifestations and provide a unique opportunity to better understand the complex human immunologic response. These continuing medical education articles will provide an update of recent advances in PIDs that may be encountered by dermatologists through their association with eczematous dermatitis, infectious, and non-infectious cutaneous manifestations. Part I will discuss new primary immunodeficiencies that have an eczematous dermatitis. Part II will focus on primary immunodeficiencies that greatly increase susceptibility to fungal infection and the noninfectious presentations of PIDs. C1 [Pichard, Dominique C.; Cowen, Edward W.] NCI, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Consultat Serv, Dermatol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute FX Supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. NR 55 TC 3 Z9 3 U1 1 U2 5 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 SEP PY 2015 VL 73 IS 3 BP 355 EP 364 DI 10.1016/j.jaad.2015.01.054 PG 10 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500018 PM 26282794 ER PT J AU Pichard, DC Freeman, AF Cowen, EW AF Pichard, Dominique C. Freeman, Alexandra F. Cowen, Edward W. TI Primary immunodeficiency update Part II. Syndromes associated with mucocutaneous candidiasis and noninfectious cutaneous manifestations SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CXCR4 ANTAGONIST PLERIXAFOR; ACUTE MYELOID-LEUKEMIA; ADENOSINE-DEAMINASE DEFICIENCY; COMPLETE CLINICAL REMISSION; HYPOMORPHIC RAG1 MUTATIONS; FUNCTION STAT1 MUTATIONS; OF-FUNCTION MUTATIONS; WHIM-SYNDROME; GRANULOMATOUS-DISEASE; AUTOSOMAL-DOMINANT AB Several primary immunodeficiencies (PIDs) have recently been described that confer an elevated risk of fungal infections and noninfectious cutaneousmanifestations. In addition, immunologic advances have provided new insights into our understanding of the pathophysiology of fungal infections in established PIDs. We reviewed PIDs that present with an eczematous dermatitis in part I. In part II of this continuing medical education article we discuss updates on PIDs associated with fungal infections, their biologic basis in PIDs, and noninfectious cutaneous manifestations. C1 [Pichard, Dominique C.; Cowen, Edward W.] NCI, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Consultat Serv, Dermatol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute FX Supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. NR 74 TC 5 Z9 5 U1 0 U2 4 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 SEP PY 2015 VL 73 IS 3 BP 367 EP 381 DI 10.1016/j.jaad.2015.01.055 PG 15 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500019 PM 26282795 ER PT J AU Katz, SI AF Katz, Stephen I. TI Commentary: Setting priorities for research funding at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material DE arthritis C1 [Katz, Stephen I.] NIAMSD, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, 31 Ctr Dr,Room 4C32,MSC 2350, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov NR 14 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2015 VL 73 IS 3 BP 392 EP 394 DI 10.1016/j.jaad.2015.06.014 PG 3 WC Dermatology SC Dermatology GA CP7KO UT WOS:000360066500021 PM 26282796 ER PT J AU Saleh, KJ Kurdi, AJ El-Othmani, MM Voss, BA Tzeng, TH Saleh, J Lane, JM Mihalko, WM AF Saleh, Khaled J. Kurdi, Alexander J. El-Othmani, Mouhanad M. Voss, Benjamin A. Tzeng, Tony H. Saleh, Jasmine Lane, Joseph M. Mihalko, William M. TI Perioperative Treatment of Patients with Rheumatoid Arthritis SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID TUMOR-NECROSIS-FACTOR; TOTAL KNEE ARTHROPLASTY; ELECTIVE ORTHOPEDIC-SURGERY; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; LOWER-EXTREMITY ARTHROPLASTY; CARDIOVASCULAR RISK-FACTORS; INTERSTITIAL LUNG-DISEASE; TOTAL JOINT ARTHROPLASTY; TOTAL ELBOW REPLACEMENT; ANTI-TNF THERAPY AB Rheumatoid arthritis is an autoimmune disease mediated by a widespread chronic systematic inflammatory process that causes joint deterioration, which leads to pain, disability, and poor quality of life. The increased use of disease-modifying antirheumatic drugs has been shown to markedly slow disease progression, which has translated into a decrease in the need for orthopaedic intervention in this population. However, a substantial percentage of patients with the disease fail optimal pharmacologic treatment and still require surgical intervention. A thorough understanding of medical considerations in these patients and improved knowledge of the medical complications caused by the disease process and the pharmacologic therapy used to treat it may lead to improved preoperative planning and medical clearance, which may ultimately improve the overall postoperative outcome. C1 [Saleh, Khaled J.; Kurdi, Alexander J.; El-Othmani, Mouhanad M.; Voss, Benjamin A.; Tzeng, Tony H.] So Illinois Univ, Sch Med, Div Orthopaed Surg, Springfield, IL 62901 USA. [Saleh, Jasmine] NIH, Bethesda, MD 20892 USA. [Lane, Joseph M.] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Mihalko, William M.] Campbell Clin, Memphis, TN USA. RP Saleh, KJ (reprint author), So Illinois Univ, Sch Med, Div Orthopaed Surg, Springfield, IL 62901 USA. OI El-Othmani, Mouhanad/0000-0001-7211-4072 FU Aesculap/B. Braun; Memorial Medical Center; Watermark Research Partners; Smith Nephew; Orthopaedic Research and Education Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Bone Therapeutics; CollPlant; Graftys; Harvest; ISTO Technologies; BiologicsMD; Merck; Medtronic; Panoramic Healthcare Communications; MicroPort; Stryker FX Dr. Khaled Saleh or an immediate family member has received royalties from and is a member of a speakers' bureau or has made paid presentations on behalf of Aesculap/B. Braun; is an employee of Southern Illinois University School of Medicine; serves as a paid consultant to Aesculap/B. Braun, Memorial Medical Center, and Watermark Research Partners; has received research or institutional support from Smith & Nephew, the Orthopaedic Research and Education Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and serves as a board member, owner, officer, or committee member of the American Academy of Orthopaedic Surgeons, the American Orthopaedic Association, the Orthopaedic Research and Education Foundation, the American Board of Orthopaedic Surgeons, the Board of Specialty Societies, and Notify. Dr. Lane or an immediate family member serves as a paid consultant to Bone Therapeutics, CollPlant, Graftys, Harvest, ISTO Technologies, and BiologicsMD; has stock or stock options held in Dfine and CollPlant; has received research or institutional support from Merck; and serves as a board member, owner, officer, or committee member of the American Academy of Orthopaedic Surgeons, the Orthopaedic Research Society, the Musculoskeletal Tumor Society, the Association of Bone and Joint Surgeons, the American Osteopathic Association, and the American Society for Bone and Mineral Research. Dr. Mihalko or an immediate family member has received royalties from and is a member of a speakers' bureau or has made paid presentations on behalf of Aesculap/B. Braun; serves as a paid consultant to Aesculap/B. Braun, Medtronic, and Panoramic Healthcare Communications; has received research or institutional support from Aesculap/B. Braun, MicroPort, Smith & Nephew, and Stryker; and serves as a board member, owner, officer, or committee member of the American Board of Orthopaedic Surgery, the American Orthopaedic Association, and ASTM International. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Mr. Kurdi, Dr. El-Othmani, Mr. Voss, Mr. Tzeng, and Dr. Jasmine Saleh. NR 123 TC 0 Z9 0 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD SEP PY 2015 VL 23 IS 9 BP e38 EP e48 DI 10.5435/JAAOS-D-15-00014 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CQ1NO UT WOS:000360364600002 PM 26271759 ER PT J AU Bouhrara, M Reiter, DA Spencer, RG AF Bouhrara, Mustapha Reiter, David A. Spencer, Richard G. TI Bayesian analysis of transverse signal decay with application to human brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE Bayesian probability; nonlinear least squares algorithm; transverse relaxation; brain; accuracy; precision; Rician noise ID MAXIMUM-LIKELIHOOD-ESTIMATION; STRETCHED-EXPONENTIAL MODEL; MAGNETIC-RESONANCE IMAGES; IRON-LOADED LIVER; T-2 RELAXATION; PROBABILITY-THEORY; PARAMETER-ESTIMATION; ARTICULAR-CARTILAGE; IN-VIVO; MR DATA AB PurposeTransverse relaxation analysis with several signal models has been used extensively to determine tissue and material properties. However, the derivation of corresponding parameter values is notoriously unreliable. We evaluate improvements in the quality of parameter estimation using Bayesian analysis and incorporating the Rician noise model, as appropriate for magnitude MR images. Theory and MethodsMonoexponential, stretched exponential, and biexponential signal models were analyzed using nonlinear least squares (NLLS) and Bayesian approaches. Simulations and phantom and human brain data were analyzed using three different approaches to account for noise. Parameter estimation bias (reflecting accuracy) and dispersion (reflecting precision) were derived for a range of signal-to-noise ratios (SNR) and relaxation parameters. ResultsAll methods performed well at high SNR. At lower SNR, the Bayesian approach yielded parameter estimates of considerably greater precision, as well as greater accuracy, than did NLLS. Incorporation of the Rician noise model greatly improved accuracy and, to a somewhat lesser extent, precision, in derived transverse relaxation parameters. Analyses of data obtained from solution phantoms and from brain were consistent with simulations. ConclusionOverall, estimation of parameters characterizing several different transverse relaxation models was markedly improved through use of Bayesian analysis and through incorporation of the Rician noise model. Magn Reson Med 74:785-802, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Bouhrara, Mustapha; Reiter, David A.; Spencer, Richard G.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, NIH, Intramural Res Program, BRC 04B-116,251 Bayview Blvd, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov FU National Institute on Aging, Intramural Research Program FX Grant sponsor: National Institute on Aging, Intramural Research Program. NR 80 TC 4 Z9 4 U1 1 U2 7 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2015 VL 74 IS 3 BP 785 EP 802 DI 10.1002/mrm.25457 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP9OC UT WOS:000360222900020 PM 25242062 ER PT J AU Langenhan, T Barr, MM Bruchas, MR Ewer, J Griffith, LC Maiellaro, I Taghert, PH White, BH Monk, KR AF Langenhan, Tobias Barr, Maureen M. Bruchas, Michael R. Ewer, John Griffith, Leslie C. Maiellaro, Isabella Taghert, Paul H. White, Benjamin H. Monk, Kelly R. TI Model Organisms in G Protein-Coupled Receptor Research SO MOLECULAR PHARMACOLOGY LA English DT Review ID POLYCYSTIC KIDNEY-DISEASE; RESONANCE ENERGY-TRANSFER; BETA-ADRENERGIC-RECEPTOR; MATE-SEARCHING BEHAVIOR; CAENORHABDITIS-ELEGANS; C. ELEGANS; CIRCADIAN PACEMAKER; CALCIUM INDICATORS; CRYSTAL-STRUCTURE; TETHERED AGONIST AB The study of G protein-coupled receptors (GPCRs) has benefited greatly from experimental approaches that interrogate their functions in controlled, artificial environments. Working in vitro, GPCR receptorologists discovered the basic biologic mechanisms by which GPCRs operate, including their eponymous capacity to couple to G proteins; their molecular makeup, including the famed serpentine transmembrane unit; and ultimately, their three-dimensional structure. Although the insights gained from working outside the native environments of GPCRs have allowed for the collection of low-noise data, such approaches cannot directly address a receptor's native (in vivo) functions. An in vivo approach can complement the rigor of in vitro approaches: as studied in model organisms, it imposes physiologic constraints on receptor action and thus allows investigators to deduce the most salient features of receptor function. Here, we briefly discuss specific examples in which model organisms have successfully contributed to the elucidation of signals controlled through GPCRs and other surface receptor systems. We list recent examples that have served either in the initial discovery of GPCR signaling concepts or in their fuller definition. Furthermore, we selectively highlight experimental advantages, shortcomings, and tools of each model organism. C1 [Langenhan, Tobias] Univ Wurzburg, Inst Physiol, Dept Neurophysiol, D-97070 Wurzburg, Germany. [Maiellaro, Isabella] Univ Wurzburg, Inst Pharmacol & Toxicol, Rudolf Virchow Ctr, D-97070 Wurzburg, Germany. [Barr, Maureen M.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Barr, Maureen M.] Washington Univ, Basic Res Div, Dept Anesthesiol, Pain Ctr, St Louis, MO USA. [Bruchas, Michael R.; Taghert, Paul H.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Monk, Kelly R.] Washington Univ, Sch Med, Dept Dev Biol, Hope Ctr Neurol Disorders, St Louis, MO USA. [Ewer, John] Univ Valparaiso, Ctr Interdisciplinario Neurociencia, Valparaiso, Chile. [Griffith, Leslie C.] Brandeis Univ, Ctr Behav Genom, Volen Ctr Complex Syst, Waltham, MA USA. [Griffith, Leslie C.] Brandeis Univ, Dept Biol, Waltham, MA USA. [White, Benjamin H.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Langenhan, T (reprint author), Univ Wurzburg, Inst Physiol, Dept Neurophysiol, Rontgenring 9, D-97070 Wurzburg, Germany. EM tobias.langenhan@uni-wuerzburg.de; monkk@wustl.edu OI Griffith, Leslie/0000-0003-3164-9876; Ewer, John/0000-0002-6806-3628 FU Deutsche Forschungsgemeinschaft [FOR2149/TP1, SFB1047/A5, TP3]; National Institutes of Health National Institute on Drug Abuse [Exceptional Unconventional Research Enabling Knowledge Acceleration [R01-DA037152]; Fondo Nacional de Desarrollo Cientifico y Tecnologico [FONDECYT-1141278]; Centro Interdisciplinario de Neurociencia de Valparaiso [P09-022-F]; Millennium Scientific Initiative of the Ministerio de Economia, Fomento y Turismo; National Institutes of Health National Institute of Diabetes and Digestive Kidney Diseases [R01-DK059418, R01-DK074746]; National Institutes of Health National Institute of General Medical Sciences [R01-GM54408]; National Institutes of Health National Institute of Mental Health [R01-MH067122]; Intramural Research Program of the National Institutes of Health National Institute of Mental Health; National Institutes of Health National Institute of Neurological Disorders and Stroke [R01-NS079445]; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01-HD080601] FX This research was supported by the Deutsche Forschungsgemeinschaft [Grants FOR2149/TP1 and TP3 and SFB1047/A5 (to T.L.)], the National Institutes of Health National Institute on Drug Abuse [Exceptional Unconventional Research Enabling Knowledge Acceleration Grant R01-DA037152 (to M.R.B.)], the Fondo Nacional de Desarrollo Cientifico y Tecnologico [Grant FONDECYT-1141278 (to J.E.)], and the Centro Interdisciplinario de Neurociencia de Valparaiso [Grant P09-022-F (to J.E.)], which is supported by the Millennium Scientific Initiative of the Ministerio de Economia, Fomento y Turismo. This research was also supported by the National Institutes of Health National Institute of Diabetes and Digestive Kidney Diseases [Grants R01-DK059418 and R01-DK074746 (to M.M.B.], the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM54408 (to L.C.G.)], the National Institutes of Health National Institute of Mental Health [Grant R01-MH067122 (to P.H.T.)], the Intramural Research Program of the National Institutes of Health National Institute of Mental Health [(to B.H.W.)], the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01-NS079445 (to K.R.M.)], and the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant R01-HD080601 (to K.R.M.)]. NR 95 TC 4 Z9 4 U1 1 U2 15 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2015 VL 88 IS 3 BP 596 EP 603 DI 10.1124/mol.115.098764 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP8JI UT WOS:000360139400008 PM 25979002 ER PT J AU Doyle, JM Quinn, K Bodenstein, YA Wu, CO Danthi, N Lauer, MS AF Doyle, J. M. Quinn, K. Bodenstein, Y. A. Wu, C. O. Danthi, N. Lauer, M. S. TI Association of percentile ranking with citation impact and productivity in a large cohort of de novo NIMH-funded R01 grants SO MOLECULAR PSYCHIATRY LA English DT Article AB Previous reports from National Institutes of Health and National Science Foundation have suggested that peer review scores of funded grants bear no association with grant citation impact and productivity. This lack of association, if true, may be particularly concerning during times of increasing competition for increasingly limited funds. We analyzed the citation impact and productivity for 1755 de novo investigator-initiated R01 grants funded for at least 2 years by National Institute of Mental Health between 2000 and 2009. Consistent with previous reports, we found no association between grant percentile ranking and subsequent productivity and citation impact, even after accounting for subject categories, years of publication, duration and amounts of funding, as well as a number of investigator-specific measures. Prior investigator funding and academic productivity were moderately strong predictors of grant citation impact. C1 [Doyle, J. M.; Quinn, K.; Bodenstein, Y. A.] NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA. [Wu, C. O.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Danthi, N.] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Lauer, M. S.] NHLBI, Off Director, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov NR 16 TC 1 Z9 1 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2015 VL 20 IS 9 BP 1030 EP 1036 DI 10.1038/mp.2015.71 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CP8WL UT WOS:000360175500003 PM 26033238 ER PT J AU Davis, R Guglieri, M Hart, K McColl, E Herr, B Martens, W Wilkinson, J Eagle, M King, W Brawn, M McDermott, M Tawil, R Hirtz, D Kirschner, J Bushby, K Griggs, RC AF Davis, R. Guglieri, M. Hart, K. McColl, E. Herr, B. Martens, W. Wilkinson, J. Eagle, M. King, W. Brawn, M. McDermott, M. Tawil, R. Hirtz, D. Kirschner, J. Bushby, K. Griggs, R. C. TI ANTICIPATING AND OVERCOMING OBSTACLES IN SETTING UP NIH FUNDED ACADEMIC LED, INTERNATIONAL CLINICAL TRIALS IN RARE DISEASE - LEARNING FROM FOR DMD SO MUSCLE & NERVE LA English DT Meeting Abstract CT Muscle-Study-Group Meeting on Experimental Therapeutics Across the Spectrum of Neuromuscular Disease CY SEP 19-21, 2015 CL UT SP Muscle Study Grp C1 [Davis, R.; Guglieri, M.; McColl, E.; Wilkinson, J.; Eagle, M.; Bushby, K.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Hart, K.; Martens, W.; King, W.; Brawn, M.; McDermott, M.; Tawil, R.; Griggs, R. C.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Hirtz, D.] NINDS, NIH, Bethesda, MD 20892 USA. [Kirschner, J.] Univ Freiburg, D-79106 Freiburg, Germany. 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 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2015 VL 52 SU 1 BP S8 EP S8 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CQ3GN UT WOS:000360490200027 ER PT J AU Guglieri, M Hart, K McColl, E Herr, B Martens, W Wilkinson, J Eagle, M King, W Brawn, M McDermott, M Tawil, R Hirtz, D Kirschner, J Griggs, RC Bushby, K AF Guglieri, M. Hart, K. McColl, E. Herr, B. Martens, W. Wilkinson, J. Eagle, M. King, W. Brawn, M. McDermott, M. Tawil, Rabi Hirtz, Deborah Kirschner, J. Griggs, R. C. Bushby, K. TI RECRUITMENT IN THE FOR-DMD STUDY - DOUBLEB-LIND RANDOMIZED TRIAL TO OPTIMIZE STEROID REGIME IN DUCHENNE MUSCULAR DYSTROPHY (DMD) SO MUSCLE & NERVE LA English DT Meeting Abstract CT Muscle-Study-Group Meeting on Experimental Therapeutics Across the Spectrum of Neuromuscular Disease CY SEP 19-21, 2015 CL UT SP Muscle Study Grp C1 [Guglieri, M.; McColl, E.; Wilkinson, J.; Eagle, M.; Bushby, K.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Hart, K.; Martens, W.; King, W.; Brawn, M.; McDermott, M.; Tawil, Rabi; Griggs, R. C.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Hirtz, Deborah] NINDS, NIH, Bethesda, MD 20892 USA. [Kirschner, J.] Univ Freiburg, D-79106 Freiburg, Germany. RI Kirschner, Janbernd/H-7418-2016 OI Kirschner, Janbernd/0000-0003-1618-7386 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2015 VL 52 SU 1 BP S9 EP S9 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CQ3GN UT WOS:000360490200030 ER PT J AU Holmes, A Chen, A AF Holmes, Andrew Chen, Alon TI GABA receptors in a state of fear SO NATURE NEUROSCIENCE LA English DT Editorial Material ID ANXIETY DISORDERS; EXTINCTION; MICRORNAS; CONTEXT; MEMORY AB Our internal states can color our memories just as powerfully as the external environment. A study finds that hippocampal GABA(A) receptors and associated microRNAs are important for generating state-dependent contextual fear memories. C1 [Holmes, Andrew] NIAAA, Lab Behav Genom Neurosci, US Natl Inst Hlth, Bethesda, MD 38152 USA. [Chen, Alon] Weizmann Inst Sci, Ruhman Family Lab Res Neurobiol Stress, Dept Neurobiol, IL-76100 Rehovot, Israel. [Chen, Alon] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, D-80804 Munich, Germany. RP Holmes, A (reprint author), NIAAA, Lab Behav Genom Neurosci, US Natl Inst Hlth, Bethesda, MD 38152 USA. EM andrew.holmes@mail.nih.gov FU Intramural NIH HHS [Z01 AA000411-05] NR 15 TC 1 Z9 1 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2015 VL 18 IS 9 BP 1194 EP 1196 PG 4 WC Neurosciences SC Neurosciences & Neurology GA CQ0NI UT WOS:000360292600003 PM 26308977 ER PT J AU Adamantidis, A Arber, S Bains, JS Bamberg, E Bonci, A Buzsaki, G Cardin, JA Costa, RM Dan, Y Goda, Y Graybiel, AM Hausser, M Hegemann, P Huguenard, JR Insel, TR Janak, PH Johnston, D Josselyn, SA Koch, C Kreitzer, AC Luscher, C Malenka, RC Miesenbock, G Nagel, G Roska, B Schnitzer, MJ Shenoy, KV Soltesz, I Sternson, SM Tsien, RW Tsien, RY Turrigiano, GG Tye, KM Wilson, RI AF Adamantidis, Antoine Arber, Silvia Bains, Jaideep S. Bamberg, Ernst Bonci, Antonello Buzsaki, Gyoergy Cardin, Jessica A. Costa, Rui M. Dan, Yang Goda, Yukiko Graybiel, Ann M. Haeusser, Michael Hegemann, Peter Huguenard, John R. Insel, Thomas R. Janak, Patricia H. Johnston, Daniel Josselyn, Sheena A. Koch, Christof Kreitzer, Anatol C. Luescher, Christian Malenka, Robert C. Miesenboeck, Gero Nagel, Georg Roska, Botond Schnitzer, Mark J. Shenoy, Krishna V. Soltesz, Ivan Sternson, Scott M. Tsien, Richard W. Tsien, Roger Y. Turrigiano, Gina G. Tye, Kay M. Wilson, Rachel I. TI Optogenetics: 10 years after ChR2 in neurons-views from the community SO NATURE NEUROSCIENCE LA English DT Letter AB On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique. C1 [Adamantidis, Antoine] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Adamantidis, Antoine] Univ Bern, Inselspital Univ Hosp, Dept Neurol, Bern, Switzerland. [Arber, Silvia] Univ Basel, Dept Cell Biol, Biozentrum, Basel, Switzerland. [Arber, Silvia] Friedrich Miescher Inst Biomed Res, Basel, Switzerland. [Bains, Jaideep S.] Univ Calgary, Hotchkiss Brain Inst, Dept Physiol & Pharmacol, Calgary, AB, Canada. [Bamberg, Ernst] Max Planck Inst Biophys, Frankfurt, Germany. [Bonci, Antonello] NIDA, Intramural Res Program, Synapt Plast Sect, Baltimore, MD USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Buzsaki, Gyoergy] NYU, Sch Med, Neurosci Inst, New York, NY USA. [Buzsaki, Gyoergy] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Cardin, Jessica A.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Cardin, Jessica A.] Yale Univ, Kavli Inst Neurosci, New Haven, CT USA. [Costa, Rui M.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, Lisbon, Portugal. [Dan, Yang] Univ Calif Berkeley, Howard Hughes Med Inst, Helen Wills Neurosci Inst, Div Neurobiol,Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Goda, Yukiko] RIKEN Brain Sci Inst, Wako, Saitama, Japan. [Graybiel, Ann M.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Graybiel, Ann M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Haeusser, Michael] UCL, Wolfson Inst Biomed Res, London, England. [Haeusser, Michael] UCL, Dept Neurosci Physiol & Pharmacol, London, England. [Hegemann, Peter] Humboldt Univ, Inst Biol Expt Biophys, D-10099 Berlin, Germany. [Huguenard, John R.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. [Janak, Patricia H.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA. [Janak, Patricia H.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. [Johnston, Daniel] Univ Texas Austin, Dept Neurosci, Austin, TX 78712 USA. [Johnston, Daniel] Univ Texas Austin, Ctr Learning & Memory, Austin, TX 78712 USA. [Josselyn, Sheena A.] Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. [Josselyn, Sheena A.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Josselyn, Sheena A.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Josselyn, Sheena A.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Koch, Christof] Allen Inst Brain Sci, Washington, DC USA. [Kreitzer, Anatol C.] Gladstone Inst, San Francisco, CA USA. [Kreitzer, Anatol C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Kreitzer, Anatol C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA. [Luescher, Christian] Univ Geneva, Dept Basic Neurosci, Geneva, Switzerland. [Luescher, Christian] Univ Hosp Geneva, Dept Clin Neurosci, Serv Neurol, Geneva, Switzerland. [Malenka, Robert C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA. [Miesenboeck, Gero] Univ Oxford, Ctr Neural Circuits & Behav, Oxford, England. [Nagel, Georg] Univ Wurzburg, Bioctr, Inst Mol Plant Physiol & Biophys, D-97070 Wurzburg, Germany. [Roska, Botond] Friedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland. [Roska, Botond] Univ Basel, Dept Ophthalmol, Basel, Switzerland. [Schnitzer, Mark J.] Stanford Univ, James H Clark Ctr Biomed Engn & Sci, Stanford, CA 94305 USA. [Schnitzer, Mark J.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Schnitzer, Mark J.] Stanford Univ, CNC Program, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Neurosci Program, Dept Elect Engn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Neurosci Program, Dept Bioengn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Neurosci Program, Dept Neurobiol, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Bio X Program, Dept Elect Engn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Bio X Program, Dept Bioengn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Bio X Program, Dept Neurobiol, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Soltesz, Ivan] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Sternson, Scott M.] Howard Hughes Med Inst, Ashburn, VA USA. [Tsien, Richard W.] NYU, Langone Med Ctr, Neurosci Inst, Dept Neurosci & Physiol, New York, NY USA. [Tsien, Roger Y.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Chem & Biochem, Dept Pharmacol, La Jolla, CA 92093 USA. [Turrigiano, Gina G.] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. [Turrigiano, Gina G.] Brandeis Univ, Ctr Behav Genom, Waltham, MA USA. [Tye, Kay M.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Wilson, Rachel I.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Adamantidis, A (reprint author), McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. EM peter.hegemann@biologie.uni-regensburg.de; rtsien@ucsd.edu RI Huguenard, John/I-5016-2012; Luscher, Christian/A-2496-2011; OI Huguenard, John/0000-0002-6950-1191; Luscher, Christian/0000-0001-7917-4596; Nagel, Georg/0000-0001-8174-8712; Koch, Christof/0000-0001-6482-8067 FU NINDS NIH HHS [R01 NS027177, R01 NS034774, R01 NS090911]; Wellcome Trust [084655, 090309, 094077] NR 0 TC 16 Z9 19 U1 10 U2 48 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2015 VL 18 IS 9 BP 1202 EP 1212 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CQ0NI UT WOS:000360292600007 PM 26308981 ER PT J AU Wang, JX Telese, F Tan, YL Li, WB Jin, CY He, X Basnet, H Ma, Q Merkurjev, D Zhu, XY Liu, ZJ Zhang, J Ohgi, K Taylor, H White, RR Tazearslan, C Suh, Y Macfarlan, TS Pfaff, SL Rosenfeld, MG AF Wang, Jianxun Telese, Francesca Tan, Yuliang Li, Wenbo Jin, Chunyu He, Xin Basnet, Harihar Ma, Qi Merkurjev, Daria Zhu, Xiaoyan Liu, Zhijie Zhang, Jie Ohgi, Kenny Taylor, Havilah White, Ryan R. Tazearslan, Cagdas Suh, Yousin Macfarlan, Todd S. Pfaff, Samuel L. Rosenfeld, Michael G. TI LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control SO NATURE NEUROSCIENCE LA English DT Article ID GENE-EXPRESSION; GENOME INTEGRITY; HISTONE H4; CELL-CYCLE; CHROMATIN; ACTIVATION; BEHAVIOR; COMPLEX; PHF8; PHOSPHORYLATION AB We found that a neuron-specific isoform of LSD1, LSD1n, which results from an alternative splicing event, acquires a new substrate specificity, targeting histone H4 Lys20 methylation, both in vitro and in vivo. Selective genetic ablation of LSD1n led to deficits in spatial learning and memory, revealing the functional importance of LSD1n in neuronal activity-regulated transcription that is necessary for long-term memory formation. LSD1n occupied neuronal gene enhancers, promoters and transcribed coding regions, and was required for transcription initiation and elongation steps in response to neuronal activity, indicating the crucial role of H4K20 methylation in coordinating gene transcription with neuronal function. Our results indicate that this alternative splicing of LSD1 in neurons, which was associated with altered substrate specificity, serves as a mechanism acquired by neurons to achieve more precise control of gene expression in the complex processes underlying learning and memory. C1 [Wang, Jianxun; Telese, Francesca; Tan, Yuliang; Li, Wenbo; Jin, Chunyu; Basnet, Harihar; Ma, Qi; Merkurjev, Daria; Zhu, Xiaoyan; Liu, Zhijie; Zhang, Jie; Ohgi, Kenny; Taylor, Havilah; Rosenfeld, Michael G.] Univ Calif San Diego, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA. [Wang, Jianxun; He, Xin] Beijing Univ Chinese Med, Coll Basic Med, Beijing, Peoples R China. [White, Ryan R.; Tazearslan, Cagdas; Suh, Yousin] Albert Einstein Coll Med, Inst Aging Res, Dept Genet & Med, Bronx, NY 10467 USA. [Macfarlan, Todd S.] NICHHD, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Pfaff, Samuel L.] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA. RP Rosenfeld, MG (reprint author), Univ Calif San Diego, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA. EM ftelese@ucsd.edu; mrosenfeld@ucsd.edu RI Ma, Qi/C-9716-2015; Jin, Chunyu/A-4506-2016 FU US National Institutes of Health T32 Postdoctoral Fellowship; Roche Extending Innovation Network Program; Department of Defense postdoctoral fellowship; Howard Hughes Medical Institute; National Institute of Neurological Disorders and Stroke [R37NS5037116]; US National Institutes of Health; National Cancer Institute [DK018477, NS034934, DK039949, HL065445, CA173903]; National Institute of General Medical Sciences [R01GM104459-01] FX We thank J. Chen (University of California San Diego, UCSD) for pLNL vector for LSD1n gene targeting, and S. Wu and M. Capecchi (University of Utah) for pCAG-LSL vector for generation of Lsd1 transgenic mice. We thank J. Zhao and E. Kothari (UCSD transgenic core) for generating knockout and transgenic mice, S. Roberts (The Scripps Research Institute Mouse Behavioral Core) for behavioral assessment, H. Karten (UCSD) for brain anatomy analysis, M. Ghassemian (UCSD) for MALDI-TOF mass spectrometry analysis, A. Gamliel, R. McEvilly, I. Garcia-Bassets, B. Bloodgood and C.K. Glass (UCSD) for discussion, comments, suggestions and critical reading of the manuscript, R. Pardee for proofreading of the manuscript, and J. Hightower for help with figure preparation. J.W. receives funding from a US National Institutes of Health T32 Postdoctoral Fellowship. F.T. was supported by grants from the Roche Extending Innovation Network Program. W.L. was supported by a Department of Defense postdoctoral fellowship. S.L.P. (Benjamin H. Lewis Chair in Neuroscience) and M.G.R. receive funding from the Howard Hughes Medical Institute. This research was supported by grants from the National Institute of Neurological Disorders and Stroke (R37NS5037116) to S.L.P. and by grants from the US National Institutes of Health and the National Cancer Institute (DK018477, NS034934, DK039949, HL065445 and CA173903) to M.G.R. Y.S. received funding from the US National Institutes of Health and the National Institute of General Medical Sciences (R01GM104459-01). NR 50 TC 20 Z9 20 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2015 VL 18 IS 9 BP 1256 EP + DI 10.1038/nn.4069 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CQ0NI UT WOS:000360292600014 PM 26214369 ER PT J AU Cole, SW Nagaraja, AS Lutgendorf, SK Green, PA Sood, AK AF Cole, Steven W. Nagaraja, Archana S. Lutgendorf, Susan K. Green, Paige A. Sood, Anil K. TI Sympathetic nervous system regulation of the tumour microenvironment SO NATURE REVIEWS CANCER LA English DT Review ID NEGATIVE BREAST-CANCER; PROMOTES PERINEURAL INVASION; CELL LUNG-CANCER; BETA-BLOCKERS; OVARIAN-CARCINOMA; PROSTATE-CANCER; CHRONIC STRESS; PANCREATIC-CANCER; BONE-MARROW; DNA-DAMAGE AB The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programmes that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and haematopoietic differentiation programmes. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacological strategies to inhibit cancer progression in vivo. C1 [Cole, Steven W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med,Mol Biol Inst,Sch Med, Los Angeles, CA 90095 USA. [Cole, Steven W.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Nagaraja, Archana S.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Nagaraja, Archana S.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Lutgendorf, Susan K.] Univ Iowa, Dept Psychol, Dept Obstet & Gynecol, Dept Urol, Iowa City, IA 52242 USA. [Lutgendorf, Susan K.] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA. [Green, Paige A.] US Natl Canc Inst, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. RP Cole, SW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med,Mol Biol Inst,Sch Med, 11-934 Factor Bldg, Los Angeles, CA 90095 USA. EM Steve.Cole@ucla.edu OI Green, Paige/0000-0001-7886-8924; Nagaraja, Archana/0000-0002-2851-9272 FU United States National Institutes of Health [CA083639, CA098258, CA104825, CA109298, CA116778, CA140933, CA151668, CA177909, AG017265, AG033590]; Department of Defense [OC120547, OC093416]; Betty Ann Asche Murray Distinguished Professorship; Cancer Prevention and Research Institute of Texas [CPRIT RP140106]; Breast Cancer Research Foundation FX This work was supported by grants from the United States National Institutes of Health (CA083639, CA098258, CA104825, CA109298, CA116778, CA140933, CA151668, CA177909, AG017265, AG033590) and Department of Defense (OC120547, OC093416), the Betty Ann Asche Murray Distinguished Professorship, the Cancer Prevention and Research Institute of Texas (CPRIT RP140106), and the Breast Cancer Research Foundation. NR 125 TC 23 Z9 24 U1 6 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2015 VL 15 IS 9 BP 563 EP 572 DI 10.1038/nrc3978 PG 10 WC Oncology SC Oncology GA CQ1UP UT WOS:000360385700010 PM 26299593 ER PT J AU Thomas, A Liu, SV Subramaniam, DS Giaccone, G AF Thomas, Anish Liu, Stephen V. Subramaniam, Deepa S. Giaccone, Giuseppe TI Refining the treatment of NSCLC according to histological and molecular subtypes SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; PACLITAXEL PLUS CARBOPLATIN; TYROSINE KINASE INHIBITOR; RANDOMIZED PHASE-II; EGFR MUTATIONS; TARGETED THERAPIES; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; OPEN-LABEL; BRONCHOGENIC CARCINOMA AB In the past decade, the characterization of non-small-cell lung cancer (NSCLC) into subtypes based on genotype and histology has resulted in dramatic improvements in disease outcome in select patient subgroups. In particular, molecularly targeted agents that inhibit EGFR or ALK are approved for the treatment of NSCLC harbouring genetic alterations in the genes encoding these proteins. Although acquired resistance usually limits the duration of response to these therapies, a number of new agents have proven effective at tackling specific resistance mechanisms to first-generation inhibitors. Large initiatives are starting to address the role of biomarker-driven targeted therapy in squamous lung cancers, and in the adjuvant setting. Immunotherapy undeniably holds great promise and our understanding of subsets of NSCLC based on patterns of immune response is continuing to evolve. In addition, efforts are underway to identify rare genomic subsets through genomic screening, functional studies, and molecular characterization of exceptional responders. This Review provides an overview of the key developments in the treatment of NSCLC, and discusses potential strategies to further optimize therapy by targeting disease subtypes. C1 [Thomas, Anish] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liu, Stephen V.; Subramaniam, Deepa S.; Giaccone, Giuseppe] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Giaccone, G (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd North West, Washington, DC 20057 USA. EM gg496@georgetown.edu RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas, Anish/0000-0003-3293-3115 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX The work of A.T. is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 104 TC 36 Z9 36 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD SEP PY 2015 VL 12 IS 9 BP 511 EP 526 DI 10.1038/nrclinonc.2015.90 PG 16 WC Oncology SC Oncology GA CQ0NZ UT WOS:000360294500005 PM 25963091 ER PT J AU Roberts-Toler, C O'Neill, BT Cypess, AM AF Roberts-Toler, Carla O'Neill, Brian T. Cypess, Aaron M. TI Diet-induced obesity causes insulin resistance in mouse brown adipose tissue SO OBESITY LA English DT Article ID INFLAMMATION; ADIPOCYTES; HUMANS; RAT AB ObjectiveDiet-induced obesity (DIO) causes several pathophysiological changes in adipose tissue. Increased inflammation reduces white adipose tissue (WAT) insulin sensitivity and contributes to the development of diabetes. However, little is known about how DIO alters the function of brown adipose tissue (BAT), an organ that consumes calories by 3-adrenergic receptor (AR)-mediated thermogenesis and helps regulate energy balance. MethodsTo test the effects of DIO on BAT, we fed 6-week-old C57BL/6 mice either a normal chow diet (NCD) or a high-fat diet (HFD). After 16 additional weeks, we measured body fat, WAT, and BAT mRNA expression, glucose tolerance, and rates of glucose uptake in response to insulin and the 3-AR agonist mirabegron. ResultsCompared with NCD, HFD increased body fat and impaired glucose tolerance. Both WAT and BAT had higher mRNA levels of markers of inflammation, including TNF and F4/80. Insulin signaling in BAT and WAT was reduced, with decreased Akt phosphorylation. Diet-normalized BAT glucose uptake rates were lower in response to mirabegron. ConclusionsThese results support a model in which DIO leads to BAT inflammation and insulin resistance, leading to a broader impairment of BAT function. C1 [Roberts-Toler, Carla; O'Neill, Brian T.; Cypess, Aaron M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [Cypess, Aaron M.] NIDDK, Translat Physiol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Cypess, AM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. EM aaron.cypess@nih.gov FU National Institutes of Health (NIH) [K23 DK081604, K08 DK100543]; Joslin DRC; National Center for Research Resources (NCRR) [UL1RR025758]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This work was supported by National Institutes of Health (NIH) grants K23 DK081604 (A.M.C.), K08 DK100543 (B.T.O.), Joslin DRC, the Clinical Translational Science Award UL1RR025758 to Harvard University and BIDMC from the National Center for Research Resources (NCRR), and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDDK, NCRR, or the NIH. NR 19 TC 19 Z9 19 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1765 EP 1770 DI 10.1002/oby.21134 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100008 PM 26242777 ER PT J AU Thearle, MS Votruba, SB Piaggi, P Muller, YL Hanson, RL Baier, LJ Knowler, W Krakoff, J AF Thearle, Marie S. Votruba, Susanne B. Piaggi, Paolo Muller, Yunhua L. Hanson, Robert L. Baier, Leslie J. Knowler, William Krakoff, Jonathan TI The effect of differing patterns of childhood body mass index gain on adult physiology in American Indians SO OBESITY LA English DT Article ID PIMA-INDIANS; DEVELOPMENTAL TRAJECTORIES; ENERGY-EXPENDITURE; BIRTH COHORTS; WEIGHT-GAIN; OBESITY; OVERWEIGHT; INCREASES; INSULIN; GROWTH AB ObjectiveIdentifying groups of individuals with similar patterns of body mass index (BMI) change during childhood may increase understanding of the relationship between childhood BMI and adult health. MethodsDiscrete classes of BMI z-score change were determined in 1,920 American Indian children with at least four non diabetic health examinations between the ages of 2 and 18 years using latent class trajectory analysis. In subsets of subjects, data were available for melanocortin-4 receptor (MC4R) sequencing; in utero exposure to type 2 diabetes (T2D); or, as adults, oral glucose tolerance tests, onset of T2D, or body composition. ResultsSix separate groups were identified. Individuals with a more modern birth year, an MC4R mutation, or in utero exposure to T2D were clustered in the two groups with high increasing and chronic overweight z-scores (P<0.0001). The z-score classes predicted adult percent fat (P<0.0001, partial r(2)=0.18 adjusted for covariates). There was a greater risk for T2D, independent from adult BMI, in three classes (lean increasing to overweight, high increasing, and chronic overweight z-scores) compared to the two leanest groups (respectively: HRR= 3.2, P=0.01; 6.0, P=0.0003; 11.6, P<0.0001). ConclusionsDistinct patterns of childhood BMI z-score change associate with adult adiposity and may impact risk of T2D. C1 [Thearle, Marie S.; Votruba, Susanne B.; Piaggi, Paolo; Muller, Yunhua L.; Hanson, Robert L.; Baier, Leslie J.; Knowler, William; Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Thearle, MS (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. EM thearlem@mail.nih.gov RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Piaggi, Paolo/0000-0003-2774-9161 FU NIDDK, NIH FX This research was supported by the Intramural Research Program of the NIDDK, NIH. NR 40 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1872 EP 1880 DI 10.1002/oby.21162 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100021 PM 26308479 ER PT J AU O'Reilly, GA Belcher, BR Davis, JN Martinez, LT Huh, J Antunez-Castillo, L Weigensberg, M Goran, MI Spruijt-Metz, D AF O'Reilly, Gillian A. Belcher, Britni R. Davis, Jaimie N. Martinez, Lauren T. Huh, Jimi Antunez-Castillo, Luz Weigensberg, Marc Goran, Michael I. Spruijt-Metz, Donna TI Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents SO OBESITY LA English DT Article ID UNITED-STATES; INSULIN SENSITIVITY; OBESITY PREVENTION; CHILDHOOD OBESITY; DIETARY-INTAKE; CHILDREN; ENERGY; YOUTH; CONSUMPTION; OVERWEIGHT AB ObjectiveThis crossover experimental study examined the acute effects of high-sugar/low-fiber (HSLF) vs. low-sugar/high-fiber (LSHF) meals on sedentary behavior (SB) and light-plus activity (L+) in minority adolescents with overweight and obesity. Methods87 Latino and African American adolescents (mean age=16.31.2 years, mean BMI z-score =2.020.52, 56.8% Latino, 51.1% male) underwent two experimental meal conditions during which they consumed HSLF or LSHF meals. Physical activity and SB were measured using accelerometers, and blood glucose and insulin were collected every 30 minutes over 5 hours. Mixed models were used to examine the temporal trends of SB and L+, whether the temporal trends of SB and L+ differed by meal condition, and the influence of blood glucose and insulin on the activity behaviors. ResultsSB and L+ fluctuated over time during the HSLF condition but were stable during the LSHF condition. SB and L+ were influenced by the blood glucose response to the HSLF meals. Insulin did not influence SB or L+ in either meal condition. ConclusionsSugar and fiber content of meals can have differing acute impacts on activity behaviors in minority adolescents with overweight and obesity, possibly due to differing metabolic responses. C1 [O'Reilly, Gillian A.; Martinez, Lauren T.; Huh, Jimi; Antunez-Castillo, Luz; Goran, Michael I.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [O'Reilly, Gillian A.; Martinez, Lauren T.; Huh, Jimi; Antunez-Castillo, Luz; Goran, Michael I.] Univ So Calif, Childhood Obes Res Ctr, Los Angeles, CA 90089 USA. [Belcher, Britni R.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Davis, Jaimie N.] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA. [Weigensberg, Marc] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA USA. RP O'Reilly, GA (reprint author), Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. EM goreilly@usc.edu FU National Institute for Minority Health and Health Disparities (NIMHD) as part of the USC Minority Health Center of Excellence [NCHMD P60 MD002254]; National Cancer Institute (NCI), NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC) as part of the USC Center for Transdisciplinary Research on Energetics and Cancer [U54 CA 116848]; NCI [T32CA009492] FX This study was supported by the National Institute for Minority Health and Health Disparities (NIMHD) as part of the USC Minority Health Center of Excellence (NCHMD P60 MD002254) and the National Cancer Institute (NCI), NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC, U54 CA 116848) as part of the USC Center for Transdisciplinary Research on Energetics and Cancer. Work on this manuscript was supported by NCI to G.A.O. (T32CA009492). NR 40 TC 1 Z9 1 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1886 EP 1894 DI 10.1002/oby.21169 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100023 PM 26256555 ER PT J AU Qi, QB Strizich, G Hanna, DB Giacinto, RE Castaneda, SF Sotres-Alvarez, D Pirzada, A Llabre, MM Schneiderman, N Aviles-Santa, LM Kaplan, RC AF Qi, Qibin Strizich, Garrett Hanna, David B. Giacinto, Rebeca E. Castaneda, Sheila F. Sotres-Alvarez, Daniela Pirzada, Amber Llabre, Maria M. Schneiderman, Neil Aviles-Santa, Larissa M. Kaplan, Robert C. TI Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults SO OBESITY LA English DT Article ID BODY-MASS INDEX; BIOELECTRICAL-IMPEDANCE ANALYSIS; FAT-FREE MASS; WAIST CIRCUMFERENCE; CARDIOVASCULAR-DISEASE; ANTHROPOMETRIC MEASURES; OPPOSITE ASSOCIATIONS; DIVERSE BACKGROUNDS; INSULIN-RESISTANCE; METABOLIC SYNDROME AB ObjectiveUS Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos. MethodsMultivariable regression assessed cross-sectional relationships of six obesity measures with cardiometabolic outcomes among 16,415 Hispanics/Latinos aged 18-74 years. ResultsBMI was moderately correlated with waist-to-hip ratio (WHR; women, r=0.37; men, r=0.58) and highly correlated with other obesity measures (r0.87) (P<0.0001). All measures of obesity were correlated with unfavorable levels of glycemic traits, blood pressure, and lipids, with similar r-estimates for each obesity measure (P<0.05). Multivariable-adjusted prevalence ratios (PRs) for diabetes (women, 6.7 [3.9, 11.5]; men, 3.9 [2.2, 6.9]), hypertension (women, 2.4 [1.9, 3.1]; men, 2.5 [1.9, 3.4]), and dyslipidemia (women, 2.1 [1.8, 2.4]; men, 2.2 [1.9, 2.6]) were highest for individuals characterized as overweight/obese (BMI25 kg/m(2)) and with abnormal WHR (women 0.85; men, 0.90), compared with those with normal BMI and WHR (P<0.0001). Among normal-weight individuals, abnormal WHR was associated with increased cardiometabolic condition prevalence (P<0.05), particularly diabetes (women, PR=4.0 [2.2, 7.1]; men, PR=3.0 [1.6, 5.7]). ConclusionsObesity measures were associated with cardiometabolic risk factors to a similar degree in US Hispanics/Latinos. WHR is useful to identify individuals with normal BMI at increased cardiometabolic risk. C1 [Qi, Qibin; Strizich, Garrett; Hanna, David B.; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Giacinto, Rebeca E.; Castaneda, Sheila F.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Sotres-Alvarez, Daniela] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Pirzada, Amber] Univ Illinois, Inst Minor Hlth Res, Chicago, IL USA. [Llabre, Maria M.; Schneiderman, Neil] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Aviles-Santa, Larissa M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Qi, QB (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. EM qibin.qi@einstein.yu.edu RI DeMarcus, Forrest/O-9190-2016; Sotres-Alvarez, Daniela/O-9085-2016 OI Sotres-Alvarez, Daniela/0000-0002-3226-6140 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237] FX The baseline examination of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes/centers/ offices contributed to the HCHS/SOL first funding period through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the NIH Office of Dietary Supplements. NR 40 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2015 VL 23 IS 9 BP 1920 EP 1928 DI 10.1002/oby.21176 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CQ1VK UT WOS:000360388100027 PM 26260150 ER PT J AU Xiao, O Morgan, IG Ellwein, LB He, MG AF Xiao, Ou Morgan, Ian G. Ellwein, Leon B. He, Mingguang CA Refractive Error Study Children TI Prevalence of Amblyopia in School-Aged Children and Variations by Age, Gender, and Ethnicity in a Multi-Country Refractive Error Study SO OPHTHALMOLOGY LA English DT Article ID SINGAPOREAN CHINESE CHILDREN; VISUAL IMPAIRMENT; PRESCHOOL-CHILDREN; EYE DISEASES; RISK-FACTORS; POPULATION; STRABISMUS; VISION; TANZANIA; STUDENTS AB Purpose: To estimate the age-, gender-, and ethnicity-specific prevalence of amblyopia in children aged 5 to 15 years using data from the multi-country Refractive Error Study in Children (RESC). Design: Population-based, cross-sectional study. Participants: Among 46 260 children aged 5 to 15 years who were enumerated from 8 sites in the RESC study, 39 551 had a detailed ocular examination and a reliable visual acuity (VA) measurement in 1 or both eyes. Information on ethnicity was available for 39 321 of these participants. This study focused on findings from the 39 321 children. Methods: The examination included VA measurements, evaluation of ocular alignment and refractive error under cycloplegia, and examination of the external eye, anterior segment, media, and fundus. Main Outcome Measures: The proportion of children aged 5 to 15 years with amblyopia in different ethnic cohorts. Amblyopia was defined as best-corrected visual acuity (BCVA) of <= 20/40 in either eye, with tropia, anisometropia (>= 2 spherical equivalent diopters [ D]), or hyperopia (>=+6 spherical equivalent D), after excluding children with fundus or anterior segment abnormalities. Results: The overall prevalence of amblyopia was 0.74% (95% confidence interval, 0.64-0.83) with significant (P < 0.001) variation across ethnic groups: 1.43% in Hispanic, 0.93% in Chinese, 0.62% in Indian, 0.52% in Malay, 0.35% in Nepali, and 0.28% in African children. Amblyopia was not associated with age or gender. The most common cause of amblyopia was anisometropia. Conclusions: In this study, the prevalence of amblyopia varied with ethnicity and was highest in Hispanic children and lowest in African children. Most cases were unilateral and developed before the age of 5 years. The impact of changes of definitions on prevalence estimates is discussed. (C) 2015 by the American Academy of Ophthalmology. C1 [Xiao, Ou; He, Mingguang] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Morgan, Ian G.] Australian Natl Univ, ARC Ctr Excellence Vis Sci, Canberra, ACT, Australia. [Morgan, Ian G.] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia. [Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA. [He, Mingguang] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Australia. RP He, MG (reprint author), Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China. EM mingguang_he@yahoo.com RI Morgan, Ian/D-1190-2009 OI Morgan, Ian/0000-0002-4548-3574 FU World Health Organization under National Institute of Health [N01-EY-2103]; Fundamental Research Funds of the State Key Laboratory in Ophthalmology; National Natural Science Foundation of China [81125007] FX Funded by the World Health Organization under National Institute of Health contract N01-EY-2103, Fundamental Research Funds of the State Key Laboratory in Ophthalmology, and National Natural Science Foundation of China (81125007). NR 42 TC 4 Z9 5 U1 4 U2 10 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 SEP PY 2015 VL 122 IS 9 BP 1924 EP 1931 DI 10.1016/j.ophtha.2015.05.034 PG 8 WC Ophthalmology SC Ophthalmology GA CP8BU UT WOS:000360116900036 PM 26278861 ER PT J AU Olivieri, LJ Cross, RR O'Brien, KE Ratnayaka, K Hansen, MS AF Olivieri, Laura J. Cross, Russell R. O'Brien, Kendall E. Ratnayaka, Kanishka Hansen, Michael S. TI Optimized protocols for cardiac magnetic resonance imaging in patients with thoracic metallic implants SO PEDIATRIC RADIOLOGY LA English DT Article DE Artifact; Children; Congenital heart disease; Heart; Magnetic resonance imaging; Metal ID AMERICAN-HEART-ASSOCIATION; SCIENTIFIC STATEMENT; ARTIFACTS; DISEASE; MRI; CATHETERIZATION; INTERVENTION; ANGIOGRAPHY; DEVICES; SAFETY AB Cardiac magnetic resonance (MR) imaging is a valuable tool in congenital heart disease; however patients frequently have metal devices in the chest from the treatment of their disease that complicate imaging. Methods are needed to improve imaging around metal implants near the heart. Basic sequence parameter manipulations have the potential to minimize artifact while limiting effects on image resolution and quality. Our objective was to design cine and static cardiac imaging sequences to minimize metal artifact while maintaining image quality. Using systematic variation of standard imaging parameters on a fluid-filled phantom containing commonly used metal cardiac devices, we developed optimized sequences for steady-state free precession (SSFP), gradient recalled echo (GRE) cine imaging, and turbo spin-echo (TSE) black-blood imaging. We imaged 17 consecutive patients undergoing routine cardiac MR with 25 metal implants of various origins using both standard and optimized imaging protocols for a given slice position. We rated images for quality and metal artifact size by measuring metal artifact in two orthogonal planes within the image. All metal artifacts were reduced with optimized imaging. The average metal artifact reduction for the optimized SSFP cine was 1.5+/-1.8 mm, and for the optimized GRE cine the reduction was 4.6+/-4.5 mm (P < 0.05). Quality ratings favored the optimized GRE cine. Similarly, the average metal artifact reduction for the optimized TSE images was 1.6+/-1.7 mm (P < 0.05), and quality ratings favored the optimized TSE imaging. Imaging sequences tailored to minimize metal artifact are easily created by modifying basic sequence parameters, and images are superior to standard imaging sequences in both quality and artifact size. Specifically, for optimized cine imaging a GRE sequence should be used with settings that favor short echo time, i.e. flow compensation off, weak asymmetrical echo and a relatively high receiver bandwidth. For static black-blood imaging, a TSE sequence should be used with fat saturation turned off and high receiver bandwidth. C1 [Olivieri, Laura J.; Cross, Russell R.; O'Brien, Kendall E.; Ratnayaka, Kanishka] Childrens Natl Hlth Syst, Div Cardiol, Washington, DC 20010 USA. [Olivieri, Laura J.; Ratnayaka, Kanishka; Hansen, Michael S.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Olivieri, LJ (reprint author), Childrens Natl Hlth Syst, Div Cardiol, W3-200,111 Michigan Ave NW, Washington, DC 20010 USA. EM lolivier@childrensnational.org FU National Institutes of Health, National Heart, Lung, and Blood Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 18 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2015 VL 45 IS 10 BP 1455 EP 1464 DI 10.1007/s00247-015-3366-0 PG 10 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CQ2NU UT WOS:000360438800004 PM 26040508 ER PT J AU Kadom, N Rosman, NP Jubouri, S Trofimova, A Egloff, AM Zein, WM AF Kadom, Nadja Rosman, N. Paul Jubouri, Shams Trofimova, Anna Egloff, Alexia M. Zein, Wadih M. TI Neuroimaging experience in pediatric Horner syndrome SO PEDIATRIC RADIOLOGY LA English DT Article DE Children; Computed tomography; Horner syndrome; Magnetic resonance imaging; Oculosympathetic pathway ID INTERNAL CAROTID-ARTERY; DISSECTION; CHILD; PARAGANGLIOMA; NEUROBLASTOMA; SYRINGOMYELIA; SECONDARY; PALSY AB Horner syndrome in children is rare. The frequency and spectrum of malignancy as the cause of Horner syndrome in children remains unclear. Also unclear is whether the imaging work-up should include the entire oculo-sympathetic pathway or should be more targeted. In addition, the value of cross-sectional angiographic imaging in Horner syndrome is uncertain. To review imaging pathology in a cohort of children with Horner syndrome at a major academic pediatric medical center. We reviewed a 22-year period of CT and MR imaging studies in children with a clinical diagnosis of Horner syndrome referred for imaging. We found 38 patients who fulfilled study criteria of Horner syndrome and 6/38 had relevant imaging findings: 2/6 etiologies were neoplastic (congenital neuroblastoma and central astrocytoma), 1/6 had a vascular abnormality (hypoplastic carotid artery), 1/6 had maldevelopment (Chiari I malformation), and 2/6 had inflammatory/traumatic etiology (viral cervical lymphadenopathy, post jugular vein cannulation). There was a similar number of congenital and acquired pathologies. The malignancies were found at any level of the oculosympathetic pathway. There are treatable causes, including malignancies, in children presenting with Horner syndrome, which justify imaging work-up of the entire oculosympathetic pathway, unless the lesion level can be determined clinically. C1 [Kadom, Nadja] Boston Univ, Dept Radiol, Med Ctr, Sch Med, Boston, MA 02118 USA. [Rosman, N. Paul] Boston Univ, Div Pediat Neurol, Dept Pediat, Boston Med Ctr,Sch Med, Boston, MA 02118 USA. [Rosman, N. Paul] Boston Univ, Div Pediat Neurol, Dept Neurol, Boston Med Ctr,Sch Med, Boston, MA 02118 USA. [Jubouri, Shams; Trofimova, Anna; Egloff, Alexia M.] Childrens Natl Med Ctr, Dept Radiol & Diagnost Imaging, Washington, DC 20010 USA. [Zein, Wadih M.] NEI, Bethesda, MD 20892 USA. RP Kadom, N (reprint author), Boston Univ, Dept Radiol, Med Ctr, Sch Med, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA. EM nkpiano@gmail.com NR 34 TC 2 Z9 2 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2015 VL 45 IS 10 BP 1535 EP 1543 DI 10.1007/s00247-015-3341-9 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CQ2NU UT WOS:000360438800014 PM 25832988 ER PT J AU O'Keefe, BR Murad, AM Vianna, GR Ramessar, K Saucedo, CJ Wilson, J Buckheit, KW da Cunha, NB Araujo, ACG Lacorte, CC Madeira, L McMahon, JB Rech, EL AF O'Keefe, Barry R. Murad, Andre M. Vianna, Giovanni R. Ramessar, Koreen Saucedo, Carrie J. Wilson, Jennifer Buckheit, Karen W. da Cunha, Nicolau B. Araujo, Ana Claudia G. Lacorte, Cristiano C. Madeira, Luisa McMahon, James B. Rech, Elibio L. TI Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV SO PLANT BIOTECHNOLOGY JOURNAL LA English DT Article DE Cyanovirin-N; soya bean; anti-HIV ID VIRUS-INACTIVATING PROTEIN; BETA-CONGLYCININ; STORAGE PROTEINS; TRANSMISSION; PLANTS; EXPRESSION; CELLS; GENE; TRANSFORMATION; COTYLEDONS AB There is an urgent need to provide effective anti-HIV microbicides to resource-poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV-N was isolated with a yield of 350g/g of dry seed weight. The observed amino acid sequence of rCV-N matched the expected sequence of native CV-N, as did the mass of rCV-N (11009Da). Purified rCV-N from soya is active in anti-HIV assays with an EC50 of 0.82-2.7nM (compared to 0.45-1.8nM for E.coli-produced CV-N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV-N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti-HIV microbicide development. C1 [O'Keefe, Barry R.; Ramessar, Koreen; Saucedo, Carrie J.; Wilson, Jennifer; McMahon, James B.] NCI, Mol Targets Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Murad, Andre M.; Vianna, Giovanni R.; da Cunha, Nicolau B.; Araujo, Ana Claudia G.; Lacorte, Cristiano C.; Madeira, Luisa; Rech, Elibio L.] EMBRAPA Genet Resources & Biotechnol, Lab Synthet Biol, Brasilia, DF, Brazil. [Saucedo, Carrie J.] Leidos, Frederick Natl Lab Canc Res, Frederick, MD USA. [Buckheit, Karen W.] ImQuest BioSci LLC, Frederick, MD USA. [Madeira, Luisa] Univ London, Div Clin Sci, London, England. RP O'Keefe, BR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM okeefeba@mail.nih.gov; elibio.rech@embrapa.br RI Lacorte, Cristiano/I-5789-2016 FU Empresa Brasileira de Pesquisa Agropecuaria (Embrapa); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Fundacao de Apoio a Pesquisa do Distrito Federal (FAP-DF); NIH Intramural AIDS Targeted Antiviral Program; Intramural Program of the Center for Cancer Research at the National Cancer Institute; National Cancer Institute, National Institutes of Health [NO1-CO1-12400] FX The authors are grateful to Luis C. Lemos for technical assistance and to Ana C.M.M. Gomes for transmission electron microscopy assistance, MS. Warley W. Almeida for green house seed support, Marly C.F. Coelho for high-throughput ELISA CV-N detection assays, Maggie Garvey for the technical performance of the CEM-SS/HIV-1 in vitro cell-based assay and Lauren H. Krumpe for assistance in manuscript preparation. The authors thank Dr. Amilcar Tanuri, University Federal of Rio de Janeiro, for discussion on CV-N assays in soya bean seeds and Dr. Jose Mandarino, Embrapa Soybean, for information on soya bean seeds processing. The authors also thank the Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute (USA) for the kind gift of XTT (NSC# 601519) for use in antiviral assays. This study was supported by funds from Empresa Brasileira de Pesquisa Agropecuaria (Embrapa), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Apoio a Pesquisa do Distrito Federal (FAP-DF), NIH Intramural AIDS Targeted Antiviral Program and the Intramural Program of the Center for Cancer Research at the National Cancer Institute (B.O., K.R., J.W., J.M.). This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health under contract no. NO1-CO1-12400 (C.S.). 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 U.S. Government. NR 46 TC 6 Z9 6 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1467-7644 EI 1467-7652 J9 PLANT BIOTECHNOL J JI Plant Biotechnol. J. PD SEP PY 2015 VL 13 IS 7 BP 884 EP 892 DI 10.1111/pbi.12309 PG 9 WC Biotechnology & Applied Microbiology; Plant Sciences SC Biotechnology & Applied Microbiology; Plant Sciences GA CP8XX UT WOS:000360179400003 PM 25572960 ER PT J AU Stamm, M Forrest, LR AF Stamm, Marcus Forrest, Lucy R. TI Structure alignment of membrane proteins: Accuracy of available tools and a consensus strategy SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE structure comparison; conformational change; integral membrane protein; homology modeling; flexible alignment; protein structure; beta barrel ID TRANSMEMBRANE PROTEINS; DATA-BANK; STRUCTURE PREDICTION; TM-SCORE; MODEL; TOPOLOGY; QUALITY; CLASSIFICATION; SEQUENCES; SYMMETRY AB Protein structure alignment methods are used for the detection of evolutionary and functionally related positions in proteins. A wide array of different methods are available, but the choice of the best method is often not apparent to the user. Several studies have assessed the alignment accuracy and consistency of structure alignment methods, but none of these explicitly considered membrane proteins, which are important targets for drug development and have distinct structural features. Here, we compared 13 widely used pairwise structural alignment methods on a test set of homologous membrane protein structures (called HOMEP3). Each pair of structures was aligned and the corresponding sequence alignment was used to construct homology models. The model accuracy compared to the known structures was assessed using scoring functions not incorporated in the tested structural alignment methods. The analysis shows that fragment-based approaches such as FR-TM-align are the most useful for aligning structures of membrane proteins. Moreover, fragment-based approaches are more suitable for comparison of protein structures that have undergone large conformational changes. Nevertheless, no method was clearly superior to all other methods. Additionally, all methods lack a measure to rate the reliability of a position within a structure alignment. To solve both of these problems, we propose a consensus-type approach, combining alignments from four different methods, namely FR-TM-align, DaliLite, MATT, and FATCAT. Agreement between the methods is used to assign confidence values to each position of the alignment. Overall, we conclude that there remains scope for the improvement of structural alignment methods for membrane proteins. Proteins 2015; 83:1720-1732. (c) 2015 Wiley Periodicals, Inc. C1 [Stamm, Marcus; Forrest, Lucy R.] Max Planck Inst Biophys, Computat Struct Biol Grp, Frankfurt, Germany. [Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, NIH, Bethesda, MD 20892 USA. RP Forrest, LR (reprint author), NINDS, Computat Struct Biol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM lucy.forrest@nih.gov FU German Research Foundation (DFG) Collaborative Research Center [SFB 807]; Max Planck Society; National Institute of Neurological Disorders and Stroke at the National Institutes of Health, USA; Transport Across Membranes (TRAM) Graduate School FX Grant sponsor: German Research Foundation (DFG) Collaborative Research Center Grant Number: SFB 807 "Transport and Communication across Biological Membranes" and Transport Across Membranes (TRAM) Graduate School; Max Planck Society; Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, USA. NR 59 TC 2 Z9 2 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD SEP PY 2015 VL 83 IS 9 BP 1720 EP 1732 DI 10.1002/prot.24857 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CP9VB UT WOS:000360242000017 PM 26178143 ER PT J AU Offringa, M Davis, JM Turner, MA Ward, R Bax, R Maldonado, S Sinha, V McCune, SK Zajicek, A Benjamin, DK Bucci-Rechtweg, C Nelson, RM AF Offringa, Martin Davis, Jonathan M. Turner, Mark A. Ward, Robert Bax, Ralph Maldonado, Sam Sinha, Vikram McCune, Susan K. Zajicek, Anne Benjamin, Daniel K., Jr. Bucci-Rechtweg, Christina Nelson, Robert M. TI Applying Regulatory Science to Develop Safe and Effective Medicines for Neonates: Report of the US Food and Drug Administration First Annual Neonatal Scientific Workshop, October 28-29, 2014 SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE extrapolation; biomarkers; clinical outcomes; adaptive designs; pediatric trials ID PRETERM INFANTS; MEDICATION USE; BIOMARKERS; AGE; SURVIVAL; OUTCOMES; TRIALS; LIFE AB The First Annual Neonatal Scientific Workshop focused on the needs of the neonate by addressing the basic question: what information is required to inform decision making both at the regulatory level and at the bedside? Priority therapeutic areas include neonatal lung, brain, and gastrointestinal injury, retinopathy of prematurity, sepsis, and neonatal abstinence syndrome. Scientific progress in these therapeutic areas, regulatory standards, and the acceptable design and conduct of clinical trials must be aligned. This report will review potential approaches to enhancing neonatal drug development. C1 [Offringa, Martin] Hosp Sick Children, Child Hlth Evaluat Sci, Toronto, ON M5G 1X8, Canada. [Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Boston, MA 02111 USA. [Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Turner, Mark A.] Univ Liverpool, Inst Translat Med, Dept Womens & Childrens Hlth, Liverpool L69 3BX, Merseyside, England. [Ward, Robert] Univ Utah, Dept Pediat & Pharmacol Toxicol, Salt Lake City, UT USA. [Bax, Ralph] European Med Agcy, Prod Dev Sci Support Dept, Paediat Med, London, England. [Maldonado, Sam] CHILD Child Hlth Innovat Leadership Dept, Janssen Res & Dev, Raritan, NJ USA. [Sinha, Vikram] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [McCune, Susan K.] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Benjamin, Daniel K., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Bucci-Rechtweg, Christina] Novartis Pharmaceut, E Hanover, NJ USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Silver Spring, MD USA. RP Davis, JM (reprint author), Tufts Med Ctr, Floating Hosp Children, Newborn Med, TMC 44,750 Washington St, Boston, MA 02111 USA. EM jdavis@tuftsmedicalcenter.org FU Burroughs Wellcome Fund; FDA grant [1U18FD005320-01] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The workshop was supported in part by the Burroughs Wellcome Fund and an FDA grant (no. 1U18FD005320-01) to the Critical Path Institute. NR 38 TC 3 Z9 3 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD SEP PY 2015 VL 49 IS 5 BP 623 EP 631 DI 10.1177/2168479015597730 PG 9 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA CQ2FG UT WOS:000360414200003 ER PT J AU Drury, S Cuthbert, B AF Drury, Stacy Cuthbert, Bruce TI Advancing Pediatric Psychiatry Research: Linking Neurobiological Processes to Novel Treatment and Diagnosis Through the Research Domain Criteria (RDoC) Project SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Review DE RDoC; genetics; neuroscience; clinical treatment ID CARDIOVASCULAR-DISEASE; CYSTIC-FIBROSIS; GENE; POLYMORPHISM; SEVERITY; LEUKEMIA; DISORDER; STRESS; ADULTS AB The concurrent release of the Diagnostic and Statistical Manual, 5th Edition (DSM-5) and the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) project both ignited controversy and raised clarifying questions, particularly related to their integration and utility in both research and clinical domains. As the initial debate quieted, it appeared that DSM-5 would reign in clinical practice and RDoC would take precedence in research. DSM-5 and RDoC, while theoretically different, have analogous goals, as both seek to improve the accuracy of diagnosis, advance treatments, and decrease morbidity from mental illness. To achieve these goals, clinicians and researchers must, at the earliest stages of RDoC, work together to ensure maximum clinical translation. Other areas of medicine have successfully leveraged enhanced molecular and neurobiological phenotypic specificity to refine treatments and design novel pharmacologic agents. These successes provide useful comparisons for child psychiatry in the era of RDoC and DSM-5. This article reviews the literature related to progress in child psychiatry, development of RDoC, and the role of genetic research in the advancement of other areas of medicine. Limited diagnostic and treatment advances have occurred in child psychiatry over recent decades, particularly in comparison to other medical fields. The rapidly evolving fields of molecular genetics, neurobiology, and behavioral science offer substantial promise for refining diagnosis and treatment modalities. Utilizing the advancement of care for other pediatric conditions such as cystic fibrosis and pediatric cancer as guides, this article outlines how RDoC may contribute to similar advancements for pediatric mental illness. Although requiring a paradigm shift and the building of novel transdisciplinary collaborations that incorporate clinicians, basic scientists, pharmaceutical companies, families and advocacy groups, the integration of RDoC into child psychiatry clinical research offers significant potential to advance diagnostic specificity, improve treatment, and decrease mental health stigma. C1 [Drury, Stacy] Tulane Univ, New Orleans, LA 70112 USA. [Cuthbert, Bruce] NIMH, Bethesda, MD 20892 USA. RP Drury, S (reprint author), Tulane Univ, 1430 Tulane Ave,8055, New Orleans, LA 70112 USA. EM sdrury@tulane.edu NR 18 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD SEP PY 2015 VL 49 IS 5 BP 643 EP 646 DI 10.1177/2168479015596019 PG 4 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA CQ2FG UT WOS:000360414200005 ER PT J AU Miousse, IR Currie, R Datta, K Ellinger-Ziegelbauer, H French, JE Harrill, AH Koturbash, I Lawton, M Mann, D Meehan, RR Moggs, JG O'Lone, R Rasoulpour, RJ Pera, RAR Thompson, K AF Miousse, Isabelle R. Currie, Richard Datta, Kaushik Ellinger-Ziegelbauer, Heidrun French, John E. Harrill, Alison H. Koturbash, Igor Lawton, Michael Mann, Derek Meehan, Richard R. Moggs, Jonathan G. O'Lone, Raegan Rasoulpour, Reza J. Pera, Renee A. Reijo Thompson, Karol TI Importance of investigating epigenetic alterations for industry, and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute SO TOXICOLOGY LA English DT Review DE Epigenetics; Safety assessment; Models; Transgenerational effects; Stem cells; Biomarkers ID EPIGENOME-WIDE ASSOCIATION; PRIMORDIAL GERM-CELLS; EMBRYONIC STEM-CELLS; EPSTEIN-BARR-VIRUS; DNA METHYLATION; NATIONAL-HEALTH; TUMOR PROMOTION; RISK ASSESSMENT; MOUSE; CANCER AB Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled "Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals" in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. C1 [Miousse, Isabelle R.; Harrill, Alison H.; Koturbash, Igor] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. [Currie, Richard] Syngenta Jealotts Hill Int Res Ctr, Bracknell, Berks, England. [Datta, Kaushik] Celgene Corp, Summit, NJ USA. [Ellinger-Ziegelbauer, Heidrun] Bayer Pharma AG, Toxicol, Wuppertal, Germany. [French, John E.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Lawton, Michael] Pfizer Inc, Groton, CT 06340 USA. [Mann, Derek] Newcastle Univ, Inst Cellular Med, Fibrosis Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Meehan, Richard R.] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. [Moggs, Jonathan G.] Novartis Inst Biomed Res, Preclin Safety, Discovery & Invest Safety, Basel, Switzerland. [O'Lone, Raegan] ILSI Hlth & Environm Sci Inst, Washington, DC 20036 USA. [Rasoulpour, Reza J.] Dow Chem Co USA, Toxicol Environm Res & Consulting, Midland, MI 48674 USA. [Pera, Renee A. Reijo] Montana State Univ, Bozeman, MT 59717 USA. [Thompson, Karol] US FDA, Div Appl Regulatory Sci, OCP, CDER, Silver Spring, MD USA. RP O'Lone, R (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC 20036 USA. RI Meehan, Richard/B-5556-2012 FU ILSI HESI FX The symposium and manuscript are activities of the ILSI HESI technical committee on the Application of Genomics to Mechanism-Based Risk Assessment and funded by ILSI HESI. NR 85 TC 5 Z9 6 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 1 PY 2015 VL 335 BP 11 EP 19 DI 10.1016/j.tox.2015.06.009 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CQ3QM UT WOS:000360517600002 PM 26134581 ER PT J AU Chambers, DA Rupp, A AF Chambers, David A. Rupp, Agnes TI Sharing State Mental Health Data for Research: Building Toward Ongoing Learning in Mental Health Care Systems SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Mental health; Health services research; State data; Data pooling AB With the rise of "big data," the opportunities to use administrative and clinical data to evaluate impact of state level program initiatives are greatly expanded. The National Institute of Mental Health has in recent years supported research studies pooling data across states to address state-relevant questions. This commentary summarizes these activities and describes future platforms that may enhance ongoing work in this area. C1 [Chambers, David A.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Rupp, Agnes] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Chambers, DA (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E440, Rockville, MD 20850 USA. EM dchamber@mail.nih.gov NR 3 TC 2 Z9 2 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2015 VL 42 IS 5 BP 586 EP 587 DI 10.1007/s10488-015-0624-2 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CP7SW UT WOS:000360089400007 PM 25583270 ER PT J AU Backeljauw, PF Bondy, C Chernausek, SD Cernich, JT Cole, DA Fasciano, LP Foodim, J Hawley, S Hong, DS Knickmeyer, RC Kruszka, P Lin, AE Lippe, BM Lorigan, GA Maslen, CL Mauras, N Page, DC Pemberton, VL Prakash, SK Quigley, CA Ranallo, KC Reiss, AL Sandberg, DE Scurlock, C Silberbach, M AF Backeljauw, Philippe F. Bondy, Carolyn Chernausek, Steven D. Cernich, Joseph T. Cole, David A. Fasciano, Laura P. Foodim, Joan Hawley, Scott Hong, David S. Knickmeyer, Rebecca C. Kruszka, Paul Lin, Angela E. Lippe, Barbara M. Lorigan, Gary A. Maslen, Cheryl L. Mauras, Nelly Page, David C. Pemberton, Victoria L. Prakash, Siddharth K. Quigley, Charmian A. Ranallo, Kelly C. Reiss, Allan L. Sandberg, David E. Scurlock, Cindy Silberbach, Michael TI Proceedings From the Turner Resource Network Symposium: The Crossroads of Health Care Research and Health Care Delivery SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE monosomy X; Turner syndrome; women; congenital heart disease; genetics; neurodevelopment; chromosome; sex chromosomes; women's health; quality of life ID GIRLS; WOMEN; CHROMOSOME; REGISTRY AB Turner syndrome, a congenital condition that affects similar to 1/2,500 births, results from absence or structural alteration of the second sex chromosome. There has been substantial effort by numerous clinical and genetic research groups to delineate the clinical, pathophysiological, cytogenetic, and molecular features of this multisystem condition. Questions about the molecular-genetic and biological basis of many of the clinical features remain unanswered, and health care providers and families seek improved care for affected individuals. The inaugural "Turner Resource Network (TRN) Symposium" brought together individuals with Turner syndrome and their families, advocacy group leaders, clinicians, basic scientists, physician-scientists, trainees and other stakeholders with interest in the well-being of individuals and families living with the condition. The goal of this symposium was to establish a structure for a TRN that will be a patient-powered organization involving those living with Turner syndrome, their families, clinicians, and scientists. The TRN will identify basic and clinical questions that might be answered with registries, clinical trials, or through bench research to promote and advocate for best practices and improved care for individuals with Turner syndrome. The symposium concluded with the consensus that two rationales justify the creation of a TRN: 1. inadequate attention has been paid to the health and psychosocial issues facing girls and women who live with Turner syndrome; 2. investigations into the susceptibility to common disorders such as cardiovascular or autoimmune diseases caused by sex chromosome deficiencies will increase understanding of disease susceptibilities in the general population. (C) 2015 Wiley Periodicals, Inc. C1 [Backeljauw, Philippe F.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Cincinnati, OH USA. [Bondy, Carolyn] NIH, Endocrine Branch NICHD, Bethesda, MD 20892 USA. [Chernausek, Steven D.] Univ Oklahoma, Childrens Hosp, Oklahoma City, OK USA. [Cernich, Joseph T.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Cole, David A.] Hagley Museum & Lib Wilmington, Wilmington, DE USA. [Fasciano, Laura P.] Turner Syndrome Fdn Inc, Hazlet, NJ USA. [Foodim, Joan] Internal Med, New Haven, CT USA. [Hawley, Scott] Stowers Inst Med Res, Kansas City, MO USA. [Hong, David S.] Stanford Univ, Palo Alto, CA 94304 USA. [Knickmeyer, Rebecca C.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Kruszka, Paul] NHGRI, NIH, Bethesda, MD 20892 USA. [Lin, Angela E.] MassGeneral Hosp Children, Genet Unit, Boston, MA USA. [Lippe, Barbara M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lorigan, Gary A.] Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 USA. [Maslen, Cheryl L.; Silberbach, Michael] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Mauras, Nelly] Nemours Childrens Clin, Jacksonville, FL USA. [Page, David C.] MIT, Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Prakash, Siddharth K.] Univ Texas Houston, Houston, TX USA. [Quigley, Charmian A.] Indiana Univ, Sch Med, Pediat Endocrinol, Indianapolis, IN USA. [Ranallo, Kelly C.] Turner Syndrome Global Alliance, Overland Pk, KS USA. [Reiss, Allan L.] Stanford Univ, Ctr Interdisciplinary Brain Sci Res, Palo Alto, CA 94304 USA. [Sandberg, David E.] Univ Michigan, Dept Pediat, Child Hlth Evaluat & Res CHEAR Unit, Ann Arbor, MI 48109 USA. [Scurlock, Cindy] Turner Syndrome Soc US, Houston, TX USA. RP Silberbach, M (reprint author), Oregon Hlth & Sci Univ, Div Pediat Cardiol, Doernbecher Childrens Hosp, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM silberm@ohsu.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [1R13HD079209-01]; Office of Women's Health Research; American Heart Association; March of Dimes; Leaping Butterfly Ministry; Turner Syndrome Society of the United States FX We thank all the organizers, families, and professionals who attended the symposium, for contributing their time and opinions that made the meeting a success. This work was supported in part by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (1R13HD079209-01), The Office of Women's Health Research, The American Heart Association, The March of Dimes, The Leaping Butterfly Ministry, and the Turner Syndrome Society of the United States. NR 17 TC 1 Z9 1 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 1962 EP 1971 DI 10.1002/ajmg.a.37121 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700005 PM 25920614 ER PT J AU Reeder, MR Botto, LD Keppler-Noreuil, KM Carey, JC Byrne, JLB Feldkamp, ML AF Reeder, Matthew R. Botto, Lorenzo D. Keppler-Noreuil, Kim M. Carey, John C. Byrne, Janice L. B. Feldkamp, Marcia L. CA Natl Birth Defects Prevention Stud TI Risk Factors for Dandy-Walker Malformation: A Population-Based Assessment SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Dandy-Walker malformation; congenital abnormality; posterior fossa malformation; risk factors ID BIRTH-DEFECTS PREVENTION; NEURAL-TUBE DEFECTS; CHROMOSOMAL-ABNORMALITIES; CONGENITAL-MALFORMATIONS; CLOMIPHENE CITRATE; MONOZYGOTIC TWINS; MULTIPLE BIRTHS; ASSOCIATION; CLASSIFICATION; REGISTER AB Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, but its causes are largely unknown. An increasing number of genes associated with congenital cerebellar malformations have been identified; however, few studies have examined the potential role of non-genetic, potentially modifiable risk factors. From the National Birth Defects Prevention Study, we examined maternal, paternal, and infant characteristics and maternal conditions and periconceptional exposures (from 1 month before to 3 months after conception) among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed using logistic regression. Maternal factors associated with DWM included non-Hispanic black race/ethnicity (aOR = 2.0, 95% CI: 1.3-3.2). Among maternal conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4, 95% CI: 1.3-4.6; multiple: aOR = 3.9, 95% CI: 1.7-8.9). The lack of association with many maternal exposures supports the hypothesis of a major contribution of genetic factors to the risk for DWM; however, the observed associations with maternal non-Hispanic black race/ethnicity and maternal history of infertility indicate that further research into factors underlying these characteristics may uncover potentially modifiable risk factors, acting alone or as a component of gene-environment interactions. (C) 2015 Wiley Periodicals, Inc. C1 [Reeder, Matthew R.; Botto, Lorenzo D.; Carey, John C.; Byrne, Janice L. B.; Feldkamp, Marcia L.] Univ Utah, Div Med Genet, Dept Pediat, Sch Med, Salt Lake City, UT 84108 USA. [Keppler-Noreuil, Kim M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Byrne, Janice L. B.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA. RP Reeder, MR (reprint author), Univ Utah, Div Med Genet, Dept Pediat, 295 Chipeta Way,Ste 2S010, Salt Lake City, UT 84108 USA. EM matthew.reeder@hsc.utah.edu FU Centers for Disease Control and Prevention [PA 96043, PA 02081, PA 09001, FOA DD000490] FX Grant sponsor: Centers for Disease Control and Prevention to the Centers for Birth Defects Research and Prevention; Grant numbers: PA 96043, PA 02081, PA 09001, FOA DD000490. NR 44 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 2009 EP 2016 DI 10.1002/ajmg.a.37124 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700009 PM 25941000 ER PT J AU Ktena, YP Paul, SM Hauser, NS Sloan, JL Gropman, A Manoli, I Venditti, CP AF Ktena, Yiouli P. Paul, Scott M. Hauser, Natalie S. Sloan, Jennifer L. Gropman, Andrea Manoli, Irini Venditti, Charles P. TI Delineating the Spectrum of Impairments, Disabilities, and Rehabilitation Needs in Methylmalonic Acidemia (MMA) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE methylmalonic acidemia; rehabilitation; outcome; disabilities; basal ganglia ID LONG-TERM MANAGEMENT; JOINT HYPERMOBILITY; PROPIONIC ACIDEMIA; SCREENING-PROGRAM; ACIDURIA; CHILDREN AB Methylmalonic acidemia patients have complex rehabilitation needs that can be targeted to optimize societal independence and quality of life. Thirty-seven individuals with isolated MMA (28 mut, 5 cblA, 4 cblB), aged 2-33 years, were enrolled in a natural history study, and underwent age-appropriate clinical assessments to characterize impairments and disabilities. Neurological examination and brain imaging studies were used to document movement disorders and the presence of basal ganglia injury. A range of impairments and disabilities were identified by a team of physical medicine experts. Movement disorders, such as chorea and tremor, were common (n = 31, 83%), even among patients without evidence of basal ganglia injury. Joint hypermobility (n = 24, 69%) and pes planus (n = 22, 60%) were frequent and, in many cases, under-recognized. 23 (62%) patients required gastrostomy feedings. 18/31 patients >4 years old (58%) had difficulties with bathing and dressing. 16 of 23 school-aged patients received various forms of educational support. Five of the 10 adult patients were employed or in college; three lived independently. Unmet needs were identified in access to rehabilitation services, such as physical therapy (unavailable to 14/31), and orthotics (unavailable to 15/22). We conclude that patients with MMA are challenged by a number of functional limitations in essential activities of mobility, self-care, and learning, in great part caused by movement disorders and ligamentous laxity. Early assessment, referral, and implementation of age-appropriate rehabilitation services should significantly improve independence and quality of life. (C) 2015 Wiley Periodicals, Inc. C1 [Ktena, Yiouli P.; Hauser, Natalie S.; Sloan, Jennifer L.; Manoli, Irini; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Paul, Scott M.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Gropman, Andrea] Childrens Natl Med Ctr, CNR, Washington, DC 20010 USA. RP Venditti, CP (reprint author), NIH, 49 Convent Dr,Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 NR 33 TC 1 Z9 1 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 2075 EP 2084 DI 10.1002/ajmg.a.37127 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700016 PM 25959030 ER PT J AU Wolters, PL Burns, KM Martin, S Baldwin, A Dombi, E Toledo-Tamula, MA Dudley, WN Gillespie, A Widemann, BC AF Wolters, Pamela L. Burns, Katherine M. Martin, Staci Baldwin, Andrea Dombi, Eva Toledo-Tamula, Mary Anne Dudley, William N. Gillespie, Andrea Widemann, Brigitte C. TI Pain Interference in Youth with Neurofibromatosis Type 1 and Plexiform Neurofibromas and Relation to Disease Severity, Social-Emotional Functioning, and Quality of Life SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurofibromatosis type 1; plexiform neurofibromas; pain; quality of life; children ID JUVENILE IDIOPATHIC ARTHRITIS; CYSTIC-FIBROSIS; MEDIATION ANALYSIS; PARENTAL REPORTS; CHILDREN; ADOLESCENTS; MANAGEMENT; EPIDEMIOLOGY; INDIVIDUALS; PHENOTYPE AB The physical manifestations of neurofibromatosis type 1 (NF1) can cause chronic pain. This study investigated the impact of pain in youth with NF1 and plexiform neurofibromas (PNs) and its relationship to disease factors, social-emotional functioning, and quality of life (QOL) within a biopsychosocial framework. Caregivers of 59 children and adolescents with NF1 and PNs (6-18 years), and 41 of these youth (10-18 years), completed questionnaires assessing social-emotional functioning and QOL, including an item on pain interference. Measures of disease severity included total PN volume by percent body weight and number of disease complications. Both caregiver (73%) and self-report (59%) ratings indicated that pain interferes with the child's daily functioning despite 33% taking pain medication. Based on care-givers' behavior ratings, more symptoms of anxiety and larger tumor volumes predicted greater pain interference, while greater pain interference, worse depressive symptoms, and more disease complications predicted poorer QOL. As rated by adolescents, more symptoms of anxiety predicted greater pain interference, while greater pain interference and social stress predicted poorer QOL. Further, social-emotional problems mediate the relationship between pain interference and QOL. Thus, pain interferes with daily functioning in the majority of youth with NF1 and PNs even when using pain medication. The impact of pain interference, disease severity, and particularly social-emotional problems on QOL highlights the interaction between physical and psychological states in NF1. Future research and treatment of pain in this population should utilize a biopsychosocial approach and involve multidisciplinary therapies including psychological interventions that target social-emotional functioning. (C) 2015 Wiley Periodicals, Inc. C1 [Wolters, Pamela L.; Burns, Katherine M.; Martin, Staci; Baldwin, Andrea; Dombi, Eva; Gillespie, Andrea; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Burns, Katherine M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Toledo-Tamula, Mary Anne] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Ft Detrick, MD 21702 USA. [Dudley, William N.] Univ N Carolina, Sch Hlth & Human Sci, Dept Publ Hlth Educ, Greensboro, NC 27412 USA. RP Wolters, PL (reprint author), NCI, 9030 Old Georgetown Rd,Bldg 82,Room 109, Bethesda, MD 20892 USA. EM woltersp@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors thank the children and caregivers who participated in this study. We also thank all members of the Pediatric Oncology Branch Psychology Group and NF Team for their assistance with the data collection and care of patients on the NF1 Natural History study. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. In addition, this project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 53 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 2103 EP 2113 DI 10.1002/ajmg.a.37123 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700019 PM 25976979 ER PT J AU Russell, B Johnston, JJ Biesecker, LG Kramer, N Pickart, A Rhead, W Tan, WH Brownstein, CA Clarkson, LK Dobson, A Rosenberg, AZ Vergano, SAS Helm, BM Harrison, RE Graham, JM AF Russell, Bianca Johnston, Jennifer J. Biesecker, Leslie G. Kramer, Nancy Pickart, Angela Rhead, William Tan, Wen-Hann Brownstein, Catherine A. Clarkson, L. Kate Dobson, Amy Rosenberg, Avi Z. Vergano, Samantha A. Schrier Helm, Benjamin M. Harrison, Rachel E. Graham, John M., Jr. TI Clinical Management of Patients with ASXL1 Mutations and Bohring-Opitz Syndrome, Emphasizing the Need for Wilms Tumor Surveillance SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE ASXL1; Bohring-Opitz syndrome; Wilms tumor; nevus flammeus; myopia; failure to thrive; intellectual disability; hypertrichosis; cyclic vomiting ID TRIGONOCEPHALY C SYNDROME; ADDITIONAL-SEX-COMBS; SEVERE END; GENE; PROTEIN AB Bohring-Opitz syndrome is a rare genetic condition characterized by distinctive facial features, variable microcephaly, hypertrichosis, nevus flammeus, severe myopia, unusual posture (flexion at the elbows with ulnar deviation, and flexion of the wrists and metacarpophalangeal joints), severe intellectual disability, and feeding issues. Nine patients with Bohring-Opitz syndrome have been identified as having a mutation in ASXL1. We report on eight previously unpublished patients with Bohring-Opitz syndrome caused by an apparent or confirmed de novo mutation in ASXL1. Of note, two patients developed bilateral Wilms tumors. Somatic mutations in ASXL1 are associated with myeloid malignancies, and these reports emphasize the need for Wilms tumor screening in patients with ASXL1 mutations. We discuss clinical management with a focus on their feeding issues, cyclic vomiting, respiratory infections, insomnia, and tumor predisposition. Many patients are noted to have distinctive personalities (interactive, happy, and curious) and rapid hair growth; features not previously reported. (C) 2015 Wiley Periodicals, Inc. C1 [Russell, Bianca] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Johnston, Jennifer J.; Biesecker, Leslie G.] NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. [Kramer, Nancy; Graham, John M., Jr.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Inst Med Genet, Div Med Genet,Harbor UCLA Med Ctr,David Geffen Sc, Los Angeles, CA 90048 USA. [Pickart, Angela; Rhead, William] Childrens Hosp Wisconsin, Med Genet Sect, Milwaukee, WI 53201 USA. [Tan, Wen-Hann; Brownstein, Catherine A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Clarkson, L. Kate; Dobson, Amy] Greenwood Genet Ctr, Columbia, SC USA. [Rosenberg, Avi Z.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. [Vergano, Samantha A. Schrier; Helm, Benjamin M.] Childrens Hosp Kings Daughters, Div Med Genet & Metab, Norfolk, VA USA. [Harrison, Rachel E.] Nottingham Univ Hosp Trust, Clin Genet Serv, Nottingham, England. RP Graham, JM (reprint author), Cedars Sinai Med Ctr, Inst Med Genet, PACT 400,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM john.graham@cshs.org OI Rosenberg, Avi/0000-0003-2356-950X FU NIH FX Grant sponsor: NIH. NR 30 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2015 VL 167 IS 9 BP 2122 EP 2131 DI 10.1002/ajmg.a.37131 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CP7HB UT WOS:000360056700021 PM 25921057 ER PT J AU Murray, DM Kaplan, RM Ngo-Metzger, Q Portnoy, B Olkkola, S Stredrick, D Kuczmarski, RJ Goldstein, AB Perl, HI O'Connell, ME AF Murray, David M. Kaplan, Robert M. Ngo-Metzger, Quyen Portnoy, Barry Olkkola, Susanne Stredrick, Denise Kuczmarski, Robert J. Goldstein, Amy B. Perl, Harold I. O'Connell, Mary E. TI Enhancing Coordination Among the US Preventive Services Task Force, Agency for Healthcare Research and Quality, and National Institutes of Health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RANDOMIZED-TRIALS; TRANSLATION; COMMUNITY; PROGRAM AB This paper focuses on the relationships among the U.S. Preventive Services Task Force (USPSTF); Agency for Healthcare Research and Quality (AHRQ); and NIH. After a brief description of the Task Force, AHRQ, NIH, and an example of how they interact, we describe the steps that have been taken recently by NIH to enhance their coordination. We also discuss several challenges that remain and consider potential remedies that NIH, AHRQ, and investigators can take to provide the USPSTF with the data it needs to make recommendations, particularly those pertaining to behavioral interventions. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. C1 [Murray, David M.; Portnoy, Barry; Olkkola, Susanne; Stredrick, Denise] NIH, Off Dis Prevent, Div Program Coordinat Planning & Strateg Initiat, Off Director, Bethesda, MD 20892 USA. [Kaplan, Robert M.; Ngo-Metzger, Quyen] Agcy Healthcare Res & Qual, Rockville, MD USA. [Kuczmarski, Robert J.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, NIH, Bethesda, MD 20892 USA. [Perl, Harold I.] NIDA, Prevent Res Branch, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. [O'Connell, Mary E.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Murray, DM (reprint author), NIH, Off Dis Prevent, Div Program Coordinat Planning & Strateg Initiat, Off Director, 6100 Execut Blvd,Suite 2B03, Bethesda, MD 20892 USA. EM david.murray2@nih.gov FU Agency for Healthcare Research and Quality (AHRQ); AHRQ [HHSA290-2010-00004i, TO 4] FX Publication of this article was supported by the Agency for Healthcare Research and Quality (AHRQ).; Administrative and logistical support for this paper was provided by AHRQ through contract HHSA290-2010-00004i, TO 4. NR 16 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2015 VL 49 IS 3 SU 2 BP S166 EP S173 DI 10.1016/j.amepre.2015.04.024 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CP4UM UT WOS:000359878100006 PM 26296551 ER PT J AU Boutin, RD Yao, L Canter, RJ Lenchik, L AF Boutin, Robert D. Yao, Lawrence Canter, Robert J. Lenchik, Leon TI Sarcopenia: Current Concepts and Imaging Implications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE body composition; imaging; muscle; sarcopenia ID CROSS-SECTIONAL AREA; CORE MUSCLE SIZE; BODY-MASS INDEX; LOW LEAN MASS; SKELETAL-MUSCLE; OLDER-ADULTS; INTERNATIONAL SOCIETY; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; POSTOPERATIVE OUTCOMES AB OBJECTIVE. The purpose of this article is to review the nomenclature, clinical impact, and diagnostic techniques characterizing sarcopenia. CONCLUSION. Sarcopenia-defined as significant loss of muscle-is associated with cachexia and frailty. Specific diagnostic criteria for sarcopenia continue to evolve, but imaging can play a role in the detection and quantification of muscle depletion. Emerging evidence indicates that sarcopenia is a relevant predictor of quality and quantity of life, particularly in patients who are elderly, have cancer, or undergo surgery. C1 [Boutin, Robert D.] Univ Calif Davis Hlth Syst, Dept Radiol, Sacramento, CA 95817 USA. [Yao, Lawrence] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Canter, Robert J.] Univ Calif Davis Hlth Syst, Dept Surg, Div Surg Oncol, Sacramento, CA 95817 USA. [Lenchik, Leon] Wake Forest Sch Med, Dept Radiol, Musculoskeletal Imaging Sect, Winston Salem, NC USA. RP Boutin, RD (reprint author), Univ Calif Davis Hlth Syst, Dept Radiol, 4860 Y St,Ste 3100, Sacramento, CA 95817 USA. EM rdboutin@ucdmc.ucdavis.edu NR 124 TC 8 Z9 8 U1 2 U2 18 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2015 VL 205 IS 3 BP W255 EP W266 DI 10.2214/AJR.15.14635 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP6KW UT WOS:000359997100004 PM 26102307 ER PT J AU Folio, LR Nelson, CJ Benjamin, M Ran, A Engelhard, G Bluemke, DA AF Folio, Les R. Nelson, Chelsye J. Benjamin, Menashe Ran, Ayelet Engelhard, Guy Bluemke, David A. TI Quantitative Radiology Reporting in Oncology: Survey of Oncologists and Radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE productivity; quality improvement; radiology reports; tumor metrics; work flow ID US CANCER CENTERS; RESPONSE CRITERIA AB OBJECTIVE. Tumor quantification is essential for determining the clinical efficacy and response to established and evolving therapeutic agents in cancer trials. The purpose of this study was to seek the opinions of oncologists and radiologists about quantitative interactive and multimedia reporting. SUBJECTS AND METHODS. Questionnaires were distributed to 253 oncologists and registrars and to 35 radiologists at our institution through an online survey application. Questions were asked about current reporting methods, methods for Response Evaluation Criteria in Solid Tumors (RECIST) tumor measurement, and preferred reporting format. RESULTS. The overall response rates were 43.1% (109/253) for oncologists and 80.0% (28/35) for radiologists. The oncologists treated more than 40 tumor types. Most of the oncologists (65.7% [67/102]) and many radiologists (44.4% [12/27]) (p = 0.020) deemed the current traditional qualitative radiology reports insufficient for reporting tumor burden and communicating measurements. Most of the radiologists (77.8% [21/27]) and oncologists (85.5% [71/83]) (p = 0.95) agreed that key images with measurement annotations helped in finding previously measured tumors; however, only 43% of radiologists regularly saved key images. Both oncologists (64.2% [70/109]) and radiologists (67.9% [19/28]) (p = 0.83) preferred the ability to hyperlink measurements from reports to images of lesions as opposed to text-only reports. Approximately 60% of oncologists indicated that they handwrote tumor measurements on RECIST forms, and 40% used various digital formats. Most of the oncologists (93%) indicated that managing tumor measurements within a PACS would be superior to handwritten data entry and retyping of data into a cancer database. CONCLUSION. Oncologists and radiologists agree that quantitative interactive reporting would be superior to traditional text-only qualitative reporting for assessing tumor burden in cancer trials. A PACS reporting system that enhances and promotes collaboration between radiologists and oncologists improves quantitative reporting of tumors. C1 [Folio, Les R.; Nelson, Chelsye J.; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Benjamin, Menashe; Ran, Ayelet; Engelhard, Guy] Carestream Co, Algotec, Raanana, Israel. RP Folio, LR (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM les.folio@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU Intramural Research Program, National Institutes of Health Clinical Center FX Supported by Intramural Research Program, National Institutes of Health Clinical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 15 TC 2 Z9 2 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2015 VL 205 IS 3 BP W233 EP W243 DI 10.2214/AJR.14.14054 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP6KW UT WOS:000359997100002 PM 26295661 ER PT J AU Koushik, A Wang, ML Anderson, KE van den Brandt, P Clendenen, TV Eliassen, AH Freudenheim, JL Genkinger, JM Hakansson, N Marshall, JR McCullough, ML Miller, AB Robien, K Rohan, TE Schairer, C Schouten, LJ Tworoger, SS Wang, Y Wolk, A Zeleniuch-Jacquotte, A Smith-Warner, SA AF Koushik, Anita Wang, Molin Anderson, Kristin E. van den Brandt, Piet Clendenen, Tess V. Eliassen, A. Heather Freudenheim, Jo L. Genkinger, Jeanine M. Hakansson, Niclas Marshall, James R. McCullough, Marjorie L. Miller, Anthony B. Robien, Kim Rohan, Thomas E. Schairer, Catherine Schouten, Leo J. Tworoger, Shelley S. Wang, Ying Wolk, Alicja Zeleniuch-Jacquotte, Anne Smith-Warner, Stephanie A. TI Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies SO CANCER CAUSES & CONTROL LA English DT Article DE Ovarian cancer; Vitamin A; Vitamin C; Vitamin E; Folate; Pooled analysis; Cohort studies ID FOOD-FREQUENCY QUESTIONNAIRE; SWEDISH MAMMOGRAPHY COHORT; DIET HISTORY QUESTIONNAIRE; ITALIAN CASE-CONTROL; WOMENS HEALTH; BREAST-CANCER; UNITED-STATES; POSTMENOPAUSAL WOMEN; ALCOHOL-CONSUMPTION; REGRESSION-MODELS AB Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95 % confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95 % CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types. These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk. C1 [Koushik, Anita] Univ Montre, Ctr Rech, CHUM, CRCHUM, Montreal, PQ H2X 0A9, Canada. [Wang, Molin; Eliassen, A. Heather; Tworoger, Shelley S.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, Molin; Eliassen, A. Heather; Tworoger, Shelley S.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wang, Molin; Eliassen, A. Heather; Tworoger, Shelley S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Wang, Molin; Eliassen, A. Heather; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Kristin E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [van den Brandt, Piet; Schouten, Leo J.] Maastricht Univ, Dept Epidemiol, Sch Oncol & Dev Biol GROW, Maastricht, Netherlands. [Clendenen, Tess V.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Freudenheim, Jo L.; Marshall, James R.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. [Genkinger, Jeanine M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [McCullough, Marjorie L.; Wang, Ying] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Schairer, Catherine] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Koushik, A (reprint author), Univ Montre, Ctr Rech, CHUM, CRCHUM, 850 St Denis St,2nd Floor, Montreal, PQ H2X 0A9, Canada. EM anita.koushik@umontreal.ca OI Wang, Ying/0000-0002-1241-6252; Koushik, Anita/0000-0001-5304-7660; Robien, Kim/0000-0002-2120-2280; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU US National Cancer Institute [P01 CA55075]; Fonds de recherche du Quebec-Sante [20010]; Canadian Institutes of Health Research FX We would like to thank the participants and staff of each of the cohorts for their valuable contributions and the organizations that funded the infrastructure for each cohort study. The centralization, checking, harmonization, and statistical analyses of the participant-level data from each of the cohorts were funded by Grant P01 CA55075 from the US National Cancer Institute and Grant 20010 from the Fonds de recherche du Quebec-Sante. Dr. Anita Koushik currently holds a New Investigator Award from the Canadian Institutes of Health Research. NR 79 TC 2 Z9 2 U1 1 U2 7 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 SEP PY 2015 VL 26 IS 9 BP 1315 EP 1327 DI 10.1007/s10552-015-0626-0 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CP5RO UT WOS:000359941800010 PM 26169298 ER PT J AU Camargo, MC Rabkin, CS Appel, N Hollenbeck, AR AF Camargo, M. C. Rabkin, C. S. Appel, N. Hollenbeck, A. R. TI Variable association of height with gastric cancer by anatomical subsite SO CANCER CAUSES & CONTROL LA English DT Letter C1 [Camargo, M. C.; Rabkin, C. S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Appel, N.] Informat Management Serv Inc, Rockville, MD 20852 USA. [Hollenbeck, A. R.] AARP, Washington, DC 20049 USA. RP Camargo, MC (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E-110, Bethesda, MD 20892 USA. EM camargomc@mail.nih.gov RI Camargo, M. Constanza/R-9891-2016 FU Intramural NIH HHS [Z99 CA999999] NR 3 TC 1 Z9 1 U1 1 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 SEP PY 2015 VL 26 IS 9 BP 1361 EP 1361 DI 10.1007/s10552-015-0616-2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CP5RO UT WOS:000359941800014 PM 26092380 ER PT J AU Brouwer, KLR Aleksunes, LM Brandys, B Giacoia, GP Knipp, G Lukacova, V Meibohm, B Nigam, SK Rieder, M de Wildt, SN AF Brouwer, K. L. R. Aleksunes, L. M. Brandys, B. Giacoia, G. P. Knipp, G. Lukacova, V. Meibohm, B. Nigam, S. K. Rieder, M. de Wildt, S. N. CA Pediat Transporter Working Grp TI Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Review ID MESSENGER-RNA EXPRESSION; P-GLYCOPROTEIN; ORGANIC ANION; HUMAN LIVER; BILE-ACID; INTERINDIVIDUAL VARIABILITY; DEVELOPMENTAL EXPRESSION; DIFFERENTIAL EXPRESSION; METABOLIZING-ENZYMES; TISSUE DISTRIBUTION AB The critical importance of membrane-bound transporters in pharmacotherapy is widely recognized, but little is known about drug transporter activity in children. In this white paper, the Pediatric Transporter Working Group presents a systematic review of the ontogeny of clinically relevant membrane transporters (e.g., SLC, ABC superfamilies) in intestine, liver, and kidney. Different developmental patterns for individual transporters emerge, but much remains unknown. Recommendations to increase our understanding of membrane transporters in pediatric pharmacotherapy are presented. C1 [Brouwer, K. L. R.] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, UNC Eshelman Sch Pharm, Chapel Hill, NC 27515 USA. [Aleksunes, L. M.] Rutgers State Univ, Dept Pharmacol & Toxicol, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA. [Brandys, B.] NIH, NIH Lib, Bethesda, MD 20892 USA. [Giacoia, G. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol & Therapeut Branch, Rockville, MD USA. [Knipp, G.] Purdue Univ, Dept Ind & Phys Pharm, Coll Pharm, W Lafayette, IN 47907 USA. [Lukacova, V.] Simulat Plus Inc, Lancaster, CA USA. [Meibohm, B.] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA. [Nigam, S. K.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Rieder, M.] Univ Western Ontario, Dept Pediat, London, ON N6A 3K7, Canada. [de Wildt, S. N.] Erasmus MC Sophia Childrens Hosp, Intens Care, Rotterdam, Netherlands. [de Wildt, S. N.] Erasmus MC Sophia Childrens Hosp, Dept Pediat Surg, Rotterdam, Netherlands. RP Brouwer, KLR (reprint author), Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, UNC Eshelman Sch Pharm, Chapel Hill, NC 27515 USA. EM kbrouwer@unc.edu OI de Wildt, Saskia/0000-0002-0502-0647; Thomson, Margaret/0000-0002-2147-6943 FU National Institutes of Health from the National Institute of Environmental Health Sciences [R01 GM41935]; National Institute of Environmental Health Sciences [R01 ES020522, P30 ES005022]; National Center for Advancing Translational Sciences, Clinical and Translational Sciences [UL1 TR001108]; National Institute of Child Health and Human Development [U54 HD07160]; National Institute of General Medical Sciences [R01 GM098449]; Netherlands Organization for Health Research and Development [90700304] FX We are grateful to the National Institute of Child Health and Human Development for coordinating this initiative and providing administrative support for the Pediatric Transporter Working Group, which is part of the BPCA (Best Pharmaceuticals for Children Act) Initiative to Advance Pediatric Therapeutics. The assistance of Erin Bahring, Daniel Kelly, and Deborah Stein in the preparation of this article is sincerely appreciated. This article has been endorsed by the International Transporter Consortium. We thank members of the International Transporter Consortium for constructive comments during the preparation of this review. This work was supported, in part, by funding from the National Institutes of Health through award number R01 GM41935 (to KLRB) from the National Institute of General Medical Sciences; R01 ES020522 (to LMA) and P30 ES005022 (to LMA) from the National Institute of Environmental Health Sciences; UL1 TR001108 (the Indiana Clinical and Translational Sciences Institute; to GK) from the National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award; U54 HD07160 (to SKN) from the National Institute of Child Health and Human Development and R01 GM098449 (to SKN) from the National Institute of General Medical Sciences; and the Netherlands Organization for Health Research and Development through a Clinical Fellowship award Number 90700304 (to SNW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the United States Food and Drug Administration. NR 84 TC 23 Z9 23 U1 3 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2015 VL 98 IS 3 BP 266 EP 287 DI 10.1002/cpt.176 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CP6RD UT WOS:000360014700008 PM 26088472 ER PT J AU Lantier, L Williams, AS Williams, IM Yang, KK Bracy, DP Goelzer, M James, FD Gius, D Wasserman, DH AF Lantier, Louise Williams, Ashley S. Williams, Ian M. Yang, Karen K. Bracy, Deanna P. Goelzer, Mickael James, Freyja D. Gius, David Wasserman, David H. TI SIRT3 Is Crucial for Maintaining Skeletal Muscle Insulin Action and Protects Against Severe Insulin Resistance in High-Fat-Fed Mice SO DIABETES LA English DT Article ID GLUCOSE-UPTAKE; MITOCHONDRIAL-FUNCTION; LYSINE ACETYLATION; HEXOKINASE BINDING; ENERGY-METABOLISM; CONSCIOUS MOUSE; ACID OXIDATION; IN-VIVO; HOMEOSTASIS; STRESS AB Protein hyperacetylation is associated with glucose intolerance and insulin resistance, suggesting that the enzymes regulating the acetylome play a role in this pathological process. Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been linked to energy homeostasis. Thus, it is hypothesized that the dysregulation of the mitochondrial acetylation state, via genetic deletion of SIRT3, will amplify the deleterious effects of a high-fat diet (HFD). Hyperinsulinemic-euglycemic clamp experiments show, for the first time, that mice lacking SIRT3 exhibit increased insulin resistance due to defects in skeletal muscle glucose uptake. Permeabilized muscle fibers from HFD-fed SIRT3 knockout (KO) mice showed that tricarboxylic acid cycle substrate-based respiration is decreased while fatty acid-based respiration is increased, reflecting a fuel switch from glucose to fatty acids. Consistent with reduced muscle glucose uptake, hexokinase II (HKII) binding to the mitochondria is decreased in muscle from HFD-fed SIRT3 KO mice, suggesting decreased HKII activity. These results show that the absence of SIRT3 in HFD-fed mice causes profound impairments in insulin-stimulated muscle glucose uptake, creating an increased reliance on fatty acids. Insulin action was not impaired in the lean SIRT3 KO mice. This suggests that SIRT3 protects against dietary insulin resistance by facilitating glucose disposal and mitochondrial function. C1 [Lantier, Louise; Williams, Ashley S.; Williams, Ian M.; Yang, Karen K.; Bracy, Deanna P.; Goelzer, Mickael; James, Freyja D.; Wasserman, David H.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Lantier, Louise; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN 37235 USA. [Gius, David] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA. [Gius, David] Northwestern Univ, Feinberg Sch Med, Dept Pharmacol, Chicago, IL 60611 USA. [Gius, David] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Lantier, L (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. EM louise.lantier@vanderbilt.edu FU National Institutes of Health [DK-054902, DK-050277, DK-059637]; National Cancer Institute [1-R01-CA-152601-01, 1-R01-CA-152799-01A1, 1-R01-CA-168292-01A1]; Northwestern Avon Foundation Breast Care Center of Excellence grant FX This work was supported by National Institutes of Health grants DK-054902, DK-050277, and DK-059637. D.G. was supported by National Cancer Institute grants 1-R01-CA-152601-01,1-R01-CA-152799-01A1, and 1-R01-CA-168292-01A1 and a Northwestern Avon Foundation Breast Care Center of Excellence grant NR 46 TC 11 Z9 11 U1 1 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3081 EP 3092 DI 10.2337/db14-1810 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300007 PM 25948682 ER PT J AU Cordoba-Chacon, J Majumdar, N List, EO Diaz-Ruiz, A Frank, SJ Manzano, A Bartrons, R Puchowicz, M Kopchick, JJ Kineman, RD AF Cordoba-Chacon, Jose Majumdar, Neena List, Edward O. Diaz-Ruiz, Alberto Frank, Stuart J. Manzano, Anna Bartrons, Ramon Puchowicz, Michelle Kopchick, John J. Kineman, Rhonda D. TI Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice SO DIABETES LA English DT Article ID NONALCOHOLIC FATTY LIVER; BODY-COMPOSITION; GH DEFICIENCY; TRIGLYCERIDE SYNTHESIS; RECEPTOR ANTAGONIST; ENDOGENOUS GH; IGF-I; INSULIN; DISEASE; STEATOSIS AB Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. C1 [Cordoba-Chacon, Jose; Majumdar, Neena; Kineman, Rhonda D.] Jesse Brown VA Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. [Cordoba-Chacon, Jose; Majumdar, Neena; Kineman, Rhonda D.] Univ Illinois, Coll Med, Div Endocrinol Diabet & Metab, Dept Med, Chicago, IL USA. [List, Edward O.; Kopchick, John J.] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. [List, Edward O.] Ohio Univ, Heritage Coll Osteopath Med, Dept Special Med, Athens, OH 45701 USA. [Diaz-Ruiz, Alberto] NIA, NIH, Translat Gerontol Branch, Expt Gerontol Sect, Baltimore, MD 21224 USA. [Frank, Stuart J.] Univ Alabama Birmingham, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Endocrinol Sect Med Serv, Birmingham, AL USA. [Manzano, Anna; Bartrons, Ramon] Univ Barcelona, Dept Physiol Sci, Barcelona, Spain. [Puchowicz, Michelle] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH USA. [Kopchick, John J.] Ohio Univ, Heritage Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. RP Kineman, RD (reprint author), Jesse Brown VA Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. EM kineman@uic.edu RI Kineman, Rhonda/H-2221-2011 OI Kineman, Rhonda/0000-0001-7322-1152 FU Endocrine Society/Genentech, Inc.; Endocrine Scholars Award in Growth Hormone Research; Intramural Research Program of the National Institutes of Health; National Institute on Aging; Institute de Salud Carlos III (Madrid, Spain) [PI13-00096]; Mouse Metabolic Phenotyping Center of Case Western Reserve University grant [U24 DK76174]; State of Ohio's Eminent Scholar Program; National Institutes of Health [P01AG031736, R01DK088133]; U.S. Department of Veterans Affairs, Office of Research and Development Merit Award [BX001114] FX This work was supported by an Endocrine Society/Genentech, Inc. Endocrine Scholars Award in Growth Hormone Research (to J.C.-C.); Intramural Research Program of the National Institutes of Health, National Institute on Aging (to A.D.-R.); Institute de Salud Carlos III (Madrid, Spain) grant PI13-00096 (to R.B.); Mouse Metabolic Phenotyping Center of Case Western Reserve University grant U24 DK76174 (to M.P.); State of Ohio's Eminent Scholar Program, which includes a gift by Milton and Lawrence Goll, and National Institutes of Health grant P01AG031736 (to J.J.K.); U.S. Department of Veterans Affairs, Office of Research and Development Merit Award BX001114; and National Institutes of Health grant R01DK088133 (to R.D.K.). NR 61 TC 6 Z9 6 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3093 EP 3103 DI 10.2337/db15-0370 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300008 PM 26015548 ER PT J AU Williams, AJK Lampasona, V Schlosser, M Mueller, PW Pittman, DL Winter, WE Akolkar, B Wyatt, R Brigatti, C Krause, S Achenbach, P AF Williams, Alistair J. K. Lampasona, Vito Schlosser, Michael Mueller, Patricia W. Pittman, David L. Winter, William E. Akolkar, Beena Wyatt, Rebecca Brigatti, Cristina Krause, Stephanie Achenbach, Peter CA Participating Labs TI Detection of Antibodies Directed to the N-Terminal Region of GAD Is Dependent on Assay Format and Contributes to Differences in the Specificity of GAD Autoantibody Assays for Type 1 Diabetes SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; STIFF-MAN SYNDROME; STANDARDIZATION PROGRAM; INSULIN AUTOANTIBODIES; PROFICIENCY EVALUATION; EPITOPE RECOGNITION; ISLET ANTIGEN-2; AFFINITY; RISK; MELLITUS AB GAD autoantibodies (GADAs) are sensitive markers of islet autoimmunity and type 1 diabetes. They form the basis of robust prediction models and are widely used for the recruitment of subjects at high risk of type 1 diabetes to prevention trials. However, GADAs are also found in many individuals at low risk of diabetes progression. To identify the sources of diabetes-irrelevant GADA reactivity, we analyzed data from the 2009 and 2010 Diabetes Autoantibody Standardization Program GADA workshop and found that binding of healthy control sera varied according to assay type. The characterization of control sera found positive by radiobinding assay (RBA), but negative by ELISA, showed that many of these sera reacted to epitopes in the N-terminal region of the molecule. This finding prompted development of an N-terminally truncated GAD(65) radiolabel, S-35-GAD(65)(96-585), which improved the performance of most GADA RBAs participating in an Islet Autoantibody Standardization Program GADA substudy. These detailed workshop comparisons have identified a source of disease-irrelevant signals in GADA RBAs and suggest that N-terminally truncated GAD labels will enable more specific measurement of GADAs in type 1 diabetes. C1 [Williams, Alistair J. K.; Wyatt, Rebecca] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. [Lampasona, Vito] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Schlosser, Michael] Univ Med Ctr Greifswald, Dept Med Biochem & Mol Biol, Karlsburg, Germany. [Schlosser, Michael] Univ Med Ctr Greifswald, Inst Pathophysiol, Karlsburg, Germany. [Mueller, Patricia W.] Ctr Dis Control & Prevent, Mol Risk Assessment Lab, Atlanta, GA USA. [Pittman, David L.; Winter, William E.] Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD USA. [Brigatti, Cristina] Ist Sci San Raffaele, Diabet Res Inst, I-20132 Milan, Italy. [Krause, Stephanie; Achenbach, Peter] Tech Univ Munich, Klinikum Rechts Isar, Diabet Res Inst, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Krause, Stephanie; Achenbach, Peter] Tech Univ Munich, Klinikum Rechts Isar, Forschergrp Diabet, Neuherberg, Germany. RP Williams, AJK (reprint author), Univ Bristol, Sch Clin Sci, Bristol, Avon, England. EM a.j.k.williams@bristol.ac.uk OI Lampasona, Vito/0000-0001-5162-8445; Williams, Alistair/0000-0002-3615-3899 FU Centers for Disease Control and Prevention [PL105-33, 106-310, 106-554, 107-360]; National Institute of Diabetes and Digestive and Kidney Diseases [93.847]; Associazione ltaliana per la Ricerca sul Cancro "AIRC bando 5 x 1000 N_12182" grant; German Federal Ministry of Education and Research (BMBF) [FKZ 01GI0805] FX The Diabetes Antibody Standardization Program was funded at the Centers for Disease Control and Prevention by grants PL105-33,106-310,106-554, and 107-360, which were administered by the National Institutes of Health. The Islet Autoantibody Standardization Program was funded at the University of Florida by Catalog of Federal Domestic Assistance grant #93.847: Diabetes, Digestive, and Kidney Diseases Extramural Research of the National Institute of Diabetes and Digestive and Kidney Diseases. V.L. and C.B worked within the framework of the Italian Ministry of Research "Ivascomar project, Cluster Tecnologico Nazionale Scienze della Vita ALISEI" and were supported by the Associazione ltaliana per la Ricerca sul Cancro "AIRC bando 5 x 1000 N_12182" grant. P.A. was supported by grants from the German Federal Ministry of Education and Research (BMBF) to the Competence Network for Diabetes Mellitus (FKZ 01GI0805) and to the German Center for Diabetes Research (DZD e.V.). NR 30 TC 9 Z9 9 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2015 VL 64 IS 9 BP 3239 EP 3246 DI 10.2337/db14-1693 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP9AE UT WOS:000360185300022 PM 25972570 ER PT J AU Mehta, SN Nansel, TR Volkening, LK Butler, DA Haynie, DL Laffel, LMB AF Mehta, S. N. Nansel, T. R. Volkening, L. K. Butler, D. A. Haynie, D. L. Laffel, L. M. B. TI Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire SO DIABETIC MEDICINE LA English DT Article ID GLYCEMIC CONTROL; SELF-MANAGEMENT; STRUCTURED INTERVIEW; YOUNG-PEOPLE; ADOLESCENTS; YOUTH; CHILDHOOD; CARE; ASSOCIATIONS; INVOLVEMENT AB AimsTo evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. MethodsA total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8-18years) had Type 1 diabetes for 1year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. ResultsThe children (49% female) had a mean sd (range) age 13.32.9 (8-18) years and their meansd HbA1c was 7115mmol/mol (8.6 +/- 1.4%). Internal consistency was good for parents (=0.83) and children (=0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient=0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient=0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r=-0.41, P<0.0001; children: r=-0.27, P<0.0001). Psychometrics were stronger in the children aged 13years compared with those aged <13years, but were acceptable in both age groups. Mean +/- sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n=181) than in children receiving multiple daily injections (n=92) according to parent (75.9 +/- 11.8 vs. 70.5 +/- 15.5; P=0.004) and child report (72.2 +/- 12.1 vs. 67.6 +/- 13.9; P=0.006). ConclusionsThe Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8-18years who are receiving either multiple daily injections or insulin pump therapy. C1 [Mehta, S. N.; Volkening, L. K.; Butler, D. A.; Laffel, L. M. B.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Adolescent & Young Adult Sect, Pediat, Boston, MA 02215 USA. [Nansel, T. R.; Haynie, D. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Hlth Behav Branch, Bethesda, MD USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Genet & Epidemiol Sect, Adolescent & Young Adult Sect, Pediat, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN26720070 3434C]; Joslin Diabetes Center's Diabetes and Endocrinology Research Center [NIH P30DK036836] FX This research was supported by the intramural research programme of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN26720070 3434C and the Joslin Diabetes Center's Diabetes and Endocrinology Research Center (NIH P30DK036836). NR 27 TC 4 Z9 4 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2015 VL 32 IS 9 BP 1232 EP 1238 DI 10.1111/dme.12682 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP4LK UT WOS:000359853000017 PM 26280463 ER PT J AU Abeldenova, S Talhaoui, I Zharkov, DO Ishchenko, AA Ramanculov, E Saparbaev, M Khassenov, B AF Abeldenova, Sailau Talhaoui, Ibtissam Zharkov, Dmitry O. Ishchenko, Alexander A. Ramanculov, Erlan Saparbaev, Murat Khassenov, Bekbolat TI Characterization of DNA substrate specificities of apurinic/apyrimidinic endonucleases from Mycobacterium tuberculosis SO DNA REPAIR LA English DT Article DE Oxidative DNA damage; Abasic sites; DNA repair; AP endonucleases; 3 '-repair phosphodiesterases ID INCISION REPAIR PATHWAY; ESCHERICHIA-COLI; EXONUCLEASE-III; BASE EXCISION; STRUCTURAL CHEMISTRY; OXIDATIVE DAMAGE; AP-ENDONUCLEASES; ABASIC SITES; IV; RECOGNITION AB Apurinic/apyrimidinic (AP) endonucleases are key enzymes involved in the repair of abasic sites and DNA strand breaks. Pathogenic bacteria Mycobacterium tuberculosis contains two AP endonucleases: MtbXthA and MtbNfo members of the exonuclease III and endonuclease IV families, which are exemplified by Escherichia coil Xth and Nfo, respectively. It has been shown that both MtbXthA and MtbNfo contain AP endonuclease and 3' -> 5' exonuclease activities. However, it remains unclear whether these enzymes hold 3'-repair phosphodiesterase and nucleotide incision repair (NIR) activities. Here, we report that both mycobacterial enzymes have 3'-repair phosphodiesterase and 3'-phosphatase, and MtbNfo contains in addition a very weak NIR activity. Interestingly, depending on pH, both enzymes require different concentrations of divalent cations: 0.5 mM MnCl2 at pH 7.6 and 10 mM at pH 6.5. MtbXthA requires a low ionic strength and 37 degrees C, while MtbNfo requires high ionic strength (200 mM KCl) and has a temperature optimum at 60 degrees C. Point mutation analysis showed that D180 and N182 in MtbXthA and H206 and El 29 in MtbNfo are critical for enzymes activities. The steady-state kinetic parameters indicate that MtbXthA removes 3'-blocking sugar-phosphate and 3'-phosphate moieties at DNA strand breaks with an extremely high efficiency (k(cat)/K-M = 440 and 1280 mu M-1.min(-1), respectively), while MtbNfo exhibits much lower 3'-repair activities (k(cat)/K-M = 0.26 and 0.65 mu M-1.min(-1), respectively). Surprisingly, both MtbXthA and MtbNfo exhibited very weak AP site cleavage activities, with kinetic parameters 100-and 300-fold lower, respectively, as compared with the results reported previously. Expression of MtbXthA and MtbNfo reduced the sensitivity of AP endonuclease-deficient E. coil xth nfo strain to methylmethanesulfonate and H2O2 to various degrees. Taken together, these data establish the DNA substrate specificity of M. tuberculosis AP endonucleases and suggest their possible role in the repair of oxidative DNA damage generated by endogenous and host- imposed factors. (C) 2015 Elsevier B.V. All rights reserved. C1 [Abeldenova, Sailau; Ramanculov, Erlan; Khassenov, Bekbolat] Natl Biotechnol Ctr, Astana 010000, Kazakhstan. [Abeldenova, Sailau] LN Gumilyov Eurasian Natl Univ, Astana 010008, Kazakhstan. [Talhaoui, Ibtissam; Ishchenko, Alexander A.; Saparbaev, Murat] Univ Paris Sud Lab, Stabilite Genet & Oncogenese, Grp Reparat ADN, CNRS,UMR 8200, F-94805 Villejuif, France. [Zharkov, Dmitry O.] SB RAS Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. [Zharkov, Dmitry O.] Novosibirsk State Univ, Novosibirsk 630090, Russia. RP Saparbaev, M (reprint author), Univ Paris Sud Lab, Stabilite Genet & Oncogenese, Grp Reparat ADN, CNRS,UMR 8200, F-94805 Villejuif, France. EM smurat@igr.fr; khassenov@biocenter.kz RI Saparbaev, Murat/N-3225-2015; Zharkov, Dmitry/K-2158-2012; OI Saparbaev, Murat/0000-0002-4630-1074; Zharkov, Dmitry/0000-0001-5013-0194; Khassenov, Bekbolat/0000-0003-4572-948X FU Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan [0806/GF, 5137/GF]; Agence Nationale pour la Recherche [ANR Blanc Projet] [ANR- 09-GENO-000]; Electricite de France [RB 2014-26]; Fondation de France [2012 00029161]; Russian Foundation for Basic Research [14-04-01879-a]; Presidium of the Russian Academy of Sciences [MKB 6.12]; L.N. Gumilyov Eurasian National University, Kazakhstan; Fondation ARC [PDF20110603195] FX We wish to thank Dr Olga Lavrik for the recombinant Tdp1 protein. This work was supported by grants to B.K. and S.A. from Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (http://sc.edu.gov.kz/) [0806/GF to B.K. and 5137/GF to S.A.], to MS. from Agence Nationale pour la Recherche (http://www.agence-nationale-recherche.fr) [ANR Blanc 2010 Projet ANR- 09-GENO-000] and Electricite de France RB 2014-26 (http://www.edf.fr), to A.A.I. from Fondation de France (http://www.fondationdefrance.org) [#2012 00029161 to A.A.I.]; and to D.O.Z. from the Russian Foundation for Basic Research (14-04-01879-a) and Presidium of the Russian Academy of Sciences (MKB 6.12). S.A. and I.T. were supported by PhD and postdoctoral fellowships from the L.N. Gumilyov Eurasian National University, Kazakhstan and Fondation ARC PDF20110603195, respectively. NR 55 TC 2 Z9 2 U1 1 U2 13 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 SEP PY 2015 VL 33 BP 1 EP 16 DI 10.1016/j.dnarep.2015.05.007 PG 16 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA CP4XE UT WOS:000359885100001 PM 26043425 ER PT J AU Khan, I Sommers, JA Brosh, RM AF Khan, Irfan Sommers, Joshua A. Brosh, Robert M., Jr. TI Close encounters for the first time: Helicase interactions with DNA damage SO DNA REPAIR LA English DT Review DE Helicase; DNA damage; Genomic instability; DNA repair; Genetic disease ID REPLICATION PROTEIN-A; NUCLEOTIDE EXCISION-REPAIR; SINGLE-STRANDED-DNA; VINYLPHOSPHONATE INTERNUCLEOTIDE LINKAGES; ANEMIA GROUP J; ESCHERICHIA-COLI; FANCONI-ANEMIA; XERODERMA-PIGMENTOSUM; BLOOMS SYNDROME; UVRD HELICASE AB DNA helicases are molecular motors that harness the energy of nucleoside triphosphate hydrolysis to unwinding structured DNA molecules that must be resolved during cellular replication, DNA repair, recombination, and transcription. In vivo, DNA helicases are expected to encounter a wide spectrum of covalent DNA modifications to the sugar phosphate backbone or the nitrogenous bases; these modifications can be induced by endogenous biochemical processes or exposure to environmental agents. The frequency of lesion abundance can vary depending on the lesion type. Certain adducts such as oxidative base modifications can be quite numerous, and their effects can be helix-distorting or subtle perturbations to DNA structure. Helicase encounters with specific DNA lesions and more novel forms of DNA damage will be discussed. We will also review the battery of assays that have been used to characterize helicase-catalyzed unwinding of damaged DNA substrates. Characterization of the effects of specific DNA adducts on unwinding by various DNA repair and replication helicases has proven to be insightful for understanding mechanistic and biological aspects of helicase function in cellular DNA metabolism. Published by Elsevier B.V. C1 [Khan, Irfan; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov FU Intramural Research Program of the NIH, National Institute on Aging FX This work was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 97 TC 5 Z9 5 U1 3 U2 19 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 SEP PY 2015 VL 33 BP 43 EP 59 DI 10.1016/j.dnarep.2015.06.003 PG 17 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA CP4XE UT WOS:000359885100005 PM 26160335 ER PT J AU Folio, LR Turkbey, EB Steinberg, SM Apolo, AB AF Folio, Les Roger Turkbey, Evrim B. Steinberg, Seth M. Apolo, Andrea B. TI Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Segmentation; Tumor burden assessment; Cancer; Oncology ID RENAL-CELL CARCINOMA; SOLID TUMORS; IMATINIB MESYLATE; TARGETED THERAPY; CT; RECIST; ATTENUATION; SIZE AB Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan-Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2-14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to further validate these findings. Published by Elsevier Ireland Ltd. C1 [Folio, Les Roger] NIH, Lead Radiologist CT, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Turkbey, Evrim B.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Folio, LR (reprint author), NIH, Lead Radiologist CT, Radiol & Imaging Sci, 10 Ctr Dr, Bethesda, MD 20892 USA. EM Les.folio@nih.gov; evrimbengi@yahoo.com; steinbes@mail.nih.gov FU NIH intramural program FX Supported by the NIH intramural program. Clinical trials number NCT01688999. NR 24 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD SEP PY 2015 VL 84 IS 9 BP 1708 EP 1714 DI 10.1016/j.ejrad.2015.05.026 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CP1EI UT WOS:000359618700012 PM 26149529 ER PT J AU Csoka, B Nemeth, ZH Toro, G Idzko, M Zech, A Koscso, B Spolarics, Z Antonioli, L Cseri, K Erdelyi, K Pacher, P Hasko, G AF Csoka, Balazs Nemeth, Zoltan H. Toero, Gabor Idzko, Marco Zech, Andreas Koscso, Balazs Spolarics, Zoltan Antonioli, Luca Cseri, Karolina Erdelyi, Katalin Pacher, Pal Hasko, Gyoergy TI Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing SO FASEB JOURNAL LA English DT Article DE connexin; inflammasome; inflammation; pannexin; phagocytosis ID INFLAMMATORY RESPONSE; POLYMICROBIAL SEPSIS; MURINE MACROPHAGES; IMMUNITY; MORTALITY; INNATE; NEUTROPHILS; ACTIVATION; ADENOSINE; CHANNELS AB Extracellular ATP binds to and signals through P2X7 receptors (P2X7Rs) to modulate immune function in both inflammasome-dependent and -independent manners. In this study, P2X7(-/-) mice, the pharmacological agonists ATP-magnesiumsalt (Mg-ATP; 100 mg/kg, EC50 approximate to 1.32 mM) and benzoylbenzoyl-ATP (Bz-ATP; 10 mg/kg, EC50 approximate to 285 mu M), and antagonist oxidized ATP (oxi-ATP; 40 mg/kg, IC50 approximate to 100 mu M) were used to show that P2X7R activation is crucial for the control of mortality, bacterial dissemination, and inflammation in cecal ligation and puncture-induced polymicrobial sepsis in mice. Our results with P2X7(-/-) bone marrow chimeric mice, adoptive transfer of peritoneal macrophages, and myeloid-specific P2X7(-/-) mice indicate that P2X7R signaling on macrophages is essential for the protective effect of P2X7Rs. P2X7R signaling protects through enhancing bacterial killing by macrophages, which is independent of the inflammasome. By using the connexin (Cx) channel inhibitor Gap27 (0.1 mg/kg, IC50 approximate to 0.25 mu M) and pannexin channel inhibitor probenecid (10 mg/kg, IC50 approximate to 11.7 mu M), we showed that ATP release through Cx is important for inhibiting inflammation and bacterial burden. In summary, targeting P2X7Rs provides a new opportunity for harnessing an endogenous protective immune mechanism in the treatment of sepsis. C1 [Csoka, Balazs; Nemeth, Zoltan H.; Toero, Gabor; Koscso, Balazs; Spolarics, Zoltan; Hasko, Gyoergy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Csoka, Balazs; Toero, Gabor; Spolarics, Zoltan; Hasko, Gyoergy] Rutgers New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA. [Nemeth, Zoltan H.] Morristown Med Ctr, Dept Surg, Morristown, NJ USA. [Idzko, Marco; Zech, Andreas] Univ Freiburg, Freiburg Univ Med Ctr, Dept Pneumol, D-79106 Freiburg, Germany. [Antonioli, Luca] Univ Pisa, Dept Clin & Expt Med, Pisa, Italy. [Cseri, Karolina] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, Debrecen, Hungary. [Erdelyi, Katalin; Pacher, Pal] NIAAA, NIH, Bethesda, MD USA. RP Hasko, G (reprint author), Rutgers New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@njms.rutgers.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU U.S. National Institutes of Health (NIH) Grant from National Institute of General Medical Sciences [R01GM66189]; U.S. Army Medical Research and Materiel Command Grant [09065004/W81XWH-10-1-1015]; Hungarian Scientific Research Fund Grants (OTKA) [CK 78275, K109178]; Intramural Research Program of NIH, National Institute on Alcohol Abuse and Alcoholism FX This work was supported by U.S. National Institutes of Health (NIH) Grant R01GM66189 from the National Institute of General Medical Sciences, U.S. Army Medical Research and Materiel Command Grant 09065004/W81XWH-10-1-1015, and Hungarian Scientific Research Fund Grants (OTKA) CK 78275 and K109178 (all to G.H.) and by funding from the Intramural Research Program of the NIH, National Institute on Alcohol Abuse and Alcoholism (to P.P.). The authors declare no conflicts of interests. NR 47 TC 7 Z9 8 U1 3 U2 15 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 SEP PY 2015 VL 29 IS 9 BP 3626 EP 3637 DI 10.1096/fj.15-272450 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CP5IU UT WOS:000359915600003 PM 26060214 ER PT J AU Pivarunas, B Kelly, NR Pickworth, CK Cassidy, O Radin, RM Shank, LM Vannucci, A Courville, AB Chen, KY Tanofsky-Kraff, M Yanovski, JA Shomaker, LB AF Pivarunas, Bernadette Kelly, Nichole R. Pickworth, Courtney K. Cassidy, Omni Radin, Rachel M. Shank, Lisa M. Vannucci, Anna Courville, Amber B. Chen, Kong Y. Tanofsky-Kraff, Marian Yanovski, Jack A. Shomaker, Lauren B. TI Mindfulness and eating behavior in adolescent girls at risk for type 2 diabetes SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE type 2 diabetes; adolescents; mindfulness; disordered eating attitudes; food reinforcement; binge eating ID DISPOSITIONAL MINDFULNESS; COLLEGE-STUDENTS; CHILDREN; WEIGHT; QUESTIONNAIRE; DISORDERS; OBESITY; FOOD; BENEFITS; MELLITUS AB ObjectiveThe purpose of this investigation was to examine the relationship of dispositional mindfulness to binge eating and associated eating attitudes and behaviors among adolescent girls at risk for type 2 diabetes (T2D). MethodsParticipants were 114 overweight or obese adolescents enrolled in a study of girls with a family history of T2D and mild depressive symptoms. Adolescent self-reports of mindfulness, eating in the absence of hunger, and depressive symptoms were collected. An interview was administered to determine presence of binge eating episodes and a behavioral task was used to assess the reinforcing value of food relative to other nonsnack food rewards. Body composition was assessed using dual-energy X-ray absorptiometry. ResultsIn analyses accounting for race, percent body fat, lean mass, height, age, and depressive symptoms, dispositional mindfulness was associated with a lower odds of binge eating (p=.002). Controlling for the same potential confounds, mindfulness was also inversely associated with eating concern, eating in the absence of hunger in response to fatigue/boredom, and higher food reinforcement relative to physical activity (all p<.05). DiscussionIn girls with a family history of T2D, independent of body composition and depressive symptoms, intraindividual differences in mindfulness are related to binge eating and associated attitudes and behaviors that may confer risk for obesity and metabolic problems. Further research is needed to determine the extent to which mindfulness plays a role in the etiology and/or maintenance of disinhibited eating in adolescents at risk for T2D. (c) 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:563-569) C1 [Pivarunas, Bernadette] Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. [Kelly, Nichole R.; Pickworth, Courtney K.; Cassidy, Omni; Radin, Rachel M.; Shank, Lisa M.; Vannucci, Anna; Tanofsky-Kraff, Marian; Yanovski, Jack A.; Shomaker, Lauren B.] NICHD, DHHS, Sect Growth & Obes, NIH, Bethesda, MD USA. [Kelly, Nichole R.; Shomaker, Lauren B.] Colorado State Univ, Dept Human Dev & Family Studies, Ft Collins, CO 80523 USA. [Cassidy, Omni; Radin, Rachel M.; Shank, Lisa M.; Courville, Amber B.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD USA. [Courville, Amber B.] NIH Clin Ctr, Dept Nutr, DHHS, Bethesda, MD USA. [Chen, Kong Y.] NIDDKD, DHHS, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 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; Shank, Lisa/0000-0002-6922-7946 FU NICHD [K99/R00HD069516]; NIH Intramural Research Program from NICHD [1ZIAHD000641]; NIH Bench to Bedside Program; Office of Disease Prevention, NIH; Office of Behavioral and Social Sciences Research; NIH Office of Intramural Training and Education FX Supported by K99/R00HD069516 (to L.B.S.) from NICHD, NIH Intramural Research Program Grant 1ZIAHD000641 (to J.A.Y.) from NICHD with supplemental funding from the NIH Bench to Bedside Program (to J.A.Y., L.B.S., and M.T.-K.), the Office of Disease Prevention, NIH (to J.A.Y.), the Office of Behavioral and Social Sciences Research (to J.A.Y.), and NIH Office of Intramural Training and Education (to C.K.P.). NR 43 TC 2 Z9 2 U1 5 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2015 VL 48 IS 6 BP 563 EP 569 DI 10.1002/eat.22435 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA CP7NW UT WOS:000360075900003 PM 26172157 ER PT J AU Schvey, NA Sbrocco, T Stephens, M Bryant, EJ Ress, R Spieker, EA Conforte, A Bakalar, JL Pickworth, CK Barmine, M Klein, D Brady, SM Yanovski, JA Tanofsky-Kraff, M AF Schvey, Natasha A. Sbrocco, Tracy Stephens, Mark Bryant, Edny J. Ress, Rachel Spieker, Elena A. Conforte, Allison Bakalar, Jennifer L. Pickworth, Courtney K. Barmine, Marissa Klein, David Brady, Sheila M. Yanovski, Jack A. Tanofsky-Kraff, Marian TI Comparison of overweight and obese military-dependent and civilian adolescent girls with loss-of-control eating SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE military dependents; adolescents; loss of control and binge eating; disordered-eating; overweight; obesity ID BECK DEPRESSION INVENTORY; CONTRIBUTING FACTORS; DISORDER BEHAVIORS; ADULT OBESITY; RISK-FACTORS; INSULIN-RESISTANCE; WEIGHT-GAIN; SELF-REPORT; CHILDREN; PREVALENCE AB ObjectiveLimited data suggest that the children of U.S. service members may be at increased risk for disordered-eating. To date, no study has directly compared adolescent military-dependents to their civilian peers along measures of eating pathology and associated correlates. We, therefore, compared overweight and obese adolescent female military-dependents to their civilian counterparts along measures of eating-related pathology and psychosocial functioning. MethodAdolescent females with a BMI between the 85th and 97th percentiles and who reported loss-of-control eating completed interview and questionnaire assessments of eating-related and general psychopathology. ResultsTwenty-three military-dependents and 105 civilians participated. Controlling for age, race, and BMI-z, military-dependents reported significantly more binge episodes per month (p<0.01), as well as greater eating-concern, shape-concern, and weight-concern (p's<0.01) than civilians. Military-dependents also reported more severe depression (p<0.05). DiscussionAdolescent female military-dependents may be particularly vulnerable to disordered-eating compared with civilian peers. This potential vulnerability should be considered when assessing military-dependents. (c) 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:790-794) C1 [Schvey, Natasha A.; Sbrocco, Tracy; Stephens, Mark; Bryant, Edny J.; Ress, Rachel; Conforte, Allison; Bakalar, Jennifer L.; Barmine, Marissa; Yanovski, Jack A.; Tanofsky-Kraff, Marian] USUHS, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Schvey, Natasha A.; Ress, Rachel; Pickworth, Courtney K.; Brady, Sheila M.; Yanovski, Jack A.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD USA. [Spieker, Elena A.] Madigan Army Med Ctr, Dept Family Med, Ft Lewis, WA USA. [Klein, David] FBCH, Dept Family Med, Ft Belvoir, VA USA. RP Tanofsky-Kraff, M (reprint author), USUHS, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM marian.tanofsky-kraff@usuhs.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK080906]; USUHS [R072IC]; USUHS Center Project Program [72NC-01]; Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program [Z1A-HD-00641] FX Supported by 1R01DK080906 from National Institute of Diabetes and Digestive and Kidney Diseases (to M.T.-K.), R072IC from USUHS (to M.T.-K.), 72NC-01 from USUHS Center Project Program (to T.S.), and Z1A-HD-00641 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program (to J.A.Y.). NR 42 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2015 VL 48 IS 6 BP 790 EP 794 DI 10.1002/eat.22424 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA CP7NW UT WOS:000360075900030 PM 25955761 ER PT J AU Gophna, U Kristensen, DM Wolf, YI Popa, O Drevet, C Koonin, EV AF Gophna, Uri Kristensen, David M. Wolf, Yuri I. Popa, Ovidiu Drevet, Christine Koonin, Eugene V. TI No evidence of inhibition of horizontal gene transfer by CRISPR-Cas on evolutionary timescales SO ISME JOURNAL LA English DT Article ID STREPTOCOCCUS-THERMOPHILUS; ACQUIRED-RESISTANCE; BACTERIAL DIVERSITY; EXPERIMENTAL-MODEL; ORTHOLOGOUS GENES; INTERFERENCE; PROKARYOTES; ARCHAEA; COMPLEX; SYSTEM AB The CRISPR (clustered, regularly, interspaced, short, palindromic repeats)-Cas (CRISPR-associated genes) systems of archaea and bacteria provide adaptive immunity against viruses and other selfish elements and are believed to curtail horizontal gene transfer (HGT). Limiting acquisition of new genetic material could be one of the sources of the fitness cost of CRISPR-Cas maintenance and one of the causes of the patchy distribution of CRISPR-Cas among bacteria, and across environments. We sought to test the hypothesis that the activity of CRISPR-Cas in microbes is negatively correlated with the extent of recent HGT. Using three independent measures of HGT, we found no significant dependence between the length of CRISPR arrays, which reflects the activity of the immune system, and the estimated number of recent HGT events. In contrast, we observed a significant negative dependence between the estimated extent of HGT and growth temperature of microbes, which could be explained by the lower genetic diversity in hotter environments. We hypothesize that the relevant events in the evolution of resistance to mobile elements and proclivity for HGT, to which CRISPR-Cas systems seem to substantially contribute, occur on the population scale rather than on the timescale of species evolution. C1 [Gophna, Uri] Natl Evolutionary Synth Ctr, Durham, NC USA. [Gophna, Uri] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, George S Wise Fac Life Sci, IL-6997801 Tel Aviv, Israel. [Kristensen, David M.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Popa, Ovidiu] Univ Kiel, Genom Microbiol Grp, Inst Microbiol, Kiel, Germany. [Drevet, Christine] Univ Paris 11, CNRS, CEA, Inst Integrat Biol Cell, Paris, France. RP Gophna, U (reprint author), Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, Haim Levanon 72, IL-6997801 Tel Aviv, Israel. EM urigo@tauex.tau.ac.il; koonin@ncbi.nlm.nih.gov FU National Evolutionary Synthesis Center (NESCent); US Department of Health and Human Services; European Research Council [281357] FX We thank Kira Makarova and Christine Pourcel for helpful discussions and suggestions, and the eBio IFB platform for bioinformatics support to CRISPRdb. UG is supported by the National Evolutionary Synthesis Center (NESCent). DMK, YIW and EVK are supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). OP is supported by the European Research Council (grant no. 281357). NR 55 TC 12 Z9 12 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 EI 1751-7370 J9 ISME J JI ISME J. PD SEP PY 2015 VL 9 IS 9 BP 2021 EP 2027 DI 10.1038/ismej.2015.20 PG 7 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA CP6SW UT WOS:000360019500011 PM 25710183 ER PT J AU Gondre-Lewis, MC Gboluaje, T Reid, SN Lin, S Wang, P Green, W Diogo, R Fidelia-Lambert, MN Herman, MM AF Gondre-Lewis, Marjorie C. Gboluaje, Temitayo Reid, Shaina N. Lin, Stephen Wang, Paul Green, William Diogo, Rui Fidelia-Lambert, Marie N. Herman, Mary M. TI The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18 SO JOURNAL OF ANATOMY LA English DT Article DE holoprosencephaly; HPE; trisomy 18; cyclopia; chromosome 18; neurocranium; viscerocranium; synophthalmia; Edwards' syndrome; SHH; Pax6; TGIF; craniofacial anomalies; eye development; nose development ID SONIC-HEDGEHOG; CRANIOFACIAL MORPHOGENESIS; TRUE CYCLOPIA; GENE; TRISOMY-18; ORIGIN; SKULL; CHICK; IDENTIFICATION; EVOLUTIONARY AB The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. C1 [Gondre-Lewis, Marjorie C.; Gboluaje, Temitayo; Reid, Shaina N.] Howard Univ, Lab Neurodev, Dept Anat, Coll Med, Washington, DC 20059 USA. [Lin, Stephen; Wang, Paul] Howard Univ, Dept Radiol, Coll Med, Washington, DC 20059 USA. [Green, William; Diogo, Rui] Howard Univ, Lab Evolutionary Biol, Dept Anat, Coll Med, Washington, DC 20059 USA. [Fidelia-Lambert, Marie N.] Howard Univ, Dept Pathol, Coll Med, Washington, DC 20059 USA. [Herman, Mary M.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Gondre-Lewis, MC (reprint author), Howard Univ, Lab Neurodev, Dept Anat, Coll Med, 520 W St NW, Washington, DC 20059 USA. EM mgondre-lewis@howard.edu FU NIH/NIMHD [G12 MD007597]; [R01AA021262] FX This research was supported in part by NIH/NIMHD G12 MD007597; MGL is supported by R01AA021262. The authors wish to thank Dr Janine Ziermann for help with staging the control specimens, Dr Duerinckx for access to imaging equipment in the Department of Radiology, and Dr Lee in the Department of Pathology for his support of this research. NR 55 TC 1 Z9 1 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8782 EI 1469-7580 J9 J ANAT JI J. Anat. PD SEP PY 2015 VL 227 IS 3 BP 255 EP 267 DI 10.1111/joa.12343 PG 13 WC Anatomy & Morphology SC Anatomy & Morphology GA CP4RD UT WOS:000359869300001 PM 26278930 ER PT J AU Hara, ES Ono, M Pham, HT Sonoyama, W Kubota, S Takigawa, M Matsumoto, T Young, MF Olsen, BR Kuboki, T AF Hara, Emilio Satoshi Ono, Mitsuaki Hai Thanh Pham Sonoyama, Wataru Kubota, Satoshi Takigawa, Masaharu Matsumoto, Takuya Young, Marian F. Olsen, Bjorn R. Kuboki, Takuo TI Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-beta 3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMP; TGF-beta; GLUCOCORTICOIDS; FLUOCINOLONE ACETONIDE; CHONDROGENESIS; STEM CELLS; CARTILAGE REGENERATION ID RANDOMIZED CONTROLLED-TRIALS; HYDROGEL SCAFFOLDS; CARTILAGE REPAIR; DIFFERENTIATION; GROWTH; MEDICINE; MODULATION; ACTIVATION; EXPRESSION; DELIVERY AB Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-3-associated chondrogenesis, and suggest that the FA/TGF-3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells. (c) 2015 American Society for Bone and Mineral Research. C1 [Hara, Emilio Satoshi; Ono, Mitsuaki; Hai Thanh Pham; Sonoyama, Wataru; Kuboki, Takuo] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Rehabil & Regenerat Med, Okayama, Okayama 7008525, Japan. [Hara, Emilio Satoshi; Matsumoto, Takuya] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biomat, Okayama, Okayama 7008525, Japan. [Kubota, Satoshi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biochem & Mol Dent, Okayama, Okayama 7008525, Japan. [Takigawa, Masaharu] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Adv Res Ctr Oral & Craniofacial Sci, Okayama, Okayama 7008525, Japan. [Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Olsen, Bjorn R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Kuboki, T (reprint author), Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Rehabil & Regenerat Med, Kita Ku, 2-5-1 Shikata Cho, Okayama, Okayama 7008525, Japan. EM kuboki@md.okayama-u.ac.jp RI Hara, Emilio/B-3922-2017 OI Hara, Emilio/0000-0001-7374-3487 FU Ministry of Education, Culture, Sports, Science, and Technology, Japan [26253088, 22249064, 19109008] FX This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (#26253088, #22249064, and #19109008; all to TK). The plasmid encoding the Col2a1 promoter used in the luciferase assay was received from Yoshihiko Yamada, NIDCR, NIH. The authors also thank Yumiko Morishita at research joint facility of Okayama University for part of the histological sectioning. NR 34 TC 4 Z9 4 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2015 VL 30 IS 9 BP 1585 EP 1596 DI 10.1002/jbmr.2502 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP4QG UT WOS:000359866800006 PM 25753754 ER PT J AU de Moor, JS Alfano, CM Breen, N Kent, EE Rowland, J AF de Moor, Janet S. Alfano, Catherine M. Breen, Nancy Kent, Erin E. Rowland, Julia TI Applying evidence from economic evaluations to translate cancer survivorship research into care SO JOURNAL OF CANCER SURVIVORSHIP LA English DT Article DE Cancer survivorship; Cost-effectiveness; Value; Intervention; Dissemination ID COST-EFFECTIVENESS ANALYSIS; STAKEHOLDER ENGAGEMENT; UNITED-STATES; HEALTH-CARE; LONG-TERM; MEDICINE; INFORMATION; OUTCOMES; QUALITY AB This paper summarizes recommendations stemming from the meeting, Applying Evidence from Economic Evaluations to Translate Cancer Survivorship Research into Care, hosted by the National Cancer Institute. The meeting convened funded investigators, experts in cancer control, survivorship, health economics, and team science to identify the economic and health services data needed to facilitate the dissemination of cancer survivorship interventions into care and how survivorship and health economic investigators can successfully collaborate together and with other stakeholders. Recommendations from the meeting are as follows. First, investigators must engage key stakeholders early in the planning process to understand the outcomes and cost domains on which they base decisions. Second, evaluations of intervention efficacy and value should be conducted using standardized and comparable measures and analytic approaches to enable comparisons across studies. Finally, a health economist should be included during the planning phase of the study so that the economic evaluation is pursued in concert with the survivorship intervention. Economic analyses, from the perspective of key stakeholders, must be incorporated into survivorship intervention research. The results from these analyses should be disseminated in a manner that is transparent, accessible, and comparable across studies. To optimize cancer survivors' health and quality of life, it is essential deliver high-quality and high-value care. Incorporating economic analyses into survivorship intervention research can inform the translation of effective interventions into practice. C1 [de Moor, Janet S.; Breen, Nancy] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Alfano, Catherine M.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kent, Erin E.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rowland, Julia] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP de Moor, JS (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,3E438,MSC 9764, Bethesda, MD 20892 USA. EM Janet.demoor@nih.gov NR 37 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 EI 1932-2267 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2015 VL 9 IS 3 BP 560 EP 566 DI 10.1007/s11764-015-0433-3 PG 7 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA CP2ZF UT WOS:000359745900020 PM 25689963 ER PT J AU Shi, YF Xu, X Fang, M Zhang, M Li, YH Gillespie, B Yorke, S Yang, N McKew, JC Gahl, WA Huizing, M Carrillo-Carrasco, N Wang, AQ AF Shi, Yifan Xu, Xin Fang, Meng Zhang, Michael Li, Yinghe Gillespie, Brad Yorke, Selwyn Yang, Nora McKew, John C. Gahl, William A. Huizing, Marjan Carrillo-Carrasco, Nuria Wang, Amy Qiu TI Quantitative hydrophilic interaction chromatography-mass spectrometry analysis of N-acetylneuraminic acid and N-acetylmannosamine in human plasma SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE N-acetylmannosamine; N-acetylneuraminic acid; HILIC; LC-MS/MS; Phospholipid removal; Validation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TOTAL SIALIC-ACID; LC-MS/MS; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; METHOD VALIDATION; GNE MYOPATHY; MOUSE MODEL; QUANTIFICATION; SERUM; GLYCOPROTEINS AB N-acetylneuraminic acid (Neu5Ac or NANA) is the most predominant sialic acid in mammals. As a terminal component in many glycoproteins and glycolipids, sialic acid is believed to be an important biomarker related to various diseases. Its precursor, N-acetylmannosamine (ManNAc), is being investigated as a potential treatment for GNE myopathy. In this work, we developed two highly sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the quantitation of ManNAc and free Neu5Ac in human plasma. A fit-for-purpose approach was adopted during method validation and sample analysis. To measure the endogenous compounds and overcome the interference from plasma samples, a surrogate matrix that contained 5% bovine serum albumin (BSA) was used for the preparation of calibration standards and certain levels of quality control (QC) samples. QC samples at higher concentrations were prepared in the authentic matrix (human plasma) to best mimic incurred samples. For both methods, an Ostro 96-well phospholipid removal plate was used for sample extraction, which efficiently removed the phospholipids from the plasma samples prior to LC injection, eliminated matrix effect, and improved sensitivity. Chromatographic separation was achieved using hydrophilic interaction chromatography (HILIC) and gradient elution in order to retain the two polar compounds. The lower limit of quantitation (LLOQ) for ManNAc and Neu5Ac was 10.0 and 25.0 ng/mL, respectively. The overall accuracy of the two assays was within 100% +/- 8.3% based on three levels of QC samples. Inter- and intra-run precision (coefficient of variation (%CV)) across three analytical runs was less than 6.7% for ManNAc and less than 10.8% for Neu5Ac. These methods have been validated to support clinical studies. (C) 2015 Elsevier B.V. All rights reserved. C1 [Shi, Yifan; Fang, Meng; Zhang, Michael; Li, Yinghe] Alliance Pharma, Malvern, PA 19355 USA. [Xu, Xin; Yang, Nora; McKew, John C.; Carrillo-Carrasco, Nuria; Wang, Amy Qiu] NIH, Therapeut Rare & Neglected Dis, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Gillespie, Brad] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Yorke, Selwyn] New Zealand Pharmaceut, Palmerston North 4472, New Zealand. [Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20895 USA. RP Shi, YF (reprint author), Alliance Pharma, 17 Lee Blvd, Malvern, PA 19355 USA. EM shiyifan@gmail.com RI Carrillo-Carrasco, Nuria/B-9034-2009; OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; Yorke, Selwyn/0000-0002-8708-9866 FU Therapeutics for Rare and Neglected Diseases (TRND), National Center of Advancing Translational Sciences, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the Therapeutics for Rare and Neglected Diseases (TRND), National Center of Advancing Translational Sciences, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors would like to thank Tatiana K. Field at Alliance Pharma for her editorial and review of the manuscript. NR 41 TC 2 Z9 2 U1 4 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 EI 1873-376X J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 1 PY 2015 VL 1000 BP 105 EP 111 DI 10.1016/j.jchromb.2015.07.018 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CP4TE UT WOS:000359874700012 PM 26218770 ER PT J AU Tynell, J Westenius, V Ronkko, E Munster, VJ Melen, K Osterlund, P Julkunen, I AF Tynell, J. Westenius, V. Ronkko, E. Munster, V. J. Melen, K. Osterlund, P. Julkunen, I. TI Middle East respiratory syndrome coronavirus (MERS-CoV) shows poor replication and weak induction of antiviral responses in human monocyte-derived macrophages and dendritic cells SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract C1 [Tynell, J.; Westenius, V.; Ronkko, E.; Melen, K.; Osterlund, P.; Julkunen, I.] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Munster, V. J.] Natl Inst Allergy & Infect Dis, Hamilton, MT USA. [Julkunen, I.] Univ Turku, Turku, Finland. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 EI 1873-5967 J9 J CLIN VIROL JI J. Clin. Virol. PD SEP PY 2015 VL 70 SU 1 MA 1667 BP S56 EP S57 DI 10.1016/j.jcv.2015.07.134 PG 2 WC Virology SC Virology GA CP7QI UT WOS:000360082500125 ER PT J AU Rua, R McGavern, DB AF Rua, Rejane McGavern, Dorian B. TI Elucidation of monocyte/macrophage dynamics and function by intravital imaging SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE two-photon; microscopy; myeloid cells; vasculature; tumors; infection ID E-DEFICIENT MICE; SUBCAPSULAR SINUS MACROPHAGES; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; CD8(+) T-CELLS; IN-VIVO; BONE-MARROW; APOLIPOPROTEIN-E; LYMPH-NODES; MAMMARY-TUMORS AB Monocytes and macrophages are a diverse population of innate immune cells that play a critical role in homeo-stasis and inflammation. These cells are surveillant by nature and closely monitor the vasculature and surrounding tissue during states of health and disease. Given their abundance and strategic positioning throughout the body, myeloid cells are among the first responders to any inflammatory challenge and are active participants in most immune-mediated diseases. Recent studies have shed new light on myeloid cell dynamics and function by use of an imaging technique referred to as intravital microscopy (IVM). This powerful approach allows researchers to gain real-time insights into monocytes and macrophages performing homeostatic and inflammatory tasks in living tissues. In this review, we will present a contemporary synopsis of how intravital microscopy has revolutionized our understanding of myeloid cell contributions to vascular maintenance, microbial defense, autoimmunity, tumorigenesis, and acute/chronic inflammatory diseases. C1 [Rua, Rejane; McGavern, Dorian B.] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20892 USA. RP McGavern, DB (reprint author), NINDS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov FU U.S. National Institutes of Health (NIH) intramural program FX This work was supported by the U.S. National Institutes of Health (NIH) intramural program. The authors thank Ethan Tyler in the NIH Medical Arts Design Section for his help with the illustrations. NR 129 TC 3 Z9 3 U1 3 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2015 VL 98 IS 3 BP 319 EP 332 DI 10.1189/jlb.4RI0115-006RR PG 14 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA CP7KS UT WOS:000360066900006 PM 26162402 ER PT J AU Richard, AC Ferdinand, JR Meylan, F Hayes, ET Gabay, O Siegel, RM AF Richard, Arianne C. Ferdinand, John R. Meylan, Francoise Hayes, Erika T. Gabay, Odile Siegel, Richard M. TI The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE autoimmune disease; DR3 ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ALLERGIC LUNG INFLAMMATION; DOMAIN-CONTAINING RECEPTOR; PRIMARY BILIARY-CIRRHOSIS; CD4(+) T-CELLS; NF-KAPPA-B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IFN-GAMMA PRODUCTION; LIGAND 1A TL1A AB Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases. C1 [Richard, Arianne C.; Ferdinand, John R.; Meylan, Francoise; Hayes, Erika T.; Gabay, Odile; Siegel, Richard M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Richard, Arianne C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Richard, Arianne C.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. [Ferdinand, John R.] Univ Southampton, Fac Med, Canc Sci Acad Unit, Southampton SO9 5NH, Hants, England. RP Siegel, RM (reprint author), NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA. EM rsiegel@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the U.S. National Institutes of Health FX This work was supported by intramural research funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the U.S. National Institutes of Health. NR 127 TC 8 Z9 8 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2015 VL 98 IS 3 BP 333 EP 345 DI 10.1189/jlb.3RI0315-095R PG 13 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA CP7KS UT WOS:000360066900007 PM 26188076 ER PT J AU MaruYama, T Kobayashi, S Ogasawara, K Yoshimura, A Chen, WJ Muta, T AF MaruYama, Takashi Kobayashi, Shuhei Ogasawara, Kouetsu Yoshimura, Akihiko Chen, WanJun Muta, Tatsushi TI Control of IFN-gamma production and regulatory function by the inducible nuclear protein I kappa B-zeta in T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T lymphocyte; cytokine; transcriptional regulator ID TRANSCRIPTION FACTOR FOXP3; MEDIATED REGULATION; GENE-EXPRESSION; RECEPTOR; DNA; DIFFERENTIATION; INFLAMMATION; DISRUPTION; ACTIVATION; INDUCTION AB The transcriptional regulator I kappa B-zeta is important for the control of apoptosis in keratinocytes. Thus, I kappa B-zeta-deficient mice develop autoimmune diseases, such as Sjogren's syndrome. However, T cells also play a pivotal role in Sjogren's syndrome. To study the role of I kappa B-zeta in T cells, we generated T cell-specific, I kappa B-zeta-deficient mice. We observed increased numbers of peripheral effector/memory CD4(+) cells and IFN-gamma-producing CD4(+) cells in 3-week-old mice. We found that I kappa B-zeta can be up-regulated by TGF-beta 1 in naive CD4(+) T cells and that it negatively regulates IFN-gamma expression. In addition, we generated T-reg-specific, I kappa B-zeta deficient mice and found that I kappa B-zeta is dispensable for the plasticity and stability of T-regs. However, T-regs from T cell-specific, I kappa B-zeta-deficient mice have reduced immunoregulatory function. Thus, our data reveal a previously unappreciated role for I kappa B-zeta in IFN-gamma production in T cells and the immunoregulatory function of T-regs. C1 [MaruYama, Takashi; Kobayashi, Shuhei; Muta, Tatsushi] Tohoku Univ, Grad Sch Life Sci, Lab Cell Recognit & Response, Sendai, Miyagi 980, Japan. [Ogasawara, Kouetsu] Tohoku Univ, Dept Immunobiol, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan. [MaruYama, Takashi] Gifu Univ, Sch Med, Gifu 5011194, Japan. [Yoshimura, Akihiko] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo, Japan. [Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP MaruYama, T (reprint author), Gifu Univ, Sch Med, 1-1 Yanagido, Gifu 5011194, Japan. EM ta-maru@umin.ac.jp RI Yoshimura, Akihiko/K-5515-2013 FU Ministry of Education [25118702]; Takeda Science Foundation [24790458, 26670019]; Uehara Memorial Foundation; Novartis Foundation; Sumitomo Foundation; Cooperative Research Project Program of the Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University FX This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas 25118702 from the Ministry of Education (to Tak.Y.); a Grant-in-Aid for Young Scientists B (Grant 24790458); Grant-in-Aid for Challenging Exploratory Research 26670019 from the Japan Society for the Promotion of Science (to Tak.Y.); and grants from the Takeda Science Foundation, Uehara Memorial Foundation, Novartis Foundation, and Sumitomo Foundation (to Tak.Y.). This work was partly supported by the Cooperative Research Project Program of the Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University. The authors are grateful to Dr. Alexander Y. Rudensky (Memorial Sloan-Kettering Cancer Center) for providing the Foxp3YFP-cre mice. The authors also thank Drs. Ono Masao, Atsushi Okuma (Tohoku University), and Maekawa Yoichi (Gifu University) for discussion. NR 34 TC 2 Z9 2 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2015 VL 98 IS 3 BP 385 EP 393 DI 10.1189/jlb.2A0814-384R PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA CP7KS UT WOS:000360066900012 PM 26019294 ER PT J AU Ballard, ED Luckenbaugh, DA Richards, EM Walls, TL Brutsche, NE Ameli, R Niciu, MJ Vande Voort, JL Zarate, CA AF Ballard, Elizabeth D. Luckenbaugh, David A. Richards, Erica M. Walls, Tessa L. Brutsche, Nancy E. Ameli, Rezvan Niciu, Mark J. Vande Voort, Jennifer L. Zarate, Carlos A., Jr. TI Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Suicidal ideation; Assessment; Ketamine; Psychometrics; Depression ID RANDOMIZED CONTROLLED-TRIAL; D-ASPARTATE ANTAGONIST; RESISTANT MAJOR DEPRESSION; ADD-ON TRIAL; RATING-SCALE; BIPOLAR DEPRESSION; KETAMINE; PREDICTORS; COGNITION; DISORDER AB Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days. Assessments were compared using correlational analyses and effect sizes at 230 min and three days after ketamine infusion. Linear mixed models evaluated change in ideation across all time points. The HAM-D and MADRS suicide items demonstrated correlations of r > .80 with the first five items of the SSI (SSI5). On linear mixed models, an effect for ketamine was found for the HAM-D, MADRS, BDI items, and SSI5 (p < .001), but not for the full SSI (p = .88), which suggests a limited ability to assess change over time in patients with low levels of suicidal thoughts. Taken together, the results suggest that repeated suicidal assessments over minutes to days appear to detect improvement in suicidal thoughts after ketamine infusion compared to placebo. The MADRS suicide item, BDI suicide item, and SSI5 may be particularly sensitive to rapid changes in suicidal thoughts. Published by Elsevier Ltd. C1 [Ballard, Elizabeth D.; Luckenbaugh, David A.; Richards, Erica M.; Walls, Tessa L.; Brutsche, Nancy E.; Ameli, Rezvan; Niciu, Mark J.; Vande Voort, Jennifer L.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ballard, ED (reprint author), Bldg 10,CRC Room 7-3345,10 Ctr Dr,MSC 1282, Bethesda, MD 20892 USA. EM Elizabeth.Ballard@nih.gov; luckenbd@mail.nih.gov; erica.richards@nih.gov; tessa.walls@nih.gov; brutschn@mail.nih.gov; amelir@mail.nih.gov; mark.niciu@nih.gov; VandeVoort.Jennifer@mayo.edu; zaratec@mail.nih.gov RI Niciu, Mark/J-1766-2014 OI Niciu, Mark/0000-0002-5612-3021 FU Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) [NCT00088699, 04-M-0222]; NARSAD; Brain & Behavior Mood Disorders Research Award FX Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; NCT00088699 and 04-M-0222), by a NARSAD Independent Investigator to CAZ, and by a Brain & Behavior Mood Disorders Research Award to CAZ. The NIMH, NARSAD, and the Brain & Behavior Research Foundation had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 27 TC 4 Z9 4 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 68 EP 73 DI 10.1016/j.jpsychires.2015.06.003 PG 6 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100011 PM 26228403 ER PT J AU Saligan, LN Luckenbaugh, DA Slonena, EE Machado-Vieira, R Zarate, CA AF Saligan, Leorey N. Luckenbaugh, David A. Slonena, Elizabeth E. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Development of a clinician-administered National Institutes of Health-Brief Fatigue Inventory: A measure of fatigue in the context of depressive disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Fatigue; Depression; Clinician-administered scale; Instrument development ID CANCER-RELATED FATIGUE; STRUCTURED INTERVIEW GUIDE; RATING-SCALE; BIPOLAR DISORDER; MULTIPLE-SCLEROSIS; ANTIDEPRESSANT TREATMENT; RADIATION-THERAPY; BREAST-CANCER; SYMPTOMS; SCHIZOPHRENIA AB Objective: Fatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales. Methods: Based on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity. Results: The 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001). Conclusions: Preliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression. Published by Elsevier Ltd. C1 [Luckenbaugh, David A.; Slonena, Elizabeth E.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA. RP Saligan, LN (reprint author), NINR, NIH, 3 Ctr Dr,Bldg 3,Room 5E14, Bethesda, MD 20892 USA. EM saliganl@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Nursing Research; National Institute of Mental Health of the National Institutes of Health, Bethesda, Maryland, USA FX This study was supported by the Intramural Research Programs of the National Institute of Nursing Research and the National Institute of Mental Health of the National Institutes of Health, Bethesda, Maryland, USA. The authors confirm that the funder had no influence over the study design, content of the article, or selection of this journal. NR 52 TC 1 Z9 1 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 99 EP 105 DI 10.1016/j.jpsychires.2015.06.012 PG 7 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100016 PM 26228407 ER PT J AU Santarelli, S Namendorf, C Anderzhanova, E Gerlach, T Bedenk, B Kaltwasser, S Wagner, K Labermaier, C Reichel, J Drgonova, J Czisch, M Uhr, M Schmidt, MV AF Santarelli, Sara Namendorf, Christian Anderzhanova, Elmira Gerlach, Tamara Bedenk, Benedikt Kaltwasser, Sebastian Wagner, Klaus Labermaier, Christiana Reichel, Judith Drgonova, Jana Czisch, Michael Uhr, Manfred Schmidt, Mathias V. TI The amino acid transporter SLC6A15 is a regulator of hippocampal neurochemistry and behavior SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Glutamate; Hippocampus; Translational psychiatry; Behavior ID GLUTAMATE HYPOTHESIS; V7-3 SLC6A15; RAT-BRAIN; MICE; SCHIZOPHRENIA; DEPRESSION; MEMORY; STRESS; DYSFUNCTION; PERFORMANCE AB Although mental disorders as major depression are highly prevalent worldwide their underlying causes remain elusive. Despite the high heritability of depression and a clear genetic contribution to the disease, the identification of genetic risk factors for depression has been very difficult. The first published candidate to reach genome-wide significance in depression was SLC6A15, a neuronal amino acid transporter. With a reported 1,42 fold increased risk of suffering from depression associated with a single nucleotide polymorphism (SNP) in a regulatory region of SLC6A15, the polymorphism was also found to affect hippocampal morphology, integrity, and hippocampus-dependent memory. However, the function of SLC6A15 in the brain is so far largely unknown. To address this question, we investigated if alterations in SLC6A15 expression, either using a full knockout or a targeted hippocampal overexpression, affect hippocampal neurochemistry and consequently behavior. We could show that a lack of SLC6A15 reduced hippocampal tissue levels of proline and other neutral amino acids. In parallel, we observed a decreased overall availability of tissue glutamate and glutamine, while at the same time the basal tone of extracellular glutamate in the hippocampus was increased. By contrast, SLC6A15 overexpression increased glutamate/glutamine tissue concentrations. These neurochemical alterations could be linked to behavioral abnormalities in sensorimotor gating, a key translational endophenotype relevant for many psychiatric disorders. Overall, our data supports SLC6A15 as a crucial factor controlling amino acid content in the hippocampus, thereby likely interfering with glutamatergic transmission and behavior. These findings emphasize SLC6A15 as pivotal risk factor for vulnerability to psychiatric diseases. (C) 2015 Published by Elsevier Ltd. C1 [Santarelli, Sara; Namendorf, Christian; Anderzhanova, Elmira; Gerlach, Tamara; Bedenk, Benedikt; Kaltwasser, Sebastian; Wagner, Klaus; Labermaier, Christiana; Reichel, Judith; Czisch, Michael; Uhr, Manfred; Schmidt, Mathias V.] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, D-80804 Munich, Germany. [Drgonova, Jana] NIDA, IRP, NIH, Baltimore, MD USA. RP Santarelli, S (reprint author), Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, Kraepelinstr 2-10, D-80804 Munich, Germany. EM sara_santarelli@psych.mpg.de OI Reichel, Judith M/0000-0002-3640-5697 FU Max Planck Institute of Psychiatry FX The Max Planck Institute of Psychiatry funded this study. The funding source had no involvement in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. NR 37 TC 3 Z9 3 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 261 EP 269 DI 10.1016/j.jpsychires.2015.07.012 PG 9 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100038 PM 26228428 ER PT J AU Meyers, JL Lowe, SR Eaton, NR Krueger, R Grant, BF Hasin, D AF Meyers, Jacquelyn L. Lowe, Sarah R. Eaton, Nicholas R. Krueger, Robert Grant, Bridget F. Hasin, Deborah TI Childhood maltreatment, 9/11 exposure, and latent dimensions of psychopathology: A test of stress sensitization SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE 9/11; World Trade Center; Child abuse; Child neglect; Externalizing; Internalizing; Stress sensitization; Psychopathology; Substance use; NESARC ID ALCOHOL-USE-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; ENVIRONMENTAL RISK-FACTORS; SUBSTANCE USE DISORDERS; FAMILY HISTORY METHOD; DRUG-USE DISORDERS; DSM-IV AB On September 11, 2001, a terrorist attack occurred in the U.S. (9/11). Research on 9/11 and psychiatric outcomes has focused on individual disorders rather than the broader internalizing (INT) and externalizing (EXT) domains of psychopathology, leaving unknown whether direct and indirect 9/11 exposure differentially impacted these domains rather than individual disorders. Further, whether such effects were exacerbated by earlier childhood maltreatment (i.e. stress sensitization) is unknown. 18,713 participants from a U.S. national sample with no history of psychiatric disorders prior to 9/11 were assessed using a structured in-person interview. Structural equation modeling conducted in a sample who endorsed no psychiatric history prior to 9/11, indicated that indirect exposure to 9/11 (i.e. media, friends/family) was related to both EXT (alcohol, nicotine, and cannabis dependence, and antisocial personality disorder) and INT (major depression, generalized anxiety, and post-traumatic stress disorder (PTSD)) dimensions of psychopathology (EXT: beta = 0.10, p < 0.001; INT: beta = 0.11, p < 0.001) whereas direct exposure was associated with the INT dimension only (beta = 0.11, p < 0.001). For individuals who had experienced childhood maltreatment, the risk for EXT and INT dimensions associated with 9/11 was exacerbated (Interactions: beta = 0.06, p < 0.01; beta = 0.07, p < 0.001, respectively). These findings indicate that 9/11 impacted latent liability to broad domains of psychopathology in the US general population rather than specific disorders with the exception of PTSD, which had independent effects beyond INT (as indicated by a significant (p < 0.05) improvement in modification indices). Findings also indicated that childhood maltreatment increases the risk associated with adult trauma exposure, providing further evidence for the concept of stress sensitization. (C) 2015 Published by Elsevier Ltd. C1 [Meyers, Jacquelyn L.; Lowe, Sarah R.; Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Eaton, Nicholas R.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Krueger, Robert] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. [Hasin, Deborah] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Hasin, D (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU National Institutes of Health [U01AA018111, T32MH13043] FX Grant Support: This research was funded by National Institutes of Health grants U01AA018111 (Hasin), T32MH13043 (Meyers/Link). Other: New York State Psychiatric Institute (Hasin). NR 67 TC 1 Z9 1 U1 2 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2015 VL 68 BP 337 EP 345 DI 10.1016/j.jpsychires.2015.05.005 PG 9 WC Psychiatry SC Psychiatry GA CP5WM UT WOS:000359956100047 PM 26037889 ER PT J AU Klase, Z Ortiz, A Deleage, C Mudd, JC Quinones, M Schwartzman, E Klatt, NR Canary, L Estes, JD Brenchley, JM AF Klase, Z. Ortiz, A. Deleage, C. Mudd, J. C. Quinones, M. Schwartzman, E. Klatt, N. R. Canary, L. Estes, J. D. Brenchley, J. M. TI Dysbiotic bacteria translocate in progressive SIV infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; SYSTEMIC IMMUNE ACTIVATION; T-CELL DEPLETION; HIV-INFECTION; MICROBIAL TRANSLOCATION; GUT MICROBIOME; DISEASE; MUCOSAL; REPLICATION; DIVERSITY AB Infection of gut-resident CD4(+) memory T cells during acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is associated with rapid loss of these cells and damage to the epithelial barrier. Damage to the epithelial barrier allows translocation of microbial products from the intestinal lumen into the body. Immune activation caused by these microbial products has been associated with disease progression. Although microbial translocation has been demonstrated in SIV-infected nonhuman primates, the identity of translocating bacteria has not been determined. In this study we examined the communities of bacteria both within the gastrointestinal (GI) tract and systemic tissues of both healthy and experimentally SIV-infected Asian macaques. Although there were only modest changes in the GI tract-associated microbiome resulting from infection, there is substantial dysbiosis after administration of antiretrovirals. Analysis of bacterial DNA isolated from tissues of infected animals revealed a preference for the phylum Proteobacteria, suggesting that they preferentially translocate. Consistent with this finding, we observed increased metabolic activity of Proteobacterial species within the colonic lumen of SIV-infected animals. Overall, these data provide insights into disease progression and suggest that therapies aimed at altering the composition and metabolic activity of the GI tract microbiome could benefit chronically HIV-infected individuals, particularly those on antiretroviral therapies. C1 [Klase, Z.; Ortiz, A.; Mudd, J. C.; Schwartzman, E.; Klatt, N. R.; Canary, L.; Brenchley, J. M.] NIAID, Program Barrier Immun & Repair, Immunopathogenesis Sect, LMM,NIH, Bethesda, MD 20892 USA. [Deleage, C.; Estes, J. D.] Leidos Biomed Res, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Quinones, M.] NIAID, Computat Biol Sect, Bioinformat & Computat Biosci Branch, OCICB,OSMO,OD,NIH, Bethesda, MD 20892 USA. [Klatt, N. R.] Univ Washington, Dept Pharmaceut, WaNPRC, Seattle, WA 98195 USA. RP Brenchley, JM (reprint author), NIAID, Program Barrier Immun & Repair, Immunopathogenesis Sect, LMM,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbrenchl@niaid.nih.gov FU Division of Intramural Research/NIAID/NIH FX We thank Julie Segre and Clayton Deming for significant technical assistance and the execution of the 454 sequencing. We also thank CLIC/BBC for advice and helpful discussions. Funding for this study was provided in part by the Division of Intramural Research/NIAID/NIH. The content of this publication does not necessarily reflect the views or policies of DHHS, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 49 TC 31 Z9 31 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2015 VL 8 IS 5 BP 1009 EP 1020 DI 10.1038/mi.2014.128 PG 12 WC Immunology SC Immunology GA CP5WB UT WOS:000359954600007 PM 25586559 ER PT J AU Choi, YS Gullicksrud, JA Xing, SJ Zeng, ZH Shan, Q Li, FY Love, PE Peng, WQ Xue, HH Crotty, S AF Choi, Youn Soo Gullicksrud, Jodi A. Xing, Shaojun Zeng, Zhouhao Shan, Qiang Li, Fengyin Love, Paul E. Peng, Weiqun Xue, Hai-Hui Crotty, Shane TI LEF-1 and TCF-1 orchestrate T-FH differentiation by regulating differentiation circuits upstream of the transcriptional repressor BcI6 SO NATURE IMMUNOLOGY LA English DT Article ID FOLLICULAR HELPER-CELL; B-CELLS; GERMINAL-CENTERS; MEMORY; ICOS; BCL6; CD4(+); GENERATION; T-HELPER-1; INFECTION AB Follicular helper T cells (T-FH cells) are specialized effector CD4(+) T cells that help B cells develop germinal centers (GCs) and memory. However, the transcription factors that regulate the differentiation of T-FH cells remain incompletely understood. Here we report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or ICE-1, respectively) resulted in T-FH cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of T-FH cells and the formation of GCs. Forced expression of LEE-1 enhanced T-FH differentiation. LEF-1 and TCF-1 coordinated such differentiation by two general mechanisms. First, they established the responsiveness of naive CD4(+) T cells to T-FH cell signals. Second, they promoted early T-FH differentiation via the multipronged approach of sustaining expression of the cytokine receptors IL-61R alpha and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor BcI6. C1 [Choi, Youn Soo; Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA. [Gullicksrud, Jodi A.; Xing, Shaojun; Shan, Qiang; Li, Fengyin; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Gullicksrud, Jodi A.; Xue, Hai-Hui] Univ Iowa, Carver Coll Med, Interdisciplinary Immunol Grad Program, Iowa City, IA USA. [Zeng, Zhouhao; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Love, Paul E.] NICHD, Sect Cellular & Dev Biol, NIH, Bethesda, MD USA. RP Xue, HH (reprint author), Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. EM hai-hui-xue@uiowa.edu; shane@lji.org FU American Cancer Society [RSG-11-161-01-MPC]; US National Institutes of Health [AI105351, AI112579, AI115149, AI119160, AI113806, AI109976, AI063107, AI072543, AI007485]; University of Iowa Presidential Graduate Research Fellowship program FX We thank J. Yang for help with ex vivo screening of target genes obtained from RNA-seq analysis of early TFH cells and TH1 cells; Z. Fu for help with GSEA and for the generation of heat maps; the La Jolla Institute Flow Cytometry Flow Cytometry Core Facility (C. Kim, K.V. Gunst and L. Nosworthy) and the University of Iowa Flow Cytometry Core facility (J. Fishbaugh, H. Vignes and G. Rasmussen) for cell sorting; T. Takemori (RIKEN, Research Center for Integrated Medical Sciences) for Bcl6fl/fl mice; I. Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory at the Caltech) for Tcf7-/-Lef1-/- RNA-seq; and J.T. Harty (University of Iowa) for vaccinia virus (for the Xue laboratory). Supported by the American Cancer Society (RSG-11-161-01-MPC to H.-H.X.), the US National Institutes of Health (AI105351, AI112579, AI115149 and AI119160 to H.-H.X.; AI113806 to W.P.; AI109976, AI063107 and AI072543 to S.C.; and AI007485 for support for to JAG.) and the University of Iowa Presidential Graduate Research Fellowship program (J.A.G.). NR 47 TC 37 Z9 39 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2015 VL 16 IS 9 BP 980 EP 990 DI 10.1038/ni.3226 PG 11 WC Immunology SC Immunology GA CP4UA UT WOS:000359876900016 PM 26214741 ER PT J AU Petralia, RS Wang, YX Mattson, MP Yao, PJ AF Petralia, Ronald S. Wang, Ya-Xian Mattson, Mark P. Yao, Pamela J. TI Structure, Distribution, and Function of Neuronal/Synaptic Spinules and Related Invaginating Projections SO NEUROMOLECULAR MEDICINE LA English DT Review DE Capitate projections; Filopodia; Spinule; Synapse; Synaptic plasticity; Trophospongium ID RETINAL HORIZONTAL CELLS; CENTRAL NERVOUS-SYSTEM; PLASTICITY; SYNAPSES; NUCLEUS; PLATYHELMINTHES AB Neurons and especially their synapses often project long thin processes that can invaginate neighboring neuronal or glial cells. These "invaginating projections" can occur in almost any combination of postsynaptic, presynaptic, and glial processes. Invaginating projections provide a precise mechanism for one neuron to communicate or exchange material exclusively at a highly localized site on another neuron, e.g., to regulate synaptic plasticity. The best-known types are postsynaptic projections called "spinules" that invaginate into presynaptic terminals. Spinules seem to be most prevalent at large very active synapses. Here, we present a comprehensive review of all kinds of invaginating projections associated with both neurons in general and more specifically with synapses; we describe them in all animals including simple, basal metazoans. These structures may have evolved into more elaborate structures in some higher animal groups exhibiting greater synaptic plasticity. In addition to classic spinules and filopodial invaginations, we describe a variety of lesser-known structures such as amphid microvilli, spinules in giant mossy terminals and en marron/brush synapses, the highly specialized fish retinal spinules, the trophospongium, capitate projections, and fly gnarls, as well as examples in which the entire presynaptic or postsynaptic process is invaginated. These various invaginating projections have evolved to modify the function of a particular synapse, or to channel an effect to one specific synapse or neuron, without affecting those nearby. We discuss how they function in membrane recycling, nourishment, and cell signaling and explore how they might change in aging and disease. C1 [Petralia, Ronald S.; Wang, Ya-Xian] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA. [Mattson, Mark P.; Yao, Pamela J.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Petralia, RS (reprint author), NIDCD, Adv Imaging Core, NIH, 35A Ctr Dr,Room 1E614, Bethesda, MD 20892 USA. EM petralia@nidcd.nih.gov FU Intramural Research Programs of NIDCD/NIH; NIA/NIH FX This work was supported by the Intramural Research Programs of NIDCD/NIH and NIA/NIH. NR 23 TC 2 Z9 2 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD SEP PY 2015 VL 17 IS 3 BP 211 EP 240 DI 10.1007/s12017-015-8358-6 PG 30 WC Neurosciences SC Neurosciences & Neurology GA CP0FW UT WOS:000359552200001 PM 26007200 ER PT J AU Nesvick, CL Khan, NR Mehta, GU Klimo, P AF Nesvick, Cody L. Khan, Nickalus R. Mehta, Gautam U. Klimo, Paul, Jr. TI Image Guidance in Ventricular Cerebrospinal Fluid Shunt Catheter Placement: A Systematic Review and Meta-Analysis SO NEUROSURGERY LA English DT Review ID IDIOPATHIC INTRACRANIAL HYPERTENSION; CLINICAL-RESEARCH NETWORK; GUIDED NEURONAVIGATION; ULTRASOUND GUIDANCE; PEDIATRIC-PATIENTS; RANDOMIZED-TRIAL; FAILURE RATES; HYDROCEPHALUS; ARTICLE; EXPERIENCE C1 [Nesvick, Cody L.] Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA. [Nesvick, Cody L.; Mehta, Gautam U.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Khan, Nickalus R.; Klimo, Paul, Jr.] Univ Tennessee, Ctr Hlth Sci, Dept Neurosurg, Memphis, TN 38163 USA. RP Klimo, P (reprint author), Semmes Murphey Neurol & Spine Inst, 6325 Humphreys Blvd, Memphis, TN 38120 USA. EM pklimo@semmes-murphey.com OI Mehta, Gautam/0000-0002-8009-6430 FU National Institutes of Health; NIH; Pfizer, Inc.; Doris Duke Charitable Foundation; Alexandria Real Estate Equities, Inc.; Howard Hughes Medical Research Institute; National Institute of Neurological Disorders and Stroke FX Mr Nesvick is supported by the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer, Inc., the Doris Duke Charitable Foundation, Alexandria Real Estate Equities, Inc., Mr and Mrs Joel S. Marcus and the Howard Hughes Medical Research Institute, as well as other private donors. For a complete list, please visit http://fnih.org/work/education-training-0/medical-research-scholars-prog ram. Dr Mehta is supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. NR 41 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2015 VL 77 IS 3 BP 321 EP 331 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CP2BB UT WOS:000359680700002 PM 26103441 ER PT J AU Flax, SM Wakeford, AGP Cheng, K Rice, KC Riley, AL AF Flax, Shaun M. Wakeford, Alison G. P. Cheng, Kejun Rice, Kenner C. Riley, Anthony L. TI Effect of norbinaltorphimine on a dagger(9)-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats SO PSYCHOPHARMACOLOGY LA English DT Article DE Delta(9)-Tetrahydrocannabinol; Taste avoidance; Norbinaltorphimine; Opioid; Drugs of abuse; Adolescent; Adult; Cannabinoid; Addiction ID MOTIVATIONAL PROPERTIES; DOPAMINERGIC-NEURONS; NOR-BINALTORPHIMINE; PREFRONTAL CORTEX; PLACE AVERSION; KAPPA; ETHANOL; DELTA-9-TETRAHYDROCANNABINOL; CANNABINOIDS; DRUGS AB The aversive effects of a dagger(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats. C1 [Flax, Shaun M.; Wakeford, Alison G. P.; Riley, Anthony L.] Amer Univ, Dept Psychol, Pscyhopharmacol Lab, Washington, DC 20016 USA. [Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD 20892 USA. RP Flax, SM (reprint author), Amer Univ, Dept Psychol, Pscyhopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM flaxshaun@gmail.com; alriley@american.edu FU Mellon Foundation; Dean's Graduate Research Grant; National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism FX This work was supported by a grant from the Mellon Foundation to ALR and a Dean's Graduate Research Grant to SMF. A portion of this work was supported by the intramural research programs of National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism. There are no conflicts of interest. NR 54 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2015 VL 232 IS 17 BP 3193 EP 3201 DI 10.1007/s00213-015-3970-6 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CP1TS UT WOS:000359659600008 PM 26025420 ER PT J AU Dutta, D Donaldson, JG AF Dutta, Dipannita Donaldson, Julie G. TI Sorting of Clathrin-Independent Cargo Proteins Depends on Rab35 Delivered by Clathrin-Mediated Endocytosis SO TRAFFIC LA English DT Article DE Arf6; cargo sorting; CD147; CD98; clathrin-independent endocytosis; clathrin-mediated endocytosis; lysosomes; Rab35 ID NEURITE OUTGROWTH; MEMBRANE-PROTEINS; EARLY ENDOSOMES; ARF6; PATHWAY; GTPASE; CELLS; CYTOKINESIS; TRAFFICKING; ACTIVATION AB Clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) co-exist in most cells but little is known about their communication and coordination. Here we show that when CME was inhibited, endocytosis by CIE continued but endosomal trafficking of CIE cargo proteins was altered. CIE cargo proteins that normally traffic directly into Arf6-associated tubules after internalization and avoid degradation (CD44, CD98 and CD147) now trafficked to lysosomes and were degraded. The endosomal tubules were also absent and Arf6-GTP levels were elevated. The altered trafficking, loss of the tubular endosomal network and elevated Arf6-GTP levels caused by inhibition of CME were rescued by expression of Rab35, a Rab associated with clathrin-coated vesicles, or its effector ACAPs, Arf6 GTPase activating proteins (GAP) that inactivate Arf6. Furthermore, siRNA knockdown of Rab35 recreated the phenotype of CME ablation on CIE cargo trafficking without altering endocytosis of transferrin. These observations suggest that Rab35 serves as a CME detector and that loss of CME, or Rab35 input, leads to elevated Arf6-GTP and shifts the sorting of CIE cargo proteins to lysosomes and degradation. C1 [Dutta, Dipannita; Donaldson, Julie G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM donaldsonj@helix.nih.gov FU Intramural Research Program in NHLBI at NIH [HL006130] FX We thank J. Caviston, L. Greene and L. Maldonado-Baez for comments on the manuscript. This study was performed with the assistance of the NHLBI Light Microscopy Core and NHLBI Flow Cytometry Core. This work was supported by the Intramural Research Program in the NHLBI at NIH (HL006130). The authors have no conflict of interest to declare. NR 48 TC 7 Z9 7 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-9219 EI 1600-0854 J9 TRAFFIC JI Traffic PD SEP PY 2015 VL 16 IS 9 BP 994 EP 1009 DI 10.1111/tra.12302 PG 16 WC Cell Biology SC Cell Biology GA CP6OH UT WOS:000360006500005 PM 25988331 ER PT J AU Olson, EJ Shaw, GC Hutchinson, EK Schultz-Darken, N Bolton, ID Parker, JB Morrison, JM Baxter, VK Pate, KAM Mankowski, JL Carlson, CS AF Olson, E. J. Shaw, G. C. Hutchinson, E. K. Schultz-Darken, N. Bolton, I. D. Parker, J. B. Morrison, J. M. Baxter, V. K. Pate, K. A. Metcalf Mankowski, J. L. Carlson, C. S. TI Bone Disease in the Common Marmoset: Radiographic and Histological Findings SO VETERINARY PATHOLOGY LA English DT Article DE common marmoset; Callithrix jacchus; New World primate; bone disease; rickets; fibrous osteodystrophy; osteopenia; animal model ID D-DEPENDENT RICKETS; CALLITHRIX-JACCHUS; VITAMIN-D; BIOMEDICAL-RESEARCH; FIBROUS DYSPLASIA; PAGETS-DISEASE; PATHOLOGY; MODEL; AGE; TAMARINS AB The common marmoset (Callithrix jacchus) is a New World primate that is used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease in common marmosets is well recognized, there are very few detailed descriptions in the literature that cover the range of lesions seen in these animals. For all animals used to model human disease, it is important to be aware of background lesions that may affect the interpretation of study findings. This retrospective study details bone diseases encountered in marmoset breeding colonies at 2 different institutions. Affected marmosets at Johns Hopkins University had lesions compatible with diagnoses of rickets, fibrous osteodystrophy and osteopenia. Affected marmosets at the Wisconsin National Primate Research Center exhibited severe lesions of osteoclastic bone resorption and remodeling that had an unusual distribution and were not easily categorized into a known disease entity. The purpose of this report is to document these naturally occurring skeletal lesions of common marmosets and suggest an approach to evaluating skeletal disease in prospective studies of these animals that will allow the most accurate diagnoses. C1 [Olson, E. J.; Parker, J. B.; Morrison, J. M.; Carlson, C. S.] Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USA. [Shaw, G. C.; Hutchinson, E. K.; Baxter, V. K.; Pate, K. A. Metcalf; Mankowski, J. L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Shaw, G. C.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. [Hutchinson, E. K.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Schultz-Darken, N.; Bolton, I. D.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Bolton, I. D.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Morrison, J. M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RP Carlson, CS (reprint author), Univ Minnesota, Coll Vet Med, 435 H AnSci VetMed,1988 Fitch Ave, St Paul, MN 55108 USA. EM Carls099@umn.edu FU American College of Laboratory Animal Medicine Foundation; US Department of Health and Human Services, National Institutes of Health, NIH Office of the Director [2T32OD010993-11, 5T32OD011089-38] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the American College of Laboratory Animal Medicine Foundation and the US Department of Health and Human Services, National Institutes of Health, NIH Office of the Director (grant numbers 2T32OD010993-11 and 5T32OD011089-38). NR 33 TC 1 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 2015 VL 52 IS 5 BP 883 EP 893 DI 10.1177/0300985815589354 PG 11 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA CP7PC UT WOS:000360079200011 PM 26077785 ER PT J AU Allen, JD Tom, LS Leyva, B Rustan, S Ospino, H Negron, R Torres, MI Galeas, AV AF Allen, Jennifer D. Tom, Laura S. Leyva, Bryan Rustan, Sarah Ospino, Hosffman Negron, Rosalyn Torres, Maria Idali Galeas, Ana V. TI Recruiting and Surveying Catholic Parishes for Cancer Control Initiatives: Lessons Learned From the CRUZA Implementation Study SO HEALTH PROMOTION PRACTICE LA English DT Article DE survey administration; organizational recruitment; faith-based organizations; churches; Hispanic; Latino health; implementation research ID HISPANIC WOMEN; NATIONAL CONGREGATIONS; PREVENTION PROGRAM; EDUCATION-PROGRAM; BLACK CHURCHES; PROMOTION; ORGANIZATIONS; INTERVENTIONS; BELIEFS; PROJECT AB Background. We describe activities undertaken to conduct organizational surveys among faith-based organizations in Massachusetts as part of a larger study designed to promote parish-based cancer control programs for Latinos. Method. Catholic parishes located in Massachusetts that provided Spanish-language mass were eligible for study participation. Parishes were identified through diocesan records and online directories. Prior to parish recruitment, we implemented a variety of activities to gain support from Catholic leaders at the diocesan level. We then recruited individual parishes to complete a four-part organizational survey, which assessed (A) parish leadership, (B) financial resources, (C) involvement in Hispanic Ministry, and (D) health and social service offerings. Our goal was to administer each survey component to a parish representatives who could best provide an organizational perspective on the content of each component (e.g., A = pastors, B = business managers, C = Hispanic Ministry leaders, and D = parish nurse or health ministry leader). Here, we present descriptive statistics on recruitment and survey administration processes. Results. Seventy-five percent of eligible parishes responded to the survey and of these, 92% completed all four components. Completed four-part surveys required an average of 16.6 contact attempts. There were an average of 2.1 respondents per site. Pastoral staff were the most frequent respondents (79%), but they also required the most contact attempts (M = 9.3, range = 1-27). While most interviews were completed by phone (71%), one quarter were completed during in-person site visits. Conclusions. We achieved a high survey completion rate among organizational representatives. Our lessons learned may inform efforts to engage and survey faith-based organizations for public health efforts. C1 [Allen, Jennifer D.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Tom, Laura S.; Galeas, Ana V.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Leyva, Bryan] NCI, NIH, Bethesda, MD 20892 USA. [Rustan, Sarah; Negron, Rosalyn; Torres, Maria Idali] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Sch Theol & Minist, Boston, MA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [U48DP001946]; NCI NIH HHS [U54 CA156732, U54 CA156734, U54CA156732]; NIMHD NIH HHS [R21MD005976] NR 34 TC 2 Z9 2 U1 5 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1524-8399 EI 1552-6372 J9 HEALTH PROMOT PRACT JI Health Promot. Pract. PD SEP PY 2015 VL 16 IS 5 BP 667 EP 676 DI 10.1177/1524839915582174 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP5LA UT WOS:000359922200006 PM 25878192 ER PT J AU Li, X Caprioli, D Marchant, NJ AF Li, Xuan Caprioli, Daniele Marchant, Nathan J. TI Recent updates on incubation of drug craving: a mini-review SO ADDICTION BIOLOGY LA English DT Review DE Addiction; cocaine; dopamine; glutamate; incubation; relapse ID COCAINE-SEEKING BEHAVIOR; TIME-DEPENDENT CHANGES; ENVIRONMENTAL ENRICHMENT; INDUCED REINSTATEMENT; EXTINCTION BEHAVIOR; NUCLEUS-ACCUMBENS; RATS; ABSTINENCE; WITHDRAWAL; STRESS AB Cue-induced drug craving progressively increases after prolonged withdrawal from drug self-administration in laboratory animals, a behavioral phenomenon termed incubation of drug craving.' Studies over the years have revealed several important neural mechanisms contributing to incubation of drug craving. In this mini-review, we first discuss three excellent AddictionBiology publications on incubation of drug craving in both human and laboratory animals. We then review several key publications from the past year on behavioral and mechanistic findings related to incubation of drug craving. C1 [Li, Xuan; Caprioli, Daniele; Marchant, Nathan J.] NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3010, Australia. RP Li, X (reprint author), NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM anna.li@nih.gov OI Marchant, Nathan/0000-0001-8269-0532 FU National Institute on Drug Abuse, Intramural Research Program; National Health and Medical Research Council [1053308] FX The authors are supported by the National Institute on Drug Abuse, Intramural Research Program funds to the Neurobiology of Relapse Section (PI: Yavin Shaham). N.J.M. received support from Early Career Fellowship 1053308 by the National Health and Medical Research Council. The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript. We thank Yavin Shaham for helpful comments on the manuscript. NR 40 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2015 VL 20 IS 5 BP 872 EP 876 DI 10.1111/adb.12205 PG 5 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CP1XF UT WOS:000359670200002 PM 25440081 ER PT J AU Caprioli, D Zeric, T Thorndike, EB Venniro, M AF Caprioli, Daniele Zeric, Tamara Thorndike, Eric B. Venniro, Marco TI Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration SO ADDICTION BIOLOGY LA English DT Article DE Discrete choice; drug priming; extended access; food satiety; limited access; palatable food; preference; progressive ratio; psychostimulants; self-administration ID EXCESSIVE SUGAR INTAKE; STRESS-INDUCED REINSTATEMENT; SEX-DIFFERENCES; DRUG-ADDICTION; REINFORCING EFFICACY; INTRAVENOUS HEROIN; UNLIMITED ACCESS; CHOICE PROCEDURE; RHESUS-MONKEYS; D-AMPHETAMINE AB Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hours/day) or extended (6 or 9 hours/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1-0.2mg/kg/infusion) or palatable food (five pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5-1.0mg/kg), following a satiety manipulation (palatable food exposure in the home cage) or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards. C1 [Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B.; Venniro, Marco] NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Venniro, Marco] Univ Verona, Neuropsychopharmacol Lab, Pharmacol Sect, Dept Publ Hlth & Community Med, I-37100 Verona, Italy. RP Caprioli, D (reprint author), NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM daniele.caprioli@nih.gov FU National Institute on Drug Abuse, Intramural Research Program funds FX Research was supported by the National Institute on Drug Abuse, Intramural Research Program funds to the Neurobiology of Relapse Section (Principal Investigator: Yavin Shaham). We thank Yavin Shaham for his help in the conceptualization of the project and the write-up of the paper, and Jennifer Bossert and Kimberly Fiscella for editorial comments. NR 90 TC 7 Z9 7 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2015 VL 20 IS 5 BP 913 EP 926 DI 10.1111/adb.12220 PG 14 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CP1XF UT WOS:000359670200006 PM 25582886 ER PT J AU Wiers, CE Ludwig, VU Gladwin, TE Park, SQ Heinz, A Wiers, RW Rinck, M Lindenmeyer, J Walter, H Bermpohl, F AF Wiers, Corinde E. Ludwig, Vera U. Gladwin, Thomas E. Park, Soyoung Q. Heinz, Andreas Wiers, Reinout W. Rinck, Mike Lindenmeyer, Johannes Walter, Henrik Bermpohl, Felix TI Effects of cognitive bias modification training on neural signatures of alcohol approach tendencies in male alcohol-dependent patients SO ADDICTION BIOLOGY LA English DT Article DE Addiction; alcohol dependence; approach bias; cognitive bias modification training; medial prefrontal cortex ID AUTOMATIC ACTION-TENDENCIES; CUE-INDUCED ACTIVATION; DRUG-ADDICTION; DECISION-MAKING; BRAIN CONNECTIVITY; PREFRONTAL CORTEX; VENTRAL STRIATUM; RELAPSE; REWARD; METAANALYSIS AB Alcohol-dependent patients have been shown to faster approach than avoid alcohol stimuli on the Approach Avoidance Task (AAT). This so-called alcohol approach bias has been associated with increased brain activation in the medial prefrontal cortex and nucleus accumbens. Cognitive bias modification (CBM) has been used to retrain the approach bias with the clinically relevant effect of decreasing relapse rates one year later. The effects of CBM on neural signatures of approach/avoidance tendencies remain hitherto unknown. In a double-blind placebo-controlled design, 26 alcohol-dependent in-patients were assigned to a CBM or a placebo training group. Both groups performed the AAT for three weeks: in CBM training, patients pushed away 90 percent of alcohol cues; this rate was 50 percent in placebo training. Before and after training, patients performed the AAT offline, and in a 3T magnetic resonance imaging scanner. The relevant neuroimaging contrast for the alcohol approach bias was the difference between approaching versus avoiding alcohol cues relative to soft drink cues: [(alcohol pull>alcohol push)>(soft drink pull>soft drink push)]. Before training, both groups showed significant alcohol approach bias-related activation in the medial prefrontal cortex. After training, patients in the CBM group showed stronger reductions in medial prefrontal cortex activation compared with the placebo group. Moreover, these reductions correlated with reductions in approach bias scores in the CBM group only. This suggests that CBM affects neural mechanisms involved in the automatic alcohol approach bias, which may be important for the clinical effectiveness of CBM. C1 [Wiers, Corinde E.; Ludwig, Vera U.; Heinz, Andreas; Walter, Henrik; Bermpohl, Felix] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany. [Heinz, Andreas; Walter, Henrik; Bermpohl, Felix] Charite, Berlin Ctr Adv Neuroimaging, Berlin, Germany. [Wiers, Corinde E.; Ludwig, Vera U.; Heinz, Andreas; Walter, Henrik; Bermpohl, Felix] Humboldt Univ, Berlin Sch Mind & Brain, Berlin, Germany. [Gladwin, Thomas E.; Wiers, Reinout W.] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands. [Park, Soyoung Q.] Univ Lubeck, Dept Psychol, Lubeck, Germany. [Rinck, Mike] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. [Lindenmeyer, Johannes] Salus Klin, Berlin, Germany. [Lindenmeyer, Johannes] Tech Univ Chemnitz, Berlin, Germany. RP Wiers, CE (reprint author), NIAAA, Lab Neuroimaging, NIH, 10 Ctr Dr,Room B2L124, Bethesda, MD 20892 USA. EM corinde.wiers@nih.gov RI Walter, Henrik/O-2612-2013; Rinck, Mike/A-6944-2010; OI Gladwin, Thomas/0000-0001-9538-6425 FU German Federal Ministry of Education and Research [BMBF-01KR1207C]; German Research Foundation [DFG_FOR_1617]; Berlin School of Mind and Brain; Humboldt Graduate School FX This study was supported by grants from the German Federal Ministry of Education and Research (BMBF-01KR1207C to A.H. and F.B.) and the German Research Foundation (DFG_FOR_1617 to A.H.). C.E.W. was funded by the Berlin School of Mind and Brain and Humboldt Graduate School. The authors thank Ulrike Malecki, Steffen Pawelczack, Silvia Hoffman, Natalie Becht, Jana Paeplow, Christiane Gawron, Sonja Gropper, Heiner Stuke, Jenny Parnack and Kristin Trapp for their assistance in recruitment, training and/or testing. NR 51 TC 12 Z9 12 U1 5 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2015 VL 20 IS 5 BP 990 EP 999 DI 10.1111/adb.12221 PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CP1XF UT WOS:000359670200012 PM 25639749 ER PT J AU ter Haar, NM Oswald, M Jeyaratnam, J Anton, J Barron, KS Brogan, PA Cantarini, L Galeotti, C Grateau, G Hentgen, V Hofer, M Kallinich, T Kone-Paut, I Lachmann, HJ Ozdogan, H Ozen, S Russo, R Simon, A Uziel, Y Wouters, C Feldman, BM Vastert, SJ Wulffraat, NM Benseler, SM Frenkel, J Gattorno, M Kuemmerle-Deschner, JB AF ter Haar, Nienke M. Oswald, Marlen Jeyaratnam, Jerold Anton, Jordi Barron, Karyl S. Brogan, Paul A. Cantarini, Luca Galeotti, Caroline Grateau, Gilles Hentgen, Veronique Hofer, Michael Kallinich, Tilmann Kone-Paut, Isabelle Lachmann, Helen J. Ozdogan, Huri Ozen, Seza Russo, Ricardo Simon, Anna Uziel, Yosef Wouters, Carine Feldman, Brian M. Vastert, Sebastiaan J. Wulffraat, Nico M. Benseler, Susanne M. Frenkel, Joost Gattorno, Marco Kuemmerle-Deschner, Jasmin B. TI Recommendations for the management of autoinflammatory diseases SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID JUVENILE IDIOPATHIC ARTHRITIS; MEVALONATE KINASE-DEFICIENCY; MUCKLE-WELLS SYNDROME; STANDARDIZED OPERATING PROCEDURES; BONE-MARROW-TRANSPLANTATION; DOSE GLUCOCORTICOID THERAPY; FAMILIAL HIBERNIAN FEVER; PERIODIC SYNDROME TRAPS; LONG-TERM EFFICACY; QUALITY-OF-LIFE AB Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with >= 80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD. C1 [ter Haar, Nienke M.] Univ Med Ctr Utrecht, Lab Translat Immunol, NL-3584 EA Utrecht, Netherlands. [ter Haar, Nienke M.; Vastert, Sebastiaan J.; Wulffraat, Nico M.; Benseler, Susanne M.; Gattorno, Marco] Univ Med Ctr Utrecht, Dept Paediat Immunol, NL-3584 EA Utrecht, Netherlands. [Oswald, Marlen; Kuemmerle-Deschner, Jasmin B.] Univ Tubingen Hosp, Div Paediat Rheumatol, Tubingen, Germany. [Jeyaratnam, Jerold; Frenkel, Joost] Univ Med Ctr Utrecht, Dept Paediat, NL-3584 EA Utrecht, Netherlands. [Anton, Jordi] Univ Barcelona, Paediat Rheumatol Unit, Hosp St Joan de Deu, Barcelona, Spain. [Barron, Karyl S.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. [Brogan, Paul A.] UCL Inst Child Hlth, Dept Rheumatol, London, England. [Cantarini, Luca] Univ Siena, Rheumatol Unit, Policlin Le Scotte, I-53100 Siena, Italy. [Galeotti, Caroline] Hop Bicetre, Dept Pediat Rheumatol, Reference Ctr Autoinflammatory Disorders CEREMAI, Paris, France. [Grateau, Gilles] Univ Paris 06, Hop Tenon, AP HP, Dept Internal Med, Paris, France. [Hentgen, Veronique] Ctr Hosp Versailles, French Reference Ctr Autoinflammatory Dis Childre, Le Chesnay, France. [Hofer, Michael] Univ Lausanne, Dept Paediat, Lausanne, Switzerland. [Kallinich, Tilmann] Charite, Dept Paediat Pneumol & Immunol, D-13353 Berlin, Germany. [Kone-Paut, Isabelle] Univ Paris 11, Reference Ctr Autoinflammatory Disorders CEREMAI, Bicetre Hosp, Dept Paediat Rheumatol, Paris, France. [Lachmann, Helen J.] UCL, Sch Med, Natl Amyloidosis Ctr, London W1N 8AA, England. [Ozdogan, Huri] Istanbul Univ, Cerrahpasa Ic Hastaliklari Klin, Div Rheumatol, Istanbul, Turkey. [Ozen, Seza] Hacettepe Univ, Fac Med, Dept Paediat, TR-06100 Ankara, Turkey. [Russo, Ricardo] Hosp Pediat Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina. [Simon, Anna] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands. [Uziel, Yosef] Tel Aviv Univ, Dept Paediat, Meir Med Ctr, IL-69978 Tel Aviv, Israel. [Wouters, Carine] Univ Hosp Leuven, Dept Microbiol & Immunol, Leuven, Belgium. [Feldman, Brian M.] Hosp Sick Children, Div Rheumatol, Toronto, ON M5G 1X8, Canada. [Benseler, Susanne M.] Univ Calgary, Dept Paediat, Alberta Childrens Hosp, Rheumatol, Calgary, AB T2N 1N4, Canada. [Gattorno, Marco] G Gaslini Inst Children, Div Paediat 2, Genoa, Italy. RP ter Haar, NM (reprint author), Univ Med Ctr Utrecht, Dept Paediat Immunol, Lundlaan 6, NL-3584 EA Utrecht, Netherlands. EM n.m.terhaar-2@umcutrecht.nl RI Simon, Anna/D-3757-2009; Anton, Jordi/A-9848-2017; OI Simon, Anna/0000-0002-6141-7921; Anton, Jordi/0000-0002-8792-4219; ter Haar, Nienke/0000-0001-6127-2438; Cantarini, Luca/0000-0002-7352-1275 FU European Agency for Health and Consumers (EAHC) [2011 1202] FX This project is supported by a grant from European Agency for Health and Consumers (EAHC), grant number 2011 1202. NR 84 TC 17 Z9 20 U1 4 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2015 VL 74 IS 9 BP 1636 EP 1644 DI 10.1136/annrheumdis-2015-207546 PG 9 WC Rheumatology SC Rheumatology GA CO7XY UT WOS:000359378100010 PM 26109736 ER PT J AU Ward, MM Guthrie, LC Alba, MI AF Ward, Michael M. Guthrie, Lori C. Alba, Maria I. TI Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ACUTE-PHASE REACTANTS; HEALTH-ASSESSMENT QUESTIONNAIRE; MINIMALLY IMPORTANT DIFFERENCE; ACCEPTABLE SYMPTOM STATE; DISEASE-ACTIVITY; IMPORTANT IMPROVEMENT; ACTIVITY SCORE; BACK-PAIN; RESPONSIVENESS; SENSITIVITY AB Objective Thresholds of minimal clinically important improvement (MCII) are needed to plan and interpret clinical trials. We estimated MCIIs for the rheumatoid arthritis (RA) activity measures of patient global assessment, pain score, Health Assessment Questionnaire Disability Index (HAQ), Disease Activity Score-28 (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Methods In this prospective longitudinal study, we studied 250 patients who had active RA. Disease activity measures were collected before and either 1 month (for patients treated with prednisone) or 4 months (for patients treated with disease modifying medications or biologics) after treatment escalation. Patient judgments of improvement in arthritis status were related to prospectively assessed changes in the measures. MCIIs were changes that had a specificity of 0.80 for improvement based on receiver operating characteristic curve analysis. We used bootstrapping to provide estimates with predictive validity. Results At baseline, the mean (+/- SD) DAS28-ESR (erythrocyte sedimentation rate) was 6.16 +/- 1.2 and mean SDAI was 38.6 +/- 14.8. Improvement in overall arthritis status was reported by 167 patients (66.8%). Patients were consistent in their ratings of improvement versus no change or worsening, with receiver operating characteristic curve areas >= 0.74. MCIIs with a specificity for improvement of 0.80 were: patient global assessment -18, pain score -20, HAQ -0.375, DAS28-ESR -1.2, DAS28-CRP (C-reactive protein) -1.0, SDAI -13, and CDAI -12. Conclusions MCIIs for individual core set measures were larger than previous estimates. Reporting the proportion of patients who meet these MCII thresholds can improve the interpretation of clinical trials in RA. C1 [Ward, Michael M.; Guthrie, Lori C.; Alba, Maria I.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, NIAMS, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health; NIH [RO1-AR45177] FX This study was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and NIH RO1-AR45177. NR 49 TC 10 Z9 10 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2015 VL 74 IS 9 BP 1691 EP 1696 DI 10.1136/annrheumdis-2013-205079 PG 6 WC Rheumatology SC Rheumatology GA CO7XY UT WOS:000359378100017 PM 24794149 ER PT J AU Sibley, CH Chioato, A Felix, S Colin, L Chakraborty, A Plass, N Rodriguez-Smith, J Brewer, C King, K Zalewski, C Kim, HJ Bishop, R Abrams, K Stone, D Chapelle, D Kost, B Snyder, C Butman, JA Wesley, R Goldbach-Mansky, R AF Sibley, Cailin H. Chioato, Andrea Felix, Sandra Colin, Laurence Chakraborty, Abhijit Plass, Nikki Rodriguez-Smith, Jackeline Brewer, Carmen King, Kelly Zalewski, Christopher Kim, H. Jeffrey Bishop, Rachel Abrams, Ken Stone, Deborah Chapelle, Dawn Kost, Bahar Snyder, Christopher Butman, John A. Wesley, Robert Goldbach-Mansky, Raphaela TI A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID COLD AUTOINFLAMMATORY SYNDROME; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MUCKLE-WELLS-SYNDROME; CEREBROSPINAL-FLUID; ARTICULAR SYNDROME; PERIODIC SYNDROME; EFFICACY; ANAKINRA; SAFETY; PREVENTION AB Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1 beta monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients <= 40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6. Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred. Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. C1 [Sibley, Cailin H.; Plass, Nikki; Rodriguez-Smith, Jackeline; Stone, Deborah; Chapelle, Dawn; Kost, Bahar; Snyder, Christopher; Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Chioato, Andrea; Felix, Sandra; Colin, Laurence; Chakraborty, Abhijit; Abrams, Ken] Novartis Inst BioMed Res, Basel, Switzerland. [Brewer, Carmen; King, Kelly; Zalewski, Christopher; Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA. [Bishop, Rachel] NEI, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Wesley, Robert] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMS, Translat Autoinflammatory Sect, NIH, Bldg 10 Room 6D47-B,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Novartis; Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH; Intramural Research Programs of the National Cancer Institute; National Institute on Deafness and Other Communication Disorders; National Eye Institute; NIH Clinical Center; NIH FX This study was funded by Novartis. This study was also supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH. Portions of this work were also supported by the Intramural Research Programs of the National Cancer Institute, the National Institute on Deafness and Other Communication Disorders, the National Eye Institute and the NIH Clinical Center. Ms Rodriguez-Smith's research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. NR 20 TC 6 Z9 8 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2015 VL 74 IS 9 BP 1714 EP 1719 DI 10.1136/annrheumdis-2013-204877 PG 6 WC Rheumatology SC Rheumatology GA CO7XY UT WOS:000359378100020 PM 24906637 ER PT J AU Salaga, M Polepally, PR Zielinska, M Marynowski, M Fabisiak, A Murawska, N Sobczak, K Sacharczuk, M Do Rego, JC Roth, BL Zjawiony, JK Fichna, J AF Salaga, M. Polepally, P. R. Zielinska, M. Marynowski, M. Fabisiak, A. Murawska, N. Sobczak, K. Sacharczuk, M. Do Rego, J. C. Roth, B. L. Zjawiony, J. K. Fichna, J. TI Salvinorin A analogues PR-37 and PR-38 attenuate compound 48/80-induced itch responses in mice SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID KAPPA-OPIOID RECEPTOR; ORALLY AVAILABLE SALVINORIN; REDUCES ABDOMINAL-PAIN; SCRATCHING BEHAVIOR; IN-VIVO; NALFURAFINE HYDROCHLORIDE; CANNABINOID RECEPTORS; EXPERIMENTAL COLITIS; ARRIVE GUIDELINES; MOUSE MODELS AB Background and PurposeThe opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR-37 and PR-38, exhibit antipruritic properties in mice. Experimental ApproachTo examine the antiscratch effect of PR-37 and PR-38 we used a mouse model of compound 48/80-induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR-37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice. Key ResultsPR-37 and PR-38, jnjected s.c., significantly reduced the number of compound 48/80-induced scratching behaviours in mice in a dose- and time-dependent manner. PR-38 was also active when orally administered. The antiscratch activity of PR-37 was blocked by the selective opioid receptor antagonist, nor-binaltorphimine, and that of PR-38 by the selective opioid receptor antagonist, -funaltrexamine. Conclusion and ImplicationsIn conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated. C1 [Salaga, M.; Zielinska, M.; Marynowski, M.; Fabisiak, A.; Murawska, N.; Sobczak, K.; Fichna, J.] Med Univ Lodz, Fac Med, Dept Biochem, PL-92215 Lodz, Poland. [Polepally, P. R.; Zjawiony, J. K.] Univ Mississippi, Sch Pharm, Div Pharmacognosy, Dept Biomol Sci, University, MS 38677 USA. [Polepally, P. R.; Zjawiony, J. K.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA. [Sacharczuk, M.] Polish Acad Sci, Inst Genet & Anim Breeding, Dept Mol Cytogenet, Jastrzebiec, Poland. [Do Rego, J. C.] Univ Rouen, Fac Med & Pharm, Inst Res & Innovat Biomed, Platform Behav Anal SCAC, Rouen, France. [Roth, B. L.] Univ N Carolina, Dept Pharmacol, Div Chem Biol & Med Chem, Med Sch,NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA. RP Fichna, J (reprint author), Med Univ Lodz, Fac Med, Dept Biochem, Mazowiecka 6-8, PL-92215 Lodz, Poland. EM jakub.fichna@umed.lodz.pl RI Roth, Bryan/F-3928-2010; Zielinska, Marta/S-9193-2016; Fichna, Jakub/S-6641-2016 OI Fichna, Jakub/0000-0002-8443-4417 FU NIH [R01 DA017204]; NIMH Psychoactive Drug Screening Program [PDSP-HHSN-271-2013-00017-C]; Iuventus Plus program of the Polish Ministry of Science and Higher Education [0107/IP1/2013/72]; Medical University of Lodz [502-03/1-156-04/502-14-140, 503/1-156-04/503-01]; National Science Centre [UMO-2013/11/N/NZ7/02354, UMO-2013/11/B/NZ7/01301, UMO-2014/13/B/NZ4/01179] FX Supported by NIH Grant R01 DA017204 and the NIMH Psychoactive Drug Screening Program (PDSP-HHSN-271-2013-00017-C to BR), the Iuventus Plus program of the Polish Ministry of Science and Higher Education (#0107/IP1/2013/72 to JF) and the grants from the Medical University of Lodz (502-03/1-156-04/502-14-140 to MS and 503/1-156-04/503-01 to JF) and National Science Centre (#UMO-2013/11/N/NZ7/02354 to MS; #UMO-2013/11/B/NZ7/01301 and #UMO-2014/13/B/NZ4/01179 to JF). NR 42 TC 3 Z9 3 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2015 VL 172 IS 17 BP 4331 EP 4341 DI 10.1111/bph.13212 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CO6VO UT WOS:000359295200009 PM 26040667 ER PT J AU Yu, JC Liu, YY Sandler, DP Zhou, HB AF Yu, Jichang Liu, Yanyan Sandler, Dale P. Zhou, Haibo TI Statistical inference for the additive hazards model under outcome-dependent sampling SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Additive hazards model; inverse probability weight; outcome-dependent sampling ID MAXIMUM-LIKELIHOOD-ESTIMATION; CASE-COHORT DESIGN; LOGISTIC-REGRESSION; URANIUM MINERS; DISEASE; EFFICIENCY; EXPOSURE AB Cost-effective study designs and proper inference procedures for data from such designs are always of particular interest to study investigators. In this article, we propose a biased sampling scheme: an outcome-dependent sampling (ODS) design for survival data with right censoring under the additive hazards model. We develop a weighted pseudo-score estimator for the regression parameters for the proposed design and derive the asymptotic properties of the proposed estimator. We also provide some suggestions for using the proposed method by evaluating the relative efficiency of the proposed method against simple random sampling design and derive the optimal allocation of the subsamples for the proposed design. Simulation studies show that the proposed ODS design is more powerful than other existing designs and the proposed estimator is more efficient than other estimators. We apply our method to analyze a cancer study conducted at NIEHS, the Cancer Incidence and Mortality of Uranium Miners Study, to study the risk of radon exposure to cancer. (c) 2015 Statistical Society of Canada C1 [Yu, Jichang] Zhongnan Univ Econ & Law, Sch Math & Stat, Wuhan 430073, Hubei, Peoples R China. [Liu, Yanyan] Wuhan Univ, Sch Math & Stat, Wuhan 430072, Hubei, Peoples R China. [Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Zhou, Haibo] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. RP Zhou, HB (reprint author), Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. EM zhou@bios.unc.edu OI Sandler, Dale/0000-0002-6776-0018 FU Fundamental Research Fund for the Central Universities [31541311216]; National Science Foundation of China [11171263]; NIH [R01 ES021900, P01 CA142538] FX The authors are grateful for the valuable comments and suggestions from the associate editor and the referees which drastically improved the article. This work is supported by the Fundamental Research Fund for the Central Universities 31541311216 (for Yu), National Science Foundation of China grant 11171263 (for Liu), and NIH R01 ES021900, P01 CA142538 (for Zhou). NR 39 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0319-5724 EI 1708-945X J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 2015 VL 43 IS 3 BP 436 EP 453 DI 10.1002/cjs.11257 PG 18 WC Statistics & Probability SC Mathematics GA CP2JZ UT WOS:000359704600006 PM 26379363 ER PT J AU Fogelman, D Sugar, EA Oliver, G Shah, N Klein, A Alewine, C Wang, HM Javle, M Shroff, R Wolff, RA Abbruzzese, JL Laheru, D Diaz, LA AF Fogelman, David Sugar, Elizabeth A. Oliver, George Shah, Neeraj Klein, Alison Alewine, Christine Wang, Huamin Javle, Milind Shroff, Rachna Wolff, Robert A. Abbruzzese, James L. Laheru, Daniel Diaz, Luis A., Jr. TI Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Pancreatic adenocarcinoma; Family history; BRCA; Chemotherapy; Survival ID PATHOLOGICAL COMPLETE RESPONSE; BRCA MUTATION CARRIERS; PHASE-III TRIAL; FANCONI-ANEMIA; POLY(ADP-RIBOSE) POLYMERASE; BREAST-CANCER; BRCA2-INTERACTING PROTEIN; CLINICAL CHARACTERISTICS; PLUS GEMCITABINE; OVARIAN-CANCER AB Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known. For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated. Emphasis was placed on treatment history and family history of breast, ovarian, and pancreatic cancers. To ensure a uniform metastatic population, patients treated with prior locoregional therapies (i.e., surgery or radiotherapy) were excluded as were patients with a prior history of stage I-III disease. Patients with family history or pedigree history of cancer had superior OS. This was especially true in patients with three or more relatives with either breast, ovarian, or pancreatic cancers [hazard ratio (HR) 0.49, 95 % confidence interval (CI) 0.30-0.80, p = 0.003]. First-line platinum chemotherapy was associated with a poor survival (hazard ratio for death 1.74, 95 % CI 1.12-2.71, p = 0.01) for patients without a family history of these cancers but not for those without such a history (p = 0.31). In fact, as the number of relatives with these cancers increased, the OS survival improved for individuals receiving first-line platinum therapy (HR 0.76, 95 % CI 0.65-0.89, p = 0.0004), which was not the case for those receiving other therapies (p = 0.98). Treatment with platinum chemotherapy in patients with a family history of breast, ovarian, or pancreatic cancers was associated with a longer survival, whereas platinum use in patients without such a family history of cancer was associated with poor survival. These findings suggest that family history may serve as a predictive marker for platinum use in patients with metastatic pancreatic adenocarcinoma. C1 [Diaz, Luis A., Jr.] Johns Hopkins, Ludwig Ctr Canc Genet & Therapeut, Swim Amer Lab, Baltimore, MD 21231 USA. [Sugar, Elizabeth A.; Oliver, George; Laheru, Daniel; Diaz, Luis A., Jr.] Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Klein, Alison; Alewine, Christine] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Klein, Alison; Alewine, Christine] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Sugar, Elizabeth A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Sugar, Elizabeth A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Fogelman, David; Shah, Neeraj; Javle, Milind; Shroff, Rachna; Wolff, Robert A.; Abbruzzese, James L.] Univ Texas Houston, MD Anderson Canc Ctr, Dept GI Med Oncol, Houston, TX 77030 USA. [Fogelman, David; Javle, Milind; Wolff, Robert A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77096 USA. [Sugar, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Shah, Neeraj] Staten Isl Univ Hosp, Staten Isl, NY 10305 USA. [Klein, Alison; Laheru, Daniel] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Klein, Alison] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Klein, Alison] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21231 USA. [Alewine, Christine] NCI, Dept Med Oncol, Bethesda, MD 20892 USA. [Abbruzzese, James L.] Duke Univ, Div Med Oncol, Durham, NC 27710 USA. RP Diaz, LA (reprint author), Johns Hopkins, Ludwig Ctr Canc Genet & Therapeut, Swim Amer Lab, 1650 Orleans St,CRB I Room 590, Baltimore, MD 21231 USA. EM dfogelman@mdanderson.org; esugar@jhsph.edu; George.Oliver@phhs.org; neerajshah86@gmail.com; Aklein1@jhmi.edu; alewinecc@mail.nih.gov; hmwang@mdanderson.org; mjavle@mdanderson.org; rwolff@mdanderson.org; James.abbruzzese@duke.edu; laherda@jhmi.edu; ldiaz1@jhmi.edu FU Swim Across America Laboratory at Johns Hopkins; Banyan Gate Foundation; Lustgarten Foundation for Pancreatic Cancer Research; Gastrointestinal SPORE grant [P50CA062924] FX This work is supported by The Swim Across America Laboratory at Johns Hopkins, The Banyan Gate Foundation, The Lustgarten Foundation for Pancreatic Cancer Research and Gastrointestinal SPORE grant P50CA062924 NR 31 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2015 VL 76 IS 3 BP 489 EP 498 DI 10.1007/s00280-015-2788-6 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CP3YC UT WOS:000359817800006 PM 26126726 ER PT J AU Do, K Cao, L Kang, ZG Turkbey, B Lindenberg, ML Larkins, E Holkova, B Steinberg, SM Raffeld, M Peer, CJ Figg, WD Eugeni, M Jacobs, P Choyke, P Wright, JJ Doroshow, JH Kummar, S AF Do, Khanh Cao, Liang Kang, Zhigang Turkbey, Baris Lindenberg, Maria L. Larkins, Erin Holkova, Beata Steinberg, Seth M. Raffeld, Mark Peer, Cody J. Figg, William D. Eugeni, Michelle Jacobs, Paula Choyke, Peter Wright, John J. Doroshow, James H. Kummar, Shivaani TI A Phase II Study of Sorafenib Combined With Cetuximab in EGFR-Expressing, KRAS-Mutated Metastatic Colorectal Cancer SO CLINICAL COLORECTAL CANCER LA English DT Article DE Antiangiogenic therapy; Biomarkers; Combination Therapy; Panitumumab imaging; Pharmacodynamics ID GROWTH-FACTOR RECEPTOR; REFRACTORY SOLID TUMORS; RENAL-CELL CARCINOMA; MULTIKINASE INHIBITOR; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; CHEMOTHERAPY; PANITUMUMAB; ANGIOGENESIS; BEVACIZUMAB AB KRAS-mutated colorectal cancer (CRC) responds poorly to cetuximab. Inhibiting resistance pathways with sorafenib might restore cetuximab sensitivity in KRAS-mutated CRC. We conducted a phase II study of this combination in 30 patients with metastatic CRC harboring KRAS mutations. Four patients had durable stable disease for 4 months, with stable disease in one lasting 8+ months. Additional biomarker development for patient selection is needed. Background: Mutations in the KRAS gene predict for resistance to anti-epidermal growth factor receptor (EGFR) therapies, including cetuximab. Upregulation of vascular endothelial growth factor (VEGF)-A has been implicated in resistance to anti-EGFR treatment. Abrogation of the VEGF and RAS/RAF/MEK/ERK pathways has the potential to restore cetuximab sensitivity. Patients and Methods: Adult patients with histologically documented, measurable, EGFR-expressing, KRAS-mutated metastatic colorectal cancer (mCRC) that had progressed after 5-fluorouracil-based regimens were treated with sorafenib 400 mg orally twice daily and intravenous cetuximab weekly in 28-day cycles. The primary endpoint was the response rate (complete response, partial response, and stable disease at 4 cycles). The secondary endpoints included plasma biomarker analysis of angiogenic cytokines and correlative imaging studies with dynamic contrast-enhanced magnetic resonance imaging and zirconium 89-panitumumab. Results: Of the 30 patients enrolled, 26 were evaluable for response. Of the 26 patients evaluated, 4 had stable disease at 4 cycles and 1 had stable disease at 8 cycles. The median progression-free survival was 1.84 months. The common toxicities were rash, diarrhea, and liver enzyme elevations. Of the angiogenic cytokines evaluated, only the placental growth factor increased significantly with treatment (P < .0001). No pharmacodynamic parameters were associated with the treatment response. Conclusion: We report the results of a trial that combined cetuximab and sorafenib for the treatment of KRAS-mutated mCRC, with correlative imaging studies and pharmacodynamic angiogenic cytokine profiling as downstream markers of EGFR and VEGF receptor (VEGFR) signaling. No objective responses were observed. Additional development of biomarkers for patient selection is needed to evaluate combined EGFR and VEGFR blockade as a therapeutic option in KRAS-mutated CRC. C1 [Do, Khanh; Eugeni, Michelle; Jacobs, Paula; Wright, John J.; Doroshow, James H.; Kummar, Shivaani] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Cao, Liang; Kang, Zhigang; Turkbey, Baris; Lindenberg, Maria L.; Larkins, Erin; Holkova, Beata; Steinberg, Seth M.; Raffeld, Mark; Peer, Cody J.; Figg, William D.; Choyke, Peter] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kummar, S (reprint author), NCI, Div Canc Treatment & Diag, 31 Ctr Dr,Bldg 31,Room 3A44, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute, National Institutes of Health FX This project has been funded in whole or part with federal funds from the National Cancer Institute, National Institutes of Health. 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 39 TC 7 Z9 7 U1 0 U2 7 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD SEP PY 2015 VL 14 IS 3 BP 154 EP 161 DI 10.1016/j.clcc.2015.02.007 PG 8 WC Oncology SC Oncology GA CP4JN UT WOS:000359847900004 PM 25861837 ER PT J AU Junn, C Bell, KR Shenouda, C Hoffman, JM AF Junn, Cherry Bell, Kathleen R. Shenouda, Christian Hoffman, Jeanne M. TI Symptoms of Concussion and Comorbid Disorders SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Concussion; Head injury; Neck pain; Headache; Comorbid disorders ID TRAUMATIC BRAIN-INJURY; PERSISTENT POSTCONCUSSION SYNDROME; PAROXYSMAL POSITIONAL VERTIGO; COLLEGIATE FOOTBALL PLAYERS; SPORT-RELATED CONCUSSION; MILD HEAD-INJURY; POSTTRAUMATIC HEADACHE; POSTURAL STABILITY; NCAA CONCUSSION; HIGH-SCHOOL AB Symptoms of concussion are divided into three major domains: physical, cognitive, and emotional. These symptoms including headache, neck pain, vision changes, cognitive deficits, and emotional changes can be seen immediately after the injury and usually resolve within the first 3 months. However, some of these symptoms may persist for several months afterward. Risk factors have been identified for prolonged symptoms. Certain early interventions may decrease persistent symptoms. In this chapter, we discuss common acute and persistent symptoms after concussion and provide an overview of assessment tools and management options. C1 [Junn, Cherry; Hoffman, Jeanne M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Bell, Kathleen R.] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Shenouda, Christian] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Hoffman, JM (reprint author), Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. EM jeanneh@u.washington.edu FU NIDILRR; University of Washington FX Kathleen R. Bell reports consultant fees from the University of Washington.; Jeanne M. Hoffman reports grants from NIDILRR. NR 80 TC 0 Z9 0 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD SEP PY 2015 VL 19 IS 9 AR 46 DI 10.1007/s11916-015-0519-7 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CO7QB UT WOS:000359354700005 PM 26253164 ER PT J AU Panagiotou, OA Trikalinos, TA AF Panagiotou, Orestis A. Trikalinos, Thomas A. TI On Effect Measures, Heterogeneity, and the Laws of Nature SO EPIDEMIOLOGY LA English DT Editorial Material ID GENERALIZED LINEAR-MODELS; CLINICAL-TRIALS; BINOMIAL REGRESSION; GRAPHICAL DISPLAY; RISK DIFFERENCES; METAANALYSIS; CHOICE C1 [Panagiotou, Orestis A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. [Trikalinos, Thomas A.] Brown Univ, Ctr Evidence Based Med, Providence, RI 02912 USA. [Trikalinos, Thomas A.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. RP Panagiotou, OA (reprint author), Div Canc Epidemiol & Genet, Room 7E602,9609 Med Ctr Dr, Bethesda, MD 20982 USA. EM orestis.panagiotou@nih.gov; thomas_trikalinos@brown.edu RI Panagiotou, Orestis/I-5934-2015 OI Panagiotou, Orestis/0000-0001-9604-8380 FU National Cancer Institute FX Supported by the Intramural Research Program of the National Cancer Institute. NR 25 TC 1 Z9 1 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2015 VL 26 IS 5 BP 710 EP 713 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP2SG UT WOS:000359726800013 PM 26196685 ER PT J AU Rappaport, SM Teijido, O Hoogerheide, DP Rostovtseva, TK Berezhkovskii, AM Bezrukov, SM AF Rappaport, Shay M. Teijido, Oscar Hoogerheide, David P. Rostovtseva, Tatiana K. Berezhkovskii, Alexander M. Bezrukov, Sergey M. TI Conductance hysteresis in the voltage-dependent anion channel SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Channel reconstitution; Lipid bilayers; Beta-barrel pores; Voltage gating ID MITOCHONDRIAL OUTER-MEMBRANE; ESCHERICHIA-COLI; LIPID-BILAYERS; SELECTIVE CHANNEL; CATION CHANNEL; OMPF PORIN; VDAC; RESIDUES; PROTEIN; SENSOR AB Hysteresis in the conductance of voltage-sensitive ion channels is observed when the transmembrane voltage is periodically varied with time. Although this phenomenon has been used in studies of gating of the voltage-dependent anion channel, VDAC, from the outer mitochondrial membrane for nearly four decades, full hysteresis curves have never been reported, because the focus was solely on the channel opening branches of the hysteresis loops. We studied the hysteretic response of a multichannel VDAC system to a triangular voltage ramp the frequency of which was varied over three orders of magnitude, from 0.5 mHz to 0.2 Hz. We found that in this wide frequency range the area encircled by the hysteresis curves changes by less than a factor of three, suggesting broad distribution of the characteristic times and strongly non-equilibrium behavior. At the same time, quasi-equilibrium two-state behavior is observed for hysteresis branches corresponding to VDAC opening. This enables calculation of the usual equilibrium gating parameters, gating charge and voltage of equipartitioning, which were found to be almost insensitive to the ramp frequency. To rationalize this peculiarity, we hypothesize that during voltage-induced closure and opening the system explores different regions of the complex free energy landscape, and, in the opening branch, follows quasi-equilibrium paths. C1 [Rappaport, Shay M.; Teijido, Oscar; Hoogerheide, David P.; Rostovtseva, Tatiana K.; Berezhkovskii, Alexander M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health; Human Development and Center for Information Technology; National Research Council FX The study was supported by the Intramural Research Program of the National Institutes of Health (NIH), the Eunice Kennedy Shriver National Institute of Child Health, and the Human Development and Center for Information Technology. D.P.H. held a National Research Council Research Associateship Award at the National Institute of Standards and Technology (NIST) and the NIH. Commercial materials, equipment, and instruments are identified in this work to describe the experimental procedure as completely as possible. In no case does such identification imply a recommendation or endorsement by NIST, nor does it imply that the materials, equipment, or instrument identified are necessarily the best available for the purpose. NR 52 TC 4 Z9 4 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 EI 1432-1017 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD SEP PY 2015 VL 44 IS 6 BP 465 EP 472 DI 10.1007/s00249-015-1049-2 PG 8 WC Biophysics SC Biophysics GA CO7ZI UT WOS:000359382700007 PM 26094068 ER PT J AU Rehman, AU Santos-Cortez, RLP Drummond, MC Shahzad, M Lee, K Morell, RJ Ansar, M Jan, A Wang, X Aziz, A Riazuddin, S Smith, JD Wang, GT Ahmed, ZM Gul, K Shearer, AE Smith, RJH Shendure, J Bamshad, MJ Nickerson, DA Hinnant, J Khan, SN Fisher, RA Ahmad, W Friderici, KH Riazuddin, S Friedman, TB Wilch, ES Leal, SM AF Rehman, Atteeq U. Santos-Cortez, Regie Lyn P. Drummond, Meghan C. Shahzad, Mohsin Lee, Kwanghyuk Morell, Robert J. Ansar, Muhammad Jan, Abid Wang, Xin Aziz, Abdul Riazuddin, Saima Smith, Joshua D. Wang, Gao T. Ahmed, Zubair M. Gul, Khitab Shearer, A. Eliot Smith, Richard J. H. Shendure, Jay Bamshad, Michael J. Nickerson, Deborah A. Hinnant, John Khan, Shaheen N. Fisher, Rachel A. Ahmad, Wasim Friderici, Karen H. Riazuddin, Sheikh Friedman, Thomas B. Wilch, Ellen S. Leal, Suzanne M. CA Univ Washington Ctr Mendelian TI Challenges and solutions for gene identification in the presence of familial locus heterogeneity SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NONSYNDROMIC HEARING-LOSS; LINKAGE ANALYSIS; RECESSIVE DEAFNESS; MUTATION SPECTRUM; GJB2; IMPAIRMENT; STRATEGIES; PROTEIN; HUMANS; REGION AB Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra-and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification. C1 [Rehman, Atteeq U.; Drummond, Meghan C.; Morell, Robert J.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Bethesda, MD USA. [Santos-Cortez, Regie Lyn P.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Wang, Gao T.; Leal, Suzanne M.] Baylor Coll Med, Ctr Stat Genet, Dept Mol & Human Genet, Houston, TX 77030 USA. [Shahzad, Mohsin; Riazuddin, Saima; Gul, Khitab; Khan, Shaheen N.; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Shahzad, Mohsin; Riazuddin, Saima; Ahmed, Zubair M.] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. [Ansar, Muhammad; Jan, Abid; Aziz, Abdul; Ahmad, Wasim] Quaid I Azam Univ, Dept Biochem, Fac Biol Sci, Islamabad, Pakistan. [Smith, Joshua D.; Shendure, Jay; Bamshad, Michael J.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Shearer, A. Eliot; Smith, Richard J. H.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Mol Otolaryngol & Renal Res Labs, Iowa City, IA 52242 USA. [Hinnant, John] Michigan State Univ, Dept Religious Studies, E Lansing, MI 48824 USA. [Fisher, Rachel A.; Friderici, Karen H.] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. [Friderici, Karen H.; Wilch, Ellen S.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. RP Leal, SM (reprint author), Baylor Coll Med, Ctr Stat Genet, Dept Mol & Human Genet, 1 Baylor Plaza 700D, Houston, TX 77030 USA. EM sleal@bcm.edu RI Ansar, Muhammad/H-5967-2011; OI Ansar, Muhammad/0000-0001-5891-7063; Morell, Robert/0000-0003-1537-7356; Kircher, Martin/0000-0001-9278-5471 FU National Institute on Deafness and Other Communication Disorders (NIDCD)/NIH intramural program [DC000039-18]; Higher Education Commission of Pakistan; NIH [R01 DC003544, R01 DC011803, R01 DC012564, R03 DC012434, R01 DC011651, R01 DC003594, U54 HG006493, N01-HG-65403]; International Center for Genetic Engineering and Biotechnology, Trieste, Italy [CRP/PAK08-01, 08/009]; Hearing Health Foundation FX We thank the family members who participated in this study and Dr Dennis Drayna and Dr Andrew Griffith for critical reviews of our manuscript. This study utilized the Biowulf Linux cluster at the National Institutes of Health (NIH), Bethesda, MD (http://biowulf.nih.gov). This work was supported by: the National Institute on Deafness and Other Communication Disorders (NIDCD)/NIH intramural program DC000039-18 (to TBF); the Higher Education Commission of Pakistan (to Sheikh Riazuddin and WA); NIH grants R01 DC003544 (to R. J. H. S.), R01 DC011803 and R01 DC012564 (to Saima Riazuddin and ZMA), R03 DC012434 (to ESW), R01 DC011651 and R01 DC003594 (to SML), and U54 HG006493 (to DAN); the International Center for Genetic Engineering and Biotechnology, Trieste, Italy CRP/PAK08-01 contract 08/009 (to Sheikh Riazuddin); and the Hearing Health Foundation (to ESW). Genome-wide genotyping of families (from WA and SML) was performed at the Center for Inherited Disease Research, which is funded through the NIH to The Johns Hopkins University, Contract Number N01-HG-65403. NR 35 TC 5 Z9 5 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD SEP PY 2015 VL 23 IS 9 BP 1207 EP 1215 DI 10.1038/ejhg.2014.266 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CO8UY UT WOS:000359448800018 PM 25491636 ER PT J AU Cui, CY Schlessinger, D AF Cui, Chang-Yi Schlessinger, David TI Eccrine sweat gland development and sweat secretion SO EXPERIMENTAL DERMATOLOGY LA English DT Review DE Best2; Ca2+; clear cell; dark cell; ectodysplasin; FoxA1; InsP3R2; Itpk; Nkcc1; Shh; Wnt ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR; NERVE GROWTH-FACTOR; CYSTIC-FIBROSIS; CHLORIDE SECRETION; HAIR-FOLLICLE; MICE LACKING; ULTRASTRUCTURAL-LOCALIZATION; CHOLINERGIC DIFFERENTIATION; HIDRADENITIS SUPPURATIVA AB Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca2+-dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers - for example InsP3 and Ca2+ - and downstream ion channels/transporters in the framework of a Na+-K+-Cl- cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid-base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. C1 [Cui, Chang-Yi; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Cui, CY (reprint author), NIA, Genet Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM cuic@mail.nih.gov FU National Institute on Aging FX Cui CY and Schlessinger D designed the study, reviewed the references and wrote the manuscript. This work was supported by Intramural Research Program of National Institute on Aging. NR 124 TC 8 Z9 8 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD SEP PY 2015 VL 24 IS 9 BP 644 EP 650 DI 10.1111/exd.12773 PG 7 WC Dermatology SC Dermatology GA CP3LR UT WOS:000359781100002 PM 26014472 ER PT J AU Macheret, F Bartz, TM Djousse, L Ix, JH Mukamal, KJ Zieman, SJ Siscovick, DS Tracy, RP Heckbert, SR Psaty, BM Kizer, JR AF Macheret, Fima Bartz, Traci M. Djousse, Luc Ix, Joachim H. Mukamal, Kenneth J. Zieman, Susan J. Siscovick, David S. Tracy, Russell P. Heckbert, Susan R. Psaty, Bruce M. Kizer, Jorge R. TI Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults SO HEART LA English DT Article ID MOLECULAR-WEIGHT ADIPONECTIN; CHRONIC HEART-FAILURE; CARDIOVASCULAR HEALTH; INFLAMMATION; RESISTANCE; MORTALITY; DISEASE; MECHANISMS; STROKE; AGE AB Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n= 3190; age= 74 +/- 5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. C1 [Macheret, Fima] Univ Penn, Sch Med, Penn Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Veteran Affairs San Diego Hlth Care Syst, Nephrol Sect, San Diego, CA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Kizer, JR (reprint author), Cardiovasc Clin Res Unit, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jorge.kizer@einstein.yu.edu FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG023629]; [R01 HL094555] FX This study was supported by R01 HL094555 (to Djousse, Ix, Kizer, Mukamal and Zieman). CHS supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm. NR 30 TC 13 Z9 13 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD SEP PY 2015 VL 101 IS 17 BP 1368 EP 1374 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO9DH UT WOS:000359472300006 PM 25855796 ER PT J AU Lazar, CH Kimchi, A Namburi, P Mutsuddi, M Zelinger, L Beryozkin, A Ben-Simhon, S Obolensky, A Ben-Neriah, Z Argov, Z Pikarsky, E Fellig, Y Marks-Ohana, D Ratnapriya, R Banin, E Sharon, D Swaroop, A AF Lazar, Csilla H. Kimchi, Adva Namburi, Prasanthi Mutsuddi, Mousumi Zelinger, Lina Beryozkin, Avigail Ben-Simhon, Shiran Obolensky, Alexey Ben-Neriah, Ziva Argov, Zohar Pikarsky, Eli Fellig, Yakov Marks-Ohana, Devorah Ratnapriya, Rinki Banin, Eyal Sharon, Dror Swaroop, Anand TI Nonsyndromic Early-Onset Cone-Rod Dystrophy and Limb-Girdle Muscular Dystrophy in a Consanguineous Israeli Family are Caused by Two Independent yet Linked Mutations in ALMS1 and DYSF SO HUMAN MUTATION LA English DT Article DE ALMS1; DYSF; retinal degeneration; pleiotropic phenotypes; photoreceptor; vision loss ID ALSTROM-SYNDROME; MIYOSHI MYOPATHY; GENE; DYSFERLIN; GENERATION; PHENOTYPE; SPECTRUM; OBESITY; IQCB1; DNA AB Genetic analysis of clinical phenotypes in consanguineous families is complicated by coinheritance of large DNA regions carrying independent variants. Here, we characterized a family with early onset cone-rod dystrophy (CRD) and muscular dystrophy. Homozygosity mapping (HM) followed by whole exome sequencing revealed a nonsense mutation, p.R270*, in ALMS1 and two novel potentially disease-causing missense variants, p.R1581C and p.Y2070C, in DYSF. ALMS1 and DYSF are genetically and physically linked on chromosome 2 in a genomic region suggested by HM and associated with Alstrom syndrome, which includes CRD, and with limb girdle muscular dystrophy, respectively. Affected family members lack additional systemic manifestations of Alstrom syndrome but exhibit mild muscular dystrophy. RNA-seq data did not reveal any significant variations in ALMS1 transcripts in the human retina. Our study thus implicates ALMS1 as a nonsyndromic retinal disease gene and suggests a potential role of variants in interacting cilia genes in modifying clinical phenotypes. (C) 2015 Wiley Periodicals, Inc. C1 [Lazar, Csilla H.; Zelinger, Lina; Ratnapriya, Rinki; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Lazar, Csilla H.] Univ Babes Bolyai, Interdisciplinary Res Inst Bionano Sci, Ctr Mol Biol, R-3400 Cluj Napoca, Romania. [Kimchi, Adva; Namburi, Prasanthi; Zelinger, Lina; Beryozkin, Avigail; Ben-Simhon, Shiran; Obolensky, Alexey; Marks-Ohana, Devorah; Banin, Eyal; Sharon, Dror] Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, Jerusalem, Israel. [Mutsuddi, Mousumi] Banaras Hindu Univ, Dept Mol & Human Genet, Varanasi 221005, Uttar Pradesh, India. [Ben-Neriah, Ziva] Hadassah Hebrew Univ Med Ctr, Dept Genet, Jerusalem, Israel. [Argov, Zohar] Hadassah Hebrew Univ Med Ctr, Dept Neurol, Jerusalem, Israel. [Pikarsky, Eli; Fellig, Yakov] Hadassah Hebrew Univ Med Ctr, Dept Pathol, Jerusalem, Israel. RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM banine@mail.huji.ac.il; dror.sharon1@gmail.com; swaroopa@nei.nih.gov RI Sharon, Dror/P-4539-2015; OI Sharon, Dror/0000-0002-1789-5811; Swaroop, Anand/0000-0002-1975-1141 FU United States-Israel Binational Science Foundation [2011202]; Yedidut Research Grant; National Eye Institute, National Institutes of Health [EY000473] FX Contract grant sponsors: United States-Israel Binational Science Foundation (no. 2011202, to D.S. and A.S.); Yedidut Research Grant (to E.B.); Intramural Research Program (no. EY000473) of the National Eye Institute, National Institutes of Health (to A.S.). NR 29 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2015 VL 36 IS 9 BP 836 EP 841 DI 10.1002/humu.22822 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CP2SC UT WOS:000359726400003 PM 26077327 ER PT J AU Rowland, AS Skipper, BJ Umbach, DM Rabiner, DL Campbell, RA Naftel, AJ Sandler, DP AF Rowland, Andrew S. Skipper, Betty J. Umbach, David M. Rabiner, David L. Campbell, Richard A. Naftel, Albert J. Sandler, Dale P. TI The Prevalence of ADHD in a Population-Based Sample SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADD/ADHD; Attention Deficit Disorder with Hyperactivity; prevalence; epidemiology; comorbidity ID DEFICIT HYPERACTIVITY DISORDER; DIAGNOSTIC INTERVIEW SCHEDULE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SCHOOL-AGE-CHILDREN; OF-ONSET CRITERION; IV FIELD TRIALS; VERSION DISC-R; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; EPIDEMIOLOGY AB Objective: Few studies of ADHD prevalence have used population-based samples, multiple informants, and Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria. Moreover, children who are asymptomatic while receiving ADHD medication often have been misclassified. Therefore, we conducted a population-based study to estimate the prevalence of ADHD in elementary school children using DSM-IV criteria. Method: We screened 7,587 children for ADHD. Teachers of 81% of the children completed a DSM-IV checklist. We then interviewed parents using a structured interview (DISC). Of these, 72% participated. Parent and teacher ratings were combined to determine ADHD status. We also estimated the proportion of cases attributable to other conditions. Results: Overall, 15.5% of our sample met DSM- (4th ed.; text rev., DSM-IV-TR) criteria for ADHD (95% CI [14.6%, 16.4%]); 42% of cases reported no previous diagnosis. With additional information, other conditions explained 9% of cases. Conclusion: The prevalence of ADHD in this population-based sample was considerably higher than 3% to 7%. To compare study results, the DSM criteria need standardization. C1 [Rowland, Andrew S.; Skipper, Betty J.; Campbell, Richard A.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Umbach, David M.; Sandler, Dale P.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Rabiner, David L.] Duke Univ, Durham, NC USA. [Naftel, Albert J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Rowland, AS (reprint author), Univ New Mexico, Publ Hlth Program, Dept Family & Community Med, Hlth Sci Ctr, Mail Stop 09 5060,1 Univ New Mexico, Albuquerque, NM 87131 USA. EM arowland@salud.unm.edu OI Sandler, Dale/0000-0002-6776-0018 FU NIH, National Institute of Environmental Health Sciences; NM NIEHS Center [P30 ES-012072]; RAC grant from the University of New Mexico Health Sciences Center; National Institute of Mental Health [5 R01 MH071563-01] FX The author(s) declared receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported in part by Intramural Research Programs of the NIH, National Institute of Environmental Health Sciences. Data analysis was supported, in part, by the NM NIEHS Center, P30 ES-012072, by a RAC grant from the University of New Mexico Health Sciences Center, and by 5 R01 MH071563-01 from the National Institute of Mental Health. NR 65 TC 7 Z9 7 U1 7 U2 27 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 EI 1557-1246 J9 J ATTEN DISORD JI J. Atten. Disord. PD SEP PY 2015 VL 19 IS 9 SI SI BP 741 EP 754 DI 10.1177/1087054713513799 PG 14 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA CO4TM UT WOS:000359153500002 PM 24336124 ER PT J AU Mian, ND Carter, AS Pine, DS Wakschlag, LS Briggs-Gowan, MJ AF Mian, Nicholas D. Carter, Alice S. Pine, Daniel S. Wakschlag, Lauren S. Briggs-Gowan, Margaret J. TI Development of a novel observational measure for anxiety in young children: The Anxiety Dimensional Observation Scale SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Anxiety; fear; preschool; observation; attention bias; assessment ID PRESCHOOL DISRUPTIVE BEHAVIOR; EARLY-CHILDHOOD; DIAGNOSTIC-OBSERVATION; DISORDERS; PSYCHOPATHOLOGY; RELIABILITY; INHIBITION; SYMPTOMS; EXPOSURE; TODDLERS AB BackgroundIdentifying anxiety disorders in preschool-age children represents an important clinical challenge. Observation is essential to clinical assessment and can help differentiate normative variation from clinically significant anxiety. Yet, most anxiety assessment methods for young children rely on parent-reports. The goal of this article is to present and preliminarily test the reliability and validity of a novel observational paradigm for assessing a range of fearful and anxious behaviors in young children, the Anxiety Dimensional Observation Schedule (Anx-DOS). MethodsA diverse sample of 403 children, aged 3 to 6 years, and their mothers was studied. Reliability and validity in relation to parent reports (Preschool Age Psychiatric Assessment) and known risk factors, including indicators of behavioral inhibition (latency to touch novel objects) and attention bias to threat (in the dot-probe task) were investigated. ResultsThe Anx-DOS demonstrated good inter-rater reliability and internal consistency. Evidence for convergent validity was demonstrated relative to mother-reported separation anxiety, social anxiety, phobic avoidance, trauma symptoms, and past service use. Finally, fearfulness was associated with observed latency and attention bias toward threat. ConclusionsFindings support the Anx-DOS as a method for capturing early manifestations of fearfulness and anxiety in young children. Multimethod assessments incorporating standardized methods for assessing discrete, observable manifestations of anxiety may be beneficial for early identification and clinical intervention efforts. C1 [Mian, Nicholas D.] Boston Univ, Dept Psychol & Brain Sci, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Carter, Alice S.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Pine, Daniel S.] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Wakschlag, Lauren S.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Wakschlag, Lauren S.] Northwestern Univ, Inst Policy Res, Chicago, IL 60611 USA. [Briggs-Gowan, Margaret J.] Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT 06032 USA. RP Briggs-Gowan, MJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, MC-1410,263 Farmington Ave, Farmington, CT 06032 USA. EM mbriggsgowan@uchc.edu FU National Institute of Mental Health [U01MH090301, R01MH082830]; National Institute of Mental Health Intramural Research Program FX This original article was invited by the journal as part of a special issue; it has undergone full, external peer review; Financial support for the study was provided by grants from the National Institute of Mental Health (U01MH090301 MB-G; R01MH082830 LSW) and by the National Institute of Mental Health Intramural Research Program. The authors are grateful to Barbara Danis, Grace Berman, Gerald Reid, and Ummul-Kiram Kathawalla for their thoughtful contributions to the development of the Anx-DOS. Finally, they wish to thank the many families who participated in this study and made this work possible. The authors have declared that they have no competing or potential conflicts of interest. NR 30 TC 3 Z9 3 U1 8 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2015 VL 56 IS 9 SI SI BP 1017 EP 1025 DI 10.1111/jcpp.12407 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CO7XZ UT WOS:000359378200010 PM 25773515 ER PT J AU Karasik, LB Tamis-LeMonda, CS Adolph, KE Bornstein, MH AF Karasik, Lana B. Tamis-LeMonda, Catherine S. Adolph, Karen E. Bornstein, Marc H. TI Places and Postures: A Cross-Cultural Comparison of Sitting in 5-Month-Olds SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE sitting; infants; motor development; cross-cultural ID GROSS MOTOR DEVELOPMENT; DEVELOPMENTAL SCREENING-TEST; AFRICAN INFANT PRECOCITY; MATERNAL EXPECTATIONS; CAMEROONIAN NSO; WALKING; WORLD; ETHNOTHEORIES; STIMULATION; ACHIEVEMENT AB Motor developmenttraditionally described in terms of age-related stagesis typically studied in the laboratory with participants of Western European descent. Cross-cultural studies typically focus on group differences in age-related stages relative to Western norms. We adopted a less traditional approach: We observed 5-month-olds and their mothers from six cultural groups around the world during 1 hr at home while they engaged in natural daily activities. We examined group differences in infants' sitting proficiency, everyday opportunities to practice sitting, the surfaces on which sitting took place, and mothers' proximity to sitting infants. Infants had opportunities to practice sitting in varied contextsincluding ground, infant chairs, and raised surfaces. Proficiency varied considerably within and between cultural groups: 64% of the sample sat only with support from mother or furniture and 36% sat independently. Some infants sat unsupported for 20+ min, in some cases so securely that mothers moved beyond arms' reach of their infants even while infants sat on raised surfaces. Our observations of infant sitting across cultures provide new insights into the striking range of ability, varied opportunities for practice, and contextual factors that influence the proficiency of infant motor skills. C1 [Karasik, Lana B.] CUNY Coll Staten Isl, Staten Isl, NY 10314 USA. [Karasik, Lana B.] CUNY Coll Staten Isl, Grad Ctr, Staten Isl, NY 10314 USA. [Tamis-LeMonda, Catherine S.; Adolph, Karen E.] NYU, New York, NY USA. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Karasik, LB (reprint author), CUNY Coll Staten Isl, Dept Psychol, 2800 Victory Blvd 4S-220, Staten Isl, NY 10314 USA. EM lana.karasik@csi.cuny.edu FU National Institute of Child Health and Human Develppment [R37-HD33486]; National Institute of Child Health and Human Development [R01-HD42697]; National Institutes of Health, National Institute of Child Health and Human Development 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 by National Institute of Child Health and Human Develppment Grant R37-HD33486 to Karen E. Adolph, National Institute of Child Health and Human Development Grant R01-HD42697 to Karen E. Adolph and Catherine S. Tamis-LeMonda, and by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development. NR 58 TC 1 Z9 1 U1 5 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 EI 1552-5422 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD SEP PY 2015 VL 46 IS 8 BP 1023 EP 1038 DI 10.1177/0022022115593803 PG 16 WC Psychology, Social SC Psychology GA CO8MK UT WOS:000359423300004 PM 26924852 ER PT J AU Marquardt, JU Gomez-Quiroz, L Camacho, LOA Pinna, F Lee, YH Kitade, M Dominguez, MP Castven, D Breuhahn, K Conner, EA Galle, PR Andersen, JB Factor, VM Thorgeirsson, SS AF Marquardt, Jens U. Gomez-Quiroz, Luis Camacho, Lucrecia O. Arreguin Pinna, Federico Lee, Yun-Han Kitade, Mitsuteru Dominguez, Mayrel Palestino Castven, Darko Breuhahn, Kai Conner, Elizabeth A. Galle, Peter R. Andersen, Jesper B. Factor, Valentina M. Thorgeirsson, Snorri S. TI Curcumin effectively inhibits oncogenic NF-kappa B signaling and restrains stemness features in liver cancer SO JOURNAL OF HEPATOLOGY LA English DT Article DE Liver cancer; Cancer stem cells; Hepatocarcinogenesis; NF-kappa B; Histone deacetylases ID HUMAN HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; BREAST-CANCER; CELLS; INFLAMMATION; PROGRESSION; LEUKEMIA; FIBROSIS; ALPHA; LINKS AB Background & Aims: The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kappa B signaling. Methods: We evaluated the CSCs-depleting potential of NF-kappa B inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of side population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. Results: HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-kappa B inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kappa B inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-kappa B-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-kappa B inhibition. Conclusions: These results demonstrate that blocking NF-kappa B can specifically target CSC populations and suggest a potential for combined inhibition of NF-kappa B and HDAC signaling for treatment of liver cancer patients with poor prognosis. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Marquardt, Jens U.; Lee, Yun-Han; Kitade, Mitsuteru; Conner, Elizabeth A.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Marquardt, Jens U.; Camacho, Lucrecia O. Arreguin; Castven, Darko; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55131 Mainz, Germany. [Gomez-Quiroz, Luis; Dominguez, Mayrel Palestino] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Div Ciencias Biol & Salud, Mexico City, DF, Mexico. [Pinna, Federico; Breuhahn, Kai] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany. [Andersen, Jesper B.] Univ Copenhagen, BRIC, DK-2200 Copenhagen N, Denmark. RP Marquardt, JU (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med, Langenbeckstr 1, D-55131 Mainz, Germany. EM marquarj@uni-mainz.de RI Pinna, Federico/A-8244-2017; OI Pinna, Federico/0000-0002-6815-110X; Gomez-Quiroz, Luis Enrique/0000-0002-5704-5985 FU Intramural Research Program of Center for Cancer Research, NCI; University Hospital of Mainz (MAIFOR); German Research Foundation [MA 4443/2-1]; Virtual Liver Network of BMBF [FKZ 0315761] FX This project was supported by the Intramural Research Program of the Center for Cancer Research, NCI and by internal funding of the University Hospital of Mainz (MAIFOR). J.U.M. is supported by a grant from the German Research Foundation (MA 4443/2-1). This project was supported by the Virtual Liver Network of the BMBF (to KB; FKZ 0315761). NR 50 TC 15 Z9 17 U1 2 U2 14 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 SEP PY 2015 VL 63 IS 3 BP 661 EP 669 DI 10.1016/j.jhep.2015.04.018 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP2QI UT WOS:000359721700016 PM 25937435 ER PT J AU Gelb, T Pshenichkin, S Hathaway, H Brownell, I Wolfe, B Wroblewski, J AF Gelb, T. Pshenichkin, S. Hathaway, H. Brownell, I. Wolfe, B. Wroblewski, J. TI mGlu1 Receptors and Downstream Signal Transduction Proteins as Therapeutic Targets for the Treatment of Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 09-12, 2015 CL Rotterdam, NETHERLANDS SP European Soc Dermatol Res C1 [Gelb, T.; Brownell, I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Pshenichkin, S.; Hathaway, H.; Wolfe, B.; Wroblewski, J.] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 SU 2 MA 115 BP S20 EP S20 PG 1 WC Dermatology SC Dermatology GA CP2WW UT WOS:000359739400116 ER PT J AU Namiki, T Yaguchi, T Nakamura, K Kawaguchi, M Tanemura, A Katayama, I Yokozeki, H Kawakami, Y Hearing, V AF Namiki, T. Yaguchi, T. Nakamura, K. Kawaguchi, M. Tanemura, A. Katayama, I. Yokozeki, H. Kawakami, Y. Hearing, V. TI NUAK2 amplification coupled with PTEN deficiency promote melanoma development via CDK activation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 09-12, 2015 CL Rotterdam, NETHERLANDS SP European Soc Dermatol Res C1 [Namiki, T.; Yokozeki, H.] Tokyo Med & Dent Univ, Dermatol, Tokyo, Japan. [Yaguchi, T.; Nakamura, K.; Kawakami, Y.] Keio Univ, Sch Med, Div Cellular Signaling, Inst Adv Med Res, Tokyo, Japan. [Kawaguchi, M.; Hearing, V.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Tanemura, A.; Katayama, I.] Osaka Univ, Grad Sch Med, Dermatol, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 SU 2 MA 100 BP S18 EP S18 PG 1 WC Dermatology SC Dermatology GA CP2WW UT WOS:000359739400101 ER PT J AU Ogawa, Y Kim, J Morasso, MI Udey, MC AF Ogawa, Y. Kim, J. Morasso, M. I. Udey, M. C. TI Macrophages Regulate IL-17-Associated Skin Inflammation in Mice with Dlx3-deficient keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 09-12, 2015 CL Rotterdam, NETHERLANDS SP European Soc Dermatol Res C1 [Ogawa, Y.] Yamanashi Sch Med, Dermatol, Yamanashi, Japan. [Kim, J.; Morasso, M. I.] NIAMSD, Skin Biol Lab, Bethesda, MD USA. [Udey, M. C.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2015 VL 135 SU 2 MA 427 BP S74 EP S74 PG 1 WC Dermatology SC Dermatology GA CP2WW UT WOS:000359739400427 ER PT J AU Yao, B Ikonomidou, VN Cantor, FK Ohayon, JM Duyn, J Bagnato, F AF Yao, Bing Ikonomidou, Vasiliki N. Cantor, Fredric K. Ohayon, Joan M. Duyn, Jeff Bagnato, Francesca TI Heterogeneity of Multiple Sclerosis White Matter Lesions Detected With T2*-Weighted Imaging at 7.0 Tesla SO JOURNAL OF NEUROIMAGING LA English DT Article DE Multiple sclerosis; iron; 7; 0 tesla; magnetic resonance imaging; T-2*-weighted ID HIGH-FIELD MRI; BRAIN-TISSUE; ALZHEIMERS-DISEASE; IRON CONTENT; BLACK-HOLES; CONTRAST; CHARACTERIZE; EVOLUTION; ROBUST; DAMAGE AB BACKGROUND AND PURPOSEPostmortem studies in multiple sclerosis (MS) indicate that in some white matter lesions (WM-Ls), iron is detectable with T-2*-weighted (T-2*-w), and its reciprocal R-2* relaxation rate, magnetic resonance imaging (MRI) at 7.0 Tesla (7T). This iron appears as a hyperintense rim in R-2* images surrounding a hypointense core. We describe how this observation relates to clinical/radiological characteristics of patients, in vivo. METHODSWe imaged 16 MS patients using 3T and 7T scanners. WM-Ls were identified on T-1-w/T-2-w 3T-MRIs. Thereafter, WM-Ls with a rim of elevated R-2* at 7T were counted and compared to their appearance on conventional MRIs. RESULTSWe counted 36 WM-Ls presenting a rim of elevated R-2* in 10 patients. Twenty-three (64%) lesions coincided with focal WM-Ls on T-2-w MRIs; 13 (36%) coincided with only portions of larger lesions on T-2-w images; and 20 (56%) corresponded to a hypointense chronic black hole. WM-Ls presenting a rim of elevated R-2* were seen in both relapsing-remitting patients with low disability and in those with long-standing secondary progressive MS. CONCLUSIONSWM-Ls with a contour of high R-2* are present at different MS stages, potentially representing differences in the contribution of iron in MS disease evolution. C1 [Yao, Bing; Duyn, Jeff] NINDS, Adv Magnet Resonance Imaging Sect Lab Funct & Mol, NIH, Bethesda, MD 20892 USA. [Yao, Bing] Kessler Fdn, Neuroimaging Ctr, W Orange, NJ USA. [Ikonomidou, Vasiliki N.; Cantor, Fredric K.; Ohayon, Joan M.; Bagnato, Francesca] NINDS, Neuroimmunol Branch NIB, NIH, Bethesda, MD 20892 USA. [Ikonomidou, Vasiliki N.] George Mason Univ, Volgenau Sch Engn, Dept Bioengn, Fairfax, VA 22030 USA. [Bagnato, Francesca] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. RP Bagnato, F (reprint author), Univ Maryland, Dept Neurol, 110 S,Paca St, Baltimore, MD 21201 USA. EM fbagnato@umm.edu FU NINDS-NIH, Bethesda, MD, USA FX The study was supported by the Intramural program of the NINDS-NIH, Bethesda, MD, USA. NR 31 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 EI 1552-6569 J9 J NEUROIMAGING JI J. Neuroimaging PD SEP-OCT PY 2015 VL 25 IS 5 BP 799 EP 806 DI 10.1111/jon.12193 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP3MO UT WOS:000359783900014 PM 25657078 ER PT J AU Fiedorowicz, JG Ellingrod, VL Kaplan, MJ Sen, S AF Fiedorowicz, Jess G. Ellingrod, Vicki L. Kaplan, Mariana J. Sen, Srijan TI The development of depressive symptoms during medical internship stress predicts worsening vascular function SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Biological makers; Cardiovascular diseases; Endothelial function; Major depressive disorder ID IMPAIRED ENDOTHELIAL FUNCTION; HEART-DISEASE; BIPOLAR; ASSOCIATIONS; DYSFUNCTION; ADOLESCENT; DISORDERS; MORTALITY; WOMEN; RISK AB Objective: We sought to prospectively determine whether the onset of internship stress and any subsequent depression alters physiological markers of early vascular disease Methods: We explored potential mechanisms linking stress and depression to vascular disease in a prospective cohort of 37 participants exposed to medical internship stress, an established precipitant of depressive symptomatology. Results: Change in depressive symptom score from baseline over one year of internship stress was inversely correlated with change in the reactive hyperemia index (RHI), a measure of peripheral endothelial function (r = 0.41, p = 0.01). The change in depressive symptoms in the first six months of internship was similarly related to change in RHI over one year (r = 0.38, p = 0.02). While the development of depressive symptoms did not significantly impact changes in endothelial progenitor cells (EPCs), EPCs did significantly decrease with the year of internship stress (11.9 to 3.4 cells/ml blood; p = 0.01). Conclusion: Endothelial function may be a critical link between stress, depression, and cardiovascular disease and a feasible surrogate outcome for prospective studies. (C) 2015 Elsevier Inc. All rights reserved. C1 [Fiedorowicz, Jess G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Fiedorowicz, Jess G.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Fiedorowicz, Jess G.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Ellingrod, Vicki L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Ellingrod, Vicki L.; Sen, Srijan] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Sen, Srijan] Univ Michigan, Dept Psychiat, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Sen, S (reprint author), Univ Michigan, Dept Psychiat, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. EM srijan@umich.edu FU NIMH [R01 MH101459, K23 MH095109, K23 MH083695, R01 MH082784]; Michigan Institute for Clinical and Health Research [UL1RR024986]; NHLBI [P01HL014388] FX The authors thank Srilakshmi Yalavarthi, M.S. who completed the EPC experiments. We are grateful to interns who participated in the study. Funding was provided by the NIMH (R01 MH101459, K23 MH095109) and the Michigan Institute for Clinical and Health Research (UL1RR024986). Dr. Fiedorowicz is funded by the NIMH (K23 MH083695) and the NHLBI (P01HL014388). Dr. Ellingrod is also funded by the NIMH (R01 MH082784). These funding organizations played no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation and review of the manuscript or the decision to submit the manuscript for publication. This article was prepared while Dr. Kaplan was employed at the University of Michigan. The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. NR 23 TC 0 Z9 1 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD SEP PY 2015 VL 79 IS 3 BP 243 EP 245 DI 10.1016/j.jpsychores.2015.06.004 PG 3 WC Psychiatry SC Psychiatry GA CO6NL UT WOS:000359273300013 PM 26115588 ER PT J AU Matthews, CE Moore, SC Sampson, J Blair, A Xiao, Q Keadle, SK Hollenbeck, A Park, Y AF Matthews, Charles E. Moore, Steven C. Sampson, Joshua Blair, Aaron Xiao, Qian Keadle, Sarah Kozey Hollenbeck, Albert Park, Yikyung TI Mortality Benefits for Replacing Sitting Time with Different Physical Activities SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE SEDENTARY BEHAVIOR; PREVENTION; LIFESTYLE ACTIVITIES; CANCER ID SEDENTARY BEHAVIOR; ENERGY-EXPENDITURE; ACTIVITY QUESTIONNAIRE; PROSPECTIVE COHORT; US ADULTS; ALL-CAUSE; HEALTH; WOMEN; WALKING; SPENT AB Purpose Prolonged sitting has emerged as a risk factor for early mortality, but the extent of benefit realized by replacing sitting time with exercise or activities of everyday living (i.e., nonexercise activities) is not known. Methods We prospectively followed 154,614 older adults (59-82 yr) in the National Institutes of Health-AARP Diet and Health Study who reported no major chronic diseases at baseline and reported detailed information about sitting time, exercise, and nonexercise activities. Proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (HR (95% confidence interval)) for mortality. An isotemporal modeling approach was used to estimate associations for replacing sitting time with specific types of physical activity, with separate models fit for less active and more active participants to account for nonlinear associations. Results During 6.8 yr (SD, 1.0) of follow-up, 12,201 deaths occurred. Greater sitting time (12 vs < 5 hd(-1)) was associated with increased risk for all-cause and cardiovascular mortality. In less active adults (<2 hd(-1) total activity), replacing 1 hd(-1) of sitting with an equal amount of activity was associated with lower all-cause mortality for both exercise (HR, 0.58 (0.54-0.63)) and nonexercise activities (HR, 0.70 (0.66-0.74)), including household chores, lawn and garden work, and daily walking. Among more active participants (2+ hd(-1) total activity), replacement of sitting time with purposeful exercise was associated with lower mortality (HR, 0.91 (0.88-0.94)) but not with nonexercise activity (HR, 1.00 (0.98-1.02)). Similar results were noted for cardiovascular mortality. Conclusions Physical activity intervention strategies for older adults often focus on aerobic exercise, but our findings suggest that reducing sitting time and engaging in a variety of activities is also important, particularly for inactive adults. C1 [Matthews, Charles E.; Moore, Steven C.; Xiao, Qian; Keadle, Sarah Kozey] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AR Hollenbeck Consulting, Washington, DC USA. [Park, Yikyung] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. RP Matthews, CE (reprint author), NCI Shady Grove, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E340,MSC 9704, Bethesda, MD 20892 USA. EM Charles.Matthews2@nih.gov RI Moore, Steven/D-8760-2016; OI Moore, Steven/0000-0002-8169-1661; Keadle, Sarah/0000-0002-9569-9306; Park, Yikyung/0000-0002-6281-489X FU U. S. National Institutes of Health, National Cancer Institute FX This research was supported partly by the Intramural Research Program of the U. S. National Institutes of Health, National Cancer Institute. NR 35 TC 21 Z9 21 U1 7 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 2015 VL 47 IS 9 BP 1833 EP 1840 DI 10.1249/MSS.0000000000000621 PG 8 WC Sport Sciences SC Sport Sciences GA CO9WR UT WOS:000359527500009 PM 25628179 ER PT J AU Kim, YS Sayers, TJ Colburn, NH Milner, JA Young, HA AF Kim, Young S. Sayers, Thomas J. Colburn, Nancy H. Milner, John A. Young, Howard A. TI Impact of Dietary Components on NK and Treg Cell Function for Cancer Prevention SO MOLECULAR CARCINOGENESIS LA English DT Article DE dietary components; natural killer cells; regulatory t cells; cancer prevention ID REGULATORY T-CELLS; ARYL-HYDROCARBON RECEPTOR; NATURAL-KILLER-CELLS; AGARICUS-BLAZEI MURILL; RETINOIC ACID; DENDRITIC CELLS; TUMOR-CELLS; 1,25-DIHYDROXYVITAMIN D-3; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID AB An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation of regulatory T (Treg) cells. Evidence exists that components in commonly consumed foods including vitamins A, D, and E, water-soluble constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty acids in fish oil can modulate NK cell activities, Treg cell properties, and the interactions between those two cell types. Thus, it is extremely important for cancer prevention to understand the involvement of dietary components with the early stage dynamics of interactions among these immune cells. This review addresses the potential significance of diet in supporting the function of NK cells, Treg cells, and the balance between those two cell types, which ultimately results in decreased cancer risk. Published 2015. C1 [Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20852 USA. [Sayers, Thomas J.; Colburn, Nancy H.; Young, Howard A.] NCI, Frederick Natl Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Milner, John A.] USDA ARS, Human Nutr Res Ctr, Beltsville, MD USA. RP Kim, YS (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20852 USA. FU Intramural NIH HHS [Z99 CA999999] NR 103 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2015 VL 54 IS 9 BP 669 EP 678 DI 10.1002/mc.22301 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CP2MG UT WOS:000359710600001 PM 25845339 ER PT J AU Kadosh, KC Haddad, ADM Heathcote, LC Murphy, RA Pine, DS Lau, JYF AF Kadosh, Kathrin Cohen Haddad, Anneke D. M. Heathcote, Lauren C. Murphy, Robin A. Pine, Daniel S. Lau, Jennifer Y. F. TI High trait anxiety during adolescence interferes with discriminatory context learning SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Adolescence; Anxiety; Context conditioning; Development; Individual differences ID CONDITIONED FEAR; CHILDHOOD ANXIETY; NEUTRAL FACES; DISORDERS; STARTLE; EXTINCTION; CHILDREN; THREAT; MARKER; ADULTS AB Persistent adult anxiety disorders often begin in adolescence. As emphasis on early treatment grows, we need a better understanding of how adolescent anxiety develops. In the current study, we used a fear conditioning paradigm to identify disruptions in cue and context threat-learning in 19 high anxious (HA) and 24 low anxious (LA) adolescents (12-17 years). We presented three neutral female faces (conditioned stimulus, CS) in three contingent relations with an unconditioned stimulus (UCS, a shrieking female scream) in three virtual room contexts. The degree of contingency between the CSs and the UCSs varied across the rooms: in the predictable scream condition, the scream followed the face on 100% of trials; in the unpredictable scream condition, the scream and face appeared randomly and independently of each other; in the no-scream condition the CS was presented in the absence of any UCS. We found that the LA adolescents showed higher levels of fear-potentiated startle to the faces relative to the rooms. This difference was independent of the contingency condition. The HA adolescents showed non-differential startle between the CSs, but, in contrast to previous adult data, across both cue types displayed lowest startle to the unpredictable condition and highest startle to the no-scream condition. Our study is the first to examine context conditioning in adolescents, and our results suggest that high trait anxiety early in development may be associated with an inability to disambiguate the signalling roles of cues and contexts, and a mislabelling of safety or ambiguous signals. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kadosh, Kathrin Cohen; Haddad, Anneke D. M.; Heathcote, Lauren C.; Murphy, Robin A.; Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Kadosh, Kathrin Cohen; Lau, Jennifer Y. F.] Kings Coll London, Dept Psychol, Inst Psychiat, London SE5 8AF, England. [Pine, Daniel S.] NIH, Natl Inst Mental Hlth, Bethesda, MD 20892 USA. RP Kadosh, KC (reprint author), Univ Oxford, Dept Expt Psychol, Oxford, England. EM kathrin.cohenkadosh@psy.ox.ac.uk; jennifer.lau@kcl.ac.uk OI Haddad, Anneke/0000-0003-3429-0475 FU Economic and Social Research Council grant [ES/I032959/1] FX This work was supported by a Economic and Social Research Council grant to Jennifer Y F Lau (ES/I032959/1). The authors would also like to thank Stasya Ng, Tom Sanders, and Sophie Williams for help with participant recruitment and testing. NR 34 TC 2 Z9 2 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 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2015 VL 123 BP 50 EP 57 DI 10.1016/j.nlm.2015.05.002 PG 8 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CO9QR UT WOS:000359510900007 ER PT J AU Seif, T Simms, JA Lei, K Wegner, S Bonci, A Messing, RO Hopf, FW AF Seif, Taban Simms, Jeffrey A. Lei, Kelly Wegner, Scott Bonci, Antonello Messing, Robert O. Hopf, F. Woodward TI D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID D-ASPARTATE RECEPTOR; NUCLEUS-ACCUMBENS; NMDA RECEPTOR; SYNAPTIC PLASTICITY; DRUG-ADDICTION; GLYCINE SITE; DOUBLE-BLIND; BRAIN-AREAS; MEMANTINE; ETHANOL AB There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at - 70 mV in vitro by optogenetic stimulation of mPFC-NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs. C1 [Seif, Taban; Simms, Jeffrey A.; Lei, Kelly; Wegner, Scott; Messing, Robert O.; Hopf, F. Woodward] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Messing, Robert O.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. RP Hopf, FW (reprint author), Univ Calif San Francisco, Dept Neurol, 675 Nelson Rising Lane,Room 490D, San Francisco, CA 94158 USA. EM Frederic.Hopf@ucsf.edu FU NIAAA [R21AA021445, P50AA017072]; NIDA [F32DA028065]; State of California for medical research for alcohol and substance abuse through UCSF FX This study was supported by NIAAA R21AA021445 (to FWH), NIAAA P50AA017072 (to FWH), NIDA F32DA028065 (to TS), and funds provided by the State of California for medical research for alcohol and substance abuse through UCSF (to AB and ROM). NR 60 TC 12 Z9 12 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2015 VL 40 IS 10 BP 2357 EP 2367 DI 10.1038/npp.2015.84 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CO9KE UT WOS:000359493700008 PM 25801502 ER PT J AU Umbehr, MH Gurel, B Murtola, TJ Sutcliffe, S Peskoe, SB Tangen, CM Goodman, PJ Thompson, IM Lippman, SM Lucia, MS Parnes, HL Drake, CG Nelson, WG De Marzo, AM Platz, EA AF Umbehr, M. H. Gurel, B. Murtola, T. J. Sutcliffe, S. Peskoe, S. B. Tangen, C. M. Goodman, P. J. Thompson, I. M. Lippman, S. M. Lucia, M. S. Parnes, H. L. Drake, C. G. Nelson, W. G. De Marzo, A. M. Platz, E. A. TI Intraprostatic inflammation is positively associated with serum PSA in men with PSA < 4 ng ml(-1), normal DRE and negative for prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article ID ANTIGEN LEVELS; PREVENTION TRIAL; AGGRESSIVENESS; CLASSIFICATION; HYPERPLASIA; DENSITY; BIOPSY AB BACKGROUND: Biopsies performed for elevated serum PSA often show inflammatory infiltrates. However, the influence of intraprostatic inflammation on serum PSA in men without biopsy indication and negative for prostate cancer has not been described in detail. METHODS: We studied 224 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per trial protocol, had PSA < 4 ng ml(-1), normal digital rectal examination and a biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained slides containing a mean of three biopsy cores. Inflammation measures included the extent (percentage of tissue area with inflammation) and intensity (product of scores for extent and grade) of total, acute and chronic inflammation in the entire tissue area examined, and by tissue compartment. We calculated median measures of inflammation by prebiopsy serum PSA tertile (> 0 to <= 0.8, > 0.8 to <= 1.5 and > 1.5 to < 4.0 ng ml(-1)). We estimated the association between percentage of tissue area with inflammation and natural logarithm of PSA using linear regression adjusting for age at biopsy. RESULTS: Median percentage of tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles (P-trend < 0.0001). For every 5% increase in tissue area with inflammation, log PSA increased by 0.061 ng ml(-1) (P = 0.0002). Median extent and intensity scores increased across PSA tertiles in luminal and intraepithelial compartments for acute inflammation and in stromal and intraepithelial compartments for chronic inflammation (all P-trend <= 0.05). CONCLUSIONS: In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepithelial chronic inflammation were associated with higher serum PSA. C1 [Umbehr, M. H.; Murtola, T. J.; Peskoe, S. B.; Platz, E. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Umbehr, M. H.; Drake, C. G.; Nelson, W. G.; De Marzo, A. M.; Platz, E. A.] Johns Hopkins Univ Hosp, Dept Urol, Baltimore, MD 21205 USA. [Umbehr, M. H.; Drake, C. G.; Nelson, W. G.; De Marzo, A. M.; Platz, E. A.] James Buchanan Brady Urol Inst, Baltimore, MD USA. [Umbehr, M. H.] City Hosp Triemli Zurich, Dept Urol, CH-8063 Zurich, Switzerland. [Umbehr, M. H.] Univ Zurich, Horten Ctr Patient Related Res & Knowledge Transf, Zurich, Switzerland. [Gurel, B.; De Marzo, A. M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Gurel, B.] Amasya Univ Sabuncuoglu Serefeddin Training & Res, Dept Pathol, Amasya, Turkey. [Murtola, T. J.] Univ Tampere, Dept Urol, Sch Med, Tampere Univ Hosp, FIN-33101 Tampere, Finland. [Sutcliffe, S.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Sutcliffe, S.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, Dept Surg, St Louis, MO USA. [Tangen, C. M.; Goodman, P. J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98104 USA. [Tangen, C. M.; Goodman, P. J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Thompson, I. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Lippman, S. M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Lucia, M. S.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Parnes, H. L.] NCI, Div Canc Prevent, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Drake, C. G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA. [Drake, C. G.; Nelson, W. G.; De Marzo, A. M.; Platz, E. A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Umbehr, MH (reprint author), City Hosp Triemli Zurich, Dept Urol, Birmensdorferstr 497, CH-8063 Zurich, Switzerland. EM martin.umbehr@triemli.zuerich.ch RI Gurel, Bora/A-5458-2016 OI Gurel, Bora/0000-0002-5018-8078 FU National Cancer Institute, National Institutes of Health [P01 CA108964, P50 CA58236]; Public Health Service Grants from the National Cancer Institute [U10 CA37429, UM1 CA182883]; Virginia and Warren Schwerin Scholar Award from the Patrick C Walsh Prostate Cancer Research Fund; Beth W and A Ross Myers Scholar Award from the Patrick C Walsh Prostate Cancer Research Fund FX This work was funded by the National Cancer Institute, National Institutes of Health P01 CA108964 (to IM Thompson, Project 4 EA Platz) and P50 CA58236 (to WG Nelson). The PCPT is funded by Public Health Service Grants U10 CA37429 and UM1 CA182883 (to IM Thompson/CM Tangen) from the National Cancer Institute. In addition, Dr De Marzo is the recipient of the Virginia and Warren Schwerin Scholar Award and Dr Platz is the recipient of the Beth W and A Ross Myers Scholar Award, both from the Patrick C Walsh Prostate Cancer Research Fund. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 21 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2015 VL 18 IS 3 BP 264 EP 269 DI 10.1038/pcan.2015.19 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CP1VT UT WOS:000359665400011 PM 25939516 ER PT J AU McAdams, TA Rijsdijk, FV Neiderhiser, JM Narusyte, J Shaw, DS Natsuaki, MN Spotts, EL Ganiban, JM Reiss, D Leve, LD Lichtenstein, P Eley, TC AF McAdams, T. A. Rijsdijk, F. V. Neiderhiser, J. M. Narusyte, J. Shaw, D. S. Natsuaki, M. N. Spotts, E. L. Ganiban, J. M. Reiss, David Leve, L. D. Lichtenstein, P. Eley, T. C. TI The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Adoption; children of twins; externalizing; gene-environment correlation; internalizing; parental depression ID SUBSTANCE USE DISORDERS; MATERNAL DEPRESSION; MAJOR DEPRESSION; RISK-FACTORS; ENVIRONMENTAL-INFLUENCES; ANTISOCIAL-BEHAVIOR; ADOLESCENT DEPRESSION; ASSOCIATIONS; CHILDHOOD; MOTHERS AB Background Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. Method We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. Conclusions We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations. C1 [McAdams, T. A.; Rijsdijk, F. V.; Eley, T. C.] Kings Coll London, MRC, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England. [Neiderhiser, J. M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Narusyte, J.] Karolinska Inst, Dept Clin Neusrosci, Stockholm, Sweden. [Shaw, D. S.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Natsuaki, M. N.] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. [Spotts, E. L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Ganiban, J. M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Leve, L. D.] Univ Oregon, Dept Counseling Psychol & Human Serv, Eugene, OR 97403 USA. [Leve, L. D.] Oregon Social Learning Ctr, Eugene, OR 97401 USA. [Lichtenstein, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP McAdams, TA (reprint author), Kings Coll London, London, England. EM tom.mcadams@kcl.ac.uk FU Leverhulme Trust [RPG-210]; National Institute of Mental Health [R01MH54610]; NICHD [R01HD042608]; NIDA [R01HD042608, R01 DA020585]; OBSSR [R01HD042608, R01 DA020585]; NIH [R01HD042608, R01 DA020585, R01 MH092118]; U.S. PHS [R01HD042608, R01 DA020585, R01 MH092118]; NIMH [R01 DA020585, R01 MH092118] FX The first author is supported by the Leverhulme Trust (RPG-210). The Twin and Offspring Study in Sweden was supported by Grant R01MH54610 from the National Institute of Mental Health. The Early Growth and Development Study was supported by grants R01HD042608 from NICHD, NIDA, and OBSSR, NIH, U.S. PHS, by R01 DA020585 from NIDA, NIMH, and OBSSR, NIH, U.S. PHS, by grant R01 MH092118 from NIMH, NIH, U.S. PHS. We are very grateful to the adoption agencies and families who participated in the study. We thank Xiaojia Ge, John Reid, Rand Conger, Jody Ganiban, and Laura Scaramella for their scientific contributions to the larger study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. NR 57 TC 8 Z9 8 U1 9 U2 30 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 SEP PY 2015 VL 45 IS 12 BP 2583 EP 2594 DI 10.1017/S0033291715000501 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CO6TV UT WOS:000359290100010 PM 25994116 ER PT J AU Mogg, K Salum, GA Bradley, BP Gadelha, A Pan, P Alvarenga, P Rohde, LA Pine, DS Manfro, GG AF Mogg, K. Salum, G. A. Bradley, B. P. Gadelha, A. Pan, P. Alvarenga, P. Rohde, L. A. Pine, D. S. Manfro, G. G. TI Attention network functioning in children with anxiety disorders, attention-deficit/hyperactivity disorder and non-clinical anxiety SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anxiety; attention-deficit; hyperactivity disorder; Attention Network Task; children; executive attention ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; EXECUTIVE FUNCTIONS; SELF-REGULATION; DEPRESSIVE-DISORDERS; YOUNG-ADULTS; PSYCHOPATHOLOGY; PREVALENCE; ADHD; PERFORMANCE AB Background Research with adults suggests that anxiety is associated with poor control of executive attention. However, in children, it is unclear (a) whether anxiety disorders and non-clinical anxiety are associated with deficits in executive attention, (b) whether such deficits are specific to anxiety versus other psychiatric disorders, and (c) whether there is heterogeneity among anxiety disorders (in particular, specific phobia versus other anxiety disorders). Method We examined executive attention in 860 children classified into three groups: anxiety disorders (n=67), attention-deficit/hyperactivity disorder (ADHD; n=67) and no psychiatric disorder (n=726). Anxiety disorders were subdivided into: anxiety disorders excluding specific phobia (n=43) and specific phobia (n=21). The Attention Network Task was used to assess executive attention, alerting and orienting. Results Findings indicated heterogeneity among anxiety disorders, as children with anxiety disorders (excluding specific phobia) showed impaired executive attention, compared with disorder-free children, whereas children with specific phobia showed no executive attention deficit. Among disorder-free children, executive attention was less efficient in those with high, relative to low, levels of anxiety. There were no anxiety-related deficits in orienting or alerting. Children with ADHD not only had poorer executive attention than disorder-free children, but also higher orienting scores, less accurate responses and more variable response times. Conclusions Impaired executive attention in children (reflected by difficulty inhibiting processing of task-irrelevant information) was not fully explained by general psychopathology, but instead showed specific associations with anxiety disorders (other than specific phobia) and ADHD, as well as with high levels of anxiety symptoms in disorder-free children. C1 [Mogg, K.; Bradley, B. P.] Univ Southampton, Dept Psychol, Southampton SO17 1BJ, Hants, England. [Salum, G. A.; Gadelha, A.; Pan, P.; Alvarenga, P.; Rohde, L. A.; Manfro, G. G.] Natl Inst Dev Psychiat Children & Adolescents INC, Porto Alegre, RS, Brazil. [Salum, G. A.; Rohde, L. A.; Manfro, G. G.] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Gadelha, A.; Pan, P.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Alvarenga, P.; Rohde, L. A.] Univ Sao Paulo, Sao Paulo, Brazil. [Pine, D. S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Mogg, K (reprint author), Univ Southampton, Dept Psychol, Southampton SO17 1BJ, Hants, England. EM kmogg@soton.ac.uk RI Salum, Giovanni/A-7849-2010; Mogg, Karin/C-1181-2008; Pan, Pedro/I-5167-2013; OI Salum, Giovanni/0000-0002-7537-7289; Mogg, Karin/0000-0002-2738-7378; Pan, Pedro/0000-0002-1943-6520; Gadelha, Ary/0000-0002-0993-8017 FU National Institute of Developmental Psychiatry for Children and Adolescents, a science and technology institute - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; National Council for Scientific and Technological Development) [573974/2008-0]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; Research Support Foundation of the State of Sao Paulo) [2008/57896-8]; CAPES/FAPERGS post-doctoral scholarship; CNPq FX This work is supported by the National Institute of Developmental Psychiatry for Children and Adolescents, a science and technology institute funded by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; National Council for Scientific and Technological Development; grant number 573974/2008-0) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; Research Support Foundation of the State of Sao Paulo; grant number 2008/57896-8). G.A.S. is in receipt of a CAPES/FAPERGS post-doctoral scholarship. G.G.M. and L.A.R. are in receipt of a senior research CNPq scholarship. We thank the children and families for their participation, which made this research possible; the other members of the high-risk cohort research team; the collaborators for the neuropsychological evaluation; Robert Goodman for his research support regarding the DAWBA instrument procedures; and Bacy Fleitlich-Bilyk for her clinical supervision. NR 58 TC 6 Z9 7 U1 3 U2 35 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 SEP PY 2015 VL 45 IS 12 BP 2633 EP 2646 DI 10.1017/S0033291715000586 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CO6TV UT WOS:000359290100015 PM 26234806 ER PT J AU Anvari, AA Friedman, LA Greenstein, D Gochman, P Gogtay, N Rapoport, JL AF Anvari, A. A. Friedman, L. A. Greenstein, D. Gochman, P. Gogtay, N. Rapoport, J. L. TI Hippocampal volume change relates to clinical outcome in childhood-onset schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Childhood-onset schizophrenia; hippocampus; magnetic resonance imaging; negative symptoms; psychosis ID 1ST-EPISODE PSYCHOSIS; GEOMETRICALLY ACCURATE; BRAIN MORPHOLOGY; HIGH-RISK; K-SADS; RELIABILITY; SEGMENTATION; PATHOPHYSIOLOGY; ABNORMALITIES; DYSREGULATION AB Background Fixed hippocampal volume reductions and shape abnormalities are established findings in schizophrenia, but the relationship between hippocampal volume change and clinical outcome has been relatively unexplored in schizophrenia and other psychotic disorders. In light of recent findings correlating hippocampal volume change and clinical outcome in first-episode psychotic adults, we hypothesized that fewer decreases in hippocampal volume would be associated with better functional outcome and fewer psychotic symptoms in our rare and chronically ill population of childhood-onset schizophrenia (COS) patients. Method We prospectively obtained 114 structural brain magnetic resonance images (MRIs) from 27 COS subjects, each with three or more scans between the ages of 10 and 30 years. Change in hippocampal volume, measured by fit slope and percentage change, was regressed against clinical ratings (Children's Global Assessment Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms) at last scan (controlling for sex, time between scans and total intracranial volume). Results Fewer negative symptoms were associated with less hippocampal volume decrease (fit slope: p = 0.0003, and percentage change: p = 0.005) while positive symptoms were not related to hippocampal change. There was also a relationship between improved clinical global functioning and maintained hippocampal volumes (fit slope: p = 0.025, and percentage change: p = 0.043). Conclusions These results suggest that abnormal hippocampal development in schizophrenia can be linked to global functioning and negative symptoms. The hippocampus can be considered a potential treatment target for future therapies. C1 [Anvari, A. A.; Friedman, L. A.; Greenstein, D.; Gochman, P.; Gogtay, N.; Rapoport, J. L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Anvari, AA (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM afsoon@anvari.net FU Intramural Research Program of the NIMH [03-M-0035, NCT00049738] FX This research was supported by the Intramural Research Program of the NIMH (protocol 03-M-0035, NCT00049738). The authors report no financial relationships with commercial interests. NR 49 TC 1 Z9 1 U1 5 U2 12 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 SEP PY 2015 VL 45 IS 12 BP 2667 EP 2674 DI 10.1017/S0033291715000677 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CO6TV UT WOS:000359290100018 PM 25936396 ER PT J AU Ben Dor, R Marx, CE Shampine, LJ Rubinow, DR Schmidt, PJ AF Ben Dor, Rivka Marx, Christine E. Shampine, Lawrence J. Rubinow, David R. Schmidt, Peter J. TI DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action SO PSYCHOPHARMACOLOGY LA English DT Article DE DHEA; Androsterone; Depression; Neurosteroids ID NEUROACTIVE STEROIDS; MAJOR DEPRESSION; DEHYDROEPIANDROSTERONE DHEA; DEHYDROISOANDROSTERONE SULFATE; PLASMA-CONCENTRATIONS; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; CIRCULATING LEVELS; RECEPTOR; ALLOPREGNANOLONE AB Alterations in neurosteroid secretion have been implicated in the efficacy of antidepressants. In a previous study, the adrenal androgen DHEA, a precursor of the neurosteroid androsterone, produced antidepressant and libido-enhancing effects in patients with midlife depression. To investigate the mechanisms underlying DHEA's behavioral effects in this same patient group, we examined plasma levels of four additional neurosteroids implicated in the regulation of affective behavior. Blood samples were assayed for neurosteroids in men (n = 13) and women (n = 10) with midlife depression who previously participated in a crossover study in which DHEA and placebo were administered for 6 weeks each. Depression severity was measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma levels of androsterone (ADT), allopregnanolone, pregnanolone, and pregnenolone were measured by GC-MS at baseline and week 6 of each treatment phase. Data were analyzed with repeated measures analysis of variance (ANOVA-R) and Bonferroni t tests. ADT levels (but not allopregnanolone, pregnanolone, and pregnenolone) increased after DHEA but not after placebo (F (2,42) = 3.3, p < 0.05). Post-DHEA ADT levels were higher in women than men [t (63) = 2.9, p < 0.05]. However, in both men and women who met criteria for clinical response on the CES-D, baseline ADT levels significantly increased post-DHEA, and the magnitude of the ADT increase post-DHEA treatment was similar in men and women. Consequently, it was the non-responders who accounted for the sex difference in post-DHEA plasma ADT levels, a difference that was driven by values in two women (the only female non-responders). The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA. C1 [Ben Dor, Rivka; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Publ Hlth Serv, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Marx, Christine E.; Shampine, Lawrence J.] Duke Univ, Med Ctr, Psychiat & Behav Sci, Durham, NC USA. [Marx, Christine E.; Shampine, Lawrence J.] VA Med Ctr, Durham, NC USA. [Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Publ Hlth Serv, Dept Hlth & Human Serv,NIH, Bldg 10,Room 25330,10 Ctr Dr MSC 1277, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov FU National Institute of Mental Health Intramural Research Program; VA Mid-Atlantic MIRECC; VA Career Development Transition Award; Servier FX This work was written as part of Drs. Ben Dor and Schmidt's official duties as Government employees. The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, the Department of Veterans Affairs, or the US Government. This work was supported by the National Institute of Mental Health Intramural Research Program, the VA Mid-Atlantic MIRECC, and a VA Career Development Transition Award. The NIMH had no further role in study design, the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Dr. Rubinow is a funded member of the Editorial Board for a Servier sponsored journal (Dialogues in Clinical Neuroscience). Dr. Marx is an applicant or co-applicant on pending patent applications focusing on the use of neurosteroids and derivatives for CNS disorders and for lowering cholesterol, no patents issued and no licensing in place (VA 208 waiver in place). None of the other authors have any disclosures to report. NR 47 TC 3 Z9 3 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2015 VL 232 IS 18 BP 3375 EP 3383 DI 10.1007/s00213-015-3991-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CP3WH UT WOS:000359812900008 PM 26105109 ER PT J AU Banks, N Patounakis, G Seal, P Whitcomb, BW Hartman, M Devine, K Richter, KS DeCherney, A Hill, M Levens, E AF Banks, N. Patounakis, G. Seal, P. Whitcomb, B. W. Hartman, M. Devine, K. Richter, K. S. DeCherney, A. Hill, M. Levens, E. TI FMR1 CGG REPEAT LENGTH AND ART OUTCOMES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Banks, N.; Patounakis, G.; DeCherney, A.; Hill, M.] NICHHD, NIH, Bethesda, MD 20892 USA. [Seal, P.] Univ Maryland, Baltimore, MD 21201 USA. [Whitcomb, B. W.] Univ Massachusetts, Amherst, MA 01003 USA. [Hartman, M.; Devine, K.; Richter, K. S.; Levens, E.] Shady Grove Fertil Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-287 BP E203 EP E204 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900547 ER PT J AU Banks, N Martinez, A Brown, L Hughes, J DeCherney, A Page, D Silber, SJ Muenke, M AF Banks, N. Martinez, A. Brown, L. Hughes, J. DeCherney, A. Page, D. Silber, S. J. Muenke, M. TI WHOLE EXOME SEQUENCING IN MONOZYGOTIC TWINS DISCORDANT FOR PREMATURE OVARIAN INSUFFICIENCY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Banks, N.; DeCherney, A.] NICHD, NIH, Bethesda, MD USA. [Martinez, A.; Muenke, M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Brown, L.; Hughes, J.; Page, D.] Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA USA. [Silber, S. J.] St Lukes Hosp, St Louis, MO 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-15 BP E111 EP E111 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900288 ER PT J AU Bernardi, LA De Chavez, PD Baird, D Carnethon, M Marsh, EE AF Bernardi, L. A. De Chavez, P. D. Baird, D. Carnethon, M. Marsh, E. E. TI FACTORS ASSOCIATED WITH LOW ANTI-MULLERIAN HORMONE (AMH) LEVELS IN YOUNG AFRICAN AMERICAN WOMEN (AAW). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Bernardi, L. A.; Marsh, E. E.] Northwestern Univ, Feinberg SOM, Obstet & Gynecol REI Div, Chicago, IL 60611 USA. [De Chavez, P. D.; Carnethon, M.] Northwestern Univ, Feinberg SOM, Preventat Med, Chicago, IL 60611 USA. [Baird, D.] NIEHS, Res Triangle Pk, NC 27709 USA. RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 NR 0 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 2015 VL 104 IS 3 SU S MA P-423 BP E249 EP E250 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900679 ER PT J AU Bressler, LH Bernardi, LA De Chavez, PD Baird, D Carnethon, M Marsh, EE AF Bressler, L. Hawkins Bernardi, L. A. De Chavez, P. D. Baird, D. Carnethon, M. Marsh, E. E. TI THE IMPACT OF ALCOHOL CONSUMPTION ON OVARIAN RESERVE IN REPRODUCTIVE-AGE AFRICAN AMERICAN WOMEN SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med ID ANTI-MULLERIAN HORMONE; LIFE-STYLE C1 [Bressler, L. Hawkins] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Bernardi, L. A.; De Chavez, P. D.] Northwestern Univ, Chicago, IL 60611 USA. [Baird, D.] NIEHS, Epidemiol, Res Triangle Pk, NC 27709 USA. [Carnethon, M.] Northwestern Univ, Dept Epidemiol, Chicago, IL 60611 USA. [Marsh, E. E.] Northwestern Univ, Feinberg SOM, Chicago, IL 60611 USA. RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 NR 3 TC 0 Z9 0 U1 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-77 BP E31 EP E31 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900077 ER PT J AU Charles, C Muneyyirci-Delale, O Sinaii, N Dalloul, M Stratton, P AF Charles, C. Muneyyirci-Delale, O. Sinaii, N. Dalloul, M. Stratton, P. TI EFFECT OF LUPRON VS NORETHINDRONE TREATMENT ON LIPID PROFILE OF WOMEN WITH SYMPTOMATIC ENDOMETRIOSIS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Charles, C.; Muneyyirci-Delale, O.; Dalloul, M.] Suny Downstate Med Ctr, OB GYN, Brooklyn, NY 11203 USA. [Muneyyirci-Delale, O.] Kings Cty Hosp Ctr, Ob Gyn, Brooklyn, NY USA. [Sinaii, N.] NIH, Bethesda, MD 20892 USA. [Stratton, P.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-160 BP E161 EP E161 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900427 ER PT J AU Christianson, MS Legro, R Jin, S Eisenberg, E Diamond, MP Hansen, KR Vitek, W Styer, AK Casson, PR Coutifaris, C Christman, GM Alvero, R Puscheck, EE Christy, A Zhang, H Polotsky, AJ Santoro, N AF Christianson, M. S. Legro, R. Jin, S. Eisenberg, E. Diamond, M. P. Hansen, K. R. Vitek, W. Styer, A. K. Casson, P. R. Coutifaris, C. Christman, G. M. Alvero, R. Puscheck, E. E. Christy, A. Zhang, H. Polotsky, A. J. Santoro, N. TI UTILITY OF SONOHYSTEROGRAPHY FOR TUBAL PATENCY ASSESSMENT IN THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME II TRIAL SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Legro, R.] Penn State Univ, Coll Med, University Pk, PA 16802 USA. [Jin, S.; Zhang, H.] Yale Sch Publ Hlth, New Haven, CT USA. [Eisenberg, E.] NICHD, Bethesda, MD USA. [Diamond, M. P.] Georgia Regents Univ, Augusta, GA USA. [Hansen, K. R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Vitek, W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Casson, P. R.] Northeastern Reprod Med, Colchester, VT USA. [Coutifaris, C.] Univ Penn, Philadelphia, PA 19104 USA. [Christman, G. M.] Univ Florida, Sch Med, Gainesville, FL USA. [Alvero, R.; Polotsky, A. J.; Santoro, N.] Univ Colorado, Aurora, CO USA. [Puscheck, E. E.] Wayne State Univ, Sch Med, Detroit, MI USA. [Christy, A.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-258 BP E98 EP E99 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900256 ER PT J AU Connell, MT Patounakis, G Healy, MW DeCherney, A Devine, K Widra, EA Hill, MJ AF Connell, M. T. Patounakis, G. Healy, M. W. DeCherney, A. Devine, K. Widra, E. A. Hill, M. J. TI EFFECT OF ELEVATED PROGESTERONE ON THE DAY OF TRIGGER AND PREGNANCY OUTCOMES IN GNRH AGONIST TRIGGER CYCLES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Connell, M. T.; Patounakis, G.; Healy, M. W.; DeCherney, A.; Hill, M. J.] NIH, Bethesda, MD 20892 USA. [Devine, K.] Shady Grove Fertil Ctr, Washington, DC USA. [Widra, E. A.] Shady Grove Fertil, Washington, DC 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-61 BP E24 EP E24 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900062 ER PT J AU Cox, J Malik, M Britten, JL Patel, A Nieman, L Catherino, WH AF Cox, J. Malik, M. Britten, J. L. Patel, A. Nieman, L. Catherino, W. H. TI EXTRACELLULAR MATRIX PRODUCTION DECREASES IN ULIPRISTAL ACETATE (UPA) TREATED HUMAN LEIOMYOMAS IN VITRO AND IN VIVO RESULTING IN DECREASED FIBROID SIZE SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Cox, J.; Nieman, L.] NIH, Bethesda, MD 20892 USA. [Malik, M.; Britten, J. L.; Patel, A.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-184 BP E71 EP E72 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900183 ER PT J AU Doyle, N Patounakis, G Han, T Stillman, R DeCherney, A Richter, KS AF Doyle, N. Patounakis, G. Han, T. Stillman, R. DeCherney, A. Richter, K. S. TI TOO MUCH OF A GOOD THING? HIGH MOTILE SPERM CONCENTRATIONS MAY REDUCE CONVENTIONAL INSEMINATION IN VITRO FERTILIZATION (CI-IVF) BIRTH. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Doyle, N.] Medstar Hlth, Ob Gyn, Washington, DC USA. [Patounakis, G.; DeCherney, A.] NIH, Bethesda, MD 20892 USA. [Han, T.; Stillman, R.; Richter, K. S.] Shady Grove Fertil, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-399 BP E241 EP E241 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900655 ER PT J AU Frankel, R Sjaarda, L Ye, A Michels, KA Mumford, SL AF Frankel, R. Sjaarda, L. Ye, A. Michels, K. A. Mumford, S. L. TI ASSOCIATION BETWEEN ANTIOXIDANT VITAMINS AND SYMPTOMS OF PREMENSTRUAL SYNDROME SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Frankel, R.] NICHD, DIPHR, NIH, Rockville, MD USA. [Sjaarda, L.] NICHD, Rockville, MD USA. [Ye, A.] NIH, Rockville, MD USA. [Michels, K. A.; Mumford, S. L.] NICHD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-11 BP E109 EP E110 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900285 ER PT J AU Fritz, R Kilburn, B Kohan-Ghadr, H Drewlo, S Armant, D AF Fritz, R. Kilburn, B. Kohan-Ghadr, H. Drewlo, S. Armant, D. TI GALECTIN 14 PROTECTS HUMAN TROPHOBLAST CELLS FROM OXIDATIVE STRESS AND PROMOTES EXTRAVILLOUS DIFFERENTIATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Fritz, R.; Kilburn, B.; Kohan-Ghadr, H.; Drewlo, S.; Armant, D.] Wayne State Univ, Detroit, MI USA. [Armant, D.] NICHHD, Bethesda, MD 20892 USA. NR 2 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-221 BP E85 EP E85 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900219 ER PT J AU Fru, KN Segal, T Cox, JM Mumford, SL Sharara, F AF Fru, K. N. Segal, T. Cox, J. M. Mumford, S. L. Sharara, F. TI WOMEN WITH DEFICIENT AND INSUFFICIENT VITAMIN D LEVELS HAVE LOWER IVF PREGNANCY RATES COMPARED TO WOMEN WITH REPLETE LEVELS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Fru, K. N.; Cox, J. M.] NICHD, PRAE, NIH, Bethesda, MD USA. [Segal, T.] North Shore LIJ Hlth Syst, Obstet & Gynecol, Manhasset, NY USA. [Mumford, S. L.] NICHD, NIH, Rockville, MD USA. [Sharara, F.] Virginia Ctr Reprod Med, Reston, VA 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-325 BP E216 EP E216 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900583 ER PT J AU Hansen, KR He, AW Styer, AK Butts, S Engmann, L AF Hansen, K. R. He, A. W. Styer, A. K. Butts, S. Engmann, L. CA T NICHD's Reprod Med Network TI PREDICTORS OF PREGNANCY AND LIVE-BIRTH IN COUPLES WITH UNEXPLAINED INFERTILITY FOLLOWING SUPEROVULATION-INTRAUTERINE INSEMINATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hansen, K. R.] Univ Oklahoma, Hlth Sci Ctr, Obstet & Gynecol, Oklahoma City, OK USA. [He, A. W.] Yale Univ, Sch Publ Hlth, Biostat, New Haven, CT USA. [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Butts, S.] Univ Penn, Obstet & Gynecol, Philadelphia, PA 19104 USA. [Engmann, L.] Univ Connecticut, Ctr Hlth, Obstet & Gynecol, Farmington, CT USA. [T NICHD's Reprod Med Network] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-255 BP E97 EP E98 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900253 ER PT J AU Healy, MW Patounakis, G Connell, MT Devine, K DeCherney, A Levy, M Hill, MJ AF Healy, M. W. Patounakis, G. Connell, M. T. Devine, K. DeCherney, A. Levy, M. Hill, M. J. TI DOES A FROZEN EMBRYO TRANSFER AMELIORATE THE EFFECT OF ELEVATED PROGESTERONE ON THE ENDOMETRIUM SEEN IN FRESH TRANSFER CYCLES: A PAIRED AND UNPAIRED ANALYSIS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Healy, M. W.; Patounakis, G.; Connell, M. T.; DeCherney, A.; Hill, M. J.] NIH, Bethesda, MD 20892 USA. [Devine, K.; Levy, M.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-187 BP E73 EP E73 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900186 ER PT J AU Healy, MW Schexnayder, B Connell, MT DeCherney, A Yauger, B Hill, MJ AF Healy, M. W. Schexnayder, B. Connell, M. T. DeCherney, A. Yauger, B. Hill, M. J. TI PREVENTATIVE MEASURES FOR INTRAUTERINE ADHESIONS FOLLOWING HYSTEROSCOPY: A SYSTEMATIC REVIEW AND META-ANALYSIS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Healy, M. W.; Connell, M. T.; DeCherney, A.; Hill, M. J.] NICHD, NIH, Bethesda, MD USA. [Healy, M. W.; Schexnayder, B.; Yauger, B.; Hill, M. J.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-194 BP E172 EP E172 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900456 ER PT J AU Hebisha, SA Omran, MS Sallam, HN Ahmed, AI AF Hebisha, S. A. Omran, M. S. Sallam, H. N. Ahmed, A. I. TI FOLLICULAR FLUID HOMOCYSTEINE LEVELS WITH N-ACETYL CYSTEINE SUPPLEMENTED CONTROLLED OVARIAN HYPERSTIMULATION, CORRELATION WITH OOCYTE YIELD AND ICSI CYCLE OUTCOME. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hebisha, S. A.; Omran, M. S.; Sallam, H. N.] Univ Alexandria, Fac Med, Gynecol, Alexandria, Egypt. [Ahmed, A. I.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-637 BP E324 EP E324 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900882 ER PT J AU Hebisha, SA Ahmed, AI Sallam, HN Omran, MS AF Hebisha, S. A. Ahmed, A. I. Sallam, H. N. Omran, M. S. TI DOES LASER ASSISTED HATCHING ON THAWED EMBRYO AFTER VITRIFICATION IMPROVE IMPLANTATION RATE? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hebisha, S. A.] Univ Alexandria, Fac Med, Gynecol, Alexandria, Egypt. [Ahmed, A. I.] NICHD, Obstet & Gynecol MFM Div, Perinatol Res, NIH,DHHS, Detroit, MI USA. [Sallam, H. N.] Univ Alexandria, Fac Med, Gynecol, Alexandria, Egypt. [Omran, M. S.] Univ Alexandria, Fac Med, Alexandria, Egypt. 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-581 BP E305 EP E306 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900829 ER PT J AU Hebisha, SA Omran, MS Sallam, HN Ahmed, AI AF Hebisha, S. A. Omran, M. S. Sallam, H. N. Ahmed, A. I. TI GNRH AGONIST TREATMENT IMPROVES IMPLANTATION OF FROZEN THAWED EMBRYO TRANSFER SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Hebisha, S. A.; Omran, M. S.; Sallam, H. N.] Univ Alexandria, Fac Med, Alexandria, Egypt. [Ahmed, A. I.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-484 BP E271 EP E272 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900736 ER PT J AU Louis, GMB Sapra, KJ Schisterman, E Lynch, CD Maisog, J Grantz, KL Sundaram, R AF Louis, G. M. Buck Sapra, K. J. Schisterman, E. Lynch, C. D. Maisog, J. Grantz, K. L. Sundaram, R. TI LIFESTYLE AND PREGNANCY LOSS AMONG WOMEN USING HOME PREGNANCY TEST KITS, LIFE STUDY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Louis, G. M. Buck; Sapra, K. J.; Maisog, J.; Grantz, K. L.] NICHD, Div Intramural Populat Hlth Res, Rockville, MD USA. [Schisterman, E.; Sundaram, R.] Eunice Kennedy Shriver Natl Inst Child, Rockville, MD USA. [Lynch, C. D.] Ohio State Univ, Med Ctr, Dept Reprod Med, Columbus, OH 43210 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-219 BP E85 EP E85 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900217 ER PT J AU Malik, M Cox, J Britten, J Patel, A Nieman, LK Catherino, WH AF Malik, M. Cox, J. Britten, J. Patel, A. Nieman, L. K. Catherino, W. H. TI THE SYNCHRONIZATION OF THE LEIOMYOMA EXTRACELLULAR MATRIX SIGNALING PATHWAYS OF SURGICAL SPECIMENS IN RESPONSE TO ULIPRISTAL ACETATE SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Malik, M.; Britten, J.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Obstet & Gynecol, Bethesda, MD 20814 USA. [Cox, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Patel, A.] Henry Jackson Fdn, Bethesda, MD USA. [Nieman, L. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-4 BP E3 EP E3 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900005 ER PT J AU Mendola, P Sundaram, R Louis, GMB Sun, L Wallace, ME Smarr, MM Zhu, Y Liu, D AF Mendola, P. Sundaram, R. Louis, G. M. Buck Sun, L. Wallace, M. E. Smarr, M. M. Zhu, Y. Liu, D. TI PROSPECTIVELY-MEASURED INFERTILITY AND PROXIMITY TO MAJOR ROADWAYS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Mendola, P.; Sundaram, R.; Louis, G. M. Buck; Wallace, M. E.; Smarr, M. M.; Zhu, Y.; Liu, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Sun, L.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-225 BP E86 EP E87 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900223 ER PT J AU Mumford, SL Sjaarda, L Silver, R Radin, R Mitchell, E Schisterman, E AF Mumford, S. L. Sjaarda, L. Silver, R. Radin, R. Mitchell, E. Schisterman, E. TI C-REACTIVE PROTEIN AND PREGNANCY LOSS: RESULTS FROM THE EFFECTS OF ASPIRIN IN GESTATION AND REPRODUCTION (EAGER) TRIAL. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Mumford, S. L.] NICHD, NIH, Rockville, MD USA. [Sjaarda, L.; Mitchell, E.] NICHD, Rockville, MD USA. [Silver, R.] Univ Utah, Salt Lake City, UT USA. [Radin, R.] NIH, Rockville, MD USA. [Schisterman, E.] Eunice Kennedy Shriver Natl Inst Child, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-714 BP E352 EP E352 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900959 ER PT J AU Mumford, SL Matyas, RA Silver, RM Perkins, NJ Schisterman, E AF Mumford, S. L. Matyas, R. A. Silver, R. M. Perkins, N. J. Schisterman, E. TI VITAMIN D AND PREGNANCY LOSS AND LIVE BIRTH: RESULTS FROM THE EFFECTS OF ASPIRIN IN GESTATION AND REPRODUCTION (EAGER) TRIAL SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Mumford, S. L.] NICHD, NIH, Rockville, MD USA. [Matyas, R. A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Silver, R. M.] Univ Utah, Salt Lake City, UT USA. [Perkins, N. J.] NIH, Rockville, MD USA. [Schisterman, E.] Eunice Kennedy Shriver Natl Inst Child, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-139 BP E55 EP E55 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900139 ER PT J AU Mumford, SL Alohali, A Wactawski-Wende, J AF Mumford, S. L. Alohali, A. Wactawski-Wende, J. TI DIETARY PROTEIN INTAKE AND REPRODUCTIVE HORMONES AND OVULATION: THE BIOCYCLE STUDY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Mumford, S. L.] NICHD, NIH, Rockville, MD USA. [Alohali, A.] George Mason Univ, Arlington, VA USA. [Wactawski-Wende, J.] Univ Buffalo, Buffalo, NY 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-1 BP E2 EP E2 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900002 ER PT J AU Muneyyirci-Delale, O Charles, C Sinaii, N Dalloul, M Stratton, P AF Muneyyirci-Delale, O. Charles, C. Sinaii, N. Dalloul, M. Stratton, P. TI IMPROVEMENT IN ENDOMETRIOSIS-RELATED PELVIC PAIN WITH LEUPROLIDE OR NORETHINDRONE TREATMENT SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Muneyyirci-Delale, O.; Charles, C.; Dalloul, M.] Suny Downstate Med Ctr, OB GYN, Brooklyn, NY 11203 USA. [Muneyyirci-Delale, O.] Kings Cty Hosp Ctr, Ob Gyn, Brooklyn, MD USA. [Sinaii, N.] NIH, Bethesda, MD 20892 USA. [Stratton, P.] NICHD, NIH, Bethesda, MD USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA P-168 BP E163 EP E164 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900433 ER PT J AU Owen, CM Healy, MW Patounakis, G Devine, K Widra, E DeCherney, A Hill, MJ AF Owen, C. M. Healy, M. W. Patounakis, G. Devine, K. Widra, E. DeCherney, A. Hill, M. J. TI FALLING PROGESTERONE (P) PRIOR TO TRIGGER DOES NOT AFFECT IVF PREGNANCY OUTCOME. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Owen, C. M.; Healy, M. W.; DeCherney, A.; Hill, M. J.] NIH, Bethesda, MD 20892 USA. [Devine, K.; Widra, E.] Shady Grove Fertil Ctr, Washington, DC USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA P-328 BP E217 EP E217 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900586 ER PT J AU Parikh, TP Zarek, S Dumitriu, B Young, N DeCherney, A Wolff, EF AF Parikh, T. P. Zarek, S. Dumitriu, B. Young, N. DeCherney, A. Wolff, E. F. TI TELOMERE LENGTH AND PREMATURE OVARIAN INSUFFICIENCY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Parikh, T. P.] Washington Hosp Ctr, Dept OBGYN, Washington, DC 20010 USA. [Zarek, S.; Dumitriu, B.; Young, N.; DeCherney, A.; Wolff, E. F.] NIH, 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-142 BP E56 EP E56 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900142 ER PT J AU Patel, A Malik, M Britten, JL Cox, J Catherino, WH AF Patel, A. Malik, M. Britten, J. L. Cox, J. Catherino, W. H. TI PARADOXIC EFFECT OF MIFEPRISTONE ON LEIOMYOMA EXTRACELLULAR MATRIX COMPONENT DERMATOPONTIN EXPLAINED SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Patel, A.; Malik, M.; Britten, J. L.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Obstet & Gynecol, Bethesda, MD 20814 USA. [Cox, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA P-142 BP E155 EP E155 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900409 ER PT J AU Patounakis, G Richter, KS DeCherney, A Devine, K AF Patounakis, G. Richter, K. S. DeCherney, A. Devine, K. TI PRE-WASH SPERM MORPHOLOGY PREDICTS IUI OUTCOMES BY PREDICTING POST-WASH TOTAL MOTILE SPERM COUNT (TMSC): AN ANALYSIS OF 26,373 IUI CYCLES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Patounakis, G.; DeCherney, A.] NIH, Bethesda, MD 20892 USA. [Richter, K. S.; Devine, K.] Shady Grove Fertil, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-394 BP E239 EP E240 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900651 ER PT J AU Patounakis, G Devine, K Whitcomb, BW DeCherney, A Levy, MJ AF Patounakis, G. Devine, K. Whitcomb, B. W. DeCherney, A. Levy, M. J. TI SEMEN PARAMETERS DO NOT HAVE A CLINICALLY SIGNIFICANT EFFECT ON ICSI CYCLE OUTCOMES: AN ANALYSIS USING 2,861 SHARED OOCYTE DONOR RECIPIENT CYCLES TO CONTROL FOR EGG FACTORS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Patounakis, G.; DeCherney, A.] NIH, Bethesda, MD 20892 USA. [Devine, K.; Levy, M. J.] Shady Grove Fertil, Rockville, MD USA. [Whitcomb, B. W.] Univ Massachusetts, Amherst, MA 01003 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-382 BP E235 EP E236 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900639 ER PT J AU Plowden, T Zarek, S Schisterman, E Sjaarda, L Silver, RM Galai, N DeCherney, A Mumford, SL AF Plowden, T. Zarek, S. Schisterman, E. Sjaarda, L. Silver, R. M. Galai, N. DeCherney, A. Mumford, S. L. TI ASSOCIATION BETWEEN LEPTIN AND PREGNANCY LOSS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Zarek, S.; Schisterman, E.; Sjaarda, L.; DeCherney, A.; Mumford, S. L.] NICHD, NIH, Bethesda, MD USA. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT USA. [Galai, N.] Univ Haifa, Haifa, Israel. 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-713 BP E351 EP E352 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900958 ER PT J AU Plowden, T Mumford, SL Devine, K Richter, KS DeCherney, A Beall, S AF Plowden, T. Mumford, S. L. Devine, K. Richter, K. S. DeCherney, A. Beall, S. TI DISCORDANTANTIMULLERIAN HORMONE (AMH) AND FOLLICLE STIMULATING HORMONE (FSH) AND PREGNANCY OUTCOMES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Mumford, S. L.; DeCherney, A.] NICHD, NIH, Bethesda, MD USA. [Devine, K.; Richter, K. S.; Beall, S.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-321 BP E214 EP E215 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900579 ER PT J AU Plowden, T Zarek, S Schisterman, E Sjaarda, L Silver, RM Galai, N DeCherney, A Mumford, SL AF Plowden, T. Zarek, S. Schisterman, E. Sjaarda, L. Silver, R. M. Galai, N. DeCherney, A. Mumford, S. L. TI ASSOCIATION BETWEEN LEPTIN AND ADVERSE PREGNANCY OUTCOMES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Zarek, S.; Schisterman, E.; Sjaarda, L.; DeCherney, A.; Mumford, S. L.] NICHD, NIH, Bethesda, MD USA. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT USA. [Galai, N.] Univ Haifa, Haifa, Israel. 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-6 BP E108 EP E108 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900280 ER PT J AU Plowden, T Schisterman, E Zarek, S Silver, RM Galai, N DeCherney, A Mumford, SL AF Plowden, T. Schisterman, E. Zarek, S. Silver, R. M. Galai, N. DeCherney, A. Mumford, S. L. TI IS THYROID AUTOIMMUNITY ASSOCIATED WITH PREGNANCY LOSS? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Schisterman, E.; Zarek, S.; DeCherney, A.; Mumford, S. L.] NICHD, NIH, Bethesda, MD USA. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT USA. [Galai, N.] Univ Haifa, Haifa, Israel. 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-220 BP E85 EP E85 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900218 ER PT J AU Plowden, T Schisterman, E Zarek, S Silver, RM Galai, N DeCherney, A Mumford, SL AF Plowden, T. Schisterman, E. Zarek, S. Silver, R. M. Galai, N. DeCherney, A. Mumford, S. L. TI ASSOCIATION BETWEEN SUBCLINICAL HYPOTHYROIDISM AND PREGNANCY LOSS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Schisterman, E.; Zarek, S.; DeCherney, A.; Mumford, S. L.] NICHD, NIH, Bethesda, MD USA. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT USA. [Galai, N.] Univ Haifa, Haifa, Israel. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-140 BP E55 EP E55 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900140 ER PT J AU Plowden, T Christy, A DeCherney, A Csokmay, J AF Plowden, T. Christy, A. DeCherney, A. Csokmay, J. TI PREGNANCY RATES AMONG AFRICAN-AMERICAN WOMEN UNDERGOING SINGLE EMBRYO TRANSFER (SET) SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Plowden, T.; Christy, A.; DeCherney, A.] NIH, Bethesda, MD 20892 USA. [Csokmay, J.] WRNMMC, Bethesda, MD USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-78 BP E31 EP E31 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900078 ER PT J AU Polotsky, AJ Allshouse, AA Krawetz, S Santoro, N Eisenberg, E Zhang, H Diamond, MP AF Polotsky, A. J. Allshouse, A. A. Krawetz, S. Santoro, N. Eisenberg, E. Zhang, H. Diamond, M. P. TI MALE OBESITY IS AN INDEPENDENT RISK FACTOR FOR TREATMENT FAILURE AMONG COUPLES WITH UNEXPLAINED INFERTILITY IN THE ASSESSMENT OF MULTIPLE INTRAUTERINE GESTATIONS FROM OVARIAN STIMULATION (AMIGOS) TRIAL SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Polotsky, A. J.; Allshouse, A. A.; Santoro, N.] Univ Colorado, Aurora, CO USA. [Krawetz, S.] Wayne, Detroit, MI USA. [Eisenberg, E.] NICHD, Bethesda, MD USA. [Zhang, H.] Yale, New Haven, CT USA. [Diamond, M. P.] Georgia Regents Univ, Augusta, GA USA. NR 2 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-201 BP E78 EP E78 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900200 ER PT J AU Radin, R Sjaarda, L Mumford, SL Perkins, NJ Silver, RM Schisterman, E AF Radin, R. Sjaarda, L. Mumford, S. L. Perkins, N. J. Silver, R. M. Schisterman, E. TI C-REACTIVE PROTEIN AND ANOVULATION AMONG EUMENORRHEIC WOMEN WITH PRIOR PREGNANCY LOSS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Radin, R.; Sjaarda, L.; Mumford, S. L.; Perkins, N. J.; Schisterman, E.] NICHD, NIH, Rockville, MD USA. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-18 BP E112 EP E112 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900291 ER PT J AU Royster, GD Csokmay, J Yauger, B DeCherney, A Wolff, EF Hill, MJ AF Royster, G. D. Csokmay, J. Yauger, B. DeCherney, A. Wolff, E. F. Hill, M. J. TI HIGH ESTRADIOL AND ICSI INCREASE THE RISK OF PLACENTAL COMPLICATIONS IN PREGNANCY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Royster, G. D.; DeCherney, A.; Wolff, E. F.; Hill, M. J.] NIH, Bethesda, MD 20892 USA. [Csokmay, J.; Yauger, B.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-341 BP E222 EP E222 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900599 ER PT J AU Royster, GD Zarek, S Christy, A DeCherney, A Devine, K Hill, MJ AF Royster, G. D. Zarek, S. Christy, A. DeCherney, A. Devine, K. Hill, M. J. TI DOES PREVALENCE AND EFFECT OF ELEVATED PROGESTERONE ON THE DAY OF OOCYTE MATURATION DIFFER BY ETHNICITY? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Royster, G. D.; Zarek, S.; Christy, A.; DeCherney, A.; Hill, M. J.] NIH, Bethesda, MD 20892 USA. [Devine, K.] Shady Grove Fertil Ctr, Washington, DC 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-330 BP E218 EP E218 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900588 ER PT J AU Sapra, KJ Kim, S Eisenberg, M Chen, Z Louis, GMB AF Sapra, K. J. Kim, S. Eisenberg, M. Chen, Z. Louis, G. M. Buck TI MALE UNDERWEAR AND SEMEN QUALITY IN A POPULATION-BASED PRECONCEPTION COHORT SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Sapra, K. J.; Kim, S.; Chen, Z.] Eunice Kennedy Shriver Natl Inst Child, Div Intramural Populat Hlth Res, Rockville, MD USA. [Eisenberg, M.] Stanford Univ, Stanford, CA 94305 USA. [Louis, G. M. Buck] NICHD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-114 BP E45 EP E45 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900114 ER PT J AU Schliep, KC Mitchell, E Mumford, SL Radin, R Zarek, S Schisterman, E AF Schliep, K. C. Mitchell, E. Mumford, S. L. Radin, R. Zarek, S. Schisterman, E. TI TRYING TO CONCEIVE AFTER A PREGNANCY LOSS: HOW LONG SHOULD COUPLES WAIT? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Schliep, K. C.] Univ Utah, Family & Prevent Med, Salt Lake City, UT USA. [Mitchell, E.] NICHD, Rockville, MD USA. [Mumford, S. L.] NICHD, NIH, Rockville, MD USA. [Radin, R.] NIH, Rockville, MD USA. [Zarek, S.] NIH, Bethesda, MD 20892 USA. [Schisterman, E.] Eunice Kennedy Shriver Natl Inst Child, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-30 BP E115 EP E116 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900302 ER PT J AU Seungdamrong, AM Steiner, A Gracia, C Diamond, MP Legro, R Jin, S Eisenberg, E Zhang, H Santoro, N AF Seungdamrong, A. M. Steiner, A. Gracia, C. Diamond, M. P. Legro, R. Jin, S. Eisenberg, E. Zhang, H. Santoro, N. TI ANTITHYROID ANTIBODIES, BUT NOT THYROID STIMULATING HORMONE, ARE ASSOCIATED WITH DECREASED PREGNANCY RATES IN INFERTILE WOMEN SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Seungdamrong, A. M.] Rutgers New Jersey Med Sch, Obstet Gynecol & Womens Hlth, Newark, NJ USA. [Steiner, A.] Univ N Carolina, Chapel Hill, NC USA. [Gracia, C.] Univ Penn, Philadelphia, PA 19104 USA. [Diamond, M. P.] Georgia Regents Univ, Augusta, GA USA. [Legro, R.] Penn State Univ, Coll Med, Hershey, PA USA. [Jin, S.] Yale Univ, New Haven, CT USA. [Eisenberg, E.] NICHD, Bethesda, MD USA. [Zhang, H.] Yale Sch Publ Hlth, New Haven, CT USA. [Santoro, N.] Univ Colorado, Sch Med, Aurora, CO 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-92 BP E36 EP E37 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900092 ER PT J AU Sjaarda, L Mitchell, E Mumford, SL Radin, R Perkins, NJ Galai, N Silver, RM Schisterman, E AF Sjaarda, L. Mitchell, E. Mumford, S. L. Radin, R. Perkins, N. J. Galai, N. Silver, R. M. Schisterman, E. TI PRECONCEPTION LOW DOSE ASPIRIN TREATMENT IMPROVES CLINICAL PREGNANCY AND LIVE BIRTH IN WOMEN WITH HIGHER SYSTEMIC INFLAMMATION. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Sjaarda, L.; Mitchell, E.; Mumford, S. L.; Radin, R.; Perkins, N. J.; Schisterman, E.] NICHD, NIH, Rockville, MD USA. [Galai, N.] Univ Haifa, Haifa, Israel. [Silver, R. M.] Unversiy Utah, Salt Lake City, UT 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-705 BP E349 EP E349 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900950 ER PT J AU Styer, AK Christianson, MS Vitek, W Baker, V Santoro, N Armstrong, A Polotsky, AJ Luke, B AF Styer, A. K. Christianson, M. S. Vitek, W. Baker, V. Santoro, N. Armstrong, A. Polotsky, A. J. Luke, B. TI FACTORS ASSOCIATED WITH ELECTIVE SINGLE EMBRYO TRANSFER (ESET) UTILIZATION IN THE UNITED STATES: A NATIONAL STUDY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Styer, A. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Lutherville Timonium, MD USA. [Vitek, W.] Univ Rochester, Sch Med, Rochester, NY USA. [Baker, V.] Stanford Univ, Palo Alto, CA 94304 USA. [Santoro, N.; Polotsky, A. J.] Univ Colorado, Aurora, CO USA. [Armstrong, A.] NICHD, Bethesda, MD USA. [Luke, B.] Research, Ann Arbor, MI USA. NR 0 TC 1 Z9 1 U1 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-268 BP E102 EP E102 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900266 ER PT J AU Styer, AK Vitek, W Christianson, MS Baker, V Armstrong, A Santoro, N Luke, B Polotsky, AJ AF Styer, A. K. Vitek, W. Christianson, M. S. Baker, V. Armstrong, A. Santoro, N. Luke, B. Polotsky, A. J. TI ELECTIVE SINGLE EMBRYO TRANSFER (ESET) IS ASSOCIATED WITH NON-LOW BIRTHWEIGHT TERM SINGLETON OUTCOMES: AN ANALYSIS OF 263,375 CYCLES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Styer, A. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Vitek, W.] Univ Rochester, Sch Med, Rochester, NY USA. [Christianson, M. S.] Johns Hopkins Univ, Sch Med, Lutherville Timonium, MD USA. [Baker, V.] Stanford Univ, Palo Alto, CA 94304 USA. [Armstrong, A.] NICHD, Bethesda, MD USA. [Santoro, N.; Polotsky, A. J.] Univ Colorado, Aurora, CO USA. [Luke, B.] Research, Ann Arbor, MI USA. NR 0 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 SEP PY 2015 VL 104 IS 3 SU S MA O-39 BP E16 EP E16 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900040 ER PT J AU Wise, LA Radin, R Rosenberg, L AF Wise, L. A. Radin, R. Rosenberg, L. TI HISTORY OF UTERINE LEIOMYOMATA AND TIME-TO-PREGNANCY IN BLACK WOMEN SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Wise, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Radin, R.] NIH, Rockville, MD USA. [Rosenberg, L.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-140 BP E154 EP E154 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900407 ER PT J AU Wu, X Devine, K Quaglieri, C Driggers, P Segars, J AF Wu, X. Devine, K. Quaglieri, C. Driggers, P. Segars, J. TI AKAP13 IS REQUIRED FOR NORMAL MURINE OVARIAN DEVELOPMENT SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Wu, X.; Driggers, P.; Segars, J.] Johns Hopkins Sch Med, Dept Gyn OB, Baltimore, MD USA. [Wu, X.; Devine, K.; Quaglieri, C.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Devine, K.] Shady Grove Fertil Ctr, Washington, DC 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA P-84 BP E134 EP E134 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900354 ER PT J AU Yeung, E Sundaram, R Bell, E Druschel, C Kus, C Ghassabian, A Bello, S Xie, Y Louis, GB AF Yeung, E. Sundaram, R. Bell, E. Druschel, C. Kus, C. Ghassabian, A. Bello, S. Xie, Y. Louis, G. Buck TI INFERTILITY TREATMENT AND CHILDHOOD DEVELOPMENT FROM BIRTH THROUGH 3 YEARS OF AGE SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Yeung, E.; Sundaram, R.; Ghassabian, A.; Xie, Y.; Louis, G. Buck] NICHD, Rockville, MD USA. [Bell, E.; Druschel, C.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. [Kus, C.] New York State Dept Hlth, Albany, NY USA. [Bello, S.] CapitalCare Pediat, Troy, NY USA. NR 1 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-154 BP E60 EP E60 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900154 ER PT J AU Zarek, S Plowden, T Silver, RM Sjaarda, L Stanford, J Perkins, NJ DeCherney, A Mumford, SL Schisterman, E AF Zarek, S. Plowden, T. Silver, R. M. Sjaarda, L. Stanford, J. Perkins, N. J. DeCherney, A. Mumford, S. L. Schisterman, E. TI HIGHER LEPTIN LEVELS ARE ASSOCIATED WITH DECREASED LIVE BIRTH: RESULTS FROM THE EFFECTS OF ASPIRIN IN GESTATION AND REPRODUCTION (EAGER) TRIAL SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 17-21, 2015 CL Baltimore, MD SP Amer Soc Reprod Med C1 [Zarek, S.; Plowden, T.; DeCherney, A.] NIH, Bethesda, MD 20892 USA. [Silver, R. M.; Stanford, J.] Univ Utah, Salt Lake City, UT USA. [Sjaarda, L.; Perkins, N. J.; Mumford, S. L.; Schisterman, E.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2015 VL 104 IS 3 SU S MA O-191 BP E74 EP E74 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DR6NP UT WOS:000380018900190 ER PT J AU Ivy, SP Beumer, JH AF Ivy, S. Percy Beumer, Jan H. TI Ovarian Cancer Survival and Chemotherapy Dosing, Body Mass Index, and Body Surface Area AreWe There Yet? SO JAMA ONCOLOGY LA English DT Editorial Material ID RELATIVE DOSE INTENSITY; CREATININE CLEARANCE; WOMEN; APPROPRIATE; CARBOPLATIN; WEIGHT C1 [Ivy, S. Percy] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, 9609 Med Ctr Dr,Room 5W458, Bethesda, MD 20850 USA. [Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Canc Therapeut Program, Pittsburgh, PA USA. [Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Ivy, SP (reprint author), NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, 9609 Med Ctr Dr,Room 5W458, Bethesda, MD 20850 USA. EM ivyp@ctep.nci.nih.gov FU NCI NIH HHS [P30 CA047904, UM1 CA186690, UM1-CA186690] NR 15 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2015 VL 1 IS 6 BP 732 EP 733 DI 10.1001/jamaoncol.2015.1926 PG 2 WC Oncology SC Oncology GA DW5HO UT WOS:000383674800005 PM 26181495 ER PT J AU Korde, N Roschewski, M Zingone, A Kwok, M Manasanch, EE Bhutani, M Tageja, N Kazandjian, D Mailankody, S Wu, P Morrison, C Costello, R Zhang, Y Burton, D Mulquin, M Zuchlinski, D Lamping, L Carpenter, A Wall, Y Carter, G Cunningham, SC Gounden, V Sissung, TM Peer, C Maric, I Calvo, KR Braylan, R Yuan, C Stetler-Stevenson, M Arthur, DC Kong, KA Weng, L Faham, M Lindenberg, L Kurdziel, K Choyke, P Steinberg, SM Figg, W Landgren, O AF Korde, Neha Roschewski, Mark Zingone, Adriana Kwok, Mary Manasanch, Elisabet E. Bhutani, Manisha Tageja, Nishant Kazandjian, Dickran Mailankody, Sham Wu, Peter Morrison, Candis Costello, Rene Zhang, Yong Burton, Debra Mulquin, Marcia Zuchlinski, Diamond Lamping, Liz Carpenter, Ashley Wall, Yvonne Carter, George Cunningham, Schuyler C. Gounden, Verena Sissung, Tristan M. Peer, Cody Maric, Irina Calvo, Katherine R. Braylan, Raul Yuan, Constance Stetler-Stevenson, Maryalice Arthur, Diane C. Kong, Katherine A. Weng, Li Faham, Malek Lindenberg, Liza Kurdziel, Karen Choyke, Peter Steinberg, Seth M. Figg, William Landgren, Ola TI Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma SO JAMA ONCOLOGY LA English DT Article ID MINIMAL RESIDUAL DISEASE; MULTIPARAMETER FLOW-CYTOMETRY; COMBINATION; RISK; TRANSPLANTATION; HETEROGENEITY; PROGRESSION; BORTEZOMIB; LEUKEMIA; THERAPY AB IMPORTANCE Carfilzomib-lenalidomide-dexamethasone therapy yields deep responses in patients with newly diagnosed multiplemyeloma (NDMM). It is important to gain an understanding of this combination's tolerability and impact on minimal residual disease (MRD) negativity because this end point has been associated with improved survival. OBJECTIVE To assess the safety and efficacy of carfilzomib-lenalidomide-dexamethasone therapy in NDMM and high-risk smoldering multiplemyeloma (SMM). DESIGN, SETTING, AND PARTICIPANTS Clinical and correlative pilot study at the National Institutes of Health Clinical Center. Patients with NDMM or high-risk SMM were enrolled between July 11, 2011, and October 9, 2013. Median follow-up was 17.3 (NDMM) and 15.9 months (SMM). INTERVENTIONS Eight 28-day cycles were composed of carfilzomib 20/36mg/m(2) on days 1, 2, 8, 9, 15, and 16; lenalidomide 25mg on days 1 through 21; and dexamethasone 20/10mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23. Patients who achieved at least stable disease subsequently received 24 cycles of lenalidomide extended dosing. MAIN OUTCOMES AND MEASURES Primary end pointswere neuropathy of grade 3 or greater (NDMM) and at least very good partial response rates (SMM). Minimal residual disease was also assessed. RESULTS Of 45 patients with NDMM, none had neuropathy of grade 3 or greater. Of 12 patients with high-risk SMM, the most common of any-grade adverse events were lymphopenia (12 [100%]) and gastrointestinal disorders (11 [92%]). All patients with SMM achieved at least a very good partial response during the study period. Among the 28 patients with NDMM and the 12 with SMM achieving at least a near-complete response, MRD negativity was found in 28 of 28 (100% [95% CI, 88%-100%]), 11 of 12 (92%[95% CI, 62%-100%]) (multiparametric flow cytometry), 14 of 21 (67%[95% CI, 43%-85%]), and 9 of 12 (75%[95% CI, 43%-94%]) (next-generation sequencing), respectively. In patients with NDMM, 12-month progression-free survival for MRD-negative vs MRD-positive status by flow cytometry and next-generation sequencing was 100% vs 79% (95% CI, 47%-94%; P <.001) and 100% vs 95%(95% CI, 75%-99%; P = .02), respectively. CONCLUSIONS AND RELEVANCE Carfilzomib-lenalidomide-dexamethasone therapy is tolerable and demonstrates high rates of MRD negativity in NDMM, translating into longer progression-free survival in patients achieving MRD negativity. Carfilzomib-lenalidomidedexamethasone therapy also demonstrates efficacy in high-risk SMM. C1 [Korde, Neha; Roschewski, Mark; Zingone, Adriana; Kwok, Mary; Manasanch, Elisabet E.; Bhutani, Manisha; Tageja, Nishant; Kazandjian, Dickran; Mailankody, Sham; Wu, Peter; Morrison, Candis; Costello, Rene; Zhang, Yong; Burton, Debra; Mulquin, Marcia; Zuchlinski, Diamond; Lamping, Liz; Carpenter, Ashley; Wall, Yvonne; Carter, George; Cunningham, Schuyler C.; Landgren, Ola] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, NIH, New York, NY USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, Dept Med, New York, NY 10021 USA. [Manasanch, Elisabet E.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Bhutani, Manisha; Tageja, Nishant; Mailankody, Sham] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bhutani, Manisha] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Gounden, Verena; Maric, Irina; Calvo, Katherine R.; Braylan, Raul] NIH, Hematol Serv, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA. [Sissung, Tristan M.; Peer, Cody; Figg, William] NCI, Dept Pharmacokinet, NIH, Bethesda, MD 20892 USA. [Yuan, Constance; Stetler-Stevenson, Maryalice; Arthur, Diane C.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kong, Katherine A.; Weng, Li; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Lindenberg, Liza; Kurdziel, Karen; Choyke, Peter] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA. EM landgrec@mskcc.org RI Figg Sr, William/M-2411-2016 FU Onyx; Celgene; Onyx Pharmaceuticals, Inc; Amgen subsidiary; Carfilzomib; lenalidomide FX Carfilzomib and lenalidomide, as well as funding for parts of the correlative assays for the study, were provided by Onyx and Celgene to the National Cancer Institute of the National Institutes of Health as part of a cooperative research and development agreement. Medical writing assistance was provided by Andrew Gomes, PhD, of BlueMomentum, an Ashfield business, part of UDG Healthcare plc, and funded by Onyx Pharmaceuticals, Inc, an Amgen subsidiary. NR 24 TC 42 Z9 42 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2015 VL 1 IS 6 BP 746 EP 754 DI 10.1001/jamaoncol.2015.2010 PG 9 WC Oncology SC Oncology GA DW5HO UT WOS:000383674800007 PM 26181891 ER PT J AU Jawed, I Wilkerson, J Prasad, V Duffy, AG Fojo, T AF Jawed, Irfan Wilkerson, Julia Prasad, Vinay Duffy, Austin G. Fojo, Tito TI Colorectal Cancer Survival Gains and Novel Treatment Regimens A Systematic Review and Analysis SO JAMA ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; COLON-CANCER; SURROGATE; OUTCOMES; METASTASECTOMY; CHEMOTHERAPY; BEVACIZUMAB; RESECTION; TRIALS; RISE AB IMPORTANCE The past 2 decades have witnessed progress in the management of metastatic colorectal cancer (mCRC) with more effective agents and better surgical, medical, and supportive care. While substantial progress has been made, much more must be achieved to prolong the lives of patients. OBJECTIVE To conduct a systematic review to ascertain what percentage of the life expectancy gain in locally advanced and mCRC over the past 2 decades is due to novel therapies vs improvements in supportive care or secular trends and to thus inform treatment development strategies. EVIDENCE REVIEW We searched Cochrane Controlled Trials Register, Medline, Embase, CancerLit, and Healthstar electronic databases for trials covering the period 1993 to 2015, scanned reference lists of articles, and searched recent conference abstracts. Ninety-six phase 3 trials and large (> 50 patients) phase 2 trials in mCRC were examined. Outcomes evaluated in the experimental arms (EAs) and control arms (CAs) included overall response rate, stable disease, progression-free survival (PFS), and overall survival (OS). FINDINGS Over the period covered by the studies, the OS in EAs increased at a mean (95% CI) rate of 0.80 (0.67-0.93) mo/y. Importantly, OS in the CAs improved 0.63 (0.51-0.75) mo/y, reflecting in part the use of experimental regimens in subsequent studies. Chemotherapy contributed only partly to the gains in OS, given that (1) mean (95% CI) improvements in PFS were only 0.31 (0.22-0.39) mo/y in the EAs and 0.23 (0.15-0.31) mo/y in CAs; (2) gains in survival not directly attributable to the protocol were greater than gains in PFS (0.46 [0.36-0.57] mo/y in EAs and 0.39 [0.29-0.49] mo/y in CAs; and (3) effects on OS were much lower in second-line trials (median [interquartile range] response rates, 8.6%[0%-11.0%] in EAs and 7.5%[3.8%-12.8%] in CAs) compared with first-line trials (39.5%[24.0%-50.2%] for EAs and 29.4%[16.4%-39.4%] for CAs). CONCLUSIONS AND RELEVANCE The OS of patients with mCRC has improved gradually over the past 2 decades, with gains from chemotherapy occurring alongside gains from lead-time bias and improved locoregional approaches and supportive care. Gains from first-line therapies have been modest but consistent; however, gains from second-line therapies have been disappointing. We believe that future progress will be greater if emphasis is placed on enrolling patients in experimental trials to explore and develop alternative first-line regimens and better second-line therapies. C1 [Jawed, Irfan; Wilkerson, Julia; Prasad, Vinay; Duffy, Austin G.; Fojo, Tito] NCI, Med Oncol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jawed, Irfan] Lawrence Mem Hosp, Ctr Oncol, Lawrence, KS USA. RP Fojo, T (reprint author), NCI, Med Oncol, NIH, Bldg 10,Room 122N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fojot@mail.nih.gov OI Prasad, Vinay/0000-0002-6110-8221 FU National Cancer Institute Intramural Program FX This research was funded by the National Cancer Institute Intramural Program. NR 25 TC 8 Z9 9 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2015 VL 1 IS 6 BP 787 EP 795 DI 10.1001/jamaoncol.2015.1790 PG 9 WC Oncology SC Oncology GA DW5HO UT WOS:000383674800015 PM 26181239 ER PT J AU Mailankody, S Prasad, V AF Mailankody, Sham Prasad, Vinay TI Pricing and Value of Cancer Drugs Reply SO JAMA ONCOLOGY LA English DT Letter ID TRIALS C1 [Mailankody, Sham; Prasad, Vinay] NCI, Med Oncol Serv, Bethesda, MD 20892 USA. RP Prasad, V (reprint author), NCI, Med Oncol Serv, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA. EM vinayak.k.prasad@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2015 VL 1 IS 6 BP 842 EP 843 PG 2 WC Oncology SC Oncology GA DW5HO UT WOS:000383674800031 PM 26355867 ER PT J AU Felix, AS Brinton, LA McMeekin, DS Creasman, WT Mutch, D Cohn, DE Walker, JL Moore, RG Downs, LS Soslow, RA Zaino, R Sherman, ME AF Felix, Ashley S. Brinton, Louise A. McMeekin, D. Scott Creasman, William T. Mutch, David Cohn, David E. Walker, Joan L. Moore, Richard G. Downs, Levi S. Soslow, Robert A. Zaino, Richard Sherman, Mark E. TI Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/Gynecologic Oncology Group 210 Trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UTERINE SEROUS CARCINOMA; INTRAEPITHELIAL CARCINOMA; TRANSTUBAL SPREAD; LOW-GRADE; CANCER; ADENOCARCINOMA; TUMORS; CELLS; DISSEMINATION; HYSTEROSCOPY AB Background: Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. Methods: The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for TL and mortality. All statistical tests were two-sided. Results: Compared with stage I, TL was inversely associated with stage III (OR = 0.63, 95% CI = 0.52 to 0.78) and stage IV carcinomas (OR = 0.14, 95% CI = 0.08 to 0.24) overall and among individual tumor subtypes. TL was inversely related to peritoneal metastasis overall (OR = 0.39, 95% CI = 0.22 to 0.68) and among serous carcinomas (OR = 0.28, 95% CI = 0.11 to 0.68). In multivariable models unadjusted for stage, TL was associated with lower endometrial carcinoma-specific mortality (HR = 0.74, 95% CI = 0.61 to 0.91); however, adjustment for stage eliminated the survival advantage. Similar relationships with all-cause mortality were observed. Conclusions: TL is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread is clinically important. Future studies should evaluate whether detection of intraluminal tumor cells is prognostically relevant. C1 [Felix, Ashley S.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [McMeekin, D. Scott; Walker, Joan L.] Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. [Creasman, William T.] Med Univ South Carolina, Dept Obstet & Gynecol, Charleston, SC USA. [Mutch, David] Washington Univ, Sch Med, St Louis, MO USA. [Cohn, David E.] Ohio State Univ, Coll Med, Div Gynecol Oncol, Columbus, OH 43210 USA. [Moore, Richard G.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Downs, Levi S.] Univ Minnesota, Minneapolis, MN USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Zaino, Richard] Penn State Milton S Hersey Med Ctr, Anat Pathol, Hershey, PA USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Felix, AS (reprint author), 9609 Med Ctr Dr,Room 7E214, Bethesda, MD 20892 USA. EM ashley.felix@nih.gov OI Soslow, Robert/0000-0002-7269-5898 FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group Statistical and Data Center [CA 37517]; NRG Oncology Grant [1 U10 CA180822]; National Cancer Institute, National Institutes of Health FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), and NRG Oncology Grant number 1 U10 CA180822. In addition, this research was supported in part by funds provided by the intramural research program of the National Cancer Institute, National Institutes of Health. NR 30 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2015 VL 107 IS 9 AR djv158 DI 10.1093/jnci/djv158 PG 9 WC Oncology SC Oncology GA DW9IG UT WOS:000383970600003 ER PT J AU Roth, BJ Puwal, S Basser, PJ AF Roth, Bradley J. Puwal, Steffan Basser, Peter J. TI Local magnetic field perturbations caused by magnetic susceptibility heterogeneity in myelin-water layers within an axon SO JOURNAL OF COUPLED SYSTEMS AND MULTISCALE DYNAMICS LA English DT Article DE Magnetic Resonance Imaging; Myelin; Susceptibility; Myelin Water Imaging; Perturbation ID GRADIENT-ECHO MRI; BRAIN; RELAXATION; MICROSTRUCTURE; RESONANCE; CONTRAST; 3.0T AB Magnetic resonance imaging has been used to map the myelin water fraction in neural tissue. One hypothesis is that a reduction in T-2* arises from microscopic perturbations in the magnetic field caused by heterogeneities in the magnetic susceptibility of myelin. In this paper, the perturbed magnetic field distribution is calculated analytically using a perturbation expansion written in terms of a small dimensionless parameter corresponding to the magnetic susceptibility. When the magnetic field is applied perpendicular to the axon, the magnetic field in the intracellular space is not influenced by the myelin, the magnetic field in the myelin sheath oscillates between the fat and water layers, and the magnetic field in the extracellular space just outside the myelin sheath is heterogeneous. This heterogeneity causes the spins to dephase, shortening T-2*. When the magnetic field is applied along the axon, it is homogeneous within water-filled regions between myelin layers, and therefore the spins will not dephase and the magnetic susceptibility will have no effect on T-2*. These two solutions predict the perturbed magnetic field distribution in and around an axon arbitrarily oriented in the main magnetic field. C1 [Roth, Bradley J.; Puwal, Steffan] Oakland Univ, Dept Phys, Rochester, MI 48309 USA. [Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Roth, BJ (reprint author), Oakland Univ, Dept Phys, Rochester, MI 48309 USA. EM roth@oakland.edu RI Roth, Bradley/A-4920-2008 NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 2330-152X EI 2330-1538 J9 J COUPLED SYST MULTI JI J. Coupled Syst. Multiscale Dyn. PD SEP PY 2015 VL 3 IS 3 SI SI BP 228 EP 232 DI 10.1166/jcsmd.2015.1081 PG 5 WC Mechanics SC Mechanics GA DW1KP UT WOS:000383402400006 ER PT J AU Ganini, D Petrovich, RM Edwards, LL Mason, RP AF Ganini, Douglas Petrovich, Robert M. Edwards, Lori L. Mason, Ronald P. TI Iron incorporation into MnSOD A (bacterial Mn-dependent superoxide dismutase) leads to the formation of a peroxidase/catalase implicated in oxidative damage to bacteria SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Superoxide dismutase (SOD); Peroxidase; Free radical; Metal; Iron; Manganese ID AMPLEX RED ASSAY; ESCHERICHIA-COLI; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE; PORPHYROMONAS-GINGIVALIS; RESORUFIN IMPLICATIONS; MANGANESE UPTAKE; ACTIVE-SITE; RADICALS; PROTEIN AB Background: Mn/Fe-superoxide dismutase (SOD) is a family of enzymes essential for organisms to be able to cope with oxygen. These enzymes bound to their classical metals catalyze the dismutation of the free radical superoxide anion (O-2(center dot-)) to H2O2 and molecular oxygen. E. coli has the manganese-dependent SOD A and the iron-dependent SOD B. Methods: Strains of E. coli overexpressing SOD A or SOD B were grown in media with different metal compositions. SODs were purified and their metal content and SOD activity were determined. Those proteins were incubated with H2O2 and assayed for oxidation of Amplex red or o-phenylenediamine, consumption of H2O2, release of iron and protein radical formation. Cell survival was determined in bacteria with MnSOD A or FeSOD A after being challenged with H2O2. Results: We show for the first time that the bacterial manganese-dependent SOD A when bound to iron (FeSOD A) has peroxidase activity. The in vivo formation of the peroxidase FeSOD A was increased when media had higher levels of iron because of a decreased manganese metal incorporation. In comparison to bacteria with MnSOD A, cells with FeSOD A had a higher loss of viability when exposed to H2O2. General Significance: The biological occurrence of this fundamental antioxidant enzyme in an alternative iron-dependent state represents an important source of free radical formation. Published by Elsevier B.V. C1 [Ganini, Douglas; Mason, Ronald P.] NIEHS, Free Radical Metabolites Grp, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Petrovich, Robert M.; Edwards, Lori L.] NIEHS, Prot Express Core Facil, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Ganini, D (reprint author), NIEHS, Free Radical Metabolites Grp, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM ganinidasilvad@niehs.nih.gov FU Intramural Research Program of the NIEHS, National Institute of Environmental Health Sciences/NIH FX The authors acknowledge Dr. Ann Motten, Ms. Mary Mason and Ms. Jean Corbett for their help in the revision of the manuscript. We also acknowledge Ms. Jean Corbett for her valuable technical assistance. This research was supported by the Intramural Research Program of the NIEHS, National Institute of Environmental Health Sciences/NIH. NR 60 TC 3 Z9 3 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 EI 1872-8006 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD SEP PY 2015 VL 1850 IS 9 BP 1795 EP 1805 DI 10.1016/j.bbagen.2015.05.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CO5BF UT WOS:000359173900015 PM 25964067 ER PT J AU Hammond, GRV Balla, T AF Hammond, Gerald R. V. Balla, Tamas TI Polyphosphoinositide binding domains: Key to inositol lipid biology (vol 1851, pg 746, 2015) SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Correction C1 [Hammond, Gerald R. V.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA. [Balla, Tamas] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, NIH, Bethesda, MD USA. RP Hammond, GRV (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA. EM ghammond@pitt.edu; ballat@mail.nih.gov RI Hammond, Gerald/A-5759-2016 OI Hammond, Gerald/0000-0002-6660-3272 NR 1 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD SEP PY 2015 VL 1851 IS 9 BP 1283 EP 1283 DI 10.1016/j.bbalip.2015.05.005 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CO4YY UT WOS:000359168000016 ER PT J AU Schwartz, H Scroggins, B Zuehlke, A Kijima, T Beebe, K Mishra, A Neckers, L Prince, T AF Schwartz, Harvey Scroggins, Brad Zuehlke, Abbey Kijima, Toshiki Beebe, Kristin Mishra, Alok Neckers, Len Prince, Thomas TI Combined HSP90 and kinase inhibitor therapy: Insights from The Cancer Genome Atlas SO CELL STRESS & CHAPERONES LA English DT Editorial Material DE Cancer; Drug resistance; HSP90; Kinase; Evolution; TCGA ID PROTEIN 90 INHIBITOR; CELL LUNG-CANCER; TRANSLATION INITIATION COMPLEX; HEAT-SHOCK PROTEINS; DRUG-RESISTANCE; BREAST-CANCER; TYROSINE KINASE; MOLECULAR CHAPERONE; TUMOR-SUPPRESSOR; MORPHOLOGICAL EVOLUTION AB The merging of knowledge from genomics, cellular signal transduction and molecular evolution is producing new paradigms of cancer analysis. Protein kinases have long been understood to initiate and promote malignant cell growth and targeting kinases to fight cancer has been a major strategy within the pharmaceutical industry for over two decades. Despite the initial success of kinase inhibitors (KIs), the ability of cancer to evolve resistance and reprogram oncogenic signaling networks has reduced the efficacy of kinase targeting. The molecular chaperone HSP90 physically supports global kinase function while also acting as an evolutionary capacitor. The Cancer Genome Atlas (TCGA) has compiled a trove of data indicating that a large percentage of tumors overexpress or possess mutant kinases that depend on the HSP90 molecular chaperone complex. Moreover, the overexpression or mutation of parallel activators of kinase activity (PAKA) increases the number of components that promote malignancy and indirectly associate with HSP90. Therefore, targeting HSP90 is predicted to complement kinase inhibitors by inhibiting oncogenic reprogramming and cancer evolution. Based on this hypothesis, consideration should be given by both the research and clinical communities towards combining kinase inhibitors and HSP90 inhibitors (H90Ins) in combating cancer. The purpose of this perspective is to reflect on the current understanding of HSP90 and kinase biology as well as promote the exploration of potential synergistic molecular therapy combinations through the utilization of The Cancer Genome Atlas. C1 [Schwartz, Harvey; Scroggins, Brad; Zuehlke, Abbey; Kijima, Toshiki; Beebe, Kristin; Mishra, Alok; Neckers, Len; Prince, Thomas] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Prince, T (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM thomas.prince@nih.gov OI Zuehlke, Abbey/0000-0003-0432-8823 FU Intramural NIH HHS NR 147 TC 1 Z9 1 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1355-8145 EI 1466-1268 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD SEP PY 2015 VL 20 IS 5 BP 729 EP 741 DI 10.1007/s12192-015-0604-1 PG 13 WC Cell Biology SC Cell Biology GA CO8AA UT WOS:000359385300004 PM 26070366 ER PT J AU Wadt, KAW Aoude, LG Johansson, P Solinas, A Pritchard, A Crainic, O Andersen, MT Kiilgaard, JF Heegaard, S Sunde, L Federspiel, B Madore, J Thompson, JF McCarthy, SW Goodwin, A Tsao, H Jonsson, G Busam, K Gupta, R Trent, JM Gerdes, AM Brown, KM Scolyer, RA Hayward, NK AF Wadt, K. A. W. Aoude, L. G. Johansson, P. Solinas, A. Pritchard, A. Crainic, O. Andersen, M. T. Kiilgaard, J. F. Heegaard, S. Sunde, L. Federspiel, B. Madore, J. Thompson, J. F. McCarthy, S. W. Goodwin, A. Tsao, H. Jonsson, G. Busam, K. Gupta, R. Trent, J. M. Gerdes, A. -M. Brown, K. M. Scolyer, R. A. Hayward, N. K. TI A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma SO CLINICAL GENETICS LA English DT Article DE BAP1; BCC; cancer predisposition syndrome; germline mutation; melanoma; unknown primary tumor ID UVEAL MELANOMA; MALIGNANT MESOTHELIOMA; CUTANEOUS MELANOMA; FAMILY; PHENOTYPE; CANCERS AB We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family. C1 [Wadt, K. A. W.; Andersen, M. T.; Gerdes, A. -M.] Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. [Aoude, L. G.; Johansson, P.; Pritchard, A.; Hayward, N. K.] QIMR Berghofer Med Res Inst, Genet & Computat Biol, Brisbane, Qld, Australia. [Aoude, L. G.] Univ Queensland, Brisbane, Qld, Australia. [Solinas, A.; Crainic, O.; McCarthy, S. W.; Gupta, R.; Scolyer, R. A.] Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia. [Kiilgaard, J. F.; Heegaard, S.] Univ Copenhagen, Glostrup Hosp, Dept Ophthalmol, Copenhagen, Denmark. [Heegaard, S.] Univ Copenhagen, Eye Pathol Inst, Dept Neurosci & Pharmacol, Copenhagen, Denmark. [Sunde, L.] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Federspiel, B.] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Madore, J.; Thompson, J. F.; McCarthy, S. W.; Scolyer, R. A.] Melanoma Inst Australia, North Sydney, Australia. [Thompson, J. F.; McCarthy, S. W.; Gupta, R.; Scolyer, R. A.] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia. [Goodwin, A.] Royal Prince Alfred Hosp, Dept Canc Genet, Sydney, NSW, Australia. [Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Jonsson, G.] Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden. [Busam, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Trent, J. M.] Translat Genom Res Inst, Phoenix, AZ USA. [Brown, K. M.] NCI, Lab Translat Genom, Bethesda, MD 20892 USA. RP Wadt, KAW (reprint author), Rigshosp, Dept Clin Genet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM Karin.wadt@rh.regionh.dk RI Pritchard, Antonia/F-4288-2010; Johansson, Peter/K-1053-2014; hayward, nicholas/C-1367-2015; OI Pritchard, Antonia/0000-0001-5336-0454; Johansson, Peter/0000-0001-7015-5452; hayward, nicholas/0000-0003-4760-1033; Sunde, Lone/0000-0002-8479-165X; Scolyer, Richard/0000-0002-8991-0013; Kiilgaard, Jens Folke/0000-0003-1054-1460 FU National Health and Medical Research Council of Australia (NHMRC); Cancer Council Queensland; Fight for sight, Denmark; Melanoma Research Alliance; Rigshospitalet; University Hospital of Copenhagen; US NIH [K24 CA14920]; Australia and Banking Group Limited; New Zealand Banking Group Limited; NHMRC FX Funding for this project was provided by the National Health and Medical Research Council of Australia (NHMRC), the Cancer Council Queensland, Fight for sight, Denmark, and the Melanoma Research Alliance. K. A. W. W. and L. G. A. receive PhD scholarships from Rigshospitalet, University Hospital of Copenhagen and the Australia and New Zealand Banking Group Limited Trustees respectively. Swedish Cancer Society, Swedish Research Council and Nordic Cancer Union. Aase og Ejnar Danielsens Fond. The Danish Medical Association Research Fund. H. T. is a recipient of a grant from US NIH K24 CA14920. N. K. H. is a recipient of a Senior Principal Research Fellowship from the NHMRC. The authors wish to thank the participants of the study for making this research possible. NR 22 TC 21 Z9 21 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD SEP PY 2015 VL 88 IS 3 BP 267 EP 272 DI 10.1111/cge.12501 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CO3NL UT WOS:000359064800010 PM 25225168 ER PT J AU Best, BM Burchett, S Li, H Stek, A Hu, C Wang, J Hawkins, E Byroads, M Watts, DH Smith, E Fletcher, CV Capparelli, EV Mirochnick, M AF Best, B. M. Burchett, S. Li, H. Stek, A. Hu, C. Wang, J. Hawkins, E. Byroads, M. Watts, D. H. Smith, E. Fletcher, C. V. Capparelli, E. V. Mirochnick, M. CA Int Maternal Pediat Adolescent AID TI Pharmacokinetics of tenofovir during pregnancy and postpartum SO HIV MEDICINE LA English DT Article DE antiretrovirals; HIV; pregnancy; prevention of perinatal transmission; tenofovir ID DISOPROXIL FUMARATE; ANRS 12109; WOMEN; PLASMA; EMTRICITABINE; LC/MS/MS; NEONATE; IMPACT; ASSAY AB ObjectivesTenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. MethodsInternational Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was 1.99g h/mL (nonpregnant historical control 10th percentile). ResultsThe median tenofovir AUC was decreased during the second (1.9g h/mL) and third (2.4g h/mL; P=0.005) trimesters versus postpartum (3.0g h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. ConclusionsThis study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response. C1 [Best, B. M.; Capparelli, E. V.] Univ Calif San Diego, Sch Med, Rady Childrens Hosp, San Diego, CA 92103 USA. [Best, B. M.; Capparelli, E. V.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Burchett, S.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Li, H.] Rush Univ, Dept Prevent Med, Med Ctr, Chicago, IL 60612 USA. [Stek, A.] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Hu, C.] Univ Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Wang, J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Hawkins, E.] Social & Sci Syst, Silver Spring, MD USA. [Byroads, M.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Watts, D. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Smith, E.] NIAID, Bethesda, MD 20892 USA. [Fletcher, C. V.] Univ Nebraska Med Ctr, Coll Pharm, Omaha, NE USA. [Mirochnick, M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Best, BM (reprint author), Univ Calif San Diego, 9500 Gilman Dr MC 0657, La Jolla, CA 92093 USA. EM brookie@ucsd.edu RI Hu, Chengcheng/A-8391-2017 FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [1 U01 AI068616]; IMPAACT Group; National Institute of Allergy and Infectious Diseases (NIAID); NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network - NICHD [N01-DK-9-001/HHSN267200800001C] FX 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) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). NR 16 TC 6 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD SEP PY 2015 VL 16 IS 8 BP 502 EP 511 DI 10.1111/hiv.12252 PG 10 WC Infectious Diseases SC Infectious Diseases GA CO6XT UT WOS:000359301800006 PM 25959631 ER PT J AU Scult, MA Trampush, JW Zheng, FY Conley, ED Lencz, T Malhotra, AK Dickinson, D Weinberger, DR Hariri, AR AF Scult, Matthew A. Trampush, Joey W. Zheng, Fengyu Conley, Emily Drabant Lencz, Todd Malhotra, Anil K. Dickinson, Dwight Weinberger, Daniel R. Hariri, Ahmad R. TI A Common Polymorphism in SCN2A Predicts General Cognitive Ability through Effects on PFC Physiology SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID SUBUNIT MESSENGER-RNAS; CHANNEL ALPHA-SUBUNIT; GATED SODIUM-CHANNEL; HUMAN-BRAIN; INTELLIGENCE; EXPRESSION; SEIZURES; MUTATION; SCHIZOPHRENIA; LOCALIZATION AB Here we provide novel convergent evidence across three independent cohorts of healthy adults (n = 531), demonstrating that a common polymorphism in the gene encoding the alpha 2 subunit of neuronal voltage-gated type II sodium channels (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher "g" independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort (n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral PFC and dorsal ACC, which support higher cognitive functions. Collectively, these findings fill a gap in our understanding of the genetics of general cognitive ability and highlight a specific neural mechanism through which a common polymorphism shapes interindividual variation in "g." C1 [Scult, Matthew A.; Hariri, Ahmad R.] Duke Univ, Durham, NC 27708 USA. [Trampush, Joey W.; Lencz, Todd; Malhotra, Anil K.] Zucker Hillside Hosp, Glen Oaks, NY USA. [Zheng, Fengyu; Weinberger, Daniel R.] Johns Hopkins Sch Med, Baltimore, MD USA. [Conley, Emily Drabant] 23andMe Inc, Mountain View, CA USA. [Dickinson, Dwight] US Natl Inst Hlth, Bethesda, MD USA. RP Scult, MA (reprint author), Duke Univ, 417 Chapel Dr, Durham, NC 27708 USA. EM matthew.scult@duke.edu RI Lencz, Todd/J-3418-2014; OI Lencz, Todd/0000-0001-8586-338X; Scult, Matthew/0000-0001-5554-8186 FU NSF Graduate Research Fellowship; Duke University; NIDA [R01DA031579, R01DA033369]; Advanced Center for Intervention and Services Research grant from NIH [P30 MH090590]; Center for Intervention Development and Applied Research grant from NIH [P50 MH080173]; Division of Intramural Research Programs, NIMH; NIH FX We would like to thank Yuliya S. Nikolova, Jacob Miller, Annchen Knodt, Spenser Radtke, Johnna Swartz, and Jamie Hanson from the Laboratory of NeuroGenetics at Duke University. M. S. was supported by an NSF Graduate Research Fellowship. The DNS was supported by Duke University as well as NIDA grants R01DA031579 and R01DA033369. The work conducted at Zucker Hillside Hospital was supported in part by an Advanced Center for Intervention and Services Research (P30 MH090590) grant and a Center for Intervention Development and Applied Research grant (P50 MH080173) from NIH. D. D. was supported by the Division of Intramural Research Programs, NIMH, and NIH. NR 33 TC 0 Z9 0 U1 2 U2 4 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2015 VL 27 IS 9 BP 1766 EP 1774 DI 10.1162/jocn_a_00826 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CN9KW UT WOS:000358768200007 PM 25961639 ER PT J AU Weidner, LD Zoghbi, SS Lu, SY Shukla, S Ambudkar, SV Pike, VW Mulder, J Gottesman, MM Innis, RB Hall, MD AF Weidner, Lora D. Zoghbi, Sami S. Lu, Shuiyu Shukla, Suneet Ambudkar, Suresh V. Pike, Victor W. Mulder, Jan Gottesman, Michael M. Innis, Robert B. Hall, Matthew D. TI The Inhibitor Ko143 Is Not Specific for ABCG2 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOOD-BRAIN-BARRIER; CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN EXPRESSION; DRUG EFFLUX TRANSPORTERS; CASSETTE-DOSING APPROACH; MULTIDRUG-RESISTANCE; FUMITREMORGIN-C; SUBSTRATE; EPILEPSY; DISEASES AB Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143 [[(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6] pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester], a nontoxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2, although its specificity in mouse and human systems is unclear. This study examined the selectivity of Ko143 using human embryonic kidney cell lines transfected with ABCG2, ABCB1, or ABCC1 in several in vitro assays. The stability of Ko143 in rat plasma was measured using high performance liquid chromatography. Our results show that, in addition to being a potent inhibitor of ABCG2, at higher concentrations (>= 1 mu M) Ko143 also has an effect on the transport activity of both ABCB1 and ABCC1. Furthermore, Ko143 was found to be unstable in rat plasma. These findings indicate that Ko143 lacks specificity for ABCG2 and this should be taken into consideration when using Ko143 for both in vitro and in vivo experiments. C1 [Weidner, Lora D.; Zoghbi, Sami S.; Lu, Shuiyu; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Weidner, Lora D.; Mulder, Jan] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Shukla, Suneet; Ambudkar, Suresh V.; Gottesman, Michael M.; Hall, Matthew D.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Weidner, LD (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,Room B1D43, Bethesda, MD 20892 USA. EM lora.deuitch@nih.gov RI Mulder, Jan/G-3909-2011; OI Mulder, Jan/0000-0003-3717-5018; Lu, Shuiyu/0000-0003-0310-4318 FU Intramural Research Program of the National Institutes of Health [National Institute of Mental Health]; Intramural Research Program of the National Institutes of Health [National Cancer Institute] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health [National Institute of Mental Health and National Cancer Institute]. NR 40 TC 13 Z9 14 U1 2 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2015 VL 354 IS 3 BP 384 EP 393 DI 10.1124/jpet.115.225482 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CO2PU UT WOS:000358999900015 PM 26148857 ER PT J AU Spruiell, K Gyamfi, AA Yeyeodu, ST Richardson, RM Gonzalez, FJ Gyamfi, MA AF Spruiell, Krisstonia Gyamfi, Afua A. Yeyeodu, Susan T. Richardson, Ricardo M. Gonzalez, Frank J. Gyamfi, Maxwell A. TI Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALCOHOL-DEHYDROGENASE ACTIVITY; PROLIFERATOR-ACTIVATED RECEPTORS; INDUCED LIVER-INJURY; HIGH-FAT DIET; ALDEHYDE DEHYDROGENASE; 1ST-PASS METABOLISM; DRUG-INTERACTIONS; OXIDATIVE STRESS; UP-REGULATION; SEX-HORMONES AB Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor alpha, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. C1 [Spruiell, Krisstonia; Gyamfi, Afua A.; Yeyeodu, Susan T.; Richardson, Ricardo M.; Gyamfi, Maxwell A.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gyamfi, MA (reprint author), N Carolina Cent Univ, Cardiometab Res Program, Julius L Chambers Biomed Biotechnol Res Inst, 700 George St, Durham, NC 27707 USA. EM mgyamfi@nccu.edu FU National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [AA019765]; National Institutes of Health National Institute on Minority Health and Health Disparities [MD000175]; National Institutes of Health National Cancer Institute [CA92077]; Intramural Research Program of the National Institutes of Health [National Cancer Institute] FX This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA019765]; the National Institutes of Health National Institute on Minority Health and Health Disparities [Grant MD000175]; and the National Institutes of Health National Cancer Institute [Grant CA92077]. This research was also supported in part by the Intramural Research Program of the National Institutes of Health [National Cancer Institute]. NR 55 TC 0 Z9 0 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2015 VL 354 IS 3 BP 459 EP 470 DI 10.1124/jpet.115.224295 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CO2PU UT WOS:000358999900023 PM 26159875 ER PT J AU Eggener, SE Badani, K Barocas, DA Barrisford, GW Cheng, JS Chin, AI Corcoran, A Epstein, JI George, AK Gupta, GN Hayn, MH Kauffman, EC Lane, B Liss, MA Mirza, M Morgan, TM Moses, K Nepple, KG Preston, MA Rais-Bahrami, S Resnick, MJ Siddiqui, MM Silberstein, J Singer, EA Sonn, GA Sprenkle, P Stratton, KL Taylor, J Tomaszewski, J Tollefson, M Vickers, A White, WM Lowrance, WT AF Eggener, Scott E. Badani, Ketan Barocas, Daniel A. Barrisford, Glen W. Cheng, Jed-Sian Chin, Arnold I. Corcoran, Anthony Epstein, Jonathan I. George, Arvin K. Gupta, Gopal N. Hayn, Matthew H. Kauffman, Eric C. Lane, Brian Liss, Michael A. Mirza, Moben Morgan, Todd M. Moses, Kelvin Nepple, Kenneth G. Preston, Mark A. Rais-Bahrami, Soroush Resnick, Matthew J. Siddiqui, M. Minhaj Silberstein, Jonathan Singer, Eric A. Sonn, Geoffrey A. Sprenkle, Preston Stratton, Kelly L. Taylor, Jennifer Tomaszewski, Jeffrey Tollefson, Matt Vickers, Andrew White, Wesley M. Lowrance, William T. TI Gleason 6 Prostate Cancer: Translating Biology into Population Health SO JOURNAL OF UROLOGY LA English DT Review DE prostatic neoplasms; neoplasm grading; early detection of cancer; watchful waiting; prostatectomy ID 2005 INTERNATIONAL-SOCIETY; TRIAL RISK CALCULATOR; CONSENSUS CONFERENCE; NEEDLE BIOPSIES; FOLLOW-UP; ADENOCARCINOMA; CARCINOMA; ANTIGEN; DIAGNOSIS; SURVEILLANCE AB Purpose: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. Materials and Methods: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. Results: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. Conclusions: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening. C1 [Eggener, Scott E.] Univ Chicago, Chicago, IL 60637 USA. [Badani, Ketan] Mt Sinai, New York, NY USA. [Barocas, Daniel A.; Moses, Kelvin; Resnick, Matthew J.] Vanderbilt Univ, Nashville, TN 37235 USA. [Barrisford, Glen W.; Cheng, Jed-Sian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Preston, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chin, Arnold I.] Univ Calif Los Angeles, Los Angeles, CA USA. [Corcoran, Anthony] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Epstein, Jonathan I.] Johns Hopkins Univ, Baltimore, MD USA. [George, Arvin K.] NIH, Bethesda, MD 20892 USA. [Gupta, Gopal N.] Loyola Univ, Maywood, IL 60153 USA. [Hayn, Matthew H.] Tufts Univ, Maine Med Ctr, Portland, ME USA. [Kauffman, Eric C.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Lane, Brian] Michigan State Univ, Spectrum Hlth, Grand Rapids, MI USA. [Liss, Michael A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mirza, Moben] Univ Kansas, Kansas City, KS USA. [Morgan, Todd M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nepple, Kenneth G.] Univ Iowa, Iowa City, IA USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Birmingham, AL USA. [Siddiqui, M. Minhaj] Univ Maryland, Baltimore, MD 21201 USA. [Silberstein, Jonathan] Tulane Univ, New Orleans, LA 70118 USA. [Singer, Eric A.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Sonn, Geoffrey A.] Stanford Univ, Stanford, CA 94305 USA. [Sprenkle, Preston] Yale Univ, New Haven, CT USA. [Stratton, Kelly L.] Univ Oklahoma, Oklahoma City, OK USA. Baylor Coll Med, Houston, TX 77030 USA. MD Anderson Canc Ctr Cooper, Camden, NJ USA. [Tollefson, Matt] Mayo Clin, Rochester, MN USA. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [White, Wesley M.] Univ Tennessee, Knoxville, TN USA. [Lowrance, William T.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Lowrance, WT (reprint author), Univ Utah, Huntsman Canc Inst, Div Urol, Dept Surg, 1950 Circle Hope,6405, Salt Lake City, UT 84112 USA. EM will.lowrance@hci.utah.edu OI Vickers, Andrew/0000-0003-1525-6503; Rais-Bahrami, Soroush/0000-0001-9466-9925 FU NCI NIH HHS [P50 CA092629] NR 50 TC 24 Z9 24 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD SEP PY 2015 VL 194 IS 3 BP 626 EP 634 DI 10.1016/j.juro.2015.01.126 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CO4UW UT WOS:000359157200007 PM 25849602 ER PT J AU Uren, PJ Vo, DT de Araujo, PR Potschke, R Burns, SC Bahrami-Samani, E Qiao, M Abreu, RD Nakaya, HI Correa, BR Kuehnoel, C Ule, J Martindale, JL Abdelmohsen, K Gorospe, M Smith, AD Penalva, LOF AF Uren, Philip J. Vo, Dat T. de Araujo, Patricia Rosa Poetschke, Rebecca Burns, Suzanne C. Bahrami-Samani, Emad Qiao, Mei Abreu, Raquel de Sousa Nakaya, Helder I. Correa, Bruna R. Kuehnoel, Caspar Ule, Jernej Martindale, Jennifer L. Abdelmohsen, Kotb Gorospe, Myriam Smith, Andrew D. Penalva, Luiz O. F. TI RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; NEWLY-DIAGNOSED GLIOBLASTOMA; INTEGRATED GENOMIC ANALYSIS; TUMOR-CELL-PROLIFERATION; GLIOMA-CELLS; STEM-CELLS; POSTTRANSCRIPTIONAL EVENTS; SECONDARY STRUCTURE; EXPRESSION ANALYSIS; PROGENITOR CELLS AB The conserved RNA-binding protein Musashi1 (MSI1) has emerged as a key oncogenic factor in numerous solid tumors, including glioblastoma. However, its mechanism of action has not yet been established comprehensively. To identify its target genes comprehensively and determine the main routes by which it influences glioblastoma phenotypes, we conducted individual-nucleotide resolution cross-linking and immunoprecipitation (iCLIP) experiments. We confirmed that MSI1 has a preference for UAG sequences contained in a particular structural context, especially in 3' untranslated regions. Although numerous binding sites were also identified in intronic sequences, our RNA transcriptome sequencing analysis does not favor the idea that MSI1 is a major regulator of splicing in glioblastoma cells. MSI1 target mRNAs encode proteins that function in multiple pathways of cell proliferation and cell adhesion. Since these associations indicate potentially new roles for MSI1, we investigated its impact on glioblastoma cell adhesion, morphology, migration, and invasion. These processes are known to underpin the spread and relapse of glioblastoma, in contrast to other tumors where metastasis is the main driver of recurrence and progression. C1 [Uren, Philip J.; Bahrami-Samani, Emad; Smith, Andrew D.] Univ So Calif, Div Biol Sci, Mol & Computat Biol Sect, Los Angeles, CA 90089 USA. [Vo, Dat T.; de Araujo, Patricia Rosa; Burns, Suzanne C.; Qiao, Mei; Abreu, Raquel de Sousa; Correa, Bruna R.; Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Vo, Dat T.; de Araujo, Patricia Rosa; Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Poetschke, Rebecca; Kuehnoel, Caspar] Univ Med Ctr, Dept Childrens Hosp, Halle, Saale, Germany. [Nakaya, Helder I.] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, Brazil. [Nakaya, Helder I.] Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Dept Pathol, Atlanta, GA USA. [Ule, Jernej] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Martindale, Jennifer L.; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Lab Genet & Genom, NIH, Baltimore, MD 21224 USA. RP Smith, AD (reprint author), Univ So Calif, Div Biol Sci, Mol & Computat Biol Sect, Los Angeles, CA 90089 USA. EM andrewds@usc.edu RI Ule, Jernej/C-6315-2013; CEPID, CRID/J-2644-2015; OI Ule, Jernej/0000-0002-2452-4277; Nakaya, Helder/0000-0001-5297-9108 FU National Institute on Aging Intramural Research Program, National Institutes of Health; Max and Minnie Tomerlin Voelcker Fund; CPRIT (Texas) [RP140105]; Voices Against Brain Cancer; IIMS-CTRC (UTHSCSA); NIH [R01HG006015]; [1R21CA175875-01A1] FX J.L.M., K.A., and M.G. were supported by the National Institute on Aging Intramural Research Program, National Institutes of Health. This study was supported by the Max and Minnie Tomerlin Voelcker Fund, Voices Against Brain Cancer, IIMS-CTRC (UTHSCSA), NIH R01HG006015, and 1R21CA175875-01A1. P.R.D.A. is supported by CPRIT RP140105 (Texas). NR 81 TC 5 Z9 5 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2015 VL 35 IS 17 BP 2965 EP 2978 DI 10.1128/MCB.00410-15 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CO1TV UT WOS:000358939200006 PM 26100017 ER PT J AU Winn, DM Lee, YCA Hashibe, M Boffetta, P AF Winn, D. M. Lee, Y-C A. Hashibe, M. Boffetta, P. CA INHANCE Consortium TI The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer SO ORAL DISEASES LA English DT Review DE epidemiology; head and neck cancer ID UPPER AERODIGESTIVE TRACT; BODY-MASS INDEX; POOLED ANALYSIS; INTERNATIONAL HEAD; EPIDEMIOLOGY CONSORTIUM; CIGARETTE-SMOKING; ORAL-CAVITY; ALCOHOL-CONSUMPTION; MARIJUANA SMOKING; RISK-FACTORS AB The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. C1 [Winn, D. M.] NCI, Bethesda, MD 20892 USA. [Lee, Y-C A.; Hashibe, M.] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. [Lee, Y-C A.; Hashibe, M.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Boffetta, P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, P.] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. RP Hashibe, M (reprint author), Huntsman Canc Inst, Dept Family & Prevent Med, Div Publ Hlth, 2000 Circle Hope, Salt Lake City, UT 84108 USA. EM mia.hashibe@utah.edu RI LUCE, Daniele/J-9125-2015; Castellsague Pique, Xavier/N-5795-2014; Eluf-Neto, Jose/B-2522-2009; Agudo, Antonio/J-1805-2016; Benhamou, Simone/K-6554-2015; Waterboer, Tim/G-1252-2010; Curado, Maria Paula/M-6200-2013; Menvielle, Gwenn/E-7201-2017; Thomson, Peter/L-7719-2016 OI Macfarlane, Tatiana/0000-0002-9392-0812; Serraino, Diego/0000-0003-0565-8920; La Vecchia, Carlo/0000-0003-1441-897X; Kjaerheim, Kristina/0000-0003-0691-3735; Healy, Claire M/0000-0001-7940-4611; Luce, Daniele/0000-0002-1708-4584; Pawlita, Michael/0000-0002-4720-8306; Matsuo, Keitaro/0000-0003-1761-6314; Ahrens, Wolfgang/0000-0003-3777-570X; Castellsague Pique, Xavier/0000-0002-0802-3595; Eluf-Neto, Jose/0000-0001-7504-2115; Curado, Maria Paula/0000-0001-8172-2483; Diergaarde, Brenda/0000-0002-3578-6547; dal maso, luigino/0000-0001-6163-200X; Thomson, Peter/0000-0002-2007-7975 NR 37 TC 3 Z9 3 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD SEP PY 2015 VL 21 IS 6 BP 685 EP 693 DI 10.1111/odi.12342 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CO7ND UT WOS:000359345200002 PM 25809224 ER PT J AU Lopez, MF Laber, K AF Lopez, Marcelo F. Laber, Kathy TI Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake and anxiety in C57BL/6J mice SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Alcohol; Isolation; Adolescence; Enriched environment ID ALCOHOL-DRINKING; LABORATORY MICE; REARING CONDITIONS; HOUSING CONDITIONS; NESTING MATERIAL; WISTAR RATS; DRUG-ABUSE; STRESS; BEHAVIOR; VULNERABILITY AB This study was designed to determine the impact of an enriched environment in a previously established stress model of isolation during early development that induces high alcohol (ethanol) self-administration. The study was conducted with male and female C57BL/6J mice housed in isolation or in groups that were either provided or withheld enrichment during adolescence. The impact of these housing conditions was assessed during adulthood by measuring weight gain, quantifying voluntary ethanol intake, measuring plasma corticosterone levels, and assessing anxiety-like behavior. Results showed that, regardless of sex, mice that were single-housed during adolescence showed a significant increase in voluntary ethanol intake, which was not observed in isolated mice that were provided with nesting material during adolescence (compared to group-housed non-enriched control group). Basal corticosterone was not affected by housing, enrichment conditions, or sex. Corticosterone levels did not relate to levels of voluntary ethanol intake. However, corticosterone levels were higher after three weeks of ethanol intake. Surprisingly, mice that were group-housed during adolescence showed higher levels of anxietylike behavior in the light/dark test. Overall, these results indicate that housing conditions during a criticd1 developmental period can significantly modulate voluntary ethanol intake later in life. Published by Elsevier Inc. C1 [Lopez, Marcelo F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Laber, Kathy] VA Med Ctr, Charleston, SC 29425 USA. [Laber, Kathy] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. RP Lopez, MF (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,MSC 861, Charleston, SC 29425 USA. EM lopezm@musc.edu FU GLAS; [AA020929]; [AA019967]; [AA010761] FX This work was supported by the following grants: AA020929, AA019967, and AA010761 (MFL), and by 2009 GLAS (KL). NR 55 TC 5 Z9 5 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD SEP 1 PY 2015 VL 148 SI SI BP 151 EP 156 DI 10.1016/j.physbeh.2014.11.012 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA CO0CP UT WOS:000358818000018 PM 25446196 ER PT J AU Reynolds, SE Moss, B AF Reynolds, Sara E. Moss, Bernard TI Characterization of a large, proteolytically processed cowpox virus membrane glycoprotein conserved in most chordopoxviruses SO VIROLOGY LA English DT Article DE Poxvirus pathogenesis; Cowpox virus; Poxvirus membrane protein; Signal peptide cleavage; Poxvirus virulence; Poxvirus-host interactions; Poxvirus glycoprotein ID VACCINIA-VIRUS; ENDOPLASMIC-RETICULUM; GOLGI PROTEINS; BREFELDIN-A; IDENTIFICATION; MORPHOGENESIS; INFECTION; PATHWAY; MOUSE; CELLS AB Most poxvirus proteins are either highly conserved and essential for basic steps in replication or less conserved and involved in host interactions. Homologs of the CPXV219 protein, encoded by cowpox virus, are present in nearly all chordopoxvirus genera and some species have multiple copies. The CPXV219 homologs have estimated masses of greater than 200 kDa, making them the largest known poxvirus proteins. We showed that CPXV219 was expressed early in infection and cleaved into N- and C-terminal fragments that remained associated. The protein has a signal peptide and transited the secretory pathway where extensive glycosylation and proteolytic cleavage occurred. CPXV219 was located by immunofluorescence microscopy in association with the endoplasmic reticulum, Golgi apparatus and plasma membrane. In non-permeabilized cells, CPXV219 was accessible to external antibody and biotinylation. Mutants that did not express CPXV219 replicated normally in cell culture and retained virulence in a mouse respiratory infection model. Published by Elsevier Inc. C1 [Reynolds, Sara E.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, NIAID, NIH FX We thank Catherine Cotter for her assistance with tissue culture and training in laboratory techniques, and Jeffrey Americo for discussions. Patricia Earl provided assistance with animal experiment planning and execution. The Comparative Medicine Branch provided daily weights, monitoring, and animal maintenance. The Biological Imaging Section assisted with confocal microscopy. The research was supported by the Division of Intramural Research, NIAID, NIH. S.R. is a Ph.D. candidate in the Department of Cell Biology and Molecular Genetics at the University of Maryland, College Park, MD. NR 24 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP PY 2015 VL 483 BP 209 EP 217 DI 10.1016/j.virol.2015.04.014 PG 9 WC Virology SC Virology GA CO2HG UT WOS:000358976200020 PM 25980741 ER PT J AU Bindawas, SM Al Snih, S Ottenbacher, AJ Graham, J Protas, EE Markides, KS Ottenbacher, KJ AF Bindawas, Saad M. Al Snih, Soham Ottenbacher, Allison J. Graham, James Protas, Elizabeth E. Markides, Kyriakos S. Ottenbacher, Kenneth J. TI Association Between Lower Extremity Performance and Health-Related Quality of Life in Elderly Mexican Americans SO JOURNAL OF AGING AND HEALTH LA English DT Article DE elderly; quality of life; lower extremity; Mexican Americans ID RANDOMIZED CONTROLLED-TRIAL; LOWER-BODY FUNCTION; MINI-MENTAL-STATE; OLDER-ADULTS; FUNCTIONAL LIMITATIONS; HANDGRIP STRENGTH; PHYSICAL FUNCTION; HIP FRACTURE; FALLS RISK; FOLLOW-UP AB Objective:To examine the longitudinal association between levels of lower extremity performance (LEP) and health-related quality of life (HRQoL) in older Mexican Americans aged 72 years or older participating in the Hispanic Established Population for the Epidemiological Study of the Elderly (2000-2006). Method: LEP was measured in 621 non-institutionalized participants with the Short Physical Performance Battery (SPPB). Participants were divided into high (SPPB score 10-12), intermediate (SPPB score 7-9), and low (SPPB score 0-6) groups based on LEP. HRQoL was assessed using the Medical Outcomes Study Short Form (SF-36), which includes a Physical Composite Scale (PCS) and a Mental Composite Scale (MCS). Results: Participants in the high LEP group had slower rates of decline in the PCS, and those in the intermediate LEP group had slower rates of decline in the MCS score over time. Discussion: Increased LEP was associated with slower rates of decline in physical and mental HRQoL in older Mexican Americans. C1 [Bindawas, Saad M.] King Saud Univ, Riyadh 11433, Saudi Arabia. [Al Snih, Soham; Graham, James; Protas, Elizabeth E.; Markides, Kyriakos S.; Ottenbacher, Kenneth J.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Ottenbacher, Allison J.] NCI, Bethesda, MD 20892 USA. RP Bindawas, SM (reprint author), King Saud Univ, Dept Rehabil Sci, Coll Appl Med Sci, POB 10219, Riyadh 11433, Saudi Arabia. EM sbindawas@ksu.edu.sa FU National Institutes of Health [R01AG10939, R01AG17638, R24HD065702]; UTMB Claude D. Pepper Older Americans Independence Center [P30 AG024832]; King Abdulaziz City for Science and Technology [AT-34-343] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the National Institutes of Health (R01AG10939, Kyriakos S. Markides, PI; R01AG17638, R24HD065702, Kenneth J. Ottenbacher, PI) and by the UTMB Claude D. Pepper Older Americans Independence Center (P30 AG024832). Saad M. Bindawas was supported by a research grant from King Abdulaziz City for Science and Technology (AT-34-343). NR 56 TC 1 Z9 1 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 EI 1552-6887 J9 J AGING HEALTH JI J. Aging Health PD SEP PY 2015 VL 27 IS 6 BP 1026 EP 1045 DI 10.1177/0898264315572115 PG 20 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA CN8ZA UT WOS:000358733500005 PM 25804900 ER PT J AU Bush, CA Cisar, JO Yang, JH AF Bush, C. Allen Cisar, John O. Yang, Jinghua TI Structures of Capsular Polysaccharide Serotypes 35F and 35C of Streptococcus pneumoniae Determined by Nuclear Magnetic Resonance and Their Relation to Other Cross-Reactive Serotypes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BIOSYNTHETIC LOCI; DISCOVERY; STRAINS AB The structures of Streptococcus pneumoniae capsular polysaccharides (CPSs) are essential for defining the antigenic as well as genetic relationships between CPS serotypes. The four serotypes that comprise CPS serogroup 35 (i.e., types 35F, 35A, 35B, and 35C) are known to cross-react with genetically related type 20, 29, 34, 42, or 47F. While the structures of CPS serotype 35A (CPS35A) and CPS35B are known, those of CPS35F and CPS35C are not. In the present study, the serotypes of CPS35F and CPS35C were characterized by high-resolution heteronuclear magnetic resonance (NMR) spectroscopy and glycosyl composition analyses to reveal the following repeat unit structures: CPS35F [-6Galf-(2-OAc)-beta 1-3Gal alpha 1-2ribitol-5-PO4--3Galf beta 1-3Gal beta 1-](n) CPS35C [-6Galf beta 1-1mannitol-6-PO4--3Gal beta 1-3Galf beta 1-3Glc beta 1-](n) [GRAPHICS] where OAc indicates O-acetylated. Importantly, CPS35F, the immunizing serotype for the production of group 35 serum, more closely resembles CPS34 and CPS47F than other members of serogroup 35. Moreover, CPS35C is distinct from either CPS35F or CPS35B but closely related to CPS35A and identical to de-O-acetylated CPS42. The findings provide a comprehensive view of the structural and genetic relations that exist between the members of CPS serogroup 35 and other cross-reactive serotypes. IMPORTANCE Cross-reactions of diagnostic rabbit antisera with Streptococcus pneumoniae capsular polysaccharide serotypes are generally limited to members of the same serogroup. Exceptions do, however, occur, most notably among a group of nonvaccine serotypes that includes the members of serogroup 35 (i.e., types 35F, 35A, 35B, and 35C) and other genetically related types. The presently determined structures of S. pneumoniae serotypes 35F and 35C complete the structural characterization of serogroup 35 and thereby provide the first comprehensive description of how different members of this serogroup are related to each other and to types 29, 34, 42, and 47F. The structural and genetic features of these serotypes suggest the existence of three distinct capsular polysaccharide subgroups that presumably emerged by immune selection in the human host. C1 [Bush, C. Allen] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA. [Cisar, John O.] NIH, Microbial Receptors Sect, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. [Yang, Jinghua] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China. RP Yang, JH (reprint author), Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China. EM yangjh@im.ac.cn OI Yang, Jinghua/0000-0001-7140-5548 FU NIH [P01-HL-107153]; Intramural Research Program of the NIH, NIDCR; National Natural Science Foundation of China [31470003] FX This work was supported by NIH grant P01-HL-107153 (to C.A.B.), the Intramural Research Program of the NIH, NIDCR (to J.O.C.), and grant 31470003 from the National Natural Science Foundation of China (to J.Y.). NR 20 TC 1 Z9 1 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2015 VL 197 IS 17 BP 2762 EP 2769 DI 10.1128/JB.00207-15 PG 8 WC Microbiology SC Microbiology GA CN9RI UT WOS:000358786200004 PM 26055112 ER PT J AU Taber, DR Chriqui, JF Powell, LM Perna, FM Robinson, WR Chaloupka, FJ AF Taber, Daniel R. Chriqui, Jamie F. Powell, Lisa M. Perna, Frank M. Robinson, Whitney R. Chaloupka, Frank J. TI Socioeconomic Differences in the Association Between Competitive Food Laws and the School Food Environment SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE nutrition and diet; health policy; public health; child and adolescent health; evaluation ID UNITED-STATES; OBESITY; POLICY; CONSUMPTION; ADOLESCENTS; DISPARITIES; PREVALENCE; STANDARDS; HEALTH; IMPLEMENTATION AB BACKGROUNDSchools of low socioeconomic status (SES) tend to sell fewer healthy competitive foods/beverages. This study examined whether state competitive food laws may reduce such disparities. METHODSSchool administrators for fifth- and eighth grade reported foods and beverages sold in school. Index measures of the food/beverage environments were constructed from these data. Schools were classified into SES tertiles based on median household income of students' postal zip code. Regression models were used to estimate SES differences in (1) Healthy School Food Environment Index (HSFEI) score, Healthy School Beverage Environment Index (HSBEI) score, and specific food/beverage sales, and (2) associations between state competitive food/beverage laws and HSFEI score, HSBEI score, and specific food/beverage sales. RESULTSStrong competitive food laws were positively associated with HSFEI in eighth grade, regardless of SES. Strong competitive beverage laws were positively associated with HSBEI particularly in low-SES schools in eighth grade. These associations were attributable to schools selling fewer unhealthy items, not providing healthy alternatives. High-SES schools sold more healthy items than low-SES schools regardless of state laws. CONCLUSIONSStrong competitive food laws may reduce access to unhealthy foods/beverages in middle schools, but additional initiatives are needed to provide students with healthy options, particularly in low-SES areas. C1 [Taber, Daniel R.] Univ Texas Hlth Sci Ctr Houston, Hlth Promot & Behav Sci, Austin, TX 78701 USA. [Chriqui, Jamie F.; Powell, Lisa M.] Univ Illinois, Hlth Policy & Adm, Chicago, IL 60608 USA. [Perna, Frank M.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Robinson, Whitney R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Epidemiol, Chapel Hill, NC 27599 USA. [Chaloupka, Frank J.] Univ Illinois, Econ, Chicago, IL 60608 USA. [Chaloupka, Frank J.] Univ Illinois, Ctr Hlth Policy, Chicago, IL 60608 USA. RP Taber, DR (reprint author), Univ Texas Hlth Sci Ctr Houston, Hlth Promot & Behav Sci, Hlth Promot Behav Sci, Austin Reg Campus, Austin, TX 77030 USA. EM Daniel.Taber@uth.tmc.edu; jchriqui@uic.edu; powelll@uic.edu; pernafm@mail.nih.gov; whitney_robinson@unc.edu; fjc@uic.edu FU Robert Wood Johnson Foundation; National Heart, Lung, and Blood Institute [R01HL096664]; National Institute of Child Health and Human Development [R00HD073271] FX Support for this research was provided by the Robert Wood Johnson Foundation to the Bridging the Gap program located within the Health Policy Center at the University of Illinois at Chicago (PI: F.C.), by grant number R01HL096664 from the National Heart, Lung, and Blood Institute (PI: L.P.), and by grant number R00HD073271 from the National Institute of Child Health and Human Development (PI: D.T.). The views expressed herein are solely those of the authors and do not reflect the official views or positions of the Robert Wood Johnson Foundation; the National Heart, Lung, and Blood Institute; the National Institute of Child Health and Human Development; or the National Institutes of Health. NR 39 TC 3 Z9 3 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 EI 1746-1561 J9 J SCHOOL HEALTH JI J. Sch. Health PD SEP PY 2015 VL 85 IS 9 BP 578 EP 586 DI 10.1111/josh.12288 PG 9 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA CN4TU UT WOS:000358423900002 PM 26201754 ER PT J AU Widemann, BC AF Widemann, Brigitte C. TI Practical considerations for the administration of glucarpidase in high-dose methotrexate (HDMTX) induced renal dysfunction SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID CANCER-PATIENTS; LEUCOVORIN; NEPHROTOXICITY; THYMIDINE; THERAPY; PLASMA C1 NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Widemann, BC (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5750, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2015 VL 62 IS 9 BP 1512 EP 1513 DI 10.1002/pbc.25577 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CN8NL UT WOS:000358697800003 PM 25940351 ER PT J AU Kim, A Widemann, BC Krailo, M Jayaprakash, N Fox, E Weigel, B Blaney, SM AF Kim, AeRang Widemann, Brigitte C. Krailo, Mark Jayaprakash, Nalini Fox, Elizabeth Weigel, Brenda Blaney, Susan M. TI Phase 2 trial of sorafenib in children and young adults with refractory solid tumors: A report from the Children's Oncology Group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE pediatrics; solid tumors; sorafenib ID PAPILLARY THYROID-CARCINOMA; PRECLINICAL TESTING PROGRAM; RENAL-CELL CARCINOMA; SOFT-TISSUE SARCOMAS; I CONSORTIUM REPORT; HEPATOCELLULAR-CARCINOMA; ANTIANGIOGENIC THERAPY; MULTIKINASE INHIBITOR; WILMS-TUMOR; CANCER AB BackgroundSorafenib is an oral small molecule inhibitor of multiple kinases controlling tumor growth and angiogenesis. The purpose of the phase 2 study was to determine the response rate of sorafenib and gain further information on the associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in children and young adults with relapsed or refractory tumors including rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC). ProcedureSorafenib, 200mg/m(2)/dose, was administered every 12hr continuously for 28 day cycles using a two-stage design in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata (HCC and PTC). Correlative studies in consenting patients included determination of sorafenib steady state trough concentrations and assessments of VEGF and sVEGFR2. ResultsTwenty patients (median age of 11 years; range, 5-21) enrolled. No objective responses (RECIST) were observed in the 10 evaluable patients enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated with an excessive rate of dose-limiting toxicity (DLT). The meanSD steady state concentration during cycle 1 day 15 was 6.5 +/- 3.9g/ml (n=10). ConclusionsSorafenib was well tolerated in children at 200mg/m(2)/dose twice daily on a continuous regimen with toxicity profile and steady state drug concentrations similar to those previously reported. Single agent sorafenib was inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms tumor. Pediatr Blood Cancer 2015;62:1562-1566. (c) 2015 Wiley Periodicals, Inc. C1 [Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Widemann, Brigitte C.; Jayaprakash, Nalini] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Krailo, Mark] Childrens Oncol Grp Stat, Monrovia, CA USA. [Fox, Elizabeth] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Weigel, Brenda] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Blaney, Susan M.] Baylor Coll Med, Houston, TX 77030 USA. RP Kim, A (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM aekim@childrensnational.org FU Children's Oncology Group; National Cancer Institute (NCI) of the National Institutes of Health (NIH) [U10 CA180886, U10 CA98543, SDC U10 CA98413] FX Research reported in this publication was supported by the Children's Oncology Group (www.childrensoncologygroup.org), the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under the award number U10 CA180886 as well as Chair's U10 CA98543 & SDC U10 CA98413. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 32 TC 4 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2015 VL 62 IS 9 BP 1562 EP 1566 DI 10.1002/pbc.25548 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CN8NL UT WOS:000358697800013 PM 26207356 ER PT J AU Saligan, LN Olson, K Filler, K Larkin, D Cramp, F Yennurajalingam, S Escalante, CP del Giglio, A Kober, KM Kamath, J Palesh, O Mustian, K AF Saligan, Leorey N. Olson, Karin Filler, Kristin Larkin, David Cramp, Fiona Yennurajalingam, Sriram Escalante, Carmen P. del Giglio, Auro Kober, Kord M. Kamath, Jayesh Palesh, Oxana Mustian, Karen CA Multinatl Assoc Supportive Care TI The biology of cancer-related fatigue: a review of the literature (vol 23, pg 2461, 2015) SO SUPPORTIVE CARE IN CANCER LA English DT Correction C1 [Saligan, Leorey N.; Filler, Kristin] NINR, NIH, Bethesda, MD 20892 USA. [Olson, Karin] Univ Alberta, Fac Nursing, Edmonton, AB, Canada. [Larkin, David] Univ Canberra, Australian Capital Terr Hlth, Canberra, ACT 2601, Australia. [Cramp, Fiona] Univ W England, Bristol BS16 1QY, Avon, England. [Yennurajalingam, Sriram; Escalante, Carmen P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [del Giglio, Auro] Brazilian Albert Einstein Jewish Hosp, Sao Paulo, Brazil. [Kober, Kord M.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA. [Kamath, Jayesh] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Palesh, Oxana] Stanford Univ, Med Ctr, Psychiat & Behav Sci, Stanford, CA 94305 USA. [Mustian, Karen] Univ Rochester, Med Ctr, Wilmot Canc Inst, Rochester, NY 14642 USA. RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 3,Room 5E14, Bethesda, MD 20892 USA. EM saliganl@mail.nih.gov RI Kamath, Jayesh/J-7491-2013 NR 1 TC 0 Z9 0 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD SEP PY 2015 VL 23 IS 9 BP 2853 EP 2853 DI 10.1007/s00520-015-2815-5 PG 1 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CN8GJ UT WOS:000358677600043 PM 26081598 ER PT J AU Deprez, F Pallotto, M Vogt, F Grabiec, M Virtanen, MA Tyagarajan, SK Panzanelli, P Fritschy, JM AF Deprez, Francine Pallotto, Marta Vogt, Fabia Grabiec, Marta Virtanen, Mari A. Tyagarajan, Shiva K. Panzanelli, Patrizia Fritschy, Jean-Marc TI Postsynaptic gephyrin clustering controls the development of adult-born granule cells in the olfactory bulb SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE adult neurogenesis; dendrites; GABA; lentiviruses; postsynaptic density; phosphorylation; spines; RRID:AB_1586992; RRID:AB_10000240; RRID:AB_887725; RRID:AB_887717; RRID:AB_1501344; RRID:AB_887869; RRID:AB_887869; RRID:AB_2315546 ID VESICULAR GLUTAMATE TRANSPORTERS; NEWLY GENERATED NEURONS; SYNTHASE KINASE 3-BETA; SYNAPTIC INTEGRATION; DEPENDENT MECHANISM; GABAERGIC SYNAPSES; DENDRITIC GROWTH; GABA(A) RECEPTOR; NEWBORN NEURONS; NEUROGENESIS AB In adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrinthe main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic densityand are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult-born GCs, we observed that overexpression of the phospho-deficient gephyrin mutant eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of 2-GABA(A)Rs. In contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long-term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were comparable to those infected with eGFP alone. The opposite effects induced by the two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic synapses orchestrates signaling cascades acting on the cytoskeleton to regulate neuronal growth and synapse formation. Specifically, gephyrin phosphorylation emerges as a novel mechanism regulating morphological differentiation and long-term survival of adult-born olfactory bulb neurons. J. Comp. Neurol. 523:1998-2016, 2015 (c) 2015 Wiley Periodicals, Inc. C1 [Deprez, Francine; Vogt, Fabia; Grabiec, Marta; Tyagarajan, Shiva K.; Fritschy, Jean-Marc] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland. [Deprez, Francine; Tyagarajan, Shiva K.; Fritschy, Jean-Marc] ETH, Neurosci Ctr Zurich, Zurich, Switzerland. [Deprez, Francine; Tyagarajan, Shiva K.; Fritschy, Jean-Marc] Univ Zurich, CH-8057 Zurich, Switzerland. [Pallotto, Marta] NINDS, Circuit Dynam & Connect Unit, NIH, Bethesda, MD 20892 USA. [Virtanen, Mari A.] Univ Geneva, Dept Neurosci Fondamentales CMU, CH-1211 Geneva, Switzerland. [Panzanelli, Patrizia] Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy. RP Fritschy, JM (reprint author), Univ Zurich, Inst Pharmacol & Toxicol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM fritschy@pharma.uzh.ch RI Tyagarajan, Shiva/P-3135-2015 OI Tyagarajan, Shiva/0000-0003-0074-1805 FU Swiss National Science Foundation [310030_146120]; IBRO-SNSF, Swiss Society for Neuroscience [PAIBP3-133278] FX Grant sponsor: Swiss National Science Foundation; Grant number: 310030_146120 (to J.M.F.), and international short-visit grant (to M.P.); Grant sponsor: IBRO-SNSF, Swiss Society for Neuroscience; Grant number: PAIBP3-133278 (to M.G.). NR 43 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 1 PY 2015 VL 523 IS 13 BP 1998 EP 2016 DI 10.1002/cne.23776 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA CN2CT UT WOS:000358228700008 PM 25772192 ER PT J AU DeGrazia, D AF DeGrazia, David TI The Ethics of Animal Research SO JOURNAL OF VALUE INQUIRY LA English DT Book Review C1 [DeGrazia, David] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [DeGrazia, David] George Washington Univ, Dept Philosophy, Washington, DC 20052 USA. RP DeGrazia, D (reprint author), George Washington Univ, Dept Philosophy, Washington, DC 20052 USA. EM ddd@gwu.edu FU NIH FX The views expressed are the author's own. They do not represent the position or policy of the NIH, the DHHS, or the U.S. government. This work was supported by NIH intramural funds. NR 1 TC 0 Z9 0 U1 4 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0022-5363 EI 1573-0492 J9 J VALUE INQUIRY JI J. Value Inq. PD SEP PY 2015 VL 49 IS 3 BP 485 EP 490 DI 10.1007/s10790-014-9414-4 PG 6 WC Ethics; Philosophy SC Social Sciences - Other Topics; Philosophy GA CN1ZQ UT WOS:000358220200011 ER PT J AU Webber, ES Bonci, A Krashes, MJ AF Webber, Emily S. Bonci, Antonello Krashes, Michael J. TI The elegance of energy balance: Insight from circuit-level manipulations SO SYNAPSE LA English DT Review DE optogenetics; feeding behaviors; chemogenetics ID AGOUTI-RELATED PROTEIN; ARCUATE NUCLEUS NEURONS; MELANOCORTIN-4 RECEPTOR; POMC NEURONS; FOOD-INTAKE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; HYPOTHALAMIC NEURONS; NEURAL ACTIVITY; AGRP NEURONS AB Mechanisms of energy balance were first examined using very powerful neuroscience techniques such as lesions and electrical stimulation. This early work identified the hypothalamus as a key structure involved in hunger and feeding; however, neural resolution of cell-defined populations contributing to appetite regulation remained elusive. Recent innovations in neuroscience have produced constructs that allow for a high degree of specificity in loss- and gain-of-function manipulations in molecularly circumscribed neural subsets as well as monosynaptic circuit mapping and in vivo neurophysiology. These complimentary techniques have provided researchers an unprecedented amount of empirical agility. As a result, cell populations in two subregions of the hypothalamus have emerged as key players in the physiological control of feeding behavior. The arcuate nucleus of the hypothalamus and the paraventricular nucleus of the hypothalamus contain neural populations that have a direct role in the promotion of hunger and satiety. These include neurons that express agouti-related peptide, pro-opiomelanocortin, single-minded homolog 1 protein, and the melanocortin-4 receptor. This review focuses on how these neural subsets communicate with one another, link up to build elaborate networks, and ultimately contribute to alterations in food intake. The continuing advancement of neuroscience tools, as well as a multimodal integration of findings, will be critical in illuminating an exhaustive and clinically relevant hunger circuit. Synapse 69:461-474, 2015. (c) 2015 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA. Synapse published by Wiley Periodicals, Inc. C1 [Webber, Emily S.; Krashes, Michael J.] Natl Inst Diabet, Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Bonci, Antonello; Krashes, Michael J.] NIDA, NIH, Baltimore, MD 21224 USA. RP Bonci, A (reprint author), NIDA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM antonello.bonci@nih.gov; michael.krashes@nih.gov NR 103 TC 3 Z9 3 U1 2 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD SEP PY 2015 VL 69 IS 9 BP 461 EP 474 DI 10.1002/syn.21837 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CN5AA UT WOS:000358440500005 PM 26126768 ER PT J AU Habicht, KL Singh, NS Indig, FE Wainer, IW Moaddel, R Shimmo, R AF Habicht, K-L. Singh, N. S. Indig, F. E. Wainer, I. W. Moaddel, R. Shimmo, R. TI The development of mitochondrial membrane affinity chromatography columns for the study of mitochondrial transmembrane proteins SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Mitochondrial membrane affinity chromatography; Translocator protein ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; PERMEABILITY TRANSITION PORE; TRANSLOCATOR PROTEIN; STATIONARY PHASES; BINDING; DIPYRIDAMOLE; NUCLEAR; STRESS; LIGAND; POTENT AB Mitochondrial membrane fragments from U-87 MG (U87MG) and HEK-293 cells were successfully immobilized onto immobilized artificial membrane (LAM) chromatographic support and surface of activated open tubular (OT) silica capillary, resulting in mitochondrial membrane affinity chromatography (MMAC) columns. Translocator protein (TSPO), located in mitochondrial outer membrane as well as sulfonylurea and mitochondrial permeability transition pore (mPTP) receptors, localized to the inner membrane, were characterized. Frontal displacement experiments with multiple concentrations of dipyridamole (DIPY) and PR-11195 were run on MMAC (U87MG) column, and the binding affinities (K-d) determined were 1.08 +/- 0.49 and 0.0086 +/- 0.0006 mu M, respectively, consistent with previously reported values. Furthermore, binding affinities (K-i) for DIPY binding site were determined for TSPO ligands, PK-11195, mesoporphyrin IX, protoporphyrin IX, and rotenone. In addition, the relative ranking of these TSPO ligands based on single displacement studies using DIPY as marker on MMAC (U87MG) was consistent with the obtained K-i values. The immobilization of mitochondrial membrane fragments was also confirmed by confocal microscopy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Habicht, K-L.; Shimmo, R.] Tallinn Univ, Inst Math & Nat Sci, Dept Nat Sci, EE-10120 Tallinn, Estonia. [Habicht, K-L.; Singh, N. S.; Indig, F. E.; Wainer, I. W.; Moaddel, R.] Natl Inst Aging, Biomed Res Ctr, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Shimmo, R (reprint author), Tallinn Univ, Inst Math & Nat Sci, Dept Nat Sci, EE-10120 Tallinn, Estonia. EM ruth.shimmo@tlu.ee RI Singh, Nagendra/K-8966-2015 FU National Institutes of Health (NIH); European Union through the European Regional Development Fund (Centre of Excellence, "Mesosystems: Theory and Applications.") [TK114]; Estonian Ministry of Education and Research [SF0130010s12]; European Social Fund's Doctoral Studies and Internationalization Programme DoRa FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH). Financial support was also provided by the European Union through the European Regional Development Fund (Centre of Excellence, "Mesosystems: Theory and Applications." TK114) and by the Estonian Ministry of Education and Research (targeted financing no. SF0130010s12, K-L.H. and R.S.). K-L.H. was also supported by European Social Fund's Doctoral Studies and Internationalization Programme DoRa, which is carried out by Foundation Archimedes. NR 38 TC 0 Z9 0 U1 6 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2015 VL 484 BP 154 EP 161 DI 10.1016/j.ab.2015.05.018 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CM8QU UT WOS:000357967500026 PM 26049098 ER PT J AU Driscoll, KA Young-Hyman, D AF Driscoll, Kimberly A. Young-Hyman, Deborah TI Use of Technology When Assessing Adherence to Diabetes Self-Management Behaviors SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetes; Technology; Blood glucose monitors; Insulin pumps; Physical activity; Medical nutrition therapy; Insulin pumps; Continuous glucose monitors; Health literacy; Insulin pens; Patient adherence; Provider adherence; Diabetes self-management behaviors ID INSULIN-PUMP THERAPY; GLUCOSE MONITORING-SYSTEM; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PROFESSIONALS; HEMOGLOBIN A(1C) LEVELS; GLYCEMIC CONTROL; YOUNG-CHILDREN; BLOOD-GLUCOSE; MEDICATION ADHERENCE AB During the last several decades, a proliferation of sophisticated technology has taken place to facilitate diabetes self-management and improve health outcomes. Blood glucose monitors, insulin pumps, and continuous glucose monitors have significant data storage capacity, which can be used to summarize diabetes health management and outcomes. In the absence of technology errors or failures, and in the context of the multiple psychosocial factors associated with nonadherence, these data have the potential to elucidate diabetes care because they reflect actual patient behaviors. This review provides a summary of the diabetes adherence literature in the context of current American Diabetes Association Clinical Practice Recommendations with a focus on studies that have used objective methods (ie, data derived from technology) to assess diabetes care provider and patient adherence in the areas of glucose monitoring; insulin administration and antihyperglycemic medications; medical nutrition therapy; and physical activity. C1 [Driscoll, Kimberly A.] Florida State Univ, Coll Med, Dept Behav Sci & Social Med, Tallahassee, FL 32306 USA. [Young-Hyman, Deborah] NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA. RP Driscoll, KA (reprint author), Florida State Univ, Coll Med, Dept Behav Sci & Social Med, 1115 W Call St, Tallahassee, FL 32306 USA. EM kimberly.driscoll@med.fsu.edu OI Driscoll, Kimberly/0000-0002-3006-4633 NR 99 TC 6 Z9 7 U1 3 U2 15 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD SEP PY 2015 VL 15 IS 9 AR 521 DI 10.1007/s11892-014-0521-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM7DZ UT WOS:000357851900004 PM 25023214 ER PT J AU Wu, HL Yoon, MY Verner, MA Xue, JP Luo, M Andersen, ME Longnecker, MP Clewell, HJ AF Wu, Huali Yoon, Miyoung Verner, Marc-Andre Xue, Jianping Luo, Man Andersen, Melvin E. Longnecker, Matthew P. Clewell, Harvey J., III TI Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics? SO ENVIRONMENT INTERNATIONAL LA English DT Article DE PFOA; PFOS; PBPK; Menarche; Female; Environmental exposure ID PERFLUOROOCTANOIC ACID PFOA; BODY-MASS INDEX; POLYFLUORINATED COMPOUNDS; TISSUE DISTRIBUTION; EXPOSURE ASSESSMENT; SULFONATE PFOS; GIRLS; AGE; SAMPLES; FLUID AB Background: An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. Objectives: To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. Methods: We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20 years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. Results: The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. Conclusion: The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Wu, Huali; Yoon, Miyoung; Luo, Man; Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA. [Verner, Marc-Andre] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Xue, Jianping] US Environm Protect Agcy, Res Triangle Pk, NC USA. [Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Yoon, MY (reprint author), Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA. OI Yoon, Miyoung/0000-0002-3653-3488; Longnecker, Matthew/0000-0001-6073-5322 FU E.I. du Pont de Nemours and Company; 3M; American Chemistry Council Long Range Research Initiative (ACC-LRI); Intramural Research Program of the National Institutes of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) FX We would like to thank Dr. Mark Russell at DuPont and Drs. Haluk Ozkaynak, Cecilia Tan, Kristin Isaacs, Paul Schlosser, and Cory Strope at the US Environmental Protection Agency for their helpful discussion on exposure description. We would like to thank Cody Peeples at the Hamner Institutes for Health Sciences for reviewing model code and equations. This study was supported by the E.I. du Pont de Nemours and Company, 3M, the American Chemistry Council Long Range Research Initiative (ACC-LRI), the Intramural Research Program of the National Institutes of Environmental Health Sciences (NIEHS), and the National Institutes of Health (NIH). MPL received no compensation from E.I. du Pont de Nemours and Company or 3M. The authors certify that their freedom to design, conduct, interpret, and publish research was not compromised by any sponsor. NR 35 TC 5 Z9 5 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD SEP PY 2015 VL 82 BP 61 EP 68 DI 10.1016/j.envint.2015.05.006 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA CM7XM UT WOS:000357909800008 PM 26043300 ER PT J AU Downey, RF Sullivan, FJ Wang-Johanning, F Ambs, S Giles, FJ Glynn, SA AF Downey, Ronan F. Sullivan, Francis J. Wang-Johanning, Feng Ambs, Stefan Giles, Francis J. Glynn, Sharon A. TI Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice? SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review DE human endogenous retrovirus; HERV-K; carcinogenesis; melanoma; breast cancer; prostate cancer; HERV-K activation; oncogenesis; immunomodulation; Env; Gag; Np9; Rec ID HUMAN-BREAST-CANCER; MELANOMA-CELL LINES; ZINC-FINGER PROTEIN; HERV-K; ENVELOPE PROTEIN; INSERTIONAL POLYMORPHISMS; PROSTATE-CANCER; NITRIC-OXIDE; ADOPTIVE IMMUNOTHERAPY; MOLECULAR-MECHANISMS AB Harbored as relics of ancient germline infections, human endogenous retroviruses (HERVs) now constitute up to 8% of our genome. A proportion of this sequence has been co-opted for molecular and cellular processes, beneficial to human physiology, such as the fusogenic activity of the envelope protein, a vital component of placentogenesis. However, the discovery of high levels of HERV-K mRNA and protein and even virions in a wide array of cancers has revealed that HERV-K may be playing a more sinister rolea role as an etiological agent in cancer itself. Whether the presence of this retroviral material is simply an epiphenomenon, or an actual causative factor, is a hotly debated topic. This review will summarize the current state of knowledge regarding HERV-K and cancer and attempt to outline the potential mechanisms by which HERV-K could be involved in the onset and promotion of carcinogenesis. C1 [Downey, Ronan F.; Sullivan, Francis J.; Giles, Francis J.; Glynn, Sharon A.] Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland. [Sullivan, Francis J.] Galway Univ Hosp, Dept Radiat Oncol, Galway, Ireland. [Wang-Johanning, Feng] SRI Int, Ctr Canc & Metab, Menlo Pk, CA USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Giles, Francis J.] Natl Univ Ireland Galway, HRB Clin Res Facil Galway & Dublin, Galway, Ireland. [Giles, Francis J.] Trinity Coll Dublin, Galway, Ireland. RP Glynn, SA (reprint author), Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland. EM sharon.glynn@nuigalway.ie OI Glynn, Sharon/0000-0003-1459-2580 FU Galway University Foundation [RNR1008]; Health Research Board of Ireland Clinical Research Facility, Galway [RSU004]; Department of Defense Breast Cancer Research Program [BC113114]; Breast Cancer Campaign UK [2013MayPR019]; Irish Cancer Society [PCT13MCD] FX Grant sponsor: Galway University Foundation; Grant number: RNR1008; Grant sponsor: Health Research Board of Ireland Clinical Research Facility, Galway; Grant number: RSU004; Grant sponsor: Department of Defense Breast Cancer Research Program; Grant number: BC113114; Grant sponsor: Breast Cancer Campaign UK; Grant number: 2013MayPR019; Grant sponsor: Irish Cancer Society; Grant number: PCT13MCD NR 123 TC 16 Z9 16 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP PY 2015 VL 137 IS 6 BP 1249 EP 1257 DI 10.1002/ijc.29003 PG 9 WC Oncology SC Oncology GA CM6OT UT WOS:000357808900006 PM 24890612 ER PT J AU Zhang, C Xu, YJ Hao, Q Wang, SN Li, H Li, JL Gao, Y Li, M Li, WN Xue, XC Wu, SZ Zhang, YQ Zhang, W AF Zhang, Cun Xu, Yujin Hao, Qiang Wang, Shuning Li, Hong Li, Jialin Gao, Yuan Li, Meng Li, Weina Xue, Xiaochang Wu, Shouzhen Zhang, Yingqi Zhang, Wei TI FOXP3 suppresses breast cancer metastasis through downregulation of CD44 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID IN-VIVO; CHEMOKINE RECEPTOR; CELL MOTILITY; T-CELLS; EXPRESSION; TRANSCRIPTION; INHIBITION; REPRESSOR; GROWTH; CXCR4 AB Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis. What's New? FOXP3 is an X-linked tumor suppressor gene that influences mammary carcinogenesis by acting as a transcriptional repressor of breast cancer oncogenes such as SKP2 and HER2. The present study examined the role of FOXP3 in breast cancer metastasis. In vivo and in vitro experiments demonstrated that FOXP3 inhibited breast cancer cell adhesion, invasion and metastasis, while study on the molecular mechanism revealed that FOXP3 inhibited breast cancer metastasis by down-regulating CD44 expression directly. C1 [Zhang, Cun; Xu, Yujin; Hao, Qiang; Wang, Shuning; Li, Jialin; Gao, Yuan; Li, Meng; Li, Weina; Xue, Xiaochang; Wu, Shouzhen; Zhang, Yingqi; Zhang, Wei] Fourth Mil Med Univ, Sch Pharm, Ctr Biotechnol, State Key Lab Canc Biol, Xian 710032, Peoples R China. [Li, Hong] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Zhang, YQ (reprint author), Fourth Mil Med Univ, Sch Pharm, Ctr Biotechnol, State Key Lab Canc Biol, 17 Changle West Rd, Xian 710032, Peoples R China. EM zhangyqh@fmmu.edu.cn; zhangw90@fmmu.edu.cn RI xue, xiaochang/N-2985-2014 OI xue, xiaochang/0000-0001-9875-9821 FU National Nature Science Foundation of China [81472484, 81001182, 81171978, 81402439, 30900537, 31000406, 30971188] FX Grant sponsor: National Nature Science Foundation of China; Grant numbers: 81472484, 81001182, 81171978, 81402439, 30900537, 31000406 and 30971188 NR 41 TC 8 Z9 9 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP PY 2015 VL 137 IS 6 BP 1279 EP 1290 DI 10.1002/ijc.29482 PG 12 WC Oncology SC Oncology GA CM6OT UT WOS:000357808900009 PM 25683728 ER PT J AU Mauldin, IS Wang, E Deacon, DH Olson, WC Bao, YD Slingluff, CL AF Mauldin, Ileana S. Wang, Ena Deacon, Donna H. Olson, Walter C. Bao, Yongde Slingluff, Craig L., Jr. TI TLR2/6 agonists and interferon-gamma induce human melanoma cells to produce CXCL10 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE melanoma; immune therapy; toll-like receptor; migration; tumor infiltration ID MACROPHAGE-ACTIVATING LIPOPEPTIDE-2; METASTATIC MELANOMA; IFN-GAMMA; CHEMOKINE EXPRESSION; SIGNALING PATHWAYS; GENE-THERAPY; T-CELLS; TUMOR; IMMUNOTHERAPY; PHASE AB Clinical approaches to treat advanced melanoma include immune therapies, whose benefits depend on tumor-reactive T-cell infiltration of metastases. However, most tumors lack significant immune infiltration prior to therapy. Selected chemokines promote T-cell migration into tumors; thus, agents that induce these chemokines in the tumor microenvironment (TME) may improve responses to systemic immune therapy. CXCL10 has been implicated as a critical chemokine supporting T-cell infiltration into the TME. Here, we show that toll-like receptor (TLR) agonists can induce chemokine production directly from melanoma cells when combined with IFN treatment. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize with interferon-gamma (IFN) to induce production of CXCL10 from melanoma cells. Furthermore, melanoma cells and immune cells from surgical specimens also respond to TLR2/6 agonists and IFN by upregulating CXCL10 production, compared to treatment with either agent alone. Collectively, these data identify a novel mechanism for inducing CXCL10 production directly from melanoma cells, with TLR2/6 agonists +IFN and raise the possibility that intratumoral administration of these agents may improve immune signatures in melanoma and have value in combination with other immune therapies, by supporting T-cell migration into melanoma metastases. What's New? Agents that boost the immune response against melanoma have shown promise in stemming the spread of disease, but their success depends on T-cell infiltration, in which chemokines recruit immune cells into the tumor microenvironment. The authors of the present study describe a novel means of stimulating the production of the T-cell-attracting chemokine CXCL10 by human melanoma cells, via the synergistic effects of toll-like receptor (TLR) agonists and interferon-gamma (IFN). The combined used of a TLR2/6 agonist with IFN significantly enhanced CXCL10 production over either treatment alone. The findings warrant further investigation of strategies to enhance T-cell infiltration in melanoma. C1 [Mauldin, Ileana S.; Deacon, Donna H.; Olson, Walter C.; Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Wang, Ena] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Bao, Yongde] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA. RP Slingluff, CL (reprint author), POB 800709, Charlottesville, VA 22908 USA. EM cls8h@virginia.edu FU UVA Cancer Center Grant [P30 CA044579]; Farrow Fellowship; Rebecca Harris Fellowship FX Grant sponsor: UVA Cancer Center Grant; Grant number: P30 CA044579; Grant sponsors: the Farrow Fellowship (ISM) and Rebecca Harris Fellowship (ISM) NR 37 TC 2 Z9 2 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP PY 2015 VL 137 IS 6 BP 1386 EP 1396 DI 10.1002/ijc.29515 PG 11 WC Oncology SC Oncology GA CM6OT UT WOS:000357808900018 PM 25765738 ER PT J AU Mumford, SL Kim, S Chen, Z Gore-Langton, RE Barr, DB Louis, GMB AF Mumford, Sunni L. Kim, Sungduk Chen, Zhen Gore-Langton, Robert E. Barr, Dana Boyd Louis, Germaine M. Buck TI Persistent organic pollutants and semen quality: The LIFE Study SO CHEMOSPHERE LA English DT Article DE Male fecundity; Persistent organic pollutants; Polybrominated diphenyl ethers; Polychlorinated biphenyls; Semen quality; Sperm ID MALE REPRODUCTIVE FUNCTION; CHROMATIN STRUCTURE ASSAY; POLYCHLORINATED-BIPHENYLS; HUMAN-SERUM; SPERM CONCENTRATION; HEALTHY-MEN; EXPOSURE; P,P'-DDE; NONSMOKERS; POPULATION AB Growing evidence suggests that persistent environmental chemicals such as polychlorinated biphenyls may adversely affect human fecundity. The purpose of this study was to evaluate associations between persistent environmental chemicals and semen quality among 501 male partners of couples discontinuing contraception for purposes of becoming pregnant. Men provided a blood specimen and two fresh semen samples collected approximately a month apart that underwent next day analysis for 35 semen quality endpoints. Serum samples were analyzed for 36 polychlorinated biphenyls (congeners #18, 28, 44, 49, 52, 66, 74, 87, 99, 101, 114, 118, 128, 138, 146, 149, 151, 153, 156, 157, 167, 170, 172, 177, 178, 180, 183, 187, 189, 194, 195, 196, 201, 206, 209); I polybrominated biphenyl (#153); 9 organochlorine pesticides; and 10 polybrominated diphenyl ethers (congeners #17, 28, 47, 66, 85, 99, 100, 153, 154183) using high resolution mass spectrometry. To estimate the effect of chemicals on semen quality, we regressed each semen marker on each chemical while adjusting for research site, age, body mass index, serum lipids, and cotinine levels. Males with chemical concentrations in the fourth quartile, as compared to the first quartile, showed significant associations for several individual chemicals in each chemical class and type of semen quality parameter indicating negative and positive associations with semen quality. Polybrominated diphenyl ethers in particular were associated with several measures of increased abnormal morphology. These exploratory results highlight the role of environmental influences on male fecundity, and are of particular interest given the ubiquitous exposures to these compounds. Published by Elsevier Ltd. C1 [Mumford, Sunni L.; Kim, Sungduk; Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA. [Gore-Langton, Robert E.] EMMES Corp, Rockville, MD USA. [Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA. EM mumfords@mail.nih.gov; kims2@mail.nih.gov; chenzhe@mail.nih.gov; rlangton@emmes.com; dbbarr@emory.edu; louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). We acknowledge the Reproductive Health Assessment Team, Biomonitoring and Health Assessment Branch, National Institute for Occupational Health and Safety (NIOSH) for the analysis of semen samples under a Memo of Understanding with the NICHD. We also acknowledge Andreas Sjodin, John T. Bernert and Pam Olive for analysis of chemical and lipid concentrations in serum. NR 45 TC 4 Z9 5 U1 2 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 EI 1879-1298 J9 CHEMOSPHERE JI Chemosphere PD SEP PY 2015 VL 135 BP 427 EP 435 DI 10.1016/j.chemosphere.2014.11.015 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA CL1YN UT WOS:000356740900055 PM 25441930 ER PT J AU Monteiro, T Rodrigues, PR Goncalves, AL Moura, JJG Jubete, E Anorga, L Piknova, B Schechter, AN Silveira, CM Almeida, MG AF Monteiro, Tiago Rodrigues, Patricia R. Goncalves, Ana Luisa Moura, Jose J. G. Jubete, Elena Anorga, Larraitz Piknova, Barbora Schechter, Alan N. Silveira, Celia M. Gabriela Almeida, M. TI Construction of effective disposable biosensors for point of care testing of nitrite SO TALANTA LA English DT Article DE Point of care testing; Nitrite; Cytochrome c nitrite reductase; Biosensors; Screen printed electrodes; Carbon conductive ink ID DESULFOVIBRIO-DESULFURICANS ATCC-27774; ELECTROCHEMICAL CHARACTERIZATION; CARBON NANOFIBER; REDUCTASE; ELECTRODES; BIOLOGY; NITRATE; LACTATE; SYSTEMS AB In this paper we aim to demonstrate, as a proof-of-concept, the feasibility of the mass production of effective point of care tests for nitrite quantification in environmental, food and clinical samples. Following our previous work on the development of third generation electrochemical biosensors based on the ammonia forming nitrite reductase (ccNiR), herein we reduced the size of the electrodes' system to a miniaturized format, solved the problem of oxygen interference and performed simple quantification assays in real samples. In particular, carbon paste screen printed electrodes (SPE) were coated with a ccNiR/carbon ink composite homogenized in organic solvents and cured at low temperatures. The biocompatibility of these chemical and thermal treatments was evaluated by cyclic voltammetry showing that the catalytic performance was higher with the combination acetone and a 40 degrees C curing temperature. The successful incorporation of the protein in the carbon ink/solvent composite, while remaining catalytically competent, attests for ccNiR's robustness and suitability for application in screen printed based biosensors. Because the direct electrochemical reduction of molecular oxygen occurs when electroanalytical measurements are performed at the negative potentials required to activate ccNiR (ca. - 0.4 V vs Ag/AgCl), an oxygen scavenging system based on the coupling of glucose oxidase and catalase activities was successfully used. This enabled the quantification of nitrite in different samples (milk, water, plasma and urine) in a straightforward way and with small error (1-6%). The sensitivity of the biosensor towards nitrite reduction under optimized conditions was 0.55 A M-1 cm(-2) with a linear response range 0.7-370 mu M. (C) 2015 Elsevier B.V. All rights reserved. C1 [Monteiro, Tiago; Gabriela Almeida, M.] Inst Super Ciencias Saude Egas Moniz, Ctr Invest Interdisciplinar Egas Moniz CiiEM, P-2829511 Caparica, Portugal. [Monteiro, Tiago; Rodrigues, Patricia R.; Goncalves, Ana Luisa; Moura, Jose J. G.; Silveira, Celia M.; Gabriela Almeida, M.] Univ Nova Lisboa, Fac Ciencias & Tecnol, REQUIMTE, UCIBIO, P-2829516 Monte De Caparica, Portugal. [Jubete, Elena; Anorga, Larraitz] IK4 CIDETEC, Div Mat, Sensors Unit, Donostia San Sebastian 20009, Spain. [Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Silveira, Celia M.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal. RP Almeida, MG (reprint author), Inst Super Ciencias Saude Egas Moniz, Ctr Invest Interdisciplinar Egas Moniz CiiEM, Campus Univ, P-2829511 Caparica, Portugal. EM mg.almeida@fct.unl.pt RI Almeida, Maria Gabriela/D-8265-2013; Moura, Jose/D-6426-2013; Silveira, Celia/D-8348-2013 OI Almeida, Maria Gabriela/0000-0002-4508-7379; Moura, Jose/0000-0002-4726-2388; Silveira, Celia/0000-0002-4821-2358 FU Fundacao para a Ciencia e Tecnologia [SFRH/BPD/79566/2011] FX CM Silveira thanks the financial support from Fundacao para a Ciencia e Tecnologia (Post-doctoral fellowship SFRH/BPD/79566/2011). NR 30 TC 5 Z9 5 U1 8 U2 57 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 EI 1873-3573 J9 TALANTA JI Talanta PD SEP 1 PY 2015 VL 142 BP 246 EP 251 DI 10.1016/j.talanta.2015.04.057 PG 6 WC Chemistry, Analytical SC Chemistry GA CL5KB UT WOS:000356997700035 PM 26003719 ER PT J AU Ikemoto, S Yang, C Tan, A AF Ikemoto, Satoshi Yang, Chen Tan, Aaron TI Basal ganglia circuit loops, dopamine and motivation: A review and enquiry SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE Depression; Mania; Euphoria; Dorsal striatum; Global pallidus; Mediodorsal thalamic nucleus ID NUCLEUS-ACCUMBENS DOPAMINE; VENTRAL TEGMENTAL AREA; MEDIAL PREFRONTAL CORTEX; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; NIGRA PARS RETICULATA; INTRACRANIAL SELF-STIMULATION; INTRALAMINAR THALAMIC NUCLEI; CAUDATE-EVOKED INHIBITION; NEGATIVE REWARD SIGNALS; FREELY-MOVING RATS AB Dopamine neurons located in the midbrain play a role in motivation that regulates approach behavior (approach motivation). In addition, activation and inactivation of dopamine neurons regulate mood and induce reward and aversion, respectively. Accumulating evidence suggests that such motivational role of dopamine neurons is not limited to those located in the ventral tegmental area, but also in the substantia nigra. The present paper reviews previous rodent work concerning dopamine's role in approach motivation and the connectivity of dopamine neurons, and proposes two working models: One concerns the relationship between extracellular dopamine concentration and approach motivation. High, moderate and low concentrations of extracellular dopamine induce euphoric, seeking and aversive states, respectively. The other concerns circuit loops involving the cerebral cortex, basal ganglia, thalamus, epithalamus, and midbrain through which dopaminergic activity alters approach motivation. These models should help to generate hypothesis-driven research and provide insights for understanding altered states associated with drugs of abuse and affective disorders. Published by Elsevier B.V. C1 [Ikemoto, Satoshi; Yang, Chen; Tan, Aaron] NIDA, Behav Neurosci Branch, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, Natl Inst Hlth, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM sikemoto@mail.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 FU Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health FX Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health supported the authors to write the present paper. The authors would like to thank Dong Wang and Aleksandr Talishinsky for discussion concerning the manuscript. NR 253 TC 24 Z9 27 U1 4 U2 57 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 1 PY 2015 VL 290 BP 17 EP 31 DI 10.1016/j.bbr.2015.04.018 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CK9HK UT WOS:000356551000003 PM 25907747 ER PT J AU Foster, BL Ao, M Willoughby, C Soenjaya, Y Holm, E Lukashova, L Tran, AB Wimer, HF Zerfas, PM Nociti, FH Kantovitz, KR Quan, BD Sone, ED Goldberg, HA Somerman, MJ AF Foster, B. L. Ao, M. Willoughby, C. Soenjaya, Y. Holm, E. Lukashova, L. Tran, A. B. Wimer, H. F. Zerfas, P. M. Nociti, F. H., Jr. Kantovitz, K. R. Quan, B. D. Sone, E. D. Goldberg, H. A. Somerman, M. J. TI Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein SO BONE LA English DT Article DE Extracellular matrix; Mineralization; Bone; Cementum; Dentin; Cartilage ID DENTIN MATRIX PROTEIN-1; EXTRINSIC FIBER CEMENTUM; IN-VITRO; HYDROXYAPATITE FORMATION; MOUSE MODEL; SKELETAL MINERALIZATION; PERIODONTAL ATTACHMENT; EXTRACELLULAR-MATRIX; ACELLULAR CEMENTUM; SIBLING PROTEINS AB Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteodast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp(-/-) mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp(-/-) molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors. Published by Elsevier Inc. C1 [Foster, B. L.; Ao, M.; Willoughby, C.; Tran, A. B.; Nociti, F. H., Jr.; Kantovitz, K. R.; Somerman, M. J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA. [Willoughby, C.; Goldberg, H. A.] Univ Western Ontario, Biomed Engn Program, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. [Holm, E.; Goldberg, H. A.] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. [Lukashova, L.] Hosp Special Surg, New York, NY 10021 USA. [Wimer, H. F.] Smithsonian Inst, Dept Vertebrate Zool, Natl Museum Nat Hist, Washington, DC 20560 USA. [Zerfas, P. M.] Off Res Serv, NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Nociti, F. H., Jr.] Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, BR-13414903 Piracicaba, SP, Brazil. [Kantovitz, K. R.] Univ Estadual Campinas, Dept Pediat Dent, Sch Dent, BR-13414903 Piracicaba, SP, Brazil. [Quan, B. D.; Sone, E. D.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. [Sone, E. D.] Univ Toronto, Dept Mat Sci & Engn, Toronto, ON M5S 3G9, Canada. [Sone, E. D.] Univ Toronto, Fac Dent, Toronto, ON M5S 3G9, Canada. [Goldberg, H. A.] Univ Western Ontario, Sch Dent, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. RP Foster, BL (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bldg 50 Room 4120, Bethesda, MD 20892 USA. EM brian.foster@nih.gov; fnu.aomin@nih.gov; chelseawilloughby15@gmail.com; yosoenjay@uwo.ca; eholm@uwa.ca; lukashoval@hss.edu; anne.tran2@nih.gov; helen.wimer@nih.gov; patricia.zerfas@nih.gov; nociti@unicamp.br; kamilark@yahoo.com.br; bryan.quan@utoronto.ca; eli.sone@utotonto.ca; hagoldbe@uwo.ca; Martha.somerman@nih.gov RI Foster, Brian/H-8375-2015; Kantovitz, Kamila/J-4567-2013 OI Foster, Brian/0000-0003-3444-0576; Kantovitz, Kamila/0000-0003-2045-7924 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH [AR 066110]; Intramural Research Program of NIAMS; Canadian Institutes of Health Research [130572]; CIHR Institute of Musculoskeletal Health and Arthritis [134216] FX This research was supported by sources including grant AR 066110 to BLF from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH, the Intramural Research Program of NIAMS (MJS), the Canadian Institutes of Health Research (#130572; HAG), and the CIHR Institute of Musculoskeletal Health and Arthritis (#134216; EDS). We thank Kenn Holmbeck of the National Institute of Dental and Craniofacial Research (NIDCR) for assistance with microCT analysis and Nasrin Kalantari Pour (NIAMS) for assistance with histology. NR 88 TC 5 Z9 5 U1 5 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD SEP PY 2015 VL 78 BP 150 EP 164 DI 10.1016/j.bone.2015.05.007 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9LQ UT WOS:000356562000019 PM 25963390 ER PT J AU Lamour, V Henry, A Kroonen, J Nokin, MJ von Marschall, Z Fisher, LW Chau, TL Chariot, A Sanson, M Delattre, JY Turtoi, A Peulen, O Rogister, B Castronovo, V Bellahcene, A AF Lamour, Virginie Henry, Aurelie Kroonen, Jerome Nokin, Marie-Julie von Marschall, Zofia Fisher, Larry W. Chau, Tieu-Lan Chariot, Alain Sanson, Marc Delattre, Jean-Yves Turtoi, Andrei Peulen, Olivier Rogister, Bernard Castronovo, Vincent Bellahcene, Akeila TI Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE osteopontin; glioblastoma; tumor initiating cells; Sox2; EGFR ID TUMOR-INITIATING CELLS; HUMAN GLIOMA; THERAPEUTIC TARGET; BONE SIALOPROTEIN; GENE-EXPRESSION; SELF-RENEWAL; BRAIN-TUMORS; CANCER; IDENTIFICATION; PROLIFERATION AB Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including glioblastoma (GBM), the highest grade and most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating cells (GICs) implicated in progression, therapeutic resistance and recurrence. We have previously demonstrated that OPN silencing inhibited GBM cell growth in vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has been recently implicated in the acquisition of a stem cell phenotype by GBM cells. The present study is aimed to explore OPN autocrine function using shRNA silencing strategy in GICs enriched from GBM cell lines and a human primary GBM grown in EGF and bFGF defined medium. The removal of these growth factors and addition of serum induced a significant loss of OPN expression in GICs. We showed that OPN-silenced GICs were unable to grow as spheres and this capacity was restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog, key stemness transcription factors, was significantly decreased in GICs upon OPN targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was completely abrogated upon OPN silencing. Our demonstration of endogenous OPN major regulatory effects on GICs stemness phenotype and tumorigenicity implies a greater role than anticipated for OPN in GBM pathogenesis from initiation and progression to probable recurrence. What's new? Glioblastoma (GBM) is a highly malignant and aggressive brain tumor, in which poor prognosis is associated with elevated osteopontin (OPN) expression. GBM progression also is linked to the existence of glioma-initiating cells (GICs). In this study, the loss of OPN expression in GICs was associated with reduced expression of the Sox-2, Nanog, and Oct-4 transcription factors. OPN-silenced GICs also experienced a reduction in sphere growth potential in vitro and a loss of tumorigenicity in vivo. In OPN-secreting cells, the secreted protein was found to activate EGFR, thereby stimulating the Akt/mTOR/p70S6K signaling cascade, the primary pathway implicated in GBM progression. C1 [Lamour, Virginie; Henry, Aurelie; Nokin, Marie-Julie; Turtoi, Andrei; Peulen, Olivier; Castronovo, Vincent; Bellahcene, Akeila] Univ Liege, Metastasis Res Lab, GIGA Canc, B-4000 Liege, Belgium. [Kroonen, Jerome; Rogister, Bernard] Univ Liege, GIGA Neurosci, Dev Neurobiol Lab, B-4000 Liege, Belgium. [von Marschall, Zofia; Fisher, Larry W.] NIDCR, NIH, Craniofacial & Skeletal Dis Branch, DHHS, Bethesda, MD USA. [Chau, Tieu-Lan; Chariot, Alain] Univ Liege, GIGA Signal Transduct, Med Chem Lab, B-4000 Liege, Belgium. [Sanson, Marc; Delattre, Jean-Yves] UPMC, INSERM, GH Pitie Salpetriere, UMR 975, Paris, France. [Rogister, Bernard] Univ Liege, GIGA Dev, Stem Cells & Regenerat Med, B-4000 Liege, Belgium. RP Bellahcene, A (reprint author), GIGA Canc, Metastasis Res Lab, Pathol Tour, Bldg 23, B-4000 Liege, Belgium. EM A.bellahcene@ulg.ac.be OI Peulen, Olivier/0000-0002-6933-0134 FU National Fund for Scientific Research (FNRS), Belgium; Fonds Leon Fredericq (Faculty of Medicine, University of Liege); Televie; Centre Anti-Cancereux; Intramural Research Program of NIH/NIDCR FX Grant sponsor: National Fund for Scientific Research (FNRS), Belgium; Grant sponsor: Fonds Leon Fredericq (Faculty of Medicine, University of Liege); Grant sponsor: Televie; Grant sponsor: the Centre Anti-Cancereux; Grant sponsor: Intramural Research Program of NIH/NIDCR NR 49 TC 3 Z9 3 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2015 VL 137 IS 5 BP 1047 EP 1057 DI 10.1002/ijc.29454 PG 11 WC Oncology SC Oncology GA CK7RE UT WOS:000356429000005 PM 25620078 ER PT J AU Lerro, CC Koutros, S Andreotti, G Hines, CJ Blair, A Lubin, J Ma, XM Zhang, YW Beane Freeman, LE AF Lerro, Catherine C. Koutros, Stella Andreotti, Gabriella Hines, Cynthia J. Blair, Aaron Lubin, Jay Ma, Xiaomei Zhang, Yawei Beane Freeman, Laura E. TI Use of acetochlor and cancer incidence in the Agricultural Health Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE acetochlor; Agricultural Health Study; pesticides; cancer ID PESTICIDE APPLICATORS; PANCREATIC-CANCER; OCCUPATIONAL-EXPOSURE; CUTANEOUS MELANOMA; RISK; ALACHLOR; COHORT; METABOLITES; ATRAZINE; HUMANS AB Since its registration in 1994 acetochlor has become a commonly used herbicide in the US, yet no epidemiologic study has evaluated its carcinogenicity in humans. We evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. In telephone interviews administered during 1999-2005, participants provided information on acetochlor use, use of other pesticides and additional potential confounders. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (95% CI) for cancers that occurred from the time of interview through 2011 in Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor-exposed cases. Increased risk of lung cancer was observed among acetochlor users (RR=1.74; 95% CI: 1.07-2.84) compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures (RR=2.33; 95% CI: 1.30-4.17), compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users (RR=1.75; 95% CI: 1.08-2.83) compared to never users. Additionally, borderline significantly increased risk of melanoma (RR=1.61; 95% CI: 0.98-2.66) and pancreatic cancer (RR=2.36; 95% CI: 0.98-5.65) were observed among acetochlor users. The associations between acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer are suggestive, however the lack of exposure-response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions. What's new? Acetochlor is a commonly used herbicide in the U.S., yet no epidemiologic research has evaluated its carcinogenicity in humans. In this study, the authors examined the relationship between occupational exposure to acetochlor and human cancer risk in a large prospective cohort. Acetochlor use was associated with an increased risk of lung and colorectal cancer, and possibly pancreatic cancer and melanoma. Use of mixtures of acetochlor and atrazine, another widely used herbicide often applied concurrently with acetochlor, was also associated with an increased risk of lung cancer. C1 [Lerro, Catherine C.; Koutros, Stella; Andreotti, Gabriella; Blair, Aaron; Beane Freeman, Laura E.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lerro, Catherine C.; Zhang, Yawei] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA. [Hines, Cynthia J.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Lubin, Jay] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. [Ma, Xiaomei] Yale Univ, Sch Publ Hlth, Chron Dis Epidemiol Dept, New Haven, CT USA. RP Lerro, CC (reprint author), NCI, Occupat & Environm Epidemiol Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM lerrocc@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute [Z01-CP010119]; National Institute of Environmental Health Sciences [Z01-ES049030] FX Grant sponsor: Intramural Research Program of the National Institutes of Health; Grant sponsor: National Cancer Institute; Grant number: Z01-CP010119; Grant sponsor: National Institute of Environmental Health Sciences; Grant number: Z01-ES049030 NR 39 TC 7 Z9 8 U1 2 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2015 VL 137 IS 5 BP 1167 EP 1175 DI 10.1002/ijc.29416 PG 9 WC Oncology SC Oncology GA CK7RE UT WOS:000356429000017 PM 25559664 ER PT J AU Vandraas, KF Grjibovski, AM Stoer, NC Troisi, R Stephansson, O Ording, AG Vangen, S Grotmol, T Vikanes, AV AF Vandraas, Kathrine F. Grjibovski, Andrej M. Stoer, Nathalie C. Troisi, Rebecca Stephansson, Olof Ording, Anne Gulbech Vangen, Siri Grotmol, Tom Vikanes, Ase V. TI Hyperemesis gravidarum and maternal cancer risk, a scandinavian nested case-control study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE hyperemesis; cancer; registry-based; nested case-control ID MEDICAL BIRTH REGISTRY; POPULATION-BASED COHORT; WORLD-WAR-II; BREAST-CANCER; CHORIONIC-GONADOTROPIN; THYROID-CANCER; PREGNANCY; NORWAY; SMOKING; WOMEN AB Reproductive factors have been shown to influence cancer risk. Several pathological conditions during pregnancy have also been associated with subsequent altered cancer risk in the mother. Hyperemesis gravidarum (hyperemesis) is an early pregnancy condition characterized by severe nausea and vomiting resulting in weight loss and metabolic disturbances. Studies have reported associations between hyperemesis and cancer, but results are inconsistent. In this nested case-control study we linked the population-based medical birth registries and cancer registries in Norway, Sweden and Denmark in order to examine overall cancer risk and risk of specific cancer types in women with a history of hyperemesis, using conditional logistic regression. In total, 168,501 cases of cancer in addition to up to 10 cancer-free controls per case were randomly sampled, matched on year of birth and birth registry (n=1,721,626). Hyperemesis was defined through the International Classification of Diseases. Analyses were adjusted for potential confounders. Hyperemesis was inversely associated with overall cancer risk with adjusted relative risk (aRR) of 0.93 (95% CI: 0.88-0.99), with cancer in the lungs (aRR: 0.60, 95% CI: 0.44-0.81), cervix (aRR: 0.66, 95% CI: 0.49-0.91) and rectum (aRR: 0.48, 95% CI: 0.29-0.78). Thyroid cancer was positively associated with hyperemesis (aRR 1.45, 95% CI: 1.06-1.99) and risk increased with more than one hyperemetic pregnancy (aRR 1.80, 95% CI: 1.23-2.63). Hormonal factors, in particular human chorionic gonadotropin, are likely to be involved in mediating these effects. This study is the first to systematically address these associations and provides valuable knowledge on potential long-term consequences of hyperemesis. What's new? Women who experience hyperemesis gravidarum during pregnancy may have an altered risk of cancer later in life, but results have been inconsistent. In this large case-control study, the authors found that hyperemesis was inversely associated with lung, cervical, rectal, and overall cancer risk. However, the condition was also associated with an increased risk of thyroid cancer. These results suggest that further research is needed in order to identify potential mechanisms for these associations, as hyperemesis is one of the most common complications of early pregnancy. C1 [Vandraas, Kathrine F.; Vangen, Siri] Oslo Univ Hosp, Norwegian Advisory Unit WomenS Hlth, Oslo, Norway. [Vandraas, Kathrine F.; Vikanes, Ase V.] Norwegian Inst Publ Hlth, Dept Genes & Environm, NO-0403 Oslo, Norway. [Grjibovski, Andrej M.] Norwegian Inst Publ Hlth, Dept Int Publ Hlth, NO-0403 Oslo, Norway. [Grjibovski, Andrej M.] Int Kazakh Turkish Univ, Dept Prevent Med, Turkestan, Kazakhstan. [Grjibovski, Andrej M.] Northern State Med Univ, Int Sch Publ Hlth, Arkhangelsk, Russia. [Stoer, Nathalie C.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Stephansson, Olof] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Stephansson, Olof] Karolinska Univ Hosp & Inst, Div Obstet & Gynecol, Dept Women & ChildrenS Hlth, Stockholm, Sweden. [Ording, Anne Gulbech] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. [Grotmol, Tom] Canc Registry Norway, Oslo, Norway. [Vikanes, Ase V.] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. RP Vandraas, KF (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404, NO-0403 Oslo, Norway. EM kafv@fhi.no RI Grjibovski, Andrej/B-9815-2016 OI Grjibovski, Andrej/0000-0002-5464-0498 NR 50 TC 1 Z9 1 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2015 VL 137 IS 5 BP 1209 EP 1216 DI 10.1002/ijc.29475 PG 8 WC Oncology SC Oncology GA CK7RE UT WOS:000356429000021 PM 25665163 ER PT J AU Dai, MY Wu, LJ He, ZW Zhang, SS Chen, C Xu, XZ Wang, PH Gruzdev, A Zeldin, DC Wang, DW AF Dai, Meiyan Wu, Lujin He, Zuowen Zhang, Shasha Chen, Chen Xu, Xizhen Wang, Peihua Gruzdev, Artiom Zeldin, Darryl C. Wang, Dao Wen TI Epoxyeicosatrienoic Acids Regulate Macrophage Polarization and Prevent LPS-Induced Cardiac Dysfunction SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SOLUBLE EPOXIDE HYDROLASE; SPONTANEOUSLY HYPERTENSIVE-RATS; ACTIVATED RECEPTOR-GAMMA; HEME OXYGENASE-1; ANTIINFLAMMATORY PROPERTIES; CYP2J2 OVEREXPRESSION; THERAPEUTIC TARGET; ENDOTHELIAL-CELLS; M2 MACROPHAGES; LAMINAR-FLOW AB Macrophages, owning tremendous phenotypic plasticity and diverse functions, were becoming the target cells in various inflammatory, metabolic and immune diseases. Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on cardiovascular system. In the present study, we evaluated the effects of EETs treatment on macrophage polarization and recombinant adeno-associated virus (rAAV)-mediated CYP2J2 expression on lipopolysaccharide (LPS)-induced cardiac dysfunction, and sought to investigate the underlying mechanisms. In vitro studies showed that EETs (1 mu mol/L) significantly inhibited LPS-induced M1 macrophage polarization and diminished the proinflammatory cytokines at transcriptional and post-transcriptional level; meanwhile it preserved M2 macrophage related molecules expression and upregulated anti-inflammatory cytokine IL-10. Furthermore, EETs down-regulated NF-B activation and up-regulated peroxisome proliferator-activated receptors (PPAR/) and heme oxygenase 1 (HO-1) expression, which play important roles in regulating M1 and M2 polarization. In addition, LPS treatment in mice induced cardiac dysfunction, heart tissue damage and infiltration of M1 macrophages, as well as the increase of inflammatory cytokines in serum and heart tissue, but rAAV-mediated CYP2J2 expression increased EETs generation in heart and significantly attenuated the LPS-induced harmful effects, which mechanisms were similar as the in vitro study. Taken together, the results indicate that CYP2J2/EETs regulates macrophage polarization by attenuating NF-B signaling pathway via PPAR/ and HO-1 activation and its potential use in treatment of inflammatory diseases. J. Cell. Physiol. 230: 2108-2119, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Dai, Meiyan; Wu, Lujin; He, Zuowen; Zhang, Shasha; Chen, Chen; Xu, Xizhen; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Internal Med, Tongji Med Coll, Wuhan 430030, Peoples R China. [Dai, Meiyan; Wu, Lujin; He, Zuowen; Zhang, Shasha; Chen, Chen; Xu, Xizhen; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Inst Hypertens, Tongji Med Coll, Wuhan 430030, Peoples R China. [Gruzdev, Artiom; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Dept Internal Med, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China. EM dwwang@tjh.tjmu.edu.cn FU National Natural Science Foundation of China [31130031, 81400369, 81471021]; National Basic Research Program of China [2012CB518004, 2012CB517801]; Program for Changjiang Scholars and Innovative Research Team in University [IRT_14R20] FX Contract grant sponsor: National Natural Science Foundation of China;; Contract grant numbers: 31130031, 81400369, 81471021.; Contract grant sponsor: National Basic Research Program of China;; Contract grant numbers: 2012CB518004, 2012CB517801.; Contract grant sponsor: Program for Changjiang Scholars and Innovative Research Team in University;; Contract grant number: IRT_14R20. NR 51 TC 5 Z9 5 U1 3 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2015 VL 230 IS 9 BP 2108 EP 2119 DI 10.1002/jcp.24939 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CJ1HD UT WOS:000355233700012 PM 25626689 ER PT J AU Salomon-Kent, R Marom, R John, S Dundr, M Schiltz, LR Gutierrez, J Workman, J Benayahu, D Hager, GL AF Salomon-Kent, Ronit Marom, Ronit John, Sam Dundr, Miroslav Schiltz, Louis R. Gutierrez, Jose Workman, Jerry Benayahu, Dafna Hager, Gordon L. TI New Face for Chromatin-Related Mesenchymal Modulator: n-CHD9 Localizes to Nucleoli and Interacts With Ribosomal Genes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DNA-BINDING PROTEIN; RNA-POLYMERASE-I; REMODELING COMPLEX; SACCHAROMYCES-CEREVISIAE; OSTEOGENIC CELLS; TRANSCRIPTION; CHD7; MUTATIONS; BIOGENESIS; OSTEOPROGENITORS AB Mesenchymal stem cells' differentiation into several lineages is coordinated by a complex of transcription factors and co-regulators which bind to specific gene promoters. The Chromatin-Related Mesenchymal Modulator, CHD9 demonstrated in vitro its ability for remodeling activity to reposition nucleosomes in an ATP-dependent manner. Epigenetically, CHD9 binds with modified H3-(K9me2/3 and K27me3). Previously, we presented a role for CHD9 with RNA Polymerase II (Pol II)-dependent transcription of tissue specific genes. Far less is known about CHD9 function in RNA Polymerase I (Pol I) related transcription of the ribosomal locus that also drives specific cell fate. We here describe a new form, the nucleolar CHD9 (n-CHD9) that is dynamically associated with Pol I, fibrillarin, and upstream binding factor (UBF) in the nucleoli, as shown by imaging and molecular approaches. Inhibitors of transcription disorganized the nucleolar compartment of transcription sites where rDNA is actively transcribed. Collectively, these findings link n-CHD9 with RNA pol I transcription in fibrillar centers. Using chromatin immunoprecipitation (ChIP) and tilling arrays (ChIP- chip), we find an association of n-CHD9 with Pol I related to rRNA biogenesis. Our new findings support the role for CHD9 in chromatin regulation and association with rDNA genes, in addition to its already known function in transcription control of tissue specific genes. J. Cell. Physiol. 230: 2270-2280, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Salomon-Kent, Ronit; Marom, Ronit; Benayahu, Dafna] Tel Aviv Univ, Dept Cell & Dev Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Salomon-Kent, Ronit; Marom, Ronit; John, Sam; Dundr, Miroslav; Schiltz, Louis R.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Gutierrez, Jose; Workman, Jerry] Stowers Inst Med Res, Kansas City, MO USA. RP Benayahu, D (reprint author), Tel Aviv Univ, Dept Cell & Dev Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. EM dafnab@post.tau.ac.il OI Gutierrez, Jose/0000-0002-0957-2297 FU NIH; National Cancer Institute; Center for Cancer Research FX Contract grant sponsor: NIH.; Contract grant sponsor: National Cancer Institute.; Contract grant sponsor: Center for Cancer Research. NR 48 TC 0 Z9 0 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2015 VL 230 IS 9 BP 2270 EP 2280 DI 10.1002/jcp.24960 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CJ1HD UT WOS:000355233700027 PM 25689118 ER PT J AU Luo, X Jin, CH Zhou, ZH Liu, XW Zhang, FQ Zhang, F Zhu, JZ Wang, Y Cheng, ZH Shugart, YY AF Luo, Xin Jin, Chunhui Zhou, Zhenhe Liu, Xiaowei Zhang, Fuquan Zhang, Feng Zhu, Jianzhong Wang, Ying Cheng, Zaohuo Shugart, Yin Yao TI New findings support the association of DISCI genetic variants with susceptibility to schizophrenia in the Han Chinese population SO PSYCHIATRY RESEARCH LA English DT Letter ID RISK; NEUROGENESIS; FAMILIES; LINKAGE; SAMPLE; LOCUS C1 [Luo, Xin; Jin, Chunhui; Zhou, Zhenhe; Liu, Xiaowei; Zhang, Fuquan; Zhang, Feng; Zhu, Jianzhong; Wang, Ying; Cheng, Zaohuo] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi 214151, Jiangsu, Peoples R China. [Shugart, Yin Yao] NIMH, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Jin, CH (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, 156 Qianrong Rd, Wuxi 214151, Jiangsu, Peoples R China. EM jch1029@126.com; chengzaohuo@126.com FU Wuxi Hospital Management Center Foundation [YGZXG1403]; Wuxi Municipal Health Bureau [MS201429]; National Natural Science Foundation of China [81301147]; Healthcare Guidance Project of Wuxi Science and Technology Bureau; Wuxi Municipal Health Bureau FX This work was supported by the key Program of Wuxi Hospital Management Center Foundation (No.YGZXG1403), the Research Project of Wuxi Municipal Health Bureau (No.MS201429), the National Natural Science Foundation of China (No.81301147), the Healthcare Guidance Project of Wuxi Science and Technology Bureau, and Excellent Young Talents Project of Wuxi Municipal Health Bureau. NR 23 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 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 2015 VL 228 IS 3 BP 966 EP 968 DI 10.1016/j.psychres.2015.05.115 PG 3 WC Psychiatry SC Psychiatry GA CP9YI UT WOS:000360251400113 PM 26162659 ER PT J AU Hulvershorn, LA Hummer, TA Fukunaga, R Leibenluft, E Finn, P Cyders, MA Anand, A Overhage, L Dir, A Brown, J AF Hulvershorn, Leslie A. Hummer, Tom A. Fukunaga, Rena Leibenluft, Ellen Finn, Peter Cyders, Melissa A. Anand, Amit Overhage, Lauren Dir, Allyson Brown, Joshua TI Neural activation during risky decision-making in youth at high risk for substance use disorders SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Adolescent; Decision-making; Risk; Addiction risk; Functional imaging; Prefrontal cortex ID VENTROMEDIAL PREFRONTAL CORTEX; METHAMPHETAMINE-DEPENDENT SUBJECTS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TASK BART; ALCOHOL-USE; BEHAVIORAL DISINHIBITION; CONSTRUCT-VALIDITY; INSULA RESPONSE; DRUG-USE; ADOLESCENTS AB Risky decision-making, particularly in the context of reward-seeking behavior, is strongly associated with the presence of substance use disorders (SUDs). However, there has been little research on the neural substrates underlying reward-related decision-making in drug-naive youth who are at elevated risk for SUDs. Participants comprised 23 high-risk (HR) youth with a well-established SUD risk phenotype and 27 low-risk healthy comparison (HC) youth, aged 10-14. Participants completed the balloon analog risk task (BART), a task designed to examine risky decision-making, during functional magnetic resonance imaging. The HR group had faster reaction Limes, but otherwise showed no behavioral differences from the HC group. HR youth experienced greater activation when processing outcome, as the chances of balloon explosion increased, relative to HC youth, in ventromedial prefrontal cortex (vmPFC). As explosion probability increased, group-by-condition interactions in the ventral striatum/anterior cingulate and the anterior insula showed increasing activation in HR youth, specifically on trials when explosions occurred. Thus, atypical activation increased with increasing risk of negative outcome (i.e., balloon explosion) in a cortico-striatal network in the HR group. These findings identify candidate neurobiological markers of addiction risk in youth at high familial and phenotypic risk for SUDs. (C) 2015 Elsevier Ireland Ltd. All rights reserved, C1 [Hulvershorn, Leslie A.; Hummer, Tom A.; Overhage, Lauren] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Fukunaga, Rena; Finn, Peter; Brown, Joshua] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Intramural Res Program, Bethesda, MD 20892 USA. [Cyders, Melissa A.; Dir, Allyson] Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46205 USA. [Anand, Amit] Cleveland Clin, Ctr Behav Hlth, Cleveland, OH 44106 USA. RP Hulvershorn, LA (reprint author), 705 Riley Hosp Dr,Rm 4300, Indianapolis, IN 46205 USA. EM lhulvers@iupui.edu RI Anand, Amit/D-4232-2013 FU National Institute of Drug Abuse American Academy of Child and Adolescent Psychiatry (AACAP) Physician Scientist Program [K12DA000357] FX This study was funded by the National Institute of Drug Abuse American Academy of Child and Adolescent Psychiatry (AACAP) Physician Scientist Program (K12DA000357) to L.H. NR 69 TC 5 Z9 5 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2015 VL 233 IS 2 BP 102 EP 111 DI 10.1016/j.pscychresns.2015.05.007 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CO7BU UT WOS:000359313300005 PM 26071624 ER PT J AU Wiers, CE Gawron, CK Gropper, S Spengler, S Stuke, H Lindenmeyer, J Walter, H Bermpohl, F AF Wiers, Corinde E. Gawron, Christiane K. Groepper, Sonja Spengler, Stephanie Stuke, Heiner Lindenmeyer, Johannes Walter, Henrik Bermpohl, Felix TI Decreased gray matter volume in inferior frontal gyrus is related to stop-signal task performance in alcohol-dependent patients SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Addiction; Alcohol; Inferior frontal gyrus; Gray matter volume; Response inhibition; Stop-signal task ID RESPONSE-INHIBITION; BEHAVIORAL-INHIBITION; PREFRONTAL CORTEX; HUMANS; FMRI; MORPHOMETRY; CONSUMPTION; DYSFUNCTION; HISTORY; SYSTEMS AB Impairment in inhibitory control has been proposed to contribute to habitual alcohol use, abuse and eventually dependence. Moreover, alcohol dependent (AD) patients have shown a loss of gray matter volume (GMV) in the brain, specifically in prefrontal regions associated with executive functions, including response inhibition. To date, no study has evaluated whether this prefrontal GMV reduction is related to response inhibition in alcohol dependence. To address this issue, we acquired high resolution TI weighted magnetic resonance mages from recently detoxified AD patients (n=22) and healthy controls (HC; n=21). Differences in local GMV beLvveen groups were assessed by means of voxel-based morphometry (VW). Moreover, within the AD group, mean local GMV reductions were extracted and correlated with behavioral performance on the stop signal task. We found a significantly decrease in GMV in the left inferior frontal gyms (IFG) in AD patients compared with HC subjects. Further, mean local GMV in this area correlated positively with reaction Limes on go trials during the stop signal task in AD patients. Our findings suggest that GMV losses in the IFG in AD patients are related to faster go responses on the stop signal task. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Wiers, Corinde E.; Gawron, Christiane K.; Groepper, Sonja; Spengler, Stephanie; Stuke, Heiner; Walter, Henrik; Bermpohl, Felix] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Berlin, Germany. [Wiers, Corinde E.; Walter, Henrik; Bermpohl, Felix] Humboldt Univ, Berlin Sch Mind & Brain, Berlin, Germany. [Lindenmeyer, Johannes] Salus Klin, Lindow, Germany. RP Wiers, CE (reprint author), NIAAA, Lab Neuroimaging, NIH, 10 Ctr Dr Room B2L124, Bethesda, MD 20892 USA. EM corinde.wiers@nih.gov RI Walter, Henrik/O-2612-2013 FU German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, FOR 1617) [HE2597/14-1]; Berlin School of Mind and Brain; Humboldt Graduate School FX This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, FOR 1617: Grant HE2597/14-1). C.E.W. was funded by the Berlin School of Mind and Brain and Humboldt Graduate School. The authors thank Ulrike Malecki, Steffen Pawelczack, Silvia Hoffman, Natalie Becht and Jana Paeplow for the recruitment of patients from the Salus Klinik, Lindow; Torsten Wustenberg for assistance with data analysis and helpful comments on the manuscript; and Thomas E. Gladwin for final proofreading. NR 39 TC 3 Z9 4 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2015 VL 233 IS 2 BP 125 EP 130 DI 10.1016/j.pscychresns.2015.05.006 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CO7BU UT WOS:000359313300008 PM 26078198 ER PT J AU Crommelin, DJA Shah, VP Klebovich, I McNeil, SE Weinstein, V Fluthmann, B Muhlebach, S de Vlieger, JSB AF Crommelin, Daan J. A. Shah, Vinod P. Klebovich, Imre McNeil, Scott E. Weinstein, Vera Fluthmann, Beat Muehlebach, Stefan de Vlieger, Jon S. B. TI The similarity question for biologicals and non-biological complex drugs SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE Biologicals; Biosimilars; Non-biological complex drugs; Glatiramoids; Liposomes; Nanomedicines; Iron-carbohydrate complexes ID INTRAVENOUS IRON SUCROSE; BIOSIMILARS; ORIGINATOR; BIOPHARMACEUTICALS; TERMINOLOGY; PRODUCTS AB For small low molecular weight molecule medicines a robust regulatory system has evolved over the years. This system guarantees high and constant quality of our (generic) medicines. Pharmaceutical equivalence and bioequivalence assessment are the pillars under that system. But there are complex medicines where the question of equivalence is more challenging to answer. For biologicals the paradigm of similarity rather than equality (the emergence of 'biosimilars') was developed in the past decade. This has been a program where an evolutionary, science based approach has been chosen by the frontrunner regulatory body, the EMA, with a 'learn and confirm' character. In addition, there is another group of complex drugs, the non-biological complex drugs, NBCDs, where the generic paradigm can be challenged as well. The NBCDs are defined as: I. consisting of a complex multitude of closely related structures; 2. the entire multitude is the active pharmaceutical ingredient; 3. the properties cannot be fully characterized by physicochemical analysis and 4. the consistent, tightly controlled manufacturing process is fundamental to reproduce the product. NBCDs encompass product families such as the glatiramoids, liposomes, iron carbohydrate colloids and many candidates of the group of the upcoming nanoparticulate systems. Following the main principles of regulatory pathways for biologicals (with appropriate product-by-product adjustments), instead of that for small molecules, would be the more logical strategy for these NBCDs. The status and outstanding regulatory issues for biosimilars and NBCD-similars/follow on versions were discussed at a conference in Budapest, Hungary (October 2014) and this commentary touches upon the issues brought up in the presentations, deliberations and conclusions. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). C1 [Crommelin, Daan J. A.] Univ Utrecht, Dept Pharmaceut, UIPS, NL-3508 TC Utrecht, Netherlands. [Klebovich, Imre] Semmelweis Univ, Dept Pharmaceut, H-1085 Budapest, Hungary. [McNeil, Scott E.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. Teva Pharmaceut Ind Ltd, Discovery & Product Dev, Global Res & Dev, Netanya, Israel. [Fluthmann, Beat] Vifor Fresenius Med Care Renal Pharma Ltd, Glattbrugg, Switzerland. [Muehlebach, Stefan] Vifor Pharma Ltd, Glattbrugg, Switzerland. [Muehlebach, Stefan] Univ Basel, Dept Pharmaceut Sci, Unit Clin Pharm & Epidemiol, CH-4003 Basel, Switzerland. [de Vlieger, Jon S. B.] Dutch Top Inst Pharma, NL-2300 AC Leiden, Netherlands. RP Crommelin, DJA (reprint author), Dutch Top Inst Pharma, Leiden, Netherlands. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 NR 30 TC 7 Z9 8 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 EI 1879-0720 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD AUG 30 PY 2015 VL 76 BP 10 EP 17 DI 10.1016/j.ejps.2015.04.010 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CL5DP UT WOS:000356980300002 PM 25912826 ER PT J AU Lacroix, A Feelders, RA Stratakis, CA Nieman, LK AF Lacroix, Andre Feelders, Richard A. Stratakis, Constantine A. Nieman, Lynnette K. TI Cushing's syndrome SO LANCET LA English DT Article ID MACRONODULAR ADRENAL-HYPERPLASIA; QUALITY-OF-LIFE; MULTIPLE-ENDOCRINE-NEOPLASIA; NODULAR ADRENOCORTICAL-DISEASE; INFERIOR PETROSAL SINUS; PROTEIN-KINASE-A; SECRETING PITUITARY-ADENOMAS; HORMONE STIMULATION TEST; LONG-TERM REMISSION; DIFFERENTIAL-DIAGNOSIS AB Chronic exposure to excess glucorticoids results in diverse manifestations of Cushing's syndrome, including debilitating morbidities and increased mortality. Genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and adrenocorticotropic hormone (ACTH) secretion from corticotroph or ectopic tumours have been identified. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients. The therapeutic goal is to normalise tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumour is necessay to allow eventual normalisation of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumour recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess. However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism need ongoing care. C1 [Lacroix, Andre] Univ Montreal, Dept Med, Ctr Hosp, Div Endocrinol,CHUM, Montreal, PQ H2W 1T8, Canada. [Lacroix, Andre] Univ Montreal, Res Ctr, Ctr Hosp, CHUM, Montreal, PQ H2W 1T8, Canada. [Feelders, Richard A.] Erasmus MC, Div Endocrinol, Dept Internal Med, Rotterdam, Netherlands. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Genet & Endocrinol, NIH, Bethesda, MD USA. [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Lacroix, A (reprint author), Univ Montreal, Dept Med, Ctr Hosp, Div Endocrinol, Montreal, PQ H2W 1T8, Canada. EM andre.lacroix@umontreal.ca FU Canadian Institutes of Health Research; Intramural Research Program, National Institute of Child Health and Human Development (NICHD), National Institute of Health (NIH); Intramural Research Program, NICHD, NIH FX AL receives grant support from the Canadian Institutes of Health Research. CAS is supported by the Intramural Research Program, National Institute of Child Health and Human Development (NICHD), National Institute of Health (NIH). LKN is supported by the Intramural Research Program, NICHD, NIH. NR 171 TC 49 Z9 53 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD AUG 29 PY 2015 VL 386 IS 9996 BP 913 EP 927 DI 10.1016/S0140-6736(14)61375-1 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA CQ0MJ UT WOS:000360290000034 PM 26004339 ER PT J AU Li, D Shao, L Chen, BC Zhang, X Zhang, MS Moses, B Milkie, DE Beach, JR Hammer, JA Pasham, M Kirchhausen, T Baird, MA Davidson, MW Xu, PY Betzig, E AF Li, Dong Shao, Lin Chen, Bi-Chang Zhang, Xi Zhang, Mingshu Moses, Brian Milkie, Daniel E. Beach, Jordan R. Hammer, John A., III Pasham, Mithun Kirchhausen, Tomas Baird, Michelle A. Davidson, Michael W. Xu, Pingyong Betzig, Eric TI Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics SO SCIENCE LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; LIVING CELLS; LIVE CELLS; FLUORESCENCE MICROSCOPY; CELLULAR STRUCTURES; OPTICAL NANOSCOPY; PLASMA-MEMBRANE; ACTIN DYNAMICS; F-ACTIN; PROTEIN AB Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and a-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. C1 [Li, Dong; Shao, Lin; Chen, Bi-Chang; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Zhang, Xi; Zhang, Mingshu; Xu, Pingyong] Chinese Acad Sci, Key Lab RNA Biol, Beijing 100101, Peoples R China. [Zhang, Xi; Zhang, Mingshu; Xu, Pingyong] Chinese Acad Sci, Beijing Key Lab Noncoding RNA, Inst Biophys, Beijing 100101, Peoples R China. [Zhang, Xi] Cent China Normal Univ, Coll Life Sci, Wuhan 430079, Hubei, Peoples R China. [Moses, Brian; Milkie, Daniel E.] Coleman Technol, Newtown Sq, PA 19073 USA. [Beach, Jordan R.; Hammer, John A., III; Baird, Michelle A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Pasham, Mithun; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol & Pediat, Boston, MA 02115 USA. [Pasham, Mithun; Kirchhausen, Tomas] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. RP Betzig, E (reprint author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA. EM betzige@janelia.hhmi.org RI Chen , Bi-Chang /F-3480-2014 FU Howard Hughes Medical Institute (HHMI); National Basic Research Program (973 Program) of China [2013CB910103]; National Natural Science Foundation of China [31370851]; Beijing Natural Science Foundation, China [7131011]; NIH [GM-075252] FX We thank the Shared Resource teams at Janelia for their skill and dedication in specimen handling and preparation and the Instrument Design and Fabrication team for their manufacturing expertise. D.L., L.S., B.-C.C., and E.B. are funded by the Howard Hughes Medical Institute (HHMI). X.Z., M.Z., and P.X. are funded by the National Basic Research Program (973 Program) of China (2013CB910103), the National Natural Science Foundation of China (31370851), and the Beijing Natural Science Foundation, China (7131011). M.P. and T.K. were funded in part by NIH grant GM-075252. Skylan-NS is available from P.X. upon execution of a materials transfer agreement with the Institute of Biophysics. Other fluorescent protein constructs used in this work are from the Michael Davidson Collection and are available, along with sequence information, from Addgene (www.addgene.org/fluorescent-proteins/davidson). Researchers can apply to access the microscope as visitors through the Advanced Imaging Center at Janelia (www.janelia.org/open-science/advanced-imaging-center). Technical information for the construction of a copy of the microscope is available to nonprofit entities upon execution of a no-cost Research License with HHMI. Nonlinear SIM with patterned activation, in two or three dimensions, as described here is covered within U.S. provisional patent application 62/057,220 filed by E.B. and D.L. and assigned to HHMI. NR 53 TC 78 Z9 81 U1 77 U2 193 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD AUG 28 PY 2015 VL 349 IS 6251 AR aab3500 DI 10.1126/science.aab3500 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ5LW UT WOS:000360646800044 PM 26315442 ER PT J AU Araya, N Sato, T Tomaru, U Coler-Reilly, A Yagishita, N Yamauchi, J Hasegawa, A Kannagi, M Akiyama, H Hasegawa, Y Takahashi, K Kunitomo, Y Tanaka, Y Utsunomiya, A Jacobson, S Yamano, Y AF Araya, Natsumi Sato, Tomoo Tomaru, Utano Coler-Reilly, Ariella Yagishita, Naoko Yamauchi, Junji Hasegawa, Atsuhiko Kannagi, Mari Akiyama, Hisanao Hasegawa, Yasuhiro Takahashi, Katsunori Kunitomo, Yasuo Tanaka, Yuetsu Utsunomiya, Atae Jacobson, Steven Yamano, Yoshihisa TI HTLV-1 Tax induces Th1 master regulator T-bet and thus IFN-gamma in CD4+CCR4+T-cells of virus-associated myelopathy patients SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Araya, Natsumi; Sato, Tomoo; Coler-Reilly, Ariella; Yagishita, Naoko; Yamauchi, Junji; Takahashi, Katsunori; Kunitomo, Yasuo; Yamano, Yoshihisa] St Marianna Univ, Sch Med, Inst Med Sci, Dept Rare Dis Res, Kawasaki, Kanagawa, Japan. [Tomaru, Utano] Hokkaido Univ, Grad Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan. [Hasegawa, Atsuhiko; Kannagi, Mari] Tokyo Med & Dent Univ, Grad Sch, Dept Immunotherapeut, Tokyo, Japan. [Akiyama, Hisanao; Hasegawa, Yasuhiro] St Marianna Univ, Sch Med, Dept Neurol, Kawasaki, Kanagawa, Japan. [Tanaka, Yuetsu] Univ Ryukyus, Grad Sch Med, Dept Immunol, Okinawa, Japan. [Utsunomiya, Atae] Imamura Bun In Hosp, Dept Hematol, Kagoshima, Japan. [Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. EM yyamano@marianna-u.ac.jp NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P44 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500085 ER PT J AU Barreto, FK Khouri, R Rego, FFD de Castro-Amarante, MF Bialuk, I Pise-Masison, CA Galvao-Castro, B Gessain, A Jacobson, S Franchini, G Alcantara, LC AF Barreto, Fernanda Khouri Khouri, Ricardo de Almeida Rego, Filipe Ferreira de Castro-Amarante, Maria Fernanda Bialuk, Izabela Pise-Masison, Cynthia A. Galvao-Castro, Bernardo Gessain, Antoine Jacobson, Steven Franchini, Genoveffa Alcantara, Luiz Carlos, Jr. TI ORFI genetic polymorphisms in geographically distinct HTLV-1 infections SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Barreto, Fernanda Khouri; Khouri, Ricardo; de Almeida Rego, Filipe Ferreira; Galvao-Castro, Bernardo; Alcantara, Luiz Carlos, Jr.] Fiocruz MS, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. [Barreto, Fernanda Khouri; Galvao-Castro, Bernardo] Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil. [de Castro-Amarante, Maria Fernanda; Pise-Masison, Cynthia A.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Bialuk, Izabela] Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. [Gessain, Antoine] Inst Pasteur, Dept Virol, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, France. [Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. EM fernanda.khouri@hotmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P55 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500096 ER PT J AU Castro-Amarante, MF Pise-Masison, CA McKinnon, K Parks, RW Galli, V Massoud, R Brunetto, G Caruso, B Venzon, D Jacobson, S Franchini, G AF Castro-Amarante, Maria F. Pise-Masison, Cynthia A. McKinnon, Katherine Parks, Robyn W. Galli, Veronica Massoud, Raya Brunetto, Giovanna Caruso, Breanna Venzon, David Jacobson, Steven Franchini, Genoveffa TI HTLV-1 burden dependent on hijacking monocytes chemotaxis SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Castro-Amarante, Maria F.; Pise-Masison, Cynthia A.; McKinnon, Katherine; Parks, Robyn W.; Galli, Veronica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Massoud, Raya; Brunetto, Giovanna; Caruso, Breanna; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. EM mfamarante@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P7 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500048 ER PT J AU Cavallari, I Rende, F Bona, MK Sztuba-Solinska, J LeGrice, SFJ Franchini, G D'Agostino, DM Ciminale, V AF Cavallari, Ilaria Rende, Francesca Bona, Marion K. Sztuba-Solinska, Joanna LeGrice, Stuart F. J. Franchini, Genoveffa D'Agostino, Donna M. Ciminale, Vincenzo TI Expression of alternatively spliced HTLV-1 mRNAs is influenced by mitosis and by a novel cis-acting regulatory sequence SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Cavallari, Ilaria; Rende, Francesca; Ciminale, Vincenzo] Univ Padua, Dept Surg Oncol & Gastroenterol, I-35100 Padua, Italy. [Bona, Marion K.] Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD USA. [Sztuba-Solinska, Joanna; LeGrice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21701 USA. [Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Ciminale, Vincenzo] Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy. [Ciminale, Vincenzo] Ist Oncol Veneto IRCCS, Padua, Italy. EM v.ciminale@unipd.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P90 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500131 ER PT J AU Charlip, E Liu, W Massoud, R Billioux, J Caruso, B Ohayon, J Nair, G Jacobson, S AF Charlip, Emily Liu, Winston Massoud, Raya Billioux, Jeanne Caruso, Breanna Ohayon, Joan Nair, Govind Jacobson, Steven TI Patterns of spinal cord atrophy in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Charlip, Emily; Liu, Winston; Massoud, Raya; Billioux, Jeanne; Caruso, Breanna; Ohayon, Joan; Nair, Govind; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Liu, Winston] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM JacobsonS@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P32 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500073 ER PT J AU Enose-Akahata, Y Massoud, R Caruso, B Ohayon, J Billioux, BJ von Geldern, G Smith, B Nath, A Jacobson, S AF Enose-Akahata, Yoshimi Massoud, Raya Caruso, Breanna Ohayon, Joan Billioux, Bridgette Jeanne von Geldern, Gloria Smith, Bryan Nath, Avindra Jacobson, Steven TI Immunophenotyping of cerebrospinal fluid cells in virus-associated neurologic diseases SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Enose-Akahata, Yoshimi; Massoud, Raya; Caruso, Breanna; Ohayon, Joan; Billioux, Bridgette Jeanne; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [von Geldern, Gloria; Smith, Bryan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P86 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500127 ER PT J AU Enose-Akahata, Y Caruso, B Haner, B Massoud, R Billioux, BJ Ohayon, J Switzer, WM Jacobson, S AF Enose-Akahata, Yoshimi Caruso, Breanna Haner, Benjamin Massoud, Raya Billioux, Bridgette Jeanne Ohayon, Joan Switzer, William M. Jacobson, Steven TI Development of HTLV-1 associated myelopathy/tropical spastic paraparesis in a patient with simian T-lymphotropic virus type 1-like infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Enose-Akahata, Yoshimi; Caruso, Breanna; Haner, Benjamin; Massoud, Raya; Billioux, Bridgette Jeanne; Ohayon, Joan; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Switzer, William M.] Ctr Dis Control & Prevent, Lab Branch, Div HIV AIDS, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA 30329 USA. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O30 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500029 ER PT J AU Jaworski, E Van Duyne, R Iordanskiy, S Afonso, P Sampey, G Chung, M Popratiloff, A Mahieux, R Kashanchi, F AF Jaworski, Elizabeth Van Duyne, Rachel Iordanskiy, Sergey Afonso, Philippe Sampey, Gavin Chung, Myung Popratiloff, Anastas Mahieux, Renaud Kashanchi, Fatah TI Exosomes derived from HTLV-1 infected cells contain viral proteins and mRNA SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Jaworski, Elizabeth; Van Duyne, Rachel; Iordanskiy, Sergey; Sampey, Gavin; Chung, Myung; Kashanchi, Fatah] George Mason Univ, Sch Syst Biol, Mol Virol Lab, Manassas, VA 20110 USA. [Van Duyne, Rachel; Kashanchi, Fatah] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Popratiloff, Anastas] George Washington Univ, Ctr Microscopy & Image Anal, Washington, DC 20037 USA. [Afonso, Philippe; Mahieux, Renaud] Univ Lyon 1, Equipe Labelisee Ligue Natl Canc, Int Ctr Res Infectiol,Ecole Normale Suparieure Ly, Equipe Oncogenese Retrovirale,INSERM,U1111,CNRS,U, F-69364 Lyon 07, France. EM fkashanc@gmu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P98 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500138 ER PT J AU Jesus, JG Junior, RMPS de Castro-Amarante, MF Haddad, SK Espreafico, EM Franchini, G Alcantara, LCJ AF Jesus, Jaqueline G. Junior, Rui M. P. S. de Castro-Amarante, Maria F. Haddad, Simone K. Espreafico, Enilza M. Franchini, Genoveffa Alcantara, Luiz C. J. TI Role of myosin Va on HTLV-1 p8I protein's traffic to cell surface SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Jesus, Jaqueline G.; Alcantara, Luiz C. J.] Fundacao Oswaldo Cruz, Goncalo Moniz Res Ctr, BR-40296710 Candeal Salvador, BA, Brazil. [Junior, Rui M. P. S.; Espreafico, Enilza M.] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049900 Monte Alegre Ribeirao Pr, Sao Paulov, Brazil. [de Castro-Amarante, Maria F.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Haddad, Simone K.] Univ Sao Paulo, Fac Pharmaceut Ribeirao Preto, BR-14040903 Sao Paulo, Brazil. [Haddad, Simone K.] Blood Ctr Ribeirao Preto, BR-14051140 Sao Paulo, Brazil. EM jaquelinegoesdejesus@gmail.com RI Espreafico, Enilza/O-3053-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P1 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500043 ER PT J AU Nakagawa, M Schmitz, R Xiao, WM Yang, YD Waldmann, TA Staudt, LM AF Nakagawa, Masao Schmitz, Roland Xiao, Wenming Yang, Yandan Waldmann, Thomas A. Staudt, Louis M. TI A gain-of-function CCR4 mutations in adult T-cell leukemia/lymphoma (ATL) enhance the chemotactic abilities and P13K/AKT activation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Nakagawa, Masao; Schmitz, Roland; Xiao, Wenming; Yang, Yandan; Waldmann, Thomas A.; Staudt, Louis M.] NCI, LYMB, CCR, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O31 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500030 ER PT J AU Nata, T Zapata, JC Massoud, R Jacobson, S Azimi, N Tagaya, Y AF Nata, Toshie Zapata, Juan Carlos Massoud, Raya Jacobson, Steve Azimi, Nazli Tagaya, Yutaka TI A multi-cytokine inhibitory peptide (BNZ 132-1) that is a potential therapeutic agent for HAMTSP and other necrotizing diseases SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Nata, Toshie; Zapata, Juan Carlos; Tagaya, Yutaka] Univ Maryland, Sch Med, Inst Human Virol, Cell Biol Lab, Baltimore, MD 21201 USA. [Massoud, Raya; Jacobson, Steve] NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. [Azimi, Nazli] BIONIZ Inc, Irvine, CA USA. EM ytagaya@ihv.umaryland.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O22 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500022 ER PT J AU Omsland, M Pise-Masison, C Gjertsen, BT Franchini, G Andresen, V AF Omsland, M. Pise-Masison, C. Gjertsen, B. T. Franchini, G. Andresen, V. TI The effect of chemotherapeutics on cell-to-cell transport of HTLV-1 and the p8 protein through membrane nanotubes SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Omsland, M.; Gjertsen, B. T.; Andresen, V.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers CCBIO, Translat Hematooncol Grp, Bergen, Norway. [Omsland, M.; Pise-Masison, C.; Franchini, G.] NCI, Anim Models & Retroviral Vaccine Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Gjertsen, B. T.] Haukeland Hosp, Dept Internal Med, Hematol Sect, N-5021 Bergen, Norway. EM Maria.Omsland@k2.uib.no RI Gjertsen, Bjorn T/O-1542-2015 OI Gjertsen, Bjorn T/0000-0001-9358-9704 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P8 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500049 ER PT J AU Phillips, A Fields, P Hermine, O Taylor, GP Delioukina, M Horwitz, S Ramos, JC Meniane, JC Barta, SK Brites, C Pereria, J Beltran, B Casanova, L Wandroo, F Feldman, T Dwyer, K Kurman, M Conlon, K AF Phillips, Adrienne Fields, Paul Hermine, Olivier Taylor, Graham P. Delioukina, Maria Horwitz, Steven Ramos, Juan C. Meniane, Jean-Come Barta, Stefan K. Brites, Carlos Pereria, Juliana Beltran, Brady Casanova, Luis Wandroo, Farooq Feldman, Tatyana Dwyer, Karen Kurman, Michael Conlon, Kevin TI Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator's choice in subjects with relapsed or refractory adult T-cell leukemia-lymphoma (ATL) SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Phillips, Adrienne] Weill Cornell Med Coll, New York, NY USA. [Fields, Paul] Guys Hosp, London SE1 9RT, England. [Hermine, Olivier] Hop Necker Enfants Malad, Paris, France. [Taylor, Graham P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Delioukina, Maria] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Horwitz, Steven] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Ramos, Juan C.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Meniane, Jean-Come] CHU Ft France, Fort De France, Martinique. [Barta, Stefan K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Brites, Carlos] Hosp Univ Prof Edgard Santos UFBA, Salvador, BA, Brazil. [Pereria, Juliana] Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo, Brazil. [Beltran, Brady] Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru. [Casanova, Luis] Inst Oncol Miraflores, Lima, Peru. [Wandroo, Farooq] Sandwell & West Birmingham Hosp, Birmingham, W Midlands, England. [Feldman, Tatyana] John Theurer Canc Ctr Hackensack UMC, Hackensack, NJ USA. [Dwyer, Karen; Kurman, Michael] Inc Princeton, Kyowa Hakko Kirin Pharma, Princeton, NJ USA. [Conlon, Kevin] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P31 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500072 ER PT J AU Pise-Masison, CA Nixon, CC Amarante, MFD Parks, RW McKinnon, K Caruso, B Galli, V Jacobson, S Zack, J Franchini, G AF Pise-Masison, Cynthia A. Nixon, Christopher C. Amarante, Maria Fernanda de Castro Parks, Robyn Washington McKinnon, Katherine Caruso, Breanna Galli, Veronica Jacobson, Steve Zack, Jerome Franchini, Genoveffa TI Detection of HTLV-1 replication and CD4+proliferation in the humanized BLT mouse model SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pise-Masison, Cynthia A.; Amarante, Maria Fernanda de Castro; Parks, Robyn Washington; Galli, Veronica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, Bethesda, MD 20892 USA. [Nixon, Christopher C.; Zack, Jerome] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [McKinnon, Katherine] NCI, Vaccine Branch Flow Cytometry Core, Bethesda, MD 20892 USA. [Caruso, Breanna; Jacobson, Steve] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. EM masisonc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O39 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500038 ER PT J AU Ratner, L Ramos, JC Noy, A Barta, S Parikh, S Phillips, A Ambinder, R Rauch, D Harding, J Baydoun, H Cheng, XG Caruso, B Jacobson, S AF Ratner, Lee Ramos, J. C. Noy, Ariela Barta, Stefan Parikh, Samir Phillips, Adrienne Ambinder, Richard Rauch, Dan Harding, John Baydoun, Hicham Cheng, Xiaogang Caruso, Breanna Jacobson, Steven TI Phase I/II trial of dose adjusted EPOCH chemotherapy with bortezomib combined with integrase inhibitor therapy for HTLV-1 associated T-cell leukemia lymphoma SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Ratner, Lee; Rauch, Dan; Harding, John; Baydoun, Hicham; Cheng, Xiaogang] Washington Univ, Div Oncol, St Louis, MO USA. [Ramos, J. C.] Univ Miami, Miami, FL USA. [Noy, Ariela] Mem Sloan Kettering Canc Ctr, Lymphoma & Hematol Div, New York, NY 10021 USA. [Barta, Stefan; Parikh, Samir] Montefiore Hosp, Div Hematol Oncol, New York, NY USA. [Phillips, Adrienne] Columbia Univ, New York, NY USA. [Ambinder, Richard] Johns Hopkins Univ, Div Hematol Malignancies, Baltimore, MD USA. [Caruso, Breanna; Jacobson, Steven] NINDS, NIH, Bethesda, MD 20892 USA. EM lratner@dom.wustl.edu OI Noy, Ariela/0000-0002-3001-4898 NR 0 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P21 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500062 ER PT J AU Rende, F Cavallari, I Andresen, V Valeri, VW D'Agostino, DM Franchini, G Ciminale, V AF Rende, Francesca Cavallari, Ilaria Andresen, Vibeke Valeri, Valerio W. D'Agostino, Donna M. Franchini, Genoveffa Ciminale, Vincenzo TI Identification of novel monocistronic HTLV-1 mRNAs encoding functional Rex isoforms SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Rende, Francesca; Cavallari, Ilaria; Ciminale, Vincenzo] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy. [Andresen, Vibeke; Valeri, Valerio W.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [D'Agostino, Donna M.] Univ Padua, Dept Biomed Sci, Padua, Italy. [Ciminale, Vincenzo] Ist Oncol Veneto IRCCS, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P91 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500132 ER PT J AU Sagar, D Masih, S Schell, T Jacobson, S Comber, JD Philip, R Wigdahl, B Jain, P Khan, ZK AF Sagar, Divya Masih, Shet Schell, Todd Jacobson, Steven Comber, Joseph D. Philip, Ramila Wigdahl, Brian Jain, Pooja Khan, Zafar K. TI In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sagar, Divya; Masih, Shet; Jain, Pooja; Khan, Zafar K.] Drexel Univ, Drexel Inst Biotechnol & Virol Res, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Schell, Todd] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. [Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Comber, Joseph D.; Philip, Ramila] Immunotope Inc, Doylestown, PA USA. [Wigdahl, Brian] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Wigdahl, Brian] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Ctr Mol Virol & Translat Neurosci, Philadelphia, PA 19104 USA. EM Zafar.Khan@drexelmed.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O28 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500028 ER PT J AU Sousa, ADA Johnson, KR Ohayon, J Zhu, J Muraro, P Jacobson, S AF Sousa, Alessandra de Paula A. Johnson, Kory R. Ohayon, Joan Zhu, Jun Muraro, Paolo Jacobson, Steven TI Deep sequencing of the TCR beta repertoire reveals T cell clonal expansion is associated with HTLV-1 proviral load in HAM/TSP patients SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sousa, Alessandra de Paula A.; Ohayon, Joan; Jacobson, Steven] NINDS, Neuroimmunol Branch, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. [Johnson, Kory R.] NINDS, Bioinformat Sect, NIH, Bethesda, MD 20892 USA. [Zhu, Jun] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA. [Muraro, Paolo] Imperial Coll London, Fac Med, Div Brain Sci, London, England. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O21 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500021 ER PT J AU Vahidnia, F Stramer, SL Kessler, DA Krysztof, DE Dodd, RY Notari, E Glynn, S Custer, B AF Vahidnia, Farnaz Stramer, Susan L. Kessler, Debra A. Krysztof, David E. Dodd, Roger Y. Notari, Ed Glynn, Simone Custer, Brian TI Risk factors and epidemiology of human T-lymphotropic virus types 1 and 2 in US blood donors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Vahidnia, Farnaz; Custer, Brian] Blood Syst Res Inst, San Francisco, CA USA. [Stramer, Susan L.; Krysztof, David E.; Dodd, Roger Y.; Notari, Ed] Amer Red Cross, Rockville, MD USA. [Kessler, Debra A.] New York Blood Ctr, New York, NY 10021 USA. [Glynn, Simone] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA P84 PG 1 WC Virology SC Virology GA DA0EC UT WOS:000367468500125 ER PT J AU Zhang, ML Griner, LAM Ju, W Duveau, DY Guha, R Petrus, M Wen, B Maeda, M Shinn, P Ferrer, M Conlon, KC Bamford, R O'Shea, JJ Thomas, CJ Waldmann, TA AF Zhang, Meili Griner, Lesley A. Mathews Ju, Wei Duveau, Damien Y. Guha, Rajarshi Petrus, Michael Wen, Bernard Maeda, Michiyuki Shinn, Paul Ferrer, Marc Conlon, Kevin C. Bamford, Richard O'Shea, John J. Thomas, Craig J. Waldmann, Thomas A. TI Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhang, Meili; Ju, Wei; Petrus, Michael; Wen, Bernard; Conlon, Kevin C.; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Griner, Lesley A. Mathews; Duveau, Damien Y.; Guha, Rajarshi; Shinn, Paul; Ferrer, Marc; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Zhang, Meili] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick, MD USA. [Maeda, Michiyuki] Kyoto Univ, Sakyo Ku, Kyoto, Japan. [Bamford, Richard] Transponics, Jacobus, PA USA. [O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM craigt@mail.nih.gov; tawald@helix.nih.gov NR 0 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 28 PY 2015 VL 12 SU 1 MA O42 PG 2 WC Virology SC Virology GA DA0EC UT WOS:000367468500041 ER PT J AU Yu, LM Zhang, XR Li, XB Yang, Y Wei, HY He, XX Gu, LQ Huang, ZS Pommier, Y An, LK AF Yu, Le-Mao Zhang, Xiao-Ru Li, Xiao-Bing Yang, Yuan Wei, Hong-Yu He, Xi-Xin Gu, Lian-Quan Huang, Zhi-Shu Pommier, Yves An, Lin-Kun TI Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic DNA topoisomerase I inhibitors SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Indolizinoquinolinedione; DNA topoisomerase; Inhibitor; Anticancer ID DERIVATIVES; MECHANISM; CYTOTOXICITY; DRUGS; CELLS; ASSAY AB In our previous work, indolizinoquinolinedione derivative 1 was identified as a Top1 catalytic inhibitor. Herein, a series of 6-substituted indolizinoquinolinedione derivatives were synthesized through modification of the parent compound 1. Top1 cleavage and relaxation assays indicate that none of these novel compounds act as classical Top1 poison, and that the compounds with alkylamino terminus at C-6 side chain, including 8, 11-16, 18-21, 25, 26 and 28-30, are the most potent Top1 catalytic inhibitors. Top1-mediated unwinding assay demonstrated that 14,22 and 26 were Top1 catalytic inhibitors without Top1-mediated unwinding effect. Moreover, MTT results showed that compounds 26, 28-30 exhibit significant cytotoxicity against human leukemia HL-60 cells, and that compound 26 exerts potent cytotoxicity against A549 lung cancer cells at nanomolar range. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Yu, Le-Mao; Zhang, Xiao-Ru; Li, Xiao-Bing; Yang, Yuan; Gu, Lian-Quan; Huang, Zhi-Shu; An, Lin-Kun] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China. [Wei, Hong-Yu; He, Xi-Xin] Guangzhou Univ Chinese Med, Coll Chinese Mat Med, Guangzhou 510006, Guangdong, Peoples R China. [Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP An, LK (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China. EM lssalk@mail.sysu.edu.cn FU National Natural Science Foundation of China [81373257]; Guangdong Natural Science Fund [S2013010015609]; National Institutes of Health National Cancer Institute [Z01 BC006161]; Center of Cancer Research [Z01 BC006161] FX This work was supported by the National Natural Science Foundation of China (No. 81373257), Guangdong Natural Science Fund (No. S2013010015609) and Intramural Research Program of the National Institutes of Health National Cancer Institute (Z01 BC006161), Center of Cancer Research (No. Z01 BC006161). We gratefully thank Prof. Ding Li, School of Pharmaceutical Sciences, Sun Yat-sen University for the manuscript preparation. NR 20 TC 3 Z9 3 U1 2 U2 16 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 EI 1768-3254 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD AUG 28 PY 2015 VL 101 BP 525 EP 533 DI 10.1016/j.ejmech.2015.07.007 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CQ7GV UT WOS:000360771900045 PM 26188908 ER PT J AU Kraus, A Anson, KJ Raymond, LD Martens, C Groveman, BR Dorward, DW Caughey, B AF Kraus, Allison Anson, Kelsie J. Raymond, Lynne D. Martens, Craig Groveman, Bradley R. Dorward, David W. Caughey, Byron TI Prion Protein Prolines 102 and 105 and the Surrounding Lysine Cluster Impede Amyloid Formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE amyloid; prion; prion disease; protein folding; protein structure; GSS; lysine; proline ID IN-VITRO; TRANSGENIC MICE; HYDROGEN/DEUTERIUM EXCHANGE; ALZHEIMERS-DISEASE; PRP AMYLOIDS; MOUSE-BRAIN; SCRAPIE; MUTATION; CONFORMATION; MECHANISM AB Background: We investigated how pathogenic prion protein mutations P102L and P105L lead to misfolding. Results: Mutations of these proline and adjacent lysine residues accelerated in vitro formation of amyloid with properties reminiscent of PrPSc. Conclusion: Specific proline and lysine residues might delay spontaneous prion disease by hindering PrP conversion into amyloid. Significance: These findings suggest mechanisms for genetic prion diseases. Human prion diseases can have acquired, sporadic, or genetic origins, each of which results in the conversion of prion protein (PrP) to transmissible, pathological forms. The genetic prion disease Gerstmann-Straussler-Scheinker syndrome can arise from point mutations of prolines 102 or 105. However, the structural effects of these two prolines, and mutations thereof, on PrP misfolding are not well understood. Here, we provide evidence that individual mutations of Pro-102 or Pro-105 to noncyclic aliphatic residues such as the Gerstmann-Straussler-Scheinker-linked leucines can promote the in vitro formation of PrP amyloid with extended protease-resistant cores reminiscent of infectious prions. This effect was enhanced by additional charge-neutralizing mutations of four nearby lysine residues comprising the so-called central lysine cluster. Substitution of these proline and lysine residues accelerated PrP conversion such that spontaneous amyloid formation was no longer slower than scrapie-seeded amyloid formation. Thus, Pro-102 and Pro-105, as well as the lysines in the central lysine cluster, impede amyloid formation by PrP, implicating these residues as key structural modulators in the conversion of PrP to disease-associated types of amyloid. C1 [Kraus, Allison; Anson, Kelsie J.; Raymond, Lynne D.; Groveman, Bradley R.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Martens, Craig; Dorward, David W.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM bcaughey@nih.gov FU National Institutes of Health Intramural Research Program of the NIAID FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program of the NIAID. The authors declare that they have no conflicts of interest with the contents of this article. NR 47 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2015 VL 290 IS 35 BP 21510 EP 21522 DI 10.1074/jbc.M115.665844 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ5IS UT WOS:000360637600026 PM 26175152 ER PT J AU Berezhkovskii, AM Dagdug, L Bezrukov, SM AF Berezhkovskii, Alexander M. Dagdug, Leonardo Bezrukov, Sergey M. TI A new approach to the problem of bulk-mediated surface diffusion SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID REPRESSOR-OPERATOR ASSOCIATION; CHAIN-LENGTH DEPENDENCE; TUBULIN-BLOCKED STATE; ANOMALOUS DIFFUSION; LIQUID SURFACES; ANION CHANNEL; DNA COILING; PROTEINS; KINETICS; VDAC AB This paper is devoted to bulk-mediated surface diffusion of a particle which can diffuse both on a flat surface and in the bulk layer above the surface. It is assumed that the particle is on the surface initially (at t = 0) and at time t, while in between it may escape from the surface and come back any number of times. We propose a new approach to the problem, which reduces its solution to that of a two-state problem of the particle transitions between the surface and the bulk layer, focusing on the cumulative residence times spent by the particle in the two states. These times are random variables, the sum of which is equal to the total observation time t. The advantage of the proposed approach is that it allows for a simple exact analytical solution for the double Laplace transform of the conditional probability density of the cumulative residence time spent on the surface by the particle observed for time t. This solution is used to find the Laplace transform of the particle mean square displacement and to analyze the peculiarities of its time behavior over the entire range of time. We also establish a relation between the double Laplace transform of the conditional probability density and the Fourier-Laplace transform of the particle propagator over the surface. The proposed approach treats the cases of both finite and infinite bulk layer thicknesses (where bulk-mediated surface diffusion is normal and anomalous at asymptotically long times, respectively) on equal footing. (C) 2015 AIP Publishing LLC. C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Comp Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico. RP Berezhkovskii, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. FU NIH, Center for Information Technology; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Consejo Nacional de Ciencia y Tecnologia (CONACyT) [176452] FX This study was supported by the Intramural Research Program of the NIH, Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development. L.D. thanks Consejo Nacional de Ciencia y Tecnologia (CONACyT) for partial support under Grant No. 176452. NR 36 TC 1 Z9 1 U1 2 U2 7 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD AUG 28 PY 2015 VL 143 IS 8 AR 084103 DI 10.1063/1.4928741 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CQ5OD UT WOS:000360653900006 PM 26328814 ER PT J AU Chen, GJ Yuan, A Shriner, D Tekola-Ayele, F Zhou, J Bentley, AR Zhou, YX Wang, CT Newport, MJ Adeyemo, A Rotimi, CN AF Chen, Guanjie Yuan, Ao Shriner, Daniel Tekola-Ayele, Fasil Zhou, Jie Bentley, Amy R. Zhou, Yanxun Wang, Chuntao Newport, Melanie J. Adeyemo, Adebowale Rotimi, Charles N. TI An Improved F-st Estimator SO PLOS ONE LA English DT Article ID GENE FLOW; DIFFERENTIATION; ANCESTRY AB The fixation index F-st plays a central role in ecological and evolutionary genetic studies. The estimators of Wright ((F) over cap (st1)), Weir and Cockerham ((F) over cap (st2)), and Hudson et al. ((F) over cap st3) are widely used to measure genetic differences among different populations, but all have limitations. We propose a minimum variance estimator (F) over cap (stm) using (F) over cap (st1) and (F) over cap (st2). We tested (F) over cap (stm) in simulations and applied it to 120 unrelated East African individuals from Ethiopia and 11 subpopulations in HapMap 3 with 464,642 SNPs. Our simulation study showed that (F) over cap (stm) has smaller bias than (F) over cap (st2) for small sample sizes and smaller bias than (F) over cap (st1) for large sample sizes. Also, (F) over cap (stm) has smaller variance than (F) over cap (st2) for small F-st values and smaller variance than (F) over cap (st1) for large F-st values. We demonstrated that approximately 30 subpopulations and 30 individuals per subpopulation are required in order to accurately estimate F-st. C1 [Chen, Guanjie; Shriner, Daniel; Tekola-Ayele, Fasil; Zhou, Jie; Bentley, Amy R.; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Yuan, Ao] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC USA. [Zhou, Yanxun; Wang, Chuntao] Suizhou Cent Hosp, Suizhou, Hubei, Peoples R China. [Newport, Melanie J.] Brighton & Sussex Med Sch, Brighton, E Sussex, England. RP Chen, GJ (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. EM chengu@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231; Tekola-Ayele, Fasil/0000-0003-4194-9370 FU Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH); National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; National Institutes of Health [Z01HG200362]; Wellcome Trust [079791] FX This research was supported by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). The data from the Wolaita came from a study supported by the Wellcome Trust (Grant #079791). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 2 Z9 2 U1 1 U2 5 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 28 PY 2015 VL 10 IS 8 AR e0135368 DI 10.1371/journal.pone.0135368 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ0PO UT WOS:000360299100026 PM 26317214 ER PT J AU Chen, X Xie, CS Sun, LX Ding, JH Cai, HB AF Chen, Xi Xie, Chengsong Sun, Lixin Ding, Jinhui Cai, Huaibin TI Longitudinal Metabolomics Profiling of Parkinson's Disease-Related alpha-Synuclein A53T Transgenic Mice SO PLOS ONE LA English DT Article ID AGE-RELATED-CHANGES; DOPAMINERGIC-NEURONS; ALANINE METABOLISM; ENERGY-METABOLISM; INDUCED APOPTOSIS; REDOX PROTEOMICS; RAT-BRAIN; GLUTATHIONE; GUANOSINE; HOMEOSTASIS AB Metabolic homeostasis is critical for all biological processes in the brain. The metabolites are considered the best indicators of cell states and their rapid fluxes are extremely sensitive to cellular changes. While there are a few studies on the metabolomics of Parkinson's disease, it lacks longitudinal studies of the brain metabolic pathways affected by aging and the disease. Using ultra-high performance liquid chromatography and tandem mass spectroscopy (UPLC/MS), we generated the metabolomics profiling data from the brains of young and aged male PD-related alpha-synuclein A53T transgenic mice as well as the age- and gender-matched non-transgenic (nTg) controls. Principal component and unsupervised hierarchical clustering analyses identified distinctive metabolites influenced by aging and the A53T mutation. The following metabolite set enrichment classification revealed the alanine metabolism, redox and acetyl-CoA biosynthesis pathways were substantially disturbed in the aged mouse brains regardless of the genotypes, suggesting that aging plays a more prominent role in the alterations of brain metabolism. Further examination showed that the interaction effect of aging and genotype only disturbed the guanosine levels. The young A53T mice exhibited lower levels of guanosine compared to the age- matched nTg controls. The guanosine levels remained constant between the young and aged nTg mice, whereas the aged A53T mice showed substantially increased guanosine levels compared to the young mutant ones. In light of the neuroprotective function of guanosine, our findings suggest that the increase of guanosine metabolism in aged A53T mice likely represents a protective mechanism against neurodegeneration, while monitoring guanosine levels could be applicable to the early diagnosis of the disease. C1 [Chen, Xi; Xie, Chengsong; Sun, Lixin; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Ding, Jinhui] NIA, Bioinformat Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM caih@mail.nih.gov FU National Institutes of Health [AG000928, AG000929] FX This work was supported by National Institutes of Health grants AG000928 and AG000929, http://grants.nih.gov/grants/oer.htm. NR 45 TC 2 Z9 2 U1 7 U2 17 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 28 PY 2015 VL 10 IS 8 AR e0136612 DI 10.1371/journal.pone.0136612 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ0PO UT WOS:000360299100112 PM 26317866 ER PT J AU Henshaw, DL Director, WAS AF Henshaw, Denis L. Suk, William A. TI Diet, transplacental carcinogenesis, and risk to children SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID CHILDHOOD LEUKEMIA; EXPOSURE; METAANALYSIS; ORIGINS C1 [Henshaw, Denis L.] Children Canc UK, London WC1N 3JQ, England. [Suk, William A.] NIH, Natl Inst Environm Hlth Sci, Superfund Res Programme, Stapleton, NY USA. RP Henshaw, DL (reprint author), Children Canc UK, London WC1N 3JQ, England. EM d.l.henshaw@bris.ac.uk NR 12 TC 0 Z9 0 U1 3 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD AUG 28 PY 2015 VL 351 AR h4636 DI 10.1136/bmj.h4636 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CQ2NX UT WOS:000360439100014 PM 26318965 ER PT J AU Kamal, AK Shaikh, QN Pasha, O Azam, I Islam, M Memon, AA Rehman, H Affan, M Nazir, S Aziz, S Jan, M Andani, A Muqeet, A Ahmed, B Khoja, S AF Kamal, Ayeesha Kamran Shaikh, Quratulain Nauman Pasha, Omrana Azam, Iqbal Islam, Muhammad Memon, Adeel Ali Rehman, Hasan Affan, Muhammad Nazir, Sumaira Aziz, Salman Jan, Muhammad Andani, Anita Muqeet, Abdul Ahmed, Bilal Khoja, Shariq TI Improving medication adherence in stroke patients through Short Text Messages (SMS4Stroke)-study protocol for a randomized, controlled trial SO BMC NEUROLOGY LA English DT Article DE Stroke; Medication adherence; SMS; Prevention ID ACTIVE ANTIRETROVIRAL THERAPY; LONG-TERM MORTALITY; ISCHEMIC-STROKE; PAKISTAN HEALTH; YOUNG-ADULTS; PREDICTORS; SMS; SURVIVAL; DEATH; CARE AB Background: Stroke is a major cause of morbidity and mortality, especially in low and middle income countries. Medical management is the mainstay of therapy to prevent recurrence of stroke. Current estimates are that only 1 in 6 patients have perfect adherence to medication schedules. Using SMS (Short Messaging Service) as reminders to take medicines have been used previously for diseases such as diabetes and HIV with moderate success. We aim to explore the effectiveness and acceptability of SMS in increasing adherence to medications in patients with stroke. Methods: This will be a randomized, controlled, assessor blinded single center superiority trial. Adult participants with access to a cell phone and a history of stroke longer than 1 month on multiple risk modifying medications will be selected from Neurology and Stroke Clinic. They will be randomized into two parallel groups in a 1: 1 ratio via block technique with one group receiving the standard of care as per institutional guidelines while the parallel group receiving SMS reminders for each dose of medicine in addition to the standard of care. In addition intervention group will receive messages for lifestyle changes, medication information, risk factors and motivation for medication adherence. These will bemodeled on Social Cognitive Theory and Health Belief Model and will be categorized by Michies Taxonomy of Behavioral Change Communication. Patient compliance to medicines will be measured at baseline and then after 2 months in each group by using the Morisky Medication Adherence Scale. The change in compliance to medication regimen after the intervention and the difference between the two groups will be used to determine the effectiveness of SMS reminders as a tool to increase medication compliance. The acceptability of the SMS will be determined by a tool designed for this study whose attributes are based Rogers Diffusion of innovation theory. A sample size of 86 participants in each arm will be sufficient to detect a difference of 1 point on the MMAS with a power of 90 % and significance level of 5 % between the two groups; using an attrition rate of 15 %, 200 participants in all will be randomized. Discussion: The SMS for Stroke Study will provide evidence for feasibility and effectiveness of SMS in improving post stroke medication adherence in an LMIC setting. C1 [Kamal, Ayeesha Kamran] Natl Inst Hlth, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Neurol,Stroke Serv, Karachi, Pakistan. [Kamal, Ayeesha Kamran; Rehman, Hasan] Aga Khan Univ, Dept Med, Karachi, Pakistan. [Shaikh, Quratulain Nauman] Natl Inst Hlth, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Karachi, Pakistan. [Shaikh, Quratulain Nauman; Memon, Adeel Ali; Affan, Muhammad; Nazir, Sumaira; Aziz, Salman; Jan, Muhammad; Andani, Anita] Aga Khan Univ, Karachi, Pakistan. [Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Epidemiol & Biostat Program, Karachi, Pakistan. [Azam, Iqbal; Islam, Muhammad] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Memon, Adeel Ali; Affan, Muhammad; Nazir, Sumaira; Aziz, Salman] Natl Inst Hlth, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, SMS4Stroke Study, Karachi, Pakistan. [Jan, Muhammad; Andani, Anita] Natl Inst Hlth, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Stroke Serv,Sect Neurol,Dept Med, Karachi, Pakistan. [Muqeet, Abdul] Aga Khan Dev Network, eHlth Innovat, Global, Karachi, Pakistan. [Ahmed, Bilal] Aga Khan Univ, Dept Med, Epidemiol & Biostat, Karachi, Pakistan. [Khoja, Shariq] United Nations Fdn Geneva, Evidence Capac & Policy mHlth Alliance, Geneva, Switzerland. [Khoja, Shariq] COMSATS Inst Informat Technol, Islamabad, Pakistan. RP Kamal, AK (reprint author), Natl Inst Hlth, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Neurol,Stroke Serv, Karachi, Pakistan. EM ayeesha.kamal@aku.edu RI Emchi, Karma/Q-1952-2016; OI Shaikh, Quratulain/0000-0001-6106-2713 FU Fogarty International Center [D43TW008660]; National Institute of Neurologic Disorders and Stroke; International Cerebrovascular Translational Clinical Research Training Program (Fogarty International Center, National Institutes of Health); Grand Challenges Canada, University Research Council Aga Khan University (URC, AKU), Higher Education Commission, Gov. of Pakistan, HEC; Baylor College of Medicine, BCM Center FX Dr Ayeesha Kamran Kamal is the co-director and recipient of grant entitled of The International Cerebrovascular Translational Clinical Research Training Program (Fogarty International Center, National Institutes of Health). Dr. Quratulain Shaikh is a neurovascular research fellow whose mentored research practicum training is currently funded by Award Number D43TW008660 from the Fogarty International Center and the National Institute of Neurologic Disorders and Stroke.; Dr Ayeesha Kamran Kamal is also funded by Grand Challenges Canada, University Research Council Aga Khan University (URC, AKU), Higher Education Commission, Gov. of Pakistan, HEC. She is also collaboratively funded from the Baylor College of Medicine, BCM Center for Globalization on work on medical prescription literacy. NR 46 TC 3 Z9 3 U1 3 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD AUG 28 PY 2015 VL 15 AR 157 DI 10.1186/s12883-015-0413-2 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CP7CC UT WOS:000360043800002 PM 26311325 ER PT J AU Miao, HX Gomella, AA Harmon, KJ Bennett, EE Chedid, N Znati, S Panna, A Foster, BA Bhandarkar, P Wen, H AF Miao, Houxun Gomella, Andrew A. Harmon, Katherine J. Bennett, Eric E. Chedid, Nicholas Znati, Sami Panna, Alireza Foster, Barbara A. Bhandarkar, Priya Wen, Han TI Enhancing Tabletop X-Ray Phase Contrast Imaging with Nano-Fabrication SO SCIENTIFIC REPORTS LA English DT Article ID TALBOT INTERFEROMETRY; COMPACT SOURCE; GRATINGS AB X-ray phase-contrast imaging is a promising approach for improving soft-tissue contrast and lowering radiation dose in biomedical applications. While current tabletop imaging systems adapt to common x-ray tubes and large-area detectors by employing absorptive elements such as absorption gratings or monolithic crystals to filter the beam, we developed nanometric phase gratings which enable tabletop x-ray far-field interferometry with only phase-shifting elements, leading to a substantial enhancement in the performance of phase contrast imaging. In a general sense the method transfers the demands on the spatial coherence of the x-ray source and the detector resolution to the feature size of x-ray phase masks. We demonstrate its capabilities in hard x-ray imaging experiments at a fraction of clinical dose levels and present comparisons with the existing Talbot-Lau interferometer and with conventional digital radiography. C1 [Miao, Houxun; Gomella, Andrew A.; Harmon, Katherine J.; Bennett, Eric E.; Chedid, Nicholas; Znati, Sami; Panna, Alireza; Wen, Han] NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Foster, Barbara A.; Bhandarkar, Priya] Walter Reed Natl Mil Ctr, Breast Imaging Ctr, Bethesda, MD 20889 USA. RP Wen, H (reprint author), NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 35 TC 4 Z9 4 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD AUG 28 PY 2015 VL 5 AR 13581 DI 10.1038/srep13581 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP9TO UT WOS:000360237700001 PM 26315891 ER PT J AU Jain, A Samykutty, A Jackson, C Browning, D Bollag, WB Thangaraju, M Takahashi, S Singh, SR AF Jain, Ashok Samykutty, Abhilash Jackson, Carissa Browning, Darren Bollag, Wendy B. Thangaraju, Muthusamy Takahashi, Satoru Singh, Shree Ram TI Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets SO CANCER LETTERS LA English DT Article DE Phytochemicals; Cancer prevention; Reactive oxygen species; DNA damage; DNA adduct; Heterocyclic amines ID CANCER-ASSOCIATED FIBROBLASTS; NF-KAPPA-B; HETEROCYCLIC AMINES; CELLULAR SENESCENCE; COLON-CANCER; DNA-ADDUCTS; MUTAGENIC COMPOUND; TUMOR-GROWTH; IN-VITRO; APOPTOSIS AB Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), found in cooked meat, is a known food carcinogen that causes several types of cancer, including breast cancer, as PhIP metabolites produce DNA adduct and DNA strand breaks. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity. To date, no study has examined the interaction of PhIP with curcumin in breast epithelial cells. The present study demonstrates the mechanisms by which curcumin inhibits PhIP-induced cytotoxicity in normal breast epithelial cells (MCF-10A). Curcumin significantly inhibited PhIP-induced DNA adduct formation and DNA double stand breaks with a concomitant decrease in reactive oxygen species (ROS) production. The expression of Nrf2, FOX targets; DNA repair genes BRCA-1, H2AFX and PARP-1; and tumor suppressor P16 was studied to evaluate the influence on these core signaling pathways. PhIP induced the expression of various antioxidant and DNA repair genes. However, co-treatment with curcumin inhibited this expression. PhIP suppressed the expression of the tumor suppressor P16 gene, whereas curcumin co-treatment increased its expression. Caspase-3 and -9 were slightly suppressed by curcumin with a consequent inhibition of cell death. These results suggest that curcumin appears to be an effective anti-PhIP food additive likely acting through multiple molecular targets. Published by Elsevier Ireland Ltd. C1 [Jain, Ashok; Samykutty, Abhilash; Jackson, Carissa] Albany State Univ, Dept Nat Sci, Albany, GA 31705 USA. [Browning, Darren; Thangaraju, Muthusamy] Georgia Regents Univ, Ctr Canc, Augusta, GA 30912 USA. [Bollag, Wendy B.] Georgia Regents Univ, Dept Physiol, Augusta, GA 30912 USA. [Bollag, Wendy B.] Charlie Norwood VA Med Ctr, Augusta, GA 30904 USA. [Takahashi, Satoru] Nagoya City Univ, Grad Sch Med Sci, Dept Expt Pathol & Tumor Biol, Nagoya, Aichi 4678601, Japan. [Singh, Shree Ram] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Jain, A (reprint author), Albany State Univ, Dept Nat Sci, Albany, GA 31705 USA. EM ashok.jain@asurams.edu; singhshr@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Department of Defense, U.S. Army Medical Research and Material Command [W81XWH-10-1-1042]; National Institutes of Health, Research Infrastructure in Minority Institution Grant [2P20MD001085-08]; VA Research Career Scientist Award FX This work was supported by the Department of Defense, U.S. Army Medical Research and Material Command (W81XWH-10-1-1042), and National Institutes of Health, Research Infrastructure in Minority Institution Grant (2P20MD001085-08). Dr. Bollag is supported by a VA Research Career Scientist Award. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 68 TC 5 Z9 5 U1 2 U2 35 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD AUG 28 PY 2015 VL 365 IS 1 BP 122 EP 131 DI 10.1016/j.canlet.2015.05.017 PG 10 WC Oncology SC Oncology GA CL8LV UT WOS:000357227100014 PM 26004342 ER PT J AU Fondell, E O'Reilly, EJ Fitzgerald, KC Falcone, GJ Kolonel, LN Park, Y Gapstur, SM Ascherio, A AF Fondell, Elinor O'Reilly, EIlis J. Fitzgerald, Kathryn C. Falcone, Guido J. Kolonel, Laurence N. Park, Yikyung Gapstur, Susan M. Ascherio, Alberto TI Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies SO Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration LA English DT Article DE Amyotrophic lateral sclerosis; motor neuron disease; caffeine; epidemiology; longitudinal cohort studies ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; SOCIETY CANCER PREVENTION; BASE-LINE CHARACTERISTICS; RETIRED-PERSONS DIET; PARKINSONS-DISEASE; NATIONAL-INSTITUTES; MULTIETHNIC COHORT; CONSUMPTION; WOMEN AB Caffeine is thought to be neuroprotective by antagonizing the adenosine A(2A) receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis (ALS).Longitudinal analyses based on over 1,010,000 males and females in five large cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study). Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using random-effects models. Results showed that a total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. In conclusion, the results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk. C1 [Fondell, Elinor; O'Reilly, EIlis J.; Fitzgerald, Kathryn C.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Park, Yikyung] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Fondell, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM efondell@hsph.harvard.edu RI Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU ALS Therapy Alliance; National Cancer Institute FX This work was supported by grants from the ALS Therapy Alliance and the National Cancer Institute. NR 37 TC 1 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD AUG 27 PY 2015 VL 16 IS 5-6 BP 366 EP 371 DI 10.3109/21678421.2015.1020813 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CV7TG UT WOS:000364477400012 PM 25822002 ER PT J AU Burgess, RC Misteli, T AF Burgess, Rebecca C. Misteli, Tom TI Not All DDRs Are Created Equal: Non-Canonical DNA Damage Responses SO CELL LA English DT Review ID DOUBLE-STRAND BREAKS; ACTIVATION; CHROMATIN; REPLICATION; MITOSIS; COMPLEX; STRESS; REPAIR; ATM AB It is commonly assumed that there is a single canonical DNA damage response (DDR) that protects cells from various types of double-strand breaks and that its activation occurs via recognition of DNA ends by the DDR machinery. Recent work suggests that both assumptions may be oversimplifications. Here, we discuss several variations of the DDR in which the pathway is activated by diverse cellular events and/or generates distinct signaling outcomes. The existence of multiple non-canonical DDRs provides insights into how DNA damage is sensed and suggests a highly modular organization of the DDR. C1 [Burgess, Rebecca C.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Burgess, Rebecca C.] Stevenson Univ, Sch Sci, Dept Biol Sci, Stevenson, MD 21153 USA. RP Burgess, RC (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM rburgess@stevenson.edu; mistelit@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research FX We apologize to the large number of authors whose work we could not cite due to space constraints. Thanks to Marc Raley for help with the figure. Work in the Misteli laboratory is supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research. NR 18 TC 5 Z9 5 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 27 PY 2015 VL 162 IS 5 BP 944 EP 947 DI 10.1016/j.cell.2015.08.006 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ4QO UT WOS:000360589900006 PM 26317463 ER PT J AU Kanekiyo, M Bu, W Joyce, MG Meng, G Whittle, JRR Baxa, U Yamamoto, T Narpala, S Todd, JP Rao, SS McDermott, AB Koup, RA Rossmann, MG Mascola, JR Graham, BS Cohen, JI Nabel, GJ AF Kanekiyo, Masaru Bu, Wei Joyce, M. Gordon Meng, Geng Whittle, James R. R. Baxa, Ulrich Yamamoto, Takuya Narpala, Sandeep Todd, John-Paul Rao, Srinivas S. McDermott, Adrian B. Koup, Richard A. Rossmann, Michael G. Mascola, John R. Graham, Barney S. Cohen, Jeffrey I. Nabel, Gary J. TI Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site SO CELL LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; INFECTIOUS-MONONUCLEOSIS; CRYSTAL-STRUCTURE; IN-VITRO; GLYCOPROTEIN; FERRITIN; HIV-1; NEUTRALIZATION; PROTECTION AB Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and similar to 200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses. C1 [Kanekiyo, Masaru; Joyce, M. Gordon; Whittle, James R. R.; Yamamoto, Takuya; Narpala, Sandeep; Todd, John-Paul; Rao, Srinivas S.; McDermott, Adrian B.; Koup, Richard A.; Mascola, John R.; Graham, Barney S.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Bu, Wei; Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Meng, Geng; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Baxa, Ulrich] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA. RP Cohen, JI (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov; gary.nabel@sanofi.com OI Yamamoto, Takuya/0000-0003-3753-1211 FU Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX We thank B. Hartman (VRC) for help with manuscript preparation; S.-Y. Ko, H. Bao, C. Chiedi, M. Dillon, and K. Wuddie (VRC) for help with animal studies; K. Foulds and V. Letukas (VRC) for monkey sample processing; P. Radecki (LID) for help with serum analyses; A. Wheatley, S. Andrews, T. Zhou, and H. Yassine (VRC) for technical advice; Y. Okuno (Osaka University) for providing C179 antibody; and X. Chen (VRC) for help with transfections. This work was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and in part with federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. M.K., W.B., J.I.C., and G.J.N. are named as inventors on a patent application describing the data presented in this paper, which has been filed by the National Institutes of Health. NR 53 TC 16 Z9 16 U1 3 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 27 PY 2015 VL 162 IS 5 BP 1090 EP 1100 DI 10.1016/j.cell.2015.07.043 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CQ4QO UT WOS:000360589900018 PM 26279189 ER PT J AU Klion, AD AF Klion, Amy D. TI How I treat hypereosinophilic syndromes SO BLOOD LA English DT Review ID CHRONIC EOSINOPHILIC LEUKEMIA; CHURG-STRAUSS-SYNDROME; DOSE IMATINIB MESYLATE; TERM-FOLLOW-UP; EPISODIC ANGIOEDEMA; INTERFERON-ALPHA; MYELOPROLIFERATIVE VARIANT; FAMILIAL EOSINOPHILIA; FIP1L1-PDGFRA FUSION; MOLECULAR REMISSION AB Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 x 10(9)/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. HESs are pleomorphic in clinical presentation and can be idiopathic or associated with a variety of underlying conditions, including allergic, rheumato-logic, infectious, and neoplastic disorders. Moreover, the etiology of the eosinophilia in HESs can be primary (myeloid), secondary (lymphocyte-driven), or unknown. Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. This review presents an updated treatment-based approach to the classification of patients with presumed HES and discusses the roles of conventional and novel agents in the management of these patients. C1 [Klion, Amy D.] NIAID, Human Eosinophil Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), Bldg 4,Room B1-28,4 Mem Dr, Bethesda, MD 20892 USA. EM aklion@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 95 TC 11 Z9 12 U1 2 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 27 PY 2015 VL 126 IS 9 BP 1069 EP 1077 DI 10.1182/blood-2014-11-551614 PG 9 WC Hematology SC Hematology GA CQ3XN UT WOS:000360537800006 PM 25964669 ER PT J AU Mather, KJ Pan, Q Knowler, WC Funahashi, T Bray, GA Arakaki, R Falkner, B Sharma, K Goldstein, BJ AF Mather, Kieren J. Pan, Qing Knowler, William C. Funahashi, Tohru Bray, George A. Arakaki, Richard Falkner, Bonita Sharma, Kumar Goldstein, Barry J. CA DPP Res Grp TI Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort SO PLOS ONE LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; TYPE-2; INDIVIDUALS; LEVEL; MICE; MICROALBUMINURIA; NEPHROPATHY; PROGRESSION; ABLATION AB Background and Objectives Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity. Design, Setting, Participants and Methods We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects. Results Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman's rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman's rho = (+) 0.04, p = 0.03). Conclusions In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity. C1 [Mather, Kieren J.] Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. [Pan, Qing] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Funahashi, Tohru] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka, Japan. [Bray, George A.] Pennington Biomed Ctr, Baton Rouge, LA USA. [Arakaki, Richard] Univ Hawaii, Dept Med Diabet & Endocrinol, Honolulu, HI 96822 USA. [Falkner, Bonita] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. [Sharma, Kumar] Univ Calif San Diego, Div Nephrol & Hypertens, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. [Sharma, Kumar] Univ Calif San Diego, Ctr Renal Translat Med, Vet Affairs San Diego Healthcare Syst, Dept Med, San Diego, CA 92103 USA. [Goldstein, Barry J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Div Endocrinol Diabet & Metab Dis, Philadelphia, PA 19107 USA. RP Mather, KJ (reprint author), Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. EM dppmail@bsc.gwu.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health [U01 DK048489]; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; Sandra A. Daugherty foundation; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study; and collection, management, analysis, and interpretation of the data (U01 DK048489). The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. Adiponectin analyses were supported by a grant from the Sandra A. Daugherty foundation (to KM). The sponsor of this study was represented on the Steering Committee and played a part in study design, how the study was done, and publication. The funding agency was not represented on the writing group, although all members of the Steering Committee had input into the report's contents. All authors in the writing group had access to all data. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 0 Z9 0 U1 1 U2 4 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 27 PY 2015 VL 10 IS 8 AR e0136853 DI 10.1371/journal.pone.0136853 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP8KZ UT WOS:000360144000102 PM 26312480 ER PT J AU Nagaya, T Sato, K Harada, T Nakamura, Y Choyke, PL Kobayashi, H AF Nagaya, Tadanobu Sato, Kazuhide Harada, Toshiko Nakamura, Yuko Choyke, Peter L. Kobayashi, Hisataka TI Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen SO PLOS ONE LA English DT Article ID GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODIES; ENHANCED PERMEABILITY; PHOTODYNAMIC THERAPY; TUMOR-MODEL; EXPRESSION; EFFICACY; SUBTYPES; CETUXIMAB; COCKTAIL AB Aim Triple-negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer. Near infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that employs an antibody-photosensitizer conjugate (APC) followed by exposure of NIR light for activating selective cytotoxicity on targeted cancer cells and may have application to TNBC. In order to minimize the dose of APC while maximizing the therapeutic effects, dosing of the APC and NIR light need to be optimized. In this study, we investigate in vitro and in vivo efficacy of cetuximab (cet)-IR700 NIR-PIT on two breast cancer models MDAMB231 (TNBC, EGFR moderate) and MDAMB468 (TNBC, EGFR high) cell lines, and demonstrate a method to optimize the dosing APC and NIR light. Method After validating in vitro cell-specific cytotoxicity, NIR-PIT therapeutic effects were investigated in mouse models using cell lines derived from TNBC tumors. Tumor-bearing mice were separated into 4 groups for the following treatments: (1) no treatment (control); (2) 300 mu g of cet-IR700 i.v., (APC i.v. only); (3) NIR light exposure only, NIR light was administered at 50 J/cm(2) on day 1 and 100 J/cm(2) on day 2 (NIR light only); (4) 300 mu g of cet-IR700 i.v., NIR light was administered at 50 J/cm(2) on day 1 after injection and 100 J/cm(2) of light on day 2 after injection (one shot NIR-PIT). To compare different treatment regimens with a fixed dose of APC, we added the following treatments (5) 100 mu g of cet-IR700 i.v., NIR light administered at 50 J/cm(2) on day 1 and 50 mu g of cet-IR700 i.v. immediately after NIR-PIT, then NIR light was administered at 100 J/cm(2) on day 2, which were performed two times every week ("two split" NIR-PIT) and (6) 100 mu g of cet-IR700 i.v., NIR light was administered at 50 J/cm(2) on day 1 and 100 J/cm(2) on day 2, which were performed three times per week ("three split" NIR-PIT). Result Both specific binding and NIR-PIT effects were greater with MDAMB468 than MDAMB231 cells in vitro. Tumor accumulation of cet-IR700 in MDAMB468 tumors was significantly higher (p < 0.05) than in MDAMB231 tumors in vivo. Tumor growth and survival of MDAMB231 tumor bearing mice was significantly lower in the NIR-PIT treatment group (p < 0.05). In MDAMB468 bearing mice, tumor growth and survival was significantly improved in the NIR-PIT treatment groups in all treatment regimens (one shot NIR-PIT; p < 0.05, "two split" NIR-PIT; p < 0.01, "three split" NIR-PIT; p < 0.001) compared with control groups. Conclusion NIR-PIT for TNBC was effective regardless of expression of EGFR, however, greater cell killing was shown with higher EGFR expression tumor in vitro. In all treatment regimens, NIR-PIT suppressed tumor growth, resulting in significantly prolonged survival that further improved by splitting the APC dose and using repeated light exposures. C1 [Nagaya, Tadanobu; Sato, Kazuhide; Harada, Toshiko; Nakamura, Yuko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU National Cancer Institute [ZIA BC 011513] FX HK received funding from the National Cancer Institute, ZIA BC 011513, https://ccrod.cancer.gov/confluence/display/CCRARSINFO/Z+Numbers+-+2013+ Completed+Projects. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 6 Z9 6 U1 3 U2 20 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 27 PY 2015 VL 10 IS 8 AR e0136829 DI 10.1371/journal.pone.0136829 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP8KZ UT WOS:000360144000098 PM 26313651 ER PT J AU Villalba, K Devieux, JG Rosenberg, R Cadet, JL AF Villalba, Karina Devieux, Jessy G. Rosenberg, Rhonda Cadet, Jean Lud TI DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who abuse alcohol SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE Dopamine; DRD2 gene; DRD4 gene; HIV; Alcohol abuse ID HYPERACTIVITY DISORDER ADHD; WORKING-MEMORY PERFORMANCE; DOPAMINE-D4 RECEPTOR GENE; MAJOR DEPRESSIVE DISORDER; SUSTAINED ATTENTION; EXECUTIVE FUNCTIONS; C957T POLYMORPHISM; DEFICIT/HYPERACTIVITY-DISORDER; MONOAMINERGIC MODULATION; INDIVIDUAL-DIFFERENCES AB Background: HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. The causes of neurocognitive impairment are still unclear. However, several factors have been suggested including the role of genetics. There is evidence suggesting that neurocognitive impairment is heritable and individual differences in cognition are strongly driven by genetic variations. The contribution of genetic variants affecting the metabolism and activity of dopamine may influence these individual differences. Methods: The present study explored the relationship between two candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4 48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests (ROCT) were used to measure executive function and memory. Results: Results showed significant associations with the SNP rs6277 and impaired executive function (odds ratio = 3.3, 95 % CI 1.2-2.6; p = 0.004) and cognitive flexibility (odds ratio = 1.6, 95 % CI 2.0-5.7; p = 0.001). The results were further stratified by race and sex and significant results were seen in males (odds ratio = 3.5, 95 % CI 1.5-5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95 % CI 2.3-3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with executive dysfunction. Conclusion: The study shows that genetically determined differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors for deficits in executive function and cognitive flexibility. C1 [Villalba, Karina; Devieux, Jessy G.; Rosenberg, Rhonda] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, North Miami, FL 33181 USA. [Cadet, Jean Lud] NIDA, Intramural Program, Mol Neuropsychiat Res Branch, Baltimore, MD USA. RP Villalba, K (reprint author), Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, Biscayne Bay Campus,3000 NE,151 St ACI 260, North Miami, FL 33181 USA. EM kvill012@fiu.edu FU National Institute on Alcohol Abuse and Alcoholism [R01AA017405]; National Institute of General Medical Sciences of the National Institutes of Health [R25 GM061347] FX This work was supported by National Institute on Alcohol Abuse and Alcoholism (Grant R01AA017405). Karina Villalba was supported by National Institute of General Medical Sciences of the National Institutes of Health (Grant R25 GM061347). No potential conflicts of interest by any of the authors. NR 75 TC 1 Z9 1 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD AUG 27 PY 2015 VL 11 AR 25 DI 10.1186/s12993-015-0072-x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CP6YB UT WOS:000360033300001 PM 26307064 ER PT J AU Shan, LF Diaz, O Zhang, YJ Ladenheim, B Cadet, JL Chiang, YH Olson, L Hoffer, BJ Backman, CM AF Shan, Lufei Diaz, Oscar Zhang, Yajun Ladenheim, Bruce Cadet, Jean-Lud Chiang, Yung-Hsiao Olson, Lars Hoffer, Barry J. Baeckman, Cristina M. TI L-Dopa induced dyskinesias in Parkinsonian mice: Disease severity or L-Dopa history SO BRAIN RESEARCH LA English DT Article DE Basal ganglia; Nigrostriatal function; MitoPark mouse; Behavior; Sensitization; Motor complication ID NIGROSTRIATAL FUNCTION; CELLULAR-PARAMETERS; MOTOR FLUCTUATIONS; YOUNG-ONSET; MODEL AB In Parkinson's disease, the efficacy of L-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinson's disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of L-Dopa treatment determines development of L-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with L-Dopa (10 mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to L-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting L-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with L-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying L-Dopa treatment until Parkinson's disease symptoms become more severe does not delay the development of L-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Shan, Lufei; Diaz, Oscar; Zhang, Yajun; Baeckman, Cristina M.] NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ladenheim, Bruce; Cadet, Jean-Lud] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Chiang, Yung-Hsiao; Hoffer, Barry J.] Taipei Med Univ, Grad Program Neuroregenerat, Taipei, Taiwan. [Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44124 USA. [Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden. RP Hoffer, BJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosurg, NIH, Cleveland, OH 44124 USA. EM ychiang@tmu.edu.tw; Lars.Olson@ki.se; barry.hoffer@case.edu; Cristina.Backman@nih.gov FU NIDA, NIH; NIH [NS070825]; ERC [322744]; Swedish Research Council [K2012-62X-03185-42-4]; Swedish Parkinson Foundation; [NSC101-2632-B-038-001-MY3] FX The study was supported by the Intramural Research Program, NIDA, NIH (LS, OD, YZ, BL, JC, CB), NIH grant NS070825 (BR), ERC Advanced Investigator grant (322744 LO), the Swedish Research Council (K2012-62X-03185-42-4 LO), the Swedish Parkinson Foundation (LO), and Taiwan NSC101-2632-B-038-001-MY3 (YC). NR 23 TC 2 Z9 2 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD AUG 27 PY 2015 VL 1618 BP 261 EP 269 DI 10.1016/j.brainres.2015.06.005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CP5XB UT WOS:000359957600027 PM 26086365 ER PT J AU Ertel, A Pratt, D Kellman, P Leung, S Bandettini, P Long, LM Young, M Nelson, C Arai, AE Druey, KM AF Ertel, Andrew Pratt, Drew Kellman, Peter Leung, Steve Bandettini, Patricia Long, Lauren M. Young, Michael Nelson, Celeste Arai, Andrew E. Druey, Kirk M. TI Increased myocardial extracellular volume in active idiopathic systemic capillary leak syndrome SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE Systemic capillary leak syndrome; Mycocardial edema; Cardiovascular magnetic resonance ID CARDIOVASCULAR MAGNETIC-RESONANCE; SYNDROME CLARKSON DISEASE; INVERSION-RECOVERY; CASE SERIES; INFARCTION; FIBROSIS; QUANTIFICATION; VALIDATION; EXPERIENCE; SCLEROSIS AB Background: The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of unknown etiology presenting as recurrent episodes of shock and peripheral edema due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are few due to the scarcity of cases, and the etiology of vascular barrier disruption in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR) allow for the quantitative assessment of the myocardial extracellular volume (ECV), which can be increased in conditions causing myocardial edema. We hypothesized that measurement of myocardial ECV may detect myocardial vascular leak in patients with SCLS. Methods: Fifty-six subjects underwent a standard CMR examination at the NIH Clinical Center from 2009 until 2014: 20 patients with acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected controls. Standard volumetric measurements; late gadolinium enhancement imaging and pre- and post-contrast T1 mapping were performed. ECV was calculated by calibration of pre- and post-contrast T1 values with blood hematocrit. Results: Demographics and cardiac parameters were similar in both groups. There was no significant valvular disorder in either group. Subjects with chronic SCLS had higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 +/- 44 v. 971 +/- 41, respectively; p = 0.03) and higher myocardial ECV than patients with acute intermittent SCLS or controls: 33.8 +/- 4.6, 26.9 +/- 2.6, 26 +/- 2.4, respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When patients with chronic disease were analyzed together with five patients with acute intermittent disease who had just experienced an acute SCLS flare, ECV values were significantly higher than in subjects with acute intermittent SCLS in remission or age-matched controls and (31.2 +/- 4.6 %, 26.5 +/- 2.7 %, 26 +/- 2.4 %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1 values did not distinguish these three subgroups (1008 +/- 40, 978 +/- 40, 971 +/- 41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls). Abundant myocardial edema without evidence of acute inflammation was detected in cardiac tissue postmortem in one patient. Conclusions: Patients with active SCLS have significantly higher myocardial ECV than age-matched controls or SCLS patients in remission, which correlated with histopathological findings in one patient. C1 [Ertel, Andrew; Kellman, Peter; Leung, Steve; Bandettini, Patricia; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Ertel, Andrew] Medstar Washington Hosp Ctr, Washington, DC USA. [Pratt, Drew] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Leung, Steve] Univ Kentucky, Lexington, KY USA. [Long, Lauren M.; Young, Michael; Nelson, Celeste; Druey, Kirk M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Druey, KM (reprint author), NIAID, NIH, 50 South Dr Room 4154, Bethesda, MD 20892 USA. EM kdruey@niaid.nih.gov RI Leung, Steve/E-5624-2011 OI Leung, Steve/0000-0003-2832-2258 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institutes, National Institutes of Health FX This study was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institutes, National Institutes of Health. NR 24 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD AUG 27 PY 2015 VL 17 AR 76 DI 10.1186/s12968-015-0181-6 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CP6ZU UT WOS:000360037800002 PM 26310790 ER PT J AU Mezey, E Palkovits, M AF Mezey, Eva Palkovits, Miklos TI Forgotten findings of brain lymphatics SO NATURE LA English DT Letter ID VESSELS C1 [Mezey, Eva] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Palkovits, Miklos] Semmelweis Univ, H-1085 Budapest, Hungary. RP Mezey, E (reprint author), Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. EM mezeye@nidcr.nih.gov NR 4 TC 5 Z9 5 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD AUG 27 PY 2015 VL 524 IS 7566 BP 415 EP 415 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CP7LN UT WOS:000360069300018 PM 26310754 ER PT J AU Lundgren, D Babiker, AG Gordin, F Emery, S Sharma, S Avihingsanon, AC Cooper, DA Tkenheuer, GF Llibre, JM Moli-Na, JM Munderi, P Schechter, M Wood, R Klingman, KL Collins, S Lane, HC Phillips, AN Neaton, JD AF Lundgren, Jens D. Babiker, Abdel G. Gordin, Fred Emery, Sean Sharma, Shweta Avihingsanon, An-Chalee Cooper, David A. Tkenheuer, Gerd F. Llibre, Josep M. Moli-Na, Jean-Michel Munderi, Paula Schechter, Mauro Wood, Robin Klingman, Karin L. Collins, Simon Lane, H. Clifford Phillips, Andrew N. Neaton, James D. TI Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TREATMENT START TRIAL; CLINICAL-TRIALS; BASE-LINE; CELL COUNTS; RISK; OUTCOMES; INTERRUPTION; PARTICIPANTS; SMART; DEATH AB BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. C1 [Lundgren, Jens D.] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen O, Denmark. [Babiker, Abdel G.] UCL, Med Res Council Clin Trials Unit, London WC1E 6BT, England. [Gordin, Fred] George Washington Univ, Washington Vet Affairs Med Ctr, Washington, DC USA. [Emery, Sean; Cooper, David A.] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Sharma, Shweta] Univ Minnesota, Minneapolis, MN USA. [Avihingsanon, An-Chalee] Chulalongkorn Univ, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [Tkenheuer, Gerd F.] German Ctr Infect Res, Univ Hosp Cologne, Cologne, Germany. [Llibre, Josep M.] Univ Barcelona, Univ Hosp Germans Trias, Badalona, Spain. [Moli-Na, Jean-Michel] Univ Paris Diderot, St Louis Hosp, Paris, France. [Munderi, Paula] Med Res Council Res Unit AIDS, Entebbe, Uganda. [Schechter, Mauro] Projeto Praca Onze, Rio De Janeiro, Brazil. [Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Klingman, Karin L.; Lane, H. Clifford] NIAID, Bethesda, MD 20892 USA. [Collins, Simon] HIV I Base, London, England. [Phillips, Andrew N.] UCL, London, England. [Neaton, James D.] Univ Minnesota, Minneapolis, MN USA. RP Lundgren, D (reprint author), Univ Copenhagen, Dept Infect Dis, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM jens.lundgren@regionh.dk RI Phillips, Andrew/B-4427-2008; Emery, Sean/H-4920-2013; OI Phillips, Andrew/0000-0003-2384-4807; Emery, Sean/0000-0001-6072-8309; Lundgren, Jens/0000-0001-8901-7850; Ristola, Matti/0000-0001-5115-2811 FU National Institute of Allergy and Infectious Diseases FX Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048. NR 48 TC 303 Z9 307 U1 11 U2 42 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 2015 VL 373 IS 9 BP 795 EP 807 DI 10.1056/NEJMoa1506816 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CP8VC UT WOS:000360171700006 ER EF